Association between Impella device support and elevated rates of gout flares: a retrospective propensity-matched study.

BACKGROUND: Impella is an advanced ventricular assist device frequently used as a bridge to heart transplantation. The association of Impella with increased rates of gout flares has not been studied. Our primary aim is to determine the rates of gout flares in patients on Impella support. METHODOLOGY: A retrospective study was conducted between January 2017 and September 2022 involving all patients who underwent heart transplantation. The cohort was divided into two groups based on Impella support for statistical analysis. In patients receiving Impella support, outcome measures were compared based on the development of gout flares. 1:1 nearest neighbor propensity match, as well as inverse propensity of treatment weighted analyses, were performed to explore the causal relationship between impella use and gout flare in our study population. RESULTS: Our analysis included 213 patients, among which 42 (19.71%) patients were supported by Impella. Impella and non-Impella groups had similar age, race, and BMI, but more males were in the Impella group. Gout and chronic kidney disease were more prevalent in Impella-supported patients, while coronary artery disease was less common. The prevalence of gout flare was significantly higher in Impella patients (30.9% vs. 5.3%). 42 Impella-supported patients were matched with 42 patients from the non-impella group upon performing a 1:1 propensity matching. Impella-supported patients were noted to have a significantly higher risk of gout flare (30.9% vs. 7.1%, SMD = 0.636), despite no significant difference in pre-existing gout history and use of anti-gout medications. Impella use was associated with a significantly increased risk of gout flare in unadjusted (OR 8.07), propensity-matched (OR 5.83), and the inverse propensity of treatment-weighted analysis (OR 4.21). CONCLUSION: Our study is the first to identify the potential association between Impella support and increased rates of gout flares in hospitalized patients. Future studies are required to confirm this association and further elucidate the biological pathways. It is imperative to consider introducing appropriate measures to prevent and promptly manage gout flares in Impella-supported patients.

Axillary mechanical circulatory support improves renal function prior to heart transplantation in patients with chronic kidney disease.

Impaired kidney function is often associated with acute decompensation of chronic heart failure and portends a poor prognosis. Unfortunately, current data have demonstrated worse survival in patients with acute kidney injury than in patients with chronic kidney disease during durable LVAD placement as bridge therapy. Furthermore, end-stage heart failure patients undergoing combined heart-kidney transplantation have poorer short- and long-term survival than heart transplants alone. We evaluated the kidney function recovery in our heart failure population awaiting heart transplantation at our institution, supported by temporary Mechanical Circulatory Support (tMCS) with Impella 5.5. The protocol (#22004000) was approved by the Mayo Clinic institutional review board, after which we performed a retrospective review of all patients with acute on chronic heart failure and kidney disease in patients considered for only heart and kidney combined organ transplant and supported by tMCS between January 2020 and February 2021. Hemodynamic and kidney function trends were recorded and analyzed before and after tMCS placement and transplantation. After placement of tMCS, we observed a trend towards improvement in creatinine, Fick cardiac index, mixed venous saturation, and glomerular filtration rate (GFR), which persisted through transplantation and discharge. The average duration of support with tMCS was 16.5 days before organ transplantation. The median pre-tMCS creatinine was 2.1 mg/dL (IQR 1.75-2.3). Median hematocrit at the time of tMCS placement was 32% (IQR 32-34), and the median estimated glomerular filtration rate was 34 mL/min/BSA (34-40). The median GFR improved to 44 mL/min/BSA (IQR 45-51), and serum creatinine improved to 1.5 mg/dL (1.5-1.8) after tMCS. Median discharge creatinine was 1.1 mg/dL (1.19-1.25) with a GFR of 72 (65-74). None of these six patients supported with tMCS required renal replacement therapy after heart transplantation. Early adoption of Impella 5.5 in this patient population resulted in renal recovery without needing renal replacement therapies or dual organ transplantation and should be further evaluated.

One-year survival in recipients older than 50 bridged to heart transplant with Impella 5.5 via axillary approach.

BACKGROUND: Optimizing patients with advanced heart failure before orthotopic heart transplantation (OHT), especially in patients greater than 50 years old, is imperative to achieving successful post-transplant outcomes. Complications are well-described for patients bridged to transplant (BTT) with durable left ventricular assist device (LVAD) support. Given the lack of data available in older recipients after the recent increase in mechanical support use, we felt it crucial to report our center's one-year outcomes in older recipients after heart transplantation with percutaneously placed Impella 5.5 as a BTT. METHODS: Forty-nine OHT patients were supported with the Impella 5.5 intended as a bridge between December 2019 and October 2022 at Mayo Clinic in Florida. Data were extracted from the electronic health record at baseline and during their transplant episode of care after Institutional Review Boards approval as exempt for retrospective data collection. RESULTS: Thirty-eight patients aged 50 or older were supported with Impella 5.5 as BTT. Ten patients underwent heart and kidney transplantation within this cohort. The median age at OHT was 63 (58-68) years, with 32 male (84%) and six female patients (16%). Etiology was divided into ischemic (63%) and non-ischemic cardiomyopathy (37%). The baseline median ejection fraction was 19% (15-24). Most patients were in blood group O (60%), and 50% were diabetic. The average duration of support was 27 days (range 6-94). The median duration of follow-up is 488 days (185-693). For patients that have reached the 1-year follow-up timeframe (22 of 38, 58%), the 1-year post-transplant survival is 95%. CONCLUSION: Our single-center data provides awareness for using the Impella 5.5 percutaneously placed axillary support device in older heart failure patients in cardiogenic shock as a bridge to transplantation. One-year survival outcomes after heart transplantation are excellent despite the older recipient's age and prolonged pre-transplant support.

Locomotor Muscle Microvascular Dysfunction in Heart Failure With Preserved Ejection Fraction.

[Figure: see text].

Exertional Angina Due To Fused Aortic Bioprosthesis During Left Ventricular Assist Device Support: Two Cases and Review of the Literature.

We present the case of two patients with idiopathic dilated cardiomyopathy and moderate aortic valve regurgitation that were treated with a bioprosthetic valve at the time of the left ventricular assist device (LVAD) implantation. A few months later, patients revealed partial recovery in the left ventricle systolic function. Both patients, during the LVAD turndown protocol, reported the onset of chest pain. The transthoracic echocardiography revealed the presence of a new transaortic pressure gradient. We confirmed the presence of a fused bioprosthetic valve by further performing a transesophageal echocardiogram and a left and right heart catheterization. Replacement of aortic valve at the time of an LVAD implantation constitutes a challenging case. Although a mechanical valve is contraindicated due to the increased thromboembolic risk, selecting a bioprosthetic valve increases the risk of valve leaflets fusion. The consequences of this phenomenon should be acknowledged in LVAD patients undergoing aortic valve replacement with a bioprosthetic, especially under the view of LVAD explantation for those revealing myocardial recovery under mechanical unloading.

Evidence of microvascular dysfunction in heart failure with preserved ejection fraction.

OBJECTIVE: While vascular dysfunction is well defined in patients with heart failure (HF) with reduced ejection fraction (HFrEF), disease-related alterations in the peripheral vasculature of patients with HF with preserved ejection fraction (HFpEF) are not well characterised. Thus, we sought to test the hypothesis that patients with HFpEF would demonstrate reduced vascular function, at the conduit artery and microvascular levels, compared with controls. METHODS: We examined conduit artery function via brachial artery flow-mediated dilation (FMD) and microvascular function via reactive hyperaemia (RH) following 5 min of ischaemia in 24 patients with Class II-IV HFpEF and 24 healthy controls matched for age, sex and brachial artery diameter. RESULTS: FMD was reduced in patients with HFpEF compared with controls (HFpEF: 3.1±0.7%; CONTROLS: 5.1±0.5%, p=0.03). However, shear rate at time of peak brachial artery dilation was lower in patients with HFpEF compared with controls (HFpEF: 42 070±4018/s; CONTROLS: 69 018±9509/s, p=0.01), and when brachial artery FMD was normalised for the shear stimulus, cumulative area-under-the-curve (AUC) at peak dilation, the between-group differences were eliminated (HFpEF: 0.11±0.03%/AUC; CONTROLS: 0.09±0.01%/AUC, p=0.58). RH, assessed as AUC, was lower in patients with HFpEF (HFpEF: 454±35 mL; CONTROLS: 660±63 mL, p<0.01). CONCLUSIONS: Collectively, these data suggest that maladaptations at the microvascular level contribute to the pathophysiology of HFpEF, while conduit artery vascular function is not diminished beyond that which occurs with healthy aging.

Further Peripheral Vascular Dysfunction in Heart Failure Patients With a Continuous-Flow Left Ventricular Assist Device: The Role of Pulsatility.

OBJECTIVES: Using flow-mediated vasodilation (FMD) and reactive hyperemia (RH), this study aimed to provide greater insight into left ventricular assist device (LVAD)-induced changes in peripheral vascular function. BACKGROUND: Peripheral endothelial function is recognized to be impaired in patients with heart failure with reduced ejection fraction (HFrEF), but the peripheral vascular effects of continuous-flow LVAD implantation, now used as either a bridge to transplantation or as a destination therapy, remain unclear. METHODS: Sixty-eight subjects (13 New York Heart Association [NYHA] functional class II HFrEF patients, 19 NYHA functional class III/IV HFrEF patients, 20 NYHA functional class III/IV HFrEF patients post-LVAD implantation, and 16 healthy age-matched control subjects) underwent FMD and RH testing in the brachial artery with blood flow velocity, artery diameters, and pulsatility index (PI) assessed by ultrasound Doppler. RESULTS: PI was significantly lower in the LVAD group (2.0 ± 0.4) compared with both the HFrEF II (8.6 ± 0.8) and HFrEF III/IV (8.1 ± 0.9) patients, who, in turn, had significantly lower PI than the control subjects (12.8 ± 0.9). Likewise, LVAD %FMD/shear rate (0.09 ± 0.01 %Δ/s(-1)) was significantly reduced compared with all other groups (control subjects, 0.24 ± 0.03; HFrEF II, 0.17 ± 0.02; and HFrEF III/IV, 0.13 ± 0.02 %Δ/s(-1)), and %FMD/shear rate significantly correlated with PI (r = 0.45). RH was unremarkable across groups. CONCLUSIONS: Although central hemodynamics are improved in patients with HFrEF by a continuous-flow LVAD, peripheral vascular function is further compromised, which is likely due, at least in part, to the reduction in pulsatility that is a characteristic of such a mechanical assist device.

Morbidity and mortality in heart transplant candidates supported with mechanical circulatory support: is reappraisal of the current United network for organ sharing thoracic organ allocation policy justified?

BACKGROUND: Survival of patients on left ventricular assist devices (LVADs) has improved. We examined the differences in risk of adverse outcomes between LVAD-supported and medically managed candidates on the heart transplant waiting list. METHODS AND RESULTS: We analyzed mortality and morbidity in 33,073 heart transplant candidates registered on the United Network for Organ Sharing (UNOS) waiting list between 1999 and 2011. Five groups were selected: patients without LVADs in urgency status 1A, 1B, and 2; patients with pulsatile-flow LVADs; and patients with continuous-flow LVADs. Outcomes in patients requiring biventricular assist devices, total artificial heart, and temporary VADs were also analyzed. Two eras were defined on the basis of the approval date of the first continuous-flow LVAD for bridge to transplantation in the United States (2008). Mortality was lower in the current compared with the first era (2.1%/mo versus 2.9%/mo; P<0.0001). In the first era, mortality of pulsatile-flow LVAD patients was higher than in status 2 (hazard ratio [HR], 2.15; P<0.0001) and similar to that in status 1B patients (HR, 1.04; P=0.61). In the current era, patients with continuous-flow LVADs had mortality similar to that of status 2 (HR, 0.80; P=0.12) and lower mortality compared with status 1A and 1B patients (HR, 0.24 and 0.47; P<0.0001 for both comparisons). However, status upgrade for LVAD-related complications occurred frequently (28%) and increased the mortality risk (HR, 1.75; P=0.001). Mortality was highest in patients with biventricular assist devices (HR, 5.00; P<0.0001) and temporary VADs (HR, 7.72; P<0.0001). CONCLUSIONS: Mortality and morbidity on the heart transplant waiting list have decreased. Candidates supported with contemporary continuous-flow LVADs have favorable waiting list outcomes; however, they worsen significantly once a serious LVAD-related complication occurs. Transplant candidates requiring temporary and biventricular support have the highest risk of adverse outcomes. These results may help to guide optimal allocation of donor hearts.

A differing role of oxidative stress in the regulation of central and peripheral hemodynamics during exercise in heart failure.

This study sought to characterize the role of free radicals in regulating central and peripheral hemodynamics at rest and during exercise in patients with heart failure (HF). We examined cardiovascular responses to dynamic handgrip exercise (4, 8, and 12 kg at 1 Hz) following consumption of either a placebo or acute oral antioxidant cocktail (AOC) consisting of vitamin C, E, and α-lipoic acid in a balanced, crossover design. Central and peripheral hemodynamics, mean arterial pressure, cardiac index, systemic vascular resistance (SVR), brachial artery blood flow, and peripheral (arm) vascular resistance (PVR) were determined in 10 HF patients and 10 age-matched controls. Blood assays evaluated markers of oxidative stress and efficacy of the AOC. When compared with controls, patients with HF exhibited greater oxidative stress, measured by malondialdehyde (+36%), and evidence of endogenous antioxidant compensation, measured by greater superoxide dismutase activity (+83%). The AOC increased plasma ascorbate (+50%) in both the HF patients and controls, but significant systemic hemodynamic effects were only evident in the patients with HF, both at rest and throughout exercise. Specifically, the AOC reduced mean arterial pressure (-5%) and SVR (-12%) and increased cardiac index (+7%) at each workload. In contrast, peripherally, brachial artery blood flow and PVR (arm) were unchanged by the AOC. In conclusion, these data imply that SVR in patients with HF is, at least in part, mediated by oxidative stress. However, this finding does not appear to be the direct result of muscle-specific changes in PVR.

Vascular function and the role of oxidative stress in heart failure, heart transplant, and beyond.

Using flow-mediated vasodilation (FMD), reactive hyperemia, and an acute oral antioxidant cocktail (AOC; vitamins C and E and α-lipoic acid), this study aimed to provide greater insight into altered vascular function and the role of oxidative stress in chronic heart failure patients with reduced ejection fraction (HFrEF) and at several time points beyond heart transplantation (HTx). A total of 61 age-matched subjects (12 healthy controls, 14 New York Heart Association class II and III HFrEF, and 35 HTx recipients [<3 years post-HTx, 5-10 years post-HTx, and >14 years post-HTx]) ingested either placebo (PL) or an AOC before FMD and reactive hyperemia testing of the brachial artery. Vascular function, as measured by FMD, was not different among the controls (6.8±1.9%), recent <3-year post-HTx group (8.1±1.2%), and the 5- to 10-year post-HTx group (5.5±1.0%). However, PL FMD was lower in the HFrEF (4.5±0.7%) and in the >14-year post-HTx group (2.9±0.8%). The AOC increased plasma ascorbate levels in all of the groups but only increased FMD in the controls (PL, 6.8±1.9%; AOC, 9.2±1.0%) and >14-year post-HTx recipients (PL, 2.9±0.8%; AOC, 4.5±1.3%). There were no differences in reactive hyperemia in any of the groups with PL or AOC. This cross-sectional study reveals that, compared with controls, vascular function is blunted in HFrEF, is similar soon after HTx, but is decreased with greater time post-HTx with free radicals implicated in this progression.

Changing outcomes in patients bridged to heart transplantation with continuous- versus pulsatile-flow ventricular assist devices: an analysis of the registry of the International Society for Heart and Lung Transplantation.

BACKGROUND: Patients bridged to heart transplantation with left ventricular assist devices (LVADs) have been reported to have higher post-transplant mortality compared with those without LVADs. Our aim was to determine the impact of the type of LVAD and implant era on post-transplant survival. METHODS: In this study we included 8,557 patients from the registry of the International Society for Heart and Lung Transplantation. We examined post-transplant outcomes in 1,100 patients bridged to transplant with pulsatile-flow LVADs between January 2000 and June 2004 (first era), 880 patients bridged with pulsatile-flow LVADs between July 2004 and May 2008 (second era), and 417 patients bridged with continuous-flow LVADs in the second era. Patients who required intravenous inotropes but not LVAD support (n = 2,728) and patients who did not require either LVAD or inotropes (n = 3,432) served as controls. RESULTS: Post-transplant survival of patients bridged with pulsatile LVADs improved significantly between the first and the second era (p = 0.03). In the second era, there was no significant difference in post-transplant survival of patients bridged with pulsatile- vs continuous-flow LVADs (p = 0.26), and survival rates in the 2 groups were not statistically different from that of the non-LVAD group. Graft rejection was similar in patients bridged with LVADs compared to those without LVADs. CONCLUSIONS: In the most recent era, the use of either pulsatile- or continuous-flow LVADs did not result in increased post-transplant mortality. This finding is important as the proportion of patients with LVADs at the time of transplant has been rising.

Understanding exercise-induced hyperemia: central and peripheral hemodynamic responses to passive limb movement in heart transplant recipients.

To better characterize the contribution of both central and peripheral mechanisms to passive limb movement-induced hyperemia, we studied nine recent (<2 yr) heart transplant (HTx) recipients (56 ± 4 yr) and nine healthy controls (58 ± 5 yr). Measurements of heart rate (HR), stroke volume (SV), cardiac output (CO), and femoral artery blood flow were recorded during passive knee extension. Peripheral vascular function was assessed using brachial artery flow-mediated dilation (FMD). During passive limb movement, the HTx recipients lacked an HR response (0 ± 0 beats/min, Δ0%) but displayed a significant increase in CO (0.4 ± 0.1 l/min, Δ5%) although attenuated compared with controls (1.0 ± 0.2 l/min, Δ18%). Therefore, the rise in CO in the HTx recipients was solely dependent on increased SV (5 ± 1 ml, Δ5%) in contrast with the controls who displayed significant increases in both HR (6 ± 2 beats/min, Δ11%) and SV (5 ± 2 ml, Δ7%). The transient increase in femoral blood volume entering the leg during the first 40 s of passive movement was attenuated in the HTx recipients (24 ± 8 ml) compared with controls (93 ± 7 ml), whereas peripheral vascular function (FMD) appeared similar between HTx recipients (8 ± 2%) and controls (6 ± 1%). These data reveal that the absence of an HR increase in HTx recipients significantly impacts the peripheral vascular response to passive movement in this population and supports the concept that an increase in CO is a major contributor to exercise-induced hyperemia.

Temporal trends in heart transplantation from high-risk donors: are there lessons to be learned? A multi-institutional analysis.

BACKGROUND: In 2003 the Department of Health and Human Services sponsored the Organ Donation Breakthrough Collaborative (ODBC) with the aim to increase organ donation. After the ODBC, increases in the number of all solid organs transplanted, except for heart, were seen. The aim of this study was to determine if ODBC resulted in temporal changes in the use of hearts from high-risk donors. METHODS: We analyzed data from the Cardiac Transplant Research Database in three eras: 1990-1995, 1996-2002, and 2003-2007. We explored temporal changes in high-risk donor characteristics: age, gender, hypertension, diabetes mellitus, abnormal echocardiogram, and ischemic time. RESULTS: Between 1990 and 2007, 7,220 patients underwent transplantation in 26 centers. Donors in the first era were least likely to have high-risk characteristics of higher age (mean, 30 years), female gender (30%), hypertension (8%), diabetes mellitus (1%), structural abnormalities on echocardiogram (7%), and prolonged graft ischemic time (mean, 163 minutes). In the second era, there was a significant increase in the use of donors with the above mentioned high-risk characteristics-32 years, 33%, 10%, 3%, 8% and 181 minutes, respectively. In the third post-ODBC era, no further increase was seen in high-risk donors, but rather a trend for avoidance of risk-32 years, 28%, 10%, 2%, 5% and 186 minutes, respectively. CONCLUSION: Significant temporal changes in the characteristics of heart donors have occurred in the past 17 years. Recent temporal changes, however, cannot be directly attributed to the ODBC efforts.

Effects of the 2006 U.S. thoracic organ allocation change: analysis of local impact on organ procurement and heart transplantation.

BACKGROUND: The United Network for Organ Sharing (UNOS) implemented a thoracic organ allocation policy change (APC) in July 2006 that aimed to reduce death on the waiting list by expanding regional organ sharing. As such, organs would be allocated to the sickest recipients with highest listing status across the region. Our aim was to determine the impact of the new policy on the procurement and transplant process within our program. METHODS: We analyzed data supplied by UNOS as the contractor for the Organ Procurement and Transplantation Network and from the local organ procurement organization for 2 years before and 2 years after implementation of the APC. RESULTS: The APC resulted in an increase in the proportion of Status 1A patients transplanted (24% to 43%, p = 0.015) and a decrease in the proportion of Status 2 patients transplanted (56% to 24%, p = 0.001). Significant increases were observed in mean graft ischemic time (196 minutes to 223 minutes, p = 0.022), number of patients transplanted with ventricular assist devices (17% to 31%, p = 0.036), and procurement costs. There was no significant difference in waiting-list mortality (6% to 5%, p = 0.75) and short-term post-transplant survival. CONCLUSIONS: The 2006 change in UNOS organ allocation policy resulted in an increase in Status 1A transplants, graft ischemic time and procurement costs, and a decrease in Status 2 transplants, but no effect on mortality on the waiting list within our center. To assess the full effect of the APC on outcomes, the long-term impact of the increased graft ischemic time on survival should be quantified.