Study Objective
Mycophenolate mofetil (MMF) is the gold‐standard immunosuppressive agent in heart transplantation (HT), but dose‐dependent toxicities (e.g., neutropenia) are frequent. Gut bacteria ...β‐d‐glucuronidases (GUS) modulate MMF bioavailability, and changes in the intestinal flora may influence the pharmacokinetics of MMF. The objective of this study was to evaluate the safety and efficacy of MMF 1.5 g every 12 h (q12) high‐dose, HD versus 1 g q12 low‐dose, LD and explore the association between neutropenia and GUS.
Measurements
We compared the incidence of acute cellular rejection (ACR) and neutropenia during the first 6 months post‐HT. The association between neutropenia and GUS was investigated in an exploratory analysis on a subset of patients with prospectively collected stool data. Stool samples were analyzed using 16S rRNA sequencing.
Main Results
A total of 168 patients (120 MMF‐HD, 48 MMF‐LD; mean age 55.7 years, 79% male) were studied. Neutropenia occurred in 38.6% of patients at a median of 106 64–143 days. Freedom from neutropenia was lower in MMF‐HD compared with MMF‐LD (57% vs. 73%, p = 0.03). ACR (≥1R/1B) occurred in 37.5% of patients at a median of 20 10–96 days, while high‐grade ACR (≥2R/3A) occurred in 11.3% at a median of 14 9–89 days. Freedom from ACR was similar between groups. MMF‐LD was associated with more high‐grade ACR (hazard ratio HR 3.47, 95% confidence interval CI 1.09–11.08, p = 0.03) during the first month, but less neutropenia (HR 0.54, 95% CI 0.29–1.00, p = 0.05) between 1 and 6 months. GUS‐producing bacteria were more abundant in neutropenic patients.
Conclusions
MMF‐LD was associated with higher rates of early high‐grade ACR and lower rates of later neutropenia. Further studies are warranted to test whether temporal MMF dose adjustments and gut microbial composition could improve clinical outcomes post‐HT.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Abstract Objectives The purpose of this study was to investigate the differential impact of the 2 most commonly available left ventricular assist device (LVAD) types on the right (RV) and left (LV) ...ventricles using 3-dimensional (3D) echocardiography-based analysis of ventricular morphology. Background LVADs have emerged as common therapy for advanced heart failure. Recent data suggest that the heart responds differently to speed settings in the 2 main devices available (HeartMate II HMII, St Jude Medical, Pleasanton, California, and HVAD, HeartWare International, Framingham, Massachusetts). We hypothesized that 3D echocardiographic assessment of LV and RV volumes and shape would help describe the differential impact of the 2 LVAD types on the heart. Methods Simultaneous 3D echocardiography, ramp test, and right heart catheterization were performed in 31 patients with LVADs (19 with HMII and 12 with HVAD). Device speed was increased stepwise (8,000 to 12,000 for HMII and 2,300 to 3,200 revolutions per minute for HVAD). 3D echocardiographic full-volume LV and RV datasets were acquired, and endocardial surfaces were analyzed using custom software to calculate LV sphericity, conicity (perfect sphere/cone = 1) and RV septal and free-wall curvature (0 = flat; <0 = concave; >0 = convex). Results For both devices, cardiac output increased and wedge pressure decreased with increasing speed. In HMII, LV volumes progressively decreased (meanΔ = 127 ml) as the LV became less spherical and more conical, whereas the RV volume initially remained stable, but subsequently increased at higher speeds (meanΔ = 60 ml). Findings for the HVAD were similar, but less pronounced (LV:meanΔ = 51 ml, RV:meanΔ = 22 ml), and the LV remained significantly more spherical even at high speeds. On average, in HMII patients, the RV septum became more convex (bulging into the LV) at the highest speeds whereas in HVAD patients, there was no discernable change in the RV septum. Conclusions The heart responds differently to pump speed changes with the 2 types of LVAD, as reflected by the volume and shape changes of both the LV and RV. Our study suggests that adding RV assessment to the clinical echo-ramp study may better optimize LVAD speed. Further study is needed to determine whether this would have an impact on patient outcomes.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Despite advances in our understanding of myocardial recovery among left ventricular assist device (LVAD) patients, with 10-30% of patients achieving substantial myocardial improvement, the rates of ...LVAD support cessation remain extremely low (1-2%). These numbers are in stark contrast to clinical trial data where successful LVAD cessation is reported in up to 47% of patients. The majority of LVAD programs lack structured recovery programs and targeted protocols, likely underscoring the heterogeneity that exists among LVAD patients with myocardial recovery. This perspective summarizes the current medical and surgical challenges with respect to 1) identifying the appropriate candidates for LVAD cessation; 2) methods to wean LVAD support; 3) reviewing surgical techniques for cessation of current generation HeartMate 3 LVAD; and 4) approaching shared decision making for LVAD cessation between patients and providers given the uncertainties that remain in the field.
A 77-year-old man who underwent a heart transplant 7 years ago presented with multiple bloody bowel movements. Endoscopic and histologic evaluation revealed chronic active ileitis, granulomatous ...inflammation, multinucleated giant cells, and a rare, equivocal acid-fast bacterium in the terminal ileum. Positive sputum cultures for Mycobacterium tuberculosis and acid-fast bacilli established a diagnosis of intestinal tuberculosis, and RIPE (rifabutin, isoniazid, pyrazinamide, ethambutol) therapy was initiated. Elevated IgG levels on quantitative immunoglobulin testing and a bone marrow biopsy specimen of ≥60% plasma cells confirmed the diagnosis of multiple myeloma that later transformed into its aggressive form, plasma cell leukemia. Induction chemotherapy was initiated; however, the patient experienced retroperitoneal bleeding and pancytopenias, limiting the continuation of chemotherapy, and as a result, the patient was transitioned to palliative care.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Mechanical unloading with left ventricular assist device (LVAD) support can lead to clinically meaningful reversal of stress-related compensatory mechanisms. However, true assessment of left ...ventricular ejection fraction (LVEF) is not possible, whereas the left ventricle is unloaded by LVAD therapy making identification of patients with myocardial recovery even more challenging. We introduce our new protocol, the “reverse ramp test” for HeartWare HVAD, HeartMate II, and HeartMate 3. The reverse ramp is transthoracic echo (TTE) and right heart catheterization (RHC)-based protocol with LVAD turn down steps to minimal support allowing for a more accurate assessment of myocardial function.
Background
Heart transplantation (HT) is the gold standard therapy for advanced heart failure, providing excellent long‐term outcomes. However, postoperative outcomes are limited by bleeding, ...infections, and primary graft dysfunction (PGD) that contribute to early mortality after HT. HT candidates with pre‐existing hematologic disorders, bleeding, and clotting, may represent a higher risk population. We assessed the short‐ and long‐term outcomes of patients with pre‐existing hematologic disorders undergoing HT.
Methods and results
Medical records of all adult patients who received HT from January 2010 to December 2019 at our institution were retrospectively reviewed. Hematologic disorders were identified via chart review and adjudicated by a board‐certified hematologist. Inverse probability weighting and multivariable models were used to adjust for potential pretransplant confounders. Four hundred and ninety HT recipients were included, of whom 29 (5.9%) had a hematologic disorder. Hematologic disorders were associated with severe PGD requiring mechanical circulatory support (aOR 3.15 1.01–9.86; p = .049), postoperative infections (aOR 2.93 1.38–6.23; p = .01), and 3‐year acute cellular rejection (ACR) (≥1R/1B) (aSHR 2.06 1.09–3.87; p = .03). There was no difference in in‐hospital mortality (aOR 1.23 .20–7.58, p = .82) or 3‐year mortality (aHR 1.58 .49–5.12, p = .44).
Conclusions
Patients with hematologic disorders undergoing HT are at increased risk of severe PGD, postoperative infections, and ACR, while in‐hospital and 3‐year mortality remain unaffected.
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DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
Background Indications for concomitant intervention for mitral regurgitation (MR) during left ventricular assist device (LVAD) implantation remain controversial. The objective of this study was to ...determine the impact of the surgical correction of MR during LVAD implantation. Methods From July 2008 to December 2014, 164 patients with significant preoperative MR underwent LVAD (HeartMate II; Thoratec, Pleasanton, CA) implantation. The MR resolved after LVAD implantation in 110 of 164 patients (67.1%) with either surgical or spontaneous correction. The cohort (n = 110) without significant postoperative MR was divided into two groups: a spontaneous correction group (n = 54, MR spontaneously resolved after LVAD implantation); and a surgical correction group (n = 56, MR surgically corrected). Patients who received aortic valve procedures (n = 17) were excluded from this study. Results Patient demographics, perioperative outcomes including bleeding, prolonged intubation, and stroke, and inhospital mortality did not differ in the two groups except for significantly longer cardiopulmonary bypass time in the surgical correction group (spontaneous correction 123 minutes interquartile range (IQR): 107 to 150 versus surgical correction 177 minutes IQR: 132 to 198, p < 0.001). During follow-up, pulmonary wedge pressure (spontaneous correction 17 mm Hg IQR: 12 to 23 mm Hg versus surgical correction 12 mm Hg IQR: 4 to 17 mm Hg, p = 0.015) and pulmonary vascular resistance (spontaneous correction 2.0 Wood units IQR: 1.5 to 2.4 versus surgical correction 1.7 Wood units IQR: 0.8 to 2.1, p = 0.047) were significantly improved in the surgical correction group compared with the spontaneous correction group. Overall survival rate and freedom from recurrent MR were significantly better in the surgical correction group compared with the spontaneous correction group (1-year survival, spontaneous correction 59.4% ± 6.9% versus surgical correction 69.6% ± 6.4%, log rank p = 0.030; 1-year freedom from recurrent MR, spontaneous correction 76.2% ± 7.5% versus surgical correction 95.0% ± 3.5%, log rank p = 0.028). Conclusions The LVAD patients with surgically corrected MR had improved midterm hemodynamics and survival compared with spontaneously resolved MR, along with low recurrence of MR. Aggressive surgical mitral valve intervention during LVAD implantation may be recommended.
Aortic regurgitation (AR) is a common complication following left ventricular assist device (LVAD) implantation. We evaluated the hemodynamic implications of AR in patients with HeartMate 3 (HM3) ...LVAD at baseline and in response to speed changes.
Clinically stable outpatients supported by HM3 who underwent a routine hemodynamic ramp test were retrospectively enrolled in this analysis. Patients were stratified based on the presence of at least mild AR at baseline speed. Hemodynamic and echocardiographic parameters were compared between the AR and non-AR groups. Sixty-two patients were identified. At the baseline LVAD speed, 29 patients (47%) had AR, while 33 patients (53%) did not. Patients with AR were older and supported on HM3 for a longer duration. At baseline speed, all hemodynamic parameters were similar between the groups including central venous pressure, pulmonary capillary wedge pressure, pulmonary arterial pressures, cardiac output and index, and pulmonary artery pulsatility index (p > 0.05 for all). During the subacute assessment, AR worsened in some, but not all, patients, with increases in LVAD speed. There were no significant differences in 1-year mortality or hospitalization rates between the groups, however, at 1-year, ≥ moderate AR and right ventricular failure (RVF) were detected in higher rates among the AR group compared to the non-AR group (45% vs. 0%; p < 0.01, and 75% vs. 36.8%; p = 0.02, respectively).
In a cohort of stable outpatients supported with HM3 who underwent a routine hemodynamic ramp test, the presence of mild or greater AR did not impact the ability of HM3 LVADs to effectively unload the left ventricle during early subacute assessment. Although the presence of AR did not affect mortality and hospitalization rates, it resulted in higher rates of late hemodynamic-related events in the form of progressive AR and RVF.
The Hemodynamic Effects of Aortic Regurgitation in Patients Supported with HM3. Display omitted
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
In patients supported by the HeartMate 3 left ventricular assist device (HM3 LVAD), pump speed adjustments may improve hemodynamics. We investigated the hemodynamic implications of speed adjustments ...in HM3 recipients undergoing hemodynamic ramp tests. Clinically stable HM3 recipients who underwent routine invasive hemodynamic ramp tests between 2015 and 2022 at our center were included. Filling pressure optimization, defined as central venous pressure (CVP) <12 mm Hg and pulmonary capillary wedge pressure (PCWP) <18 mm Hg, was assessed at baseline and final pump speeds. Patients with optimized pressures were compared to nonoptimized patients. Overall 60 HM3 recipients with a median age of 62 years (56, 71) and time from LVAD implantation of 187 days (124, 476) were included. Optimized filling pressures were found in 35 patients (58%) at baseline speed. Speed was adjusted in 84% of the nonoptimized patients. Consequently, 39 patients (65%) had optimized pressures at final speed. There were no significant differences in hemodynamic findings between baseline and final speeds (p > 0.05 for all). Six and 12 month readmission-free rates were higher in optimized compared with nonoptimized patients (p = 0.03 for both), predominantly due to lower cardiac readmission-free rates (p = 0.052). In stable outpatients supported with HM3 who underwent routine ramp tests, optimized hemodynamics were achieved in only 2 of 3 of the patients. Patients with optimized pressures had lower all-cause readmission rates, primarily driven by fewer cardiac-related hospitalizations.
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