Heart transplantation remains the gold standard treatment for end-stage heart failure patients without contraindications. However, limited donor availability and long wait times have created a need ...for left ventricular assist devices (LVAD) to be used as a bridge to transplantation in appropriately selected patients. Improvements in LVAD technology have resulted in improved short- and long-term outcomes, further supporting the use of these devices for a bridge-to-transplant (BTT) indication. LVAD utilization as BTT exhibits notable disparities worldwide, mainly due to variations in organ availability, allocation policies, and financial constraints. Although Europe has experienced a consistent increase in the use of LVAD for this purpose, the United Network for Organ Sharing 2018 policy amendment resulted in a significant reduction in the number of LVADs used for BTT in the US. To overcome this issue, modifications in the US allocation policy to consider factors such as days on device support, age, and type of complications may be necessary to potentially increase implantation rates.The authors provide an overview comparing the current state of heart transplantation in the US and Europe, with a particular focus on how distinct allocation policies and organ availability impact medical practices. Additionally, the review will examine critical aspects ranging from patient selection and pre-implantation optimization to post-transplant outcomes.
Following the MOMENTUM 3 trial and the discontinuation of the HeartWare HVAD, the HeartMate 3 LVAD (HM 3) has become the main durable device for bridging to transplantation; however, outcome of this ...strategy in the new heart allocation system is not well understood.
The United Network for Organ Sharing (UNOS) registry was queried to include adult patients (≥18 years old) listed for heart transplantation between 2010 and 2020. Trends in durable LVAD utilization and outcomes of patients with HM 3 LVAD were examined in the pre- vs post-heart allocation system.
From 2017 to 2020, there was a 28.3% decline in the number of patients waitlisted with an FDA-approved durable LVAD. Overall, 449 patients were waitlisted with HM 3 in the pre-allocation era compared to 1094 patients in the post-allocation. Cumulative incidence of heart transplantation (53.4% vs 50.7%, p = 0.76) and death or delisting for worsening status (5.0%, vs 4.2%, p = 0.43) at 1-year after listing with HM 3 LVAD was comparable in the pre- vs post-allocation era. Old age (>50), ischemic HF, poor functional status, elevated creatinine (>1.3 mg/dL), pulmonary hypertension (>3 WU), and obesity (body mass index > 33 kg/m
) were predictors of post-transplant graft mortality after bridging with HM 3.
While the utilization of durable devices as BTT have declined under the new heart allocation system, bridging with HM 3 LVAD remains a safe strategy in carefully selected patients. Bridging decision should be individualized based on patient risk factors.
The physiological response of the right ventricle (RV) following left ventricular assist device (LVAD) implantation is difficult to predict. We aimed to investigate RV geometric and functional ...changes after LVAD insertion and their effects on clinical outcomes.
We retrospectively reviewed 188 patients who underwent HeartMate 3 implantation at our center between November 2014 and September 2021. The RV end-diastolic diameter (RVEDD) and RV end-diastolic area (RVEDA) were measured on preoperative and predischarge transthoracic echocardiography. The nonadapted group included patients with increased RVEDD and RVEDA at discharge. The composite outcome was defined as death or readmission due to worsening right heart failure.
There were 82 patients (44%) who had a nonadapted and 106 patients (56%) who had an adapted RV. Preoperatively, the nonadapted group had smaller RVEDD (46 vs 49 mm, p < 0.001) and RVEDA (27 vs 31 cm
, p < 0.001). At discharge, the nonadapted group had larger RVEDD (51 vs 43 mm, p < 0.001) and RVEDA (33 vs 27 cm
, p < 0.001). Kaplan-Meier analysis demonstrated worse 3-year survival (77% vs 91%, p = 0.006) and freedom from composite outcome (58% vs 85%, p < 0.001) in the nonadapted group. A multivariable Cox proportional hazards model showed that nonadaption (hazard ratio HR 3.09, 95% confidence interval CI 1.29-7.40, p = 0.01) and age (HR 3.73, 95% CI 1.42-9.77, p = 0.007) were independent predictors of composite outcome.
Acute RV dimensional changes after LVAD insertion may represent intrinsic RV function and may be a useful prognostic marker.
Little is known regarding the profile of patients with multiorgan failure listed for simultaneous cardiac transplantation and secondary organ. In addition, few studies have reported how these ...patients are bridged with mechanical circulatory support (MCS). In this study, we examined national data of patients listed for multiorgan transplantation and their outcomes after bridging with or without MCS.
United Network for Organ Sharing data were reviewed for adult multiorgan transplantations from 1986 to 2019. Post-transplant patients and total waitlist listings were examined and stratified according to MCS status. Survival was assessed via Cox regression in the post-transplant cohort and Fine–Gray competing risk regression with transplantation as a competing risk in the waitlist cohort.
There were 4534 waitlist patients for multiorgan transplant during the study period, of whom 2117 received multiorgan transplants. There was no significant difference in post-transplant survival between the MCS types and those without MCS in the whole cohort and heart-kidney subgroup. Fine–Gray competing risk regression showed that patients bridged with extracorporeal membrane oxygenation had significantly greater waitlist mortality compared with those without MCS when controlling for preoperative characteristics (subdistribution hazard ratio, 2.27; 95% confidence interval, 1.48-3.47; P < .001), whereas those bridged with a ventricular assist device had a decreased incidence of death compared with those without MCS (subdistribution hazard ratio, 0.78; 95% confidence interval, 0.63-0.96; P = .017).
MCS, as currently applied, does not appear to compromise the survival of multiorgan heart transplant patients. Waitlist data show that extracorporeal membrane oxygenation patients have profoundly worse survival irrespective of preoperative factors including organ type listed. Survival on the waitlist for multiorgan transplant has improved across device eras.
Cumulative incidence curves (upper panel) that depict an increased incidence of death in patients who received extracorporeal membrane oxygenation (ECMO) while waitlisted for multiorgan transplantation. Curves were produced using Fine–Gray competing risk regression with transplantation as a competing risk. Patients were censored at the time of waitlist removal. Differences in incidence of death between mechanical circulatory support (MCS) types were assessed using the Gray test. The lower panel depicts adjusted survival curves on the basis of a Cox proportional hazards analysis that shows that there was no survival difference between patients bridged to multiorgan transplant with each MCS type and no MCS. This study suggests that ECMO is associated with increased waitlist mortality and the use of MCS bridging should not preclude patients from receiving multiorgan transplants because survival after transplantation does not appear to be compromised by its use. IABP, Intra-aortic balloon pump; TAH, total artificial heart; VAD, ventricular assist device. Display omitted
The clinical implications of the discrepancy between cystatin C (cysC)– and serum creatinine (Scr)–estimated glomerular filtration rate (eGFR) in patients with heart failure (HF) and reduced ejection ...fraction (HFrEF) are unknown.
Post-hoc analysis of randomized trial data.
1,970 patients with HFrEF enrolled in PARADIGM-HF with available baseline cysC and Scr measurements.
Intraindividual differences between eGFR based on cysC (eGFRcysC) and Scr (eGFRScr; eGFRdiffcysC-Scr).
Clinical outcomes included the PARADIGM-HF primary end point (composite of cardiovascular CV mortality or HF hospitalization), CV mortality, all-cause mortality, and worsening kidney function. We also examined poor health-related quality of life (HRQoL), frailty, and worsening HF (WHF), defined as HF hospitalization, emergency department visit, or outpatient intensification of therapy between baseline and 8-month follow-up.
Fine-Gray subdistribution hazard models and Cox proportional hazards models were used to regress clinical outcomes on baseline eGFRdiffcysC-Scr. Logistic regression was used to investigate the association of baseline eGFRdiffcysC-Scr with poor HRQoL and frailty. Linear regression models were used to assess the association of WHF with eGFRcysC, eGFRScr, and eGFRdiffcysC-Scr at 8-month follow-up.
Baseline eGFRdiffcysC-Scr was higher than +10 and lower than−10mL/min/1.73m2 in 13.0% and 35.7% of patients, respectively. More negative values of eGFRdiffcysC-Scr were associated with worse outcomes (subhazard ratio per standard deviation: PARADIGM-HF primary end point, 1.18; P=0.008; CV mortality, 1.34; P=0.001; all-cause mortality, 1.39; P<0.001; worsening kidney function, 1.31; P=0.05). For a 1–standard-deviation decrease in eGFRdiffcysC-Scr, the prevalences of poor HRQoL and frailty increased by 29% and 17%, respectively (P≤0.008). WHF was associated with a more pronounced decrease in eGFRcysC than in eGFRScr, resulting in a change in 8-month eGFRdiffcysC-Scr of−4.67mL/min/1.73m2 (P<0.001).
Lack of gold-standard assessment of kidney function.
In patients with HFrEF, discrepancies between eGFRcysC and eGFRScr are common and are associated with clinical outcomes, HRQoL, and frailty. The decline in kidney function associated with WHF is more marked when assessed with eGFRcysC than with eGFRScr.
Kidney function assessment traditionally relies on serum creatinine (Scr) to establish an estimated glomerular filtration rate (eGFR). However, this has been challenged with the introduction of an alternative marker, cystatin C (cysC). Muscle mass and nutritional status have differential effects on eGFR based on cysC (eGFRcysC) and Scr (eGFRScr). Among ambulatory patients with heart failure enrolled in PARADIGM-HF, we investigated the clinical significance of the difference between eGFRcysC and eGFRScr. More negative values (ie, eGFRScr>eGFRcysC) were associated with worse clinical outcomes (including mortality), poor quality of life, and frailty. In patients with progressive heart failure, which is characterized by muscle loss and poor nutritional status, the decline in kidney function was more pronounced when eGFR was estimated using cysC rather than Scr.
Background A subclavian intraaortic balloon pump (SC-IABP) can help to optimize patients with advanced congestive heart failure as a bridge to definitive therapy. We retrospectively reviewed our ...experience to assess the application and safety of this technique. Methods We studied 88 patients with decompensated advanced congestive heart failure who received SC-IABP placement between January 2011 and December 2014. The SC-IABP was placed through a graft in the subclavian artery. The intended therapeutic goals for SC-IABP were bridge to transplant (n = 61), mechanical circulatory support (n = 21), or recovery (n = 6). Success was defined as stroke-free survival, achievement of therapeutic goal, and maintenance or improvement in renal function, hemodynamics, and physical conditioning through ambulation and rehabilitation. Results Eighty patients were successfully bridged to the next therapy (transplant 93.4%, mechanical circulatory support 95.3%, recovery 50%). There was no mortality related to SC-IABP placement. Duration of SC-IABP support was 4 to 135 days (median 21). Failure was attributed to escalation of support (n = 5), stroke (n = 2), and sepsis (n = 1). Mean pulmonary artery pressure significantly improved from 33 ± 11 mm Hg to 28 ± 8 mm Hg ( p < 0.05). Eighty-four patients (95.5%) ambulated more than 3 times a day. Two-minute step test demonstrated significant improvement, from 50 ± 9 steps to 90 ± 23 steps (n = 16, p < 0.001). Specific complications of SC-IABP included exchange/repositioning (n = 26, 29.5%), subclavian artery thrombosis (n = 1, 1.1%), and reexploration for hematoma (n = 4, 4.5%) and infection (n = 2, 2.3%). No distal thromboembolic events were observed. Conclusions The SC-IABP provided excellent hemodynamic support with minimal morbidity and mortality, allowed for extensive rehabilitation, and permitted more than 90% of patients to receive their intended therapy. Therefore, SC-IABP is a compelling bridge device for patients with advanced congestive heart failure.
Aortic root thrombosis(ART) is a complication of continuous-flow left ventricular assist device therapy. However, the incidence and related complications of ART in HeartMate 3 (HM3) patients remain ...unknown.
Patients who underwent HM3 implantation from November 2014 to August 2020 at a quaternary academic medical center were included. Demographics and outcomes were abstracted from the medical record. Echocardiograms and contrast-enhanced computed tomography studies were reviewed to identify patients who developed ART and/or moderate or greater aortic insufficiency (AI) on HM3 support.
The study cohort included 197 HM3 patients with a median postimplant follow-up of 17.5 months. Nineteen patients (9.6%) developed ART during HM3 support, and 15 patients (7.6%) developed moderate or greater AI. Baseline age, gender, race, implantation strategy, and INTERMACS classification were similar between the ART and no-ART groups. ART was associated with an increased risk of death, stroke, or aortic valve (AV) intervention (subhazard ratio SHR 3.60 95% confidence interval (CI) 1.71-7.56; p = 0.001) and moderate or greater AI (SHR 11.1 CI 3.60-34.1; p < 0.001) but was not associated with a statistically significantly increased risk of death or stroke on HM3 support (2.12 0.86-5.22; p = 0.10). Of the 19 patients with ART, 6 (31.6%) developed moderate or greater AI, necessitating more frequent AV interventions (ART: 5 AV interventions 3 surgical repairs, 1 surgical replacement, 1 transcatheter replacement; 26.3%; no-ART: 0).
Nearly 10% of HM3 patients developed ART during device support. ART was associated with increased risk of a composite end-point of death, stroke, or AV intervention as well as moderate or greater AI.
There are limited safety data on reduced anti-thrombotic therapy (RT) in patients with HeartMate 3 (HM3) left ventricular assist device (LVAD). We conducted a single-center, retrospective study of ...patients with HM3 managed with RT from November 2014 through January 2020. We analyzed baseline characteristics, RT indications, and bleeding and thrombotic complications. We found that 50 of 161 patients with HM3 (31.1%) received RT starting at a median time of 90.5 days after LVAD implantation. Patients on RT were older and more likely to have ischemic heart failure than patients on standard anti-thrombotic therapy (ST). The most common indication for RT was gastrointestinal bleeding (29 patients 58.0%). At 1-year follow-up, 5.0% of patients on RT developed a thrombotic event. Switching patients from ST to RT reduced the occurrence of major bleeding from 1.252 to 0.324 events per patient-year (p = 0.006). In our population of patients with HM3 LVAD, RT reduces bleeding without increasing the incidence of thrombosis. Our retrospective study suggests that an upfront RT strategy in patients with HM3 may be beneficial and should be prospectively studied.
Right ventricular pressure-volume (PV) analysis characterizes ventricular systolic and diastolic properties independent of loading conditions like volume status and afterload. While long-considered ...the gold-standard method for quantifying myocardial chamber performance, it was traditionally only performed in highly specialized research settings. With recent advances in catheter technology and more sophisticated approaches to analyze PV data, it is now more commonly used in a variety of clinical and research settings. Herein, we review the basic techniques for PV loop measurement, analysis, and interpretation with the aim of providing readers with a deeper understanding of the strengths and limitations of PV analysis. In the second half of the review, we detail key scenarios in which right ventricular PV analysis has influenced our understanding of clinically relevant topics and where the technique can be applied to resolve additional areas of uncertainty. All told, PV analysis has an important role in advancing our understanding of right ventricular physiology and its contribution to cardiovascular function in health and disease.
Background: Trimethylamine N-oxide (TMAO)—a gut-derived metabolite—is elevated in heart failure (HF) and linked to poor prognosis. We investigated variations in TMAO in HF, left ventricular assist ...device (LVAD), and heart transplant (HT) and assessed its relation with inflammation, endotoxemia, oxidative stress, and gut dysbiosis. Methods: We enrolled 341 patients. TMAO, CRP (C-reactive protein), IL (interleukin)-6, TNF-α (tumor necrosis factor alpha), ET-1 (endothelin-1), adiponectin, lipopolysaccharide, soluble CD14, and isoprostane were measured in 611 blood samples in HF (New York Heart Association class I–IV) and at multiple time points post-LVAD and post-HT. Gut microbiota were assessed via 16S rRNA sequencing among 327 stool samples. Multivariable regression models were used to assess the relationship between TMAO and (1) New York Heart Association class; (2) pre- versus post-LVAD or post-HT; (3) biomarkers of inflammation, endotoxemia, oxidative stress, and microbial diversity. Results: ln-TMAO was lower among HF New York Heart Association class I (1.23 95% CI, 0.52–1.94 µM) versus either class II, III, or IV (1.99 95% CI, 1.68–2.30, 1.97 95% CI, 1.71–2.24, and 2.09 95% CI, 1.83–2.34 µM, respectively; all P <0.05). In comparison to class II–IV, ln-TMAO was lower 1 month post-LVAD (1.58 95% CI, 1.32–1.83 µM) and 1 week and 1 month post-HT (0.97 95% CI, 0.60–1.35 and 1.36 95% CI, 1.01–1.70 µM). ln-TMAO levels in long-term LVAD (>6 months: 1.99 95% CI, 1.76–2.22 µM) and HT (>6 months: 1.86 95% CI, 1.66–2.05 µM) were not different from symptomatic HF. After multivariable adjustments, TMAO was not associated with biomarkers of inflammation, endotoxemia, oxidative stress, or microbial diversity. Conclusions: TMAO levels are increased in symptomatic HF patients and remain elevated long term after LVAD and HT. TMAO levels were independent from measures of inflammation, endotoxemia, oxidative stress, and gut dysbiosis.
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