Citations

Although continuous-flow left ventricular assist devices (CF-LVADs) provide an augmentation in systemic perfusion, there is a scarcity of in vivo data regarding systemic pulsatility on support. Patients supported on CF-LVAD therapy (n = 71) who underwent combined left/right catheterization ramp study were included. Aortic pulsatility was defined by the pulsatile power index (PPI), which was also calculated in a cohort of high-output heart failure (HOHF, n = 66) and standard HF cohort (n = 44). PPI was drastically lower in CF-LVAD–supported patients with median PPI of 0.006 (interquartile range [IQR], 0.002–0.012) compared with PPI in the HF population at 0.09 (IQR, 0.06–0.17) or HOHF population at 0.25 (IQR, 0.13–0.37; p < 0.0001 among groups). With speed augmentation during ramp, PPI values fell quickly in patients with higher PPI at baseline. PPI correlated poorly with left ventricular ejection fraction (LVEF) in all groups. In CF-LVAD patients, there was a stronger correlation with LV dP/dt (r = 0.41; p = 0.001) than LVEF (r = 0.21; p = 0.08; p int < 0.001). CF-LVAD support is associated with a dramatic reduction in arterial pulsatility as measured by PPI relative to HOHF and HF cohorts and decreases with speed. Further work is needed to determine the applicability to the next generation of device therapy.

AbstractOver the last half‐century, left ventricular assist device (LVAD) technology has progressed from conceptual therapy for failed cardiopulmonary bypass weaning to an accepted destination therapy for advanced heart failure. The history of LVAD engineering is defined by an initial development phase, which demonstrated the feasibility of such an approach, to the more recent three major generations of commercial devices. In this review, we explore the engineering challenges of LVADs, how they were addressed over time, and the clinical outcomes that resulted from each major technological development. The first generation of commercial LVADs were pulsatile devices, which lacked the appropriate durability due to their number of moving components and hemocompatibility. The second generation of LVADs was defined by replacement of complex, pulsatile pumps with primarily axial, continuous‐flow systems with an impeller in the blood passageway. These devices experienced significant commercial success, but the presence of excessive trauma to the blood and in‐situ bearing resulted in an unacceptable burden of adverse events. Third generation centrifugal‐flow pumps use magnetically suspended rotors within the pump chamber. Superior outcomes with this newest generation of devices have been observed, particularly with respect to hemocompatibility‐related adverse events including pump thrombosis, with fully magnetically levitated devices. The future of LVAD engineering includes wireless charging foregoing percutaneous drivelines and more advanced pump control mechanisms, including synchronization of the pump flow with the native cardiac cycle, and varying pump output based on degree of physical exertion using sensor or advanced device‐level data triggers.

AbstractIntroductionCardiac sarcoidosis (CS) is a nonischemic cardiomyopathy (NICM) characterized by infiltration of noncaseating granulomas involving the heart with highly variable clinical manifestations that can include conduction abnormalities and systolic heart failure. Cardiac resynchronization therapy (CRT) has shown significant promise in NICM, though little is known about its efficacy in patients with CS.ObjectiveTo determine if CRT improved cardiac remodeling in patients with CS.MethodsWe retrospectively reviewed all patients with a clinical or histological diagnosis of CS who underwent CRT implantation at the Mayo Clinic enterprise from 2000 to 2021. Baseline characteristics, imaging parameters, heart failure hospitalizations and need for advanced therapies, and major adverse cardiac events (MACE) were assessed.ResultsOur cohort was comprised of 55 patients with 61.8% male and a mean age of 58.7 ± 10.9 years. Eighteen (32.7%) patients had definite CS, 21 (38.2%) had probable CS, while 16 (29.1%) had presumed CS, and 26 (47.3%) with extracardiac sarcoidosis. The majority underwent CRT‐D implantation (n = 52, 94.5%) and 3 (5.5%) underwent CRT‐P implantation with 67.3% of implanted devices being upgrades from prior pacemakers or implantable cardioverter defibrillators. At 6 months postimplantation there was no significant improvement in ejection fraction (34.8 ± 10.9% vs. 37.7 ± 14.2%, p = .331) or left ventricular end‐diastolic diameter (58.5 ± 10.2 vs. 57.5 ± 8.1 mm, p = .236), though mild improvement in left ventricular end systolic diameter (49.1 ± 9.9 vs. 45.7± 9.9 mm, p < .0001). Within the first 6 months postimplantation, 5 (9.1%) patients sustained a heart failure hospitalization. At a mean follow‐up of 4.1± 3.7 years, 14 (25.5%) patients experienced a heart failure hospitalization, 11 (20.0%) underwent cardiac transplantation, 1 (1.8%) underwent left ventricular assist device implantation and 7 (12.7%) patients died.ConclusionsOur findings suggest variable response to CRT in patients with CS with no overall improvement in ventricular function within 6 months and a substantial proportion of patients progressing to advanced heart failure therapies.

Abstract Background Lactate hydrogenase (LDH) is a common biomarker utilized in the detection and monitoring of left ventricular assist device (LVAD) hemolysis and thrombosis. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) are common laboratory tests that can be used to calculate the De Ritis ratio and the De Ritis adjusted AST. Methods A retrospective review of LVAD patients was performed to identify three cohorts of patients: those with confirmed pump thrombosis after device exchange, those with LVAD‐related hemolysis who were medically managed without pump exchange, and those who did not meet these criteria and served as the control cohort. Evaluation of AST, AST/ALT ratio (referred to as the De Ritis ratio) as well as AST x (AST/ALT) or the De Ritis‐adjusted AST (DRA) was performed. Results There were 29 patients who underwent device exchange for thrombosis, 25 patients who were diagnosed with hemolysis and treated medically (clopidogrel ( N = 6), heparin ( N = 13), tirofiban ( N = 8), eptifibatide ( N = 2), and some received more than one of these treatments), and 425 control patients. A qualitatively comparable relative and absolute rise in DRA and LDH were found in both surgically managed pump thrombosis and suspected device‐related hemolysis. Conclusions Both AST and LDH as well DRA are significantly associated with pump thrombosis ( p < 0.0001 for each). DRA is a potential screening biomarker for hemolysis and device thrombosis in stable left ventricular assist device patients.

Background: It is known that hypokalemia, hypocalcemia and hypomagnesemia cause a prolonged QTc interval and are associated with an increased risk of ventricular arrhythmias. However, there are limited data on optimal serum electrolytes for patients admitted to the coronary care unit (CCU). Objective: Here, we aimed to evaluate the relationship between serum potassium, ionized calcium and magnesium levels and in-hospital mortality in the CCU setting. Methods: This retrospective cohort study included 8,498 consecutive patients admitted to the CCU at an academic tertiary medical center from 2004 through 2013. The mean of serum electrolytes was categorized as <3.5, 3.5-<4.0, 4.0-<4.5 (reference), 4.5-<5.0, and ≥5.0 mEq/L for potassium; <4.4, 4.4-<4.6, 4.6-<4.8, 4.8-<5.0 (reference), and ≥5.0 mg/dL for ionized calcium; and <1.8, 1.8-<2.0, 2.0-<2.2 (reference), 2.2-<2.4, and ≥2.4 mg/dL for magnesium. Multivariate logistic regression analysis was used to determine the association between the mean of serum electrolytes and in-hospital mortality. Results: Of the 8,498 patients, 599 (7%) died during hospitalization. Relationship between mean serum potassium (U-shaped), ionized calcium (inverted J-shape) and magnesium (J-shaped) and in-hospital mortality was present in Figure. Serum potassium levels <3.5, 4.5-<5.0 and ≥5.0 mEq/L were independently associated with an increased risk of in-hospital mortality (adjusted OR 1.7 95% CI 1.1-2.5, OR 1.7 95% CI 1.3-2.2, and OR 3.4 95% CI 2.4-4.8, respectively), compared to the reference group. As for serum ionized calcium, the levels of <4.4, 4.4-<4.6, and 4.6-<4.8 mg/dL independently increased risk of mortality (adjusted OR 3.0 95% CI 2.3-4.0, OR 2.0 95% CI 1.5-2.6, and OR 1.4 95% CI, 1.1-1.8, respectively). As for serum magnesium, an only level above 2.4 mg/dL was associated with an increased mortality risk (OR 1.6 95% CI, 1.1-2.2). Conclusions: In the CCU setting, serum potassium 3.5-<4.5 mEq/L, ionized calcium ≥5.0 mg/dL and magnesium <2.4 mg/dL are associated with the lowest in-hospital mortality. These findings do not support supratherapeutic repletion of potassium and magnesium.

Introduction: Cardiac Sarcoidosis (CS) is a non-ischemic cardiomyopathy (NICM) characterized by infiltration of non-caseating granulomas involving in the heart with highly variable clinical manifestations. Cardiac resynchronization therapy (CRT) has shown significant promise in NICM, though little is known about its effectiveness in patients with CS. Hypothesis: We sought to determine if CRT improved cardiac remodeling and reduced hospitalizations in patients with CS. Methods: We retrospectively reviewed all patients with a clinical or histological diagnosis of CS who underwent CRT implantation at a Mayo Clinic site from 2000-2021. Baseline characteristics, echocardiographic parameters, heart failure hospitalization, and major adverse cardiac events (MACE) were assessed. Results: Our cohort was comprised of 55 patients with 61.8% male and a mean age of 58.7 ± 10.9 years. At baseline, 38 (69.1%) patients had isolated CS, while 17 (30.9%) had evidence of CS with extra-cardiac sarcoidosis. The overwhelming majority underwent CRT-D implantation (n=52, 94.5%) with 67.3% of implanted devices upgrades from prior pacemaker or implantable cardioverter defibrillator. At 6 months post-implantation there was no significant different in ejection fraction (34.8 ± 10.9 % vs. 37.7 ± 14.2 %, p = 0.237), left ventricular end systolic diameter (49.1 ± 9.9 mm vs. 45.7 ± 9.9 mm, p = 0.077) or left ventricular end-diastolic diameter (58.5 ± 10.2 mm vs. 57.5 ± 8.1 mm, p = 0.574). Within the first 6 months post-implantation, 5 (9.1%) patients sustained a heart failure hospitalization. At a mean follow up of 4.1 ± 3.7 years, 14 (25.5%) patients experienced a heart failure hospitalization, 11 (20.0%) underwent cardiac transplantation, 1 (1.8%) underwent LVAD implantation and 7 (12.7%) patients died. Conclusions: Our findings suggest a poor response to CRT in patients with CS with no significant evidence of reverse remodeling within 6 months and a substantial proportion of patients progressing to advanced heart failure therapies.

Background: Tendons are primarily acellular, limiting their intrinsic regenerative capabilities. This limited regenerative potential contributes to delayed healing, rupture, and adhesion formation after tendon injury. Purpose: To determine if a tendon’s intrinsic regenerative potential could be improved after the application of a purified exosome product (PEP) when loaded onto a collagen scaffold. Study Design: Controlled laboratory study. Methods: An in vivo rabbit Achilles tendon model was used and consisted of 3 groups: (1) Achilles tenotomy with suture repair, (2) Achilles tenotomy with suture repair and collagen scaffold, and (3) Achilles tenotomy with suture repair and collagen scaffold loaded with PEP at 1 × 10 12 exosomes/mL. Each group consisted of 15 rabbits for a total of 45 specimens. Mechanical and histologic analyses were performed at both 3 and 6 weeks. Results: The load to failure and ultimate tensile stress were found to be similar across all groups ( P ≥ .15). The tendon cross-sectional area was significantly smaller for tendons treated with PEP compared with the control groups at 6 weeks, which was primarily related to an absence of external adhesions ( P = .04). Histologic analysis confirmed these findings, demonstrating significantly lower adhesion grade both macroscopically ( P = .0006) and microscopically ( P = .0062) when tendons were treated with PEP. Immunohistochemical staining showed a greater intensity for type 1 collagen for PEP-treated tendons compared with collagen-only or control tendons. Conclusion: Mechanical and histologic results suggested that healing in the PEP-treated group favored intrinsic healing (absence of adhesions) while control animals and animals treated with collagen only healed primarily via extrinsic scar formation. Despite a smaller cross-sectional area, treated tendons had the same ultimate tensile stress. This pilot investigation shows promise for PEP as a means of effectively treating tendon injuries and enhancing intrinsic healing. Clinical Relevance: The production of a cell-free, off-the-shelf product that can promote tendon regeneration would provide a viable solution for physicians and patients to enhance tendon healing and decrease adhesions as well as shorten the time required to return to work or sports.

Procainamide is a useful agent for management of ventricular arrhythmia, however its disposition and appropriate dosing during extracorporeal membrane oxygenation (ECMO) is unknown. We report experience with continuous procainamide infusion in a critically ill adult requiring venoarterial ECMO for incessant ventricular tachycardia. Pharmacokinetic analysis of procainamide and its metabolite, N-acetylprocainamide (NAPA), was performed using serum and urine specimens. Kidney function was preserved, and sequencing of the N-acetyltransferase 2 gene revealed the patient was a phenotypic slow acetylator. Procainamide volume of distribution and half-life were calculated and found to be similar to healthy individuals. However, despite elevated serum procainamide concentrations, NAPA concentrations remained far lower in the serum and urine. The magnitude of procainamide and NAPA discordance suggested alternative contributors to the deranged pharmacokinetic profile, and we hypothesized NAPA sequestration by the ECMO circuit. Ultimately, the patient received orthotopic cardiac transplantation and was discharged home in stable condition. Procainamide should be used cautiously during ECMO, with close therapeutic drug monitoring of serum procainamide and NAPA concentrations. The achievement of therapeutic NAPA concentrations while maintaining safe serum procainamide concentrations during ECMO support may be challenging.

AbstractObjectiveEndomyocardial biopsy (EMB) is a useful diagnostic tool though the yield may be limited in many myocardial diseases. Data on the diagnostic yield and prognostic significance of EMB guided by abnormal electrograms (EGM‐Bx) in suspected cardiac sarcoidosis (CS) are scarce.MethodsSeventy‐nine patients (mean age: 56 ± 12 years; 61% men) with suspected CS based on clinical and imaging features underwent right or left ventricular EGM‐Bx guided by electroanatomic mapping. Tissue samples were obtained from sites with abnormal EGMs and/or abnormal cardiac imaging. The diagnostic yield of EGM‐Bx was evaluated in reference to histopathologic analysis. Left ventricular assist device (LVAD) and transplantation‐free survival were compared between patients with positive and negative EGM‐Bx for CS.ResultsA total of 254 samples were obtained from abnormal EGM sites, and 126 samples from normal EGM sites guided by pre‐procedure imaging findings. Abnormal histopathology was noted in 65 (26%) and 10 (8%) samples from abnormal and normal EGM sites, respectively. Histopathology confirmed CS in 16 (20%) patients, while an alternative tissue diagnosis emerged in 10 (13%) patients. Abnormal EGMs at the biopsy site had sensitivity 89% and specificity 33% for a histopathologic diagnosis of CS. LVAD and transplantation‐free survival were not significantly associated with the EGM‐Bx result (log‐rank p = .91).ConclusionIn patients with suspected CS, abnormal EGM‐Bx has high sensitivity and low specificity for establishing a definite CS diagnosis. Consideration of substrate abnormalities apparent on preprocedural imaging as an adjunct for selection of biopsy sites may further improve EGM‐Bx yield.

Introduction: Right ventricular apical (RVA) pacing appears to have detrimental effects on cardiac function and long term outcomes. Right ventricular non-apical (RVNA) pacing, especially in the septal position, has been postulated as an alternative that may lead to less morbidity and mortality. Prior studies have shown conflicting results and been limited by small numbers and short follow-up. We aimed to determine if right ventricular septal lead position was associated with a reduction in long-term mortality compared to RVA lead position. Methods: Patients who underwent dual-chamber pacemaker implantation from 2004 through 2013 were evaluated for right ventricular lead position based on chest radiographs. Lead positions were divided in to apical or non-apical. Non-apical lead positions were subdivided to isolate a septal lead position group. Mortality was compared between these groups. Results: During the study period, 3456 patients underwent dual-chamber pacemaker placement and had images appropriate for lead position evaluation. The group was 53.5% male with a mean age of 74 ± 13 years. RVNA lead position was found in 976 (28.2%) patients, including 243 (7.0%) with a septal position. There was no significant difference in age or prior heart failure diagnosis between groups. Kaplan-Meier survival analysis did not reveal a significant difference in mortality between patients with RVA versus RVNA lead position during 5 year follow-up (p = 0.82). However, septal lead position was associated with a significantly lower mortality compared with RVA position (p = 0.03) (figure). Conclusions: Right ventricular septal lead position is associated with a lower long-term mortality than RVA lead position. This has substantial implications regarding the preferred site for ventricular pacing lead placement.