ABSTRACT
Implantable left ventricular assist device (LVAD) therapy is used to improve quality of life, alleviate symptoms and extend survival rates in patients with advanced heart failure. Patients with LVADs require chronic anticoagulation to reduce the risk of thromboembolic complications, and they commonly experience bleeding events. Apixaban is a direct oral anticoagulant that has become first-line therapy for patients with nonvalvular atrial fibrillation and venous thromboembolism; however, its safety in patients with LVADs has not been well characterized. The evaluation of the hemocompatibility in the DOAC LVAD (Direct Oral Anti-Coagulant apixaban in Left Ventricular Assist Devices) trial is a phase 2, open-label trial of patients with LVADs who were randomized to either apixaban or warfarin therapy. Patients randomized to apixaban will be started on a dosage of 5 mg twice daily, whereas those randomized to warfarin will be managed at an International Normalized Ratio goal of 2.0-2.5. All patients will be treated with aspirin at 81 mg daily. We plan to randomize and follow as many as 40 patients for 24 weeks to evaluate the primary outcomes of freedom from death or hemocompatibility-related adverse events (stroke, device thrombosis, bleeding, aortic root thrombus, and arterial non-CNS thromboembolism). The DOAC LVAD trial will establish the feasibility of apixaban anticoagulant therapy in patients with LVADs. Clinicaltrials.gov: NCT04865978.
ABSTRACT
BACKGROUND: The incidence of hemodialysis (HD)-dependent renal failure after total artificial heart (TAH) implantation is high. We sought to determine the preoperative predictors of HD after TAH implantation. METHODS AND RESULTS: We studied 87 patients after TAH implantation at our institution between April 2006 and March 2017. Baseline clinical data were obtained from the medical records, and patients were followed until death or heart transplantation. We performed logistic regression analysis to identify predictors of HD after TAH implantation. Of the patients, 24 (28%) required postimplantation HD. Those requiring HD were more likely to have histories of coronary artery disease (58% vs 29%; Pâ¯=â¯0.01), required preoperative membrane oxygenation (33% vs 4.8%; Pâ¯=â¯0.001) and had lower baseline estimated glomerular filtration rates (54 ± 29 vs 67 ± 24 mL/min/1.73m2; Pâ¯=â¯0.04). Patients requiring HD were at a higher risk of death on device at 1 year (33% vs 5%, Pâ¯=â¯0.001; log rank test: P =0.001, hazard ratio 6.6 [95% CI:1.8-23], Pâ¯=â¯0.003). CONCLUSIONS: The incidence of postimplantation HD is high and is associated with increased likelihood of mortality. Lower baseline estimated glomerular filtration rates, histories of coronary artery disease and preoperative membrane oxygenation support are predictors of postimplantation requirement of HD. These data may help to identify patients at risk for adverse outcomes after TAH implantation.
Subject(s)
Heart Failure , Heart Transplantation , Heart, Artificial , Renal Insufficiency , Heart Failure/diagnosis , Heart Failure/epidemiology , Heart, Artificial/adverse effects , Humans , Renal Dialysis/adverse effects , Retrospective StudiesABSTRACT
BACKGROUND: Insufficient data delineate outcomes for Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) profile 1 patients with the total artificial heart (TAH). METHODS: We studied 66 consecutive patients implanted with the TAH at our institution from 2006 through 2012 and compared outcome by INTERMACS profile. INTERMACS profiles were adjudicated retrospectively by a reviewer blinded to clinical outcomes. RESULTS: Survival after TAH implantation at 6 and 12 months was 76% and 71%, respectively. INTERMACS profile 1 patients had decreased 6-month survival on the device compared with those in profiles 2-4 (74% vs 95%, log rank: P = .015). For the 50 patients surviving to heart transplantation, the 1-year posttransplant survival was 82%. There was no difference in 1-year survival when comparing patients in the INTERMACS 1 profile with less severe profiles (79% vs 84%; log rank test P = .7; hazard ratio [confidence interval] 1.3 [0.3-4.8]). CONCLUSIONS: Patients implanted with the TAH as INTERMACS profile 1 had reduced survival to transplantation compared with less sick profiles. INTERMACS profile at the time of TAH implantation did not affect 1-year survival after heart transplantation.
Subject(s)
Cause of Death , Heart Failure/mortality , Heart Failure/surgery , Heart Transplantation/methods , Heart-Assist Devices/statistics & numerical data , Registries , Adult , Cohort Studies , Critical Illness , Female , Follow-Up Studies , Heart Failure/diagnosis , Heart Transplantation/mortality , Heart-Assist Devices/adverse effects , Hospital Mortality , Humans , Male , Middle Aged , Multivariate Analysis , Proportional Hazards Models , Retrospective Studies , Risk Assessment , Statistics, Nonparametric , Survival Analysis , Treatment Outcome , United States , Waiting ListsABSTRACT
Currently, the fully magnetically levitated left ventricular assist device (LVAD) HeartMate 3 (HM3) is the only commercially available device for advanced heart failure (HF) patients. However, the left ventricular (LV) functional and structural changes following mechanical unloading and circulatory support (MCS) with the HM3 have not been investigated. We compared the reverse remodeling induced by the HM3 to older generation continuous-flow LVADs. Chronic HF patients (n = 405) undergoing MCS with HeartWare Ventricular Assist Device (HVAD, n = 115), HM3 (n = 186), and HeartMate II (HM2, n = 104) at four programs were included. Echocardiograms were obtained preimplant and at 1, 3, 6, and 12 months following LVAD implantation. There were no differences in the postimplant serial LV ejection fraction (LVEF) between the devices. The postimplant LV internal diastolic diameter (LVIDd) was significantly lower for HM2 at 3 and 6 months compared with HVAD and HM3. The proportion of patients achieving "cardiac reverse remodeling responder" status (defined as LVEF improvement to ≥40% and LVIDD ≤5.9 cm) was 11.9%, and was similar between devices. HeartMate 3 appears to result in similar cardiac reverse remodeling as older generation CF-LVADs, suggesting that the fully magnetically levitated device technology could provide an effective platform to further study and promote cardiac reverse remodeling.
ABSTRACT
BACKGROUND: Patients receiving left ventricular assist device (LVAD) support require long-term anticoagulation to reduce the risk of thromboembolic complications. Apixaban is a direct oral anticoagulant that has become first-line therapy; however, its safety in LVAD recipients has not been well described. OBJECTIVES: This study sought to investigate whether, in patients with a fully magnetically levitated LVAD, treatment with apixaban would be feasible and comparable with respect to safety and freedom from the primary composite outcome of death or major hemocompatibility-related adverse events (HRAEs) (stroke, device thrombosis, major bleeding, aortic root thrombus, and arterial non-central nervous system thromboembolism) as compared with treatment with warfarin. METHODS: The DOAC LVAD (Evaluation of the Hemocompatibility of the Direct Oral Anti-Coagulant Apixaban in Left Ventricular Assist Devices) trial was a phase 2, open label trial of LVAD recipients randomized 1:1 to either apixaban 5 mg twice daily or warfarin therapy. All patients were required to take low-dose aspirin. Patients were followed up for 24 weeks to evaluate the primary composite outcome. RESULTS: A total of 30 patients were randomized: 14 patients to warfarin and 16 patients to apixaban. The median patient age was 60 years (Q1-Q3: 52-71 years), and 47% were Black patients. The median time from LVAD implantation to randomization was 115 days (Q1-Q3: 56-859 days). At 24 weeks, the primary composite outcome occurred in no patients receiving apixaban and in 2 patients (14%) receiving warfarin (P = 0.12); these 2 patients experienced major bleeding from gastrointestinal sources. CONCLUSIONS: Anticoagulation with apixaban was feasible in patients with an LVAD without an excess of HRAEs or deaths. This study informs future pivotal clinical trials evaluating the safety and efficacy of apixaban in LVAD recipients. (Evaluation of the Hemocompatibility of the Direct Oral Anti-Coagulant Apixaban in Left Ventricular Assist Devices [DOAC LVAD]; NCT04865978).
ABSTRACT
Cardiogenic shock (CS) is a time-sensitive and hemodynamically complex syndrome with a broad spectrum of etiologies and clinical presentations. Despite contemporary therapies, CS continues to maintain high morbidity and mortality ranging from 35 to 50%. More recently, burgeoning observational research in this field aimed at enhancing the early recognition and characterization of the shock state through standardized team-based protocols, comprehensive hemodynamic profiling, and tailored and selective utilization of temporary mechanical circulatory support devices has been associated with improved outcomes. In this narrative review, we discuss the pathophysiology of CS, novel phenotypes, evolving definitions and staging systems, currently available pharmacologic and device-based therapies, standardized, team-based management protocols, and regionalized systems-of-care aimed at improving shock outcomes. We also explore opportunities for fertile investigation through randomized and non-randomized studies to address the prevailing knowledge gaps that will be critical to improving long-term outcomes.
ABSTRACT
Importance: The existing models predicting right ventricular failure (RVF) after durable left ventricular assist device (LVAD) support might be limited, partly due to lack of external validation, marginal predictive power, and absence of intraoperative characteristics. Objective: To derive and validate a risk model to predict RVF after LVAD implantation. Design, Setting, and Participants: This was a hybrid prospective-retrospective multicenter cohort study conducted from April 2008 to July 2019 of patients with advanced heart failure (HF) requiring continuous-flow LVAD. The derivation cohort included patients enrolled at 5 institutions. The external validation cohort included patients enrolled at a sixth institution within the same period. Study data were analyzed October 2022 to August 2023. Exposures: Study participants underwent chronic continuous-flow LVAD support. Main Outcome and Measures: The primary outcome was RVF incidence, defined as the need for RV assist device or intravenous inotropes for greater than 14 days. Bootstrap imputation and adaptive least absolute shrinkage and selection operator variable selection techniques were used to derive a predictive model. An RVF risk calculator (STOP-RVF) was then developed and subsequently externally validated, which can provide personalized quantification of the risk for LVAD candidates. Its predictive accuracy was compared with previously published RVF scores. Results: The derivation cohort included 798 patients (mean [SE] age, 56.1 [13.2] years; 668 male [83.7%]). The external validation cohort included 327 patients. RVF developed in 193 of 798 patients (24.2%) in the derivation cohort and 107 of 327 patients (32.7%) in the validation cohort. Preimplant variables associated with postoperative RVF included nonischemic cardiomyopathy, intra-aortic balloon pump, microaxial percutaneous left ventricular assist device/venoarterial extracorporeal membrane oxygenation, LVAD configuration, Interagency Registry for Mechanically Assisted Circulatory Support profiles 1 to 2, right atrial/pulmonary capillary wedge pressure ratio, use of angiotensin-converting enzyme inhibitors, platelet count, and serum sodium, albumin, and creatinine levels. Inclusion of intraoperative characteristics did not improve model performance. The calculator achieved a C statistic of 0.75 (95% CI, 0.71-0.79) in the derivation cohort and 0.73 (95% CI, 0.67-0.80) in the validation cohort. Cumulative survival was higher in patients composing the low-risk group (estimated <20% RVF risk) compared with those in the higher-risk groups. The STOP-RVF risk calculator exhibited a significantly better performance than commonly used risk scores proposed by Kormos et al (C statistic, 0.58; 95% CI, 0.53-0.63) and Drakos et al (C statistic, 0.62; 95% CI, 0.57-0.67). Conclusions and Relevance: Implementing routine clinical data, this multicenter cohort study derived and validated the STOP-RVF calculator as a personalized risk assessment tool for the prediction of RVF and RVF-associated all-cause mortality.
Subject(s)
Cardiovascular System , Heart Failure , Heart-Assist Devices , Humans , Male , Middle Aged , Cohort Studies , Heart-Assist Devices/adverse effects , Prospective Studies , Risk Factors , Female , Adult , AgedABSTRACT
BACKGROUND: The total artificial heart (TAH) replaces the heart with 2 pneumatic pumps and 4 tilting disk mechanical valves. It was hypothesized that patients receiving TAH support have persistent hemolysis that resolves after heart transplantation (HT). METHODS AND RESULTS: Hematocrit (HCT) was compared in patients on TAH to left ventricular assist device (LVAD) support for bridge to HT. Data were compared with t tests. The TAH (n = 36; mean age 47 ± 13 years) and LVAD patients (n = 14; mean age 53 ± 12 years) were supported for a median of 83 (interquartile range [IQR] 43-115) and 106 days (IQR 84-134), respectively. Hematocrit was similar between the TAH and LVAD patients (34 ± 6% vs 37 ± 5%; P = .07) at baseline. After placement, TAH patients had lower HCT at 2 (20 ± 2% vs 24 ± 3%), 4 (22 ± 3% vs 26 ± 3%), 6 (22 ± 4% vs 30 ± 4%), and 8 weeks (23 ± 4% vs 33 ± 5%; P < .001 for all). There were no differences in HCT at 1 (30 ± 4% vs 29 ± 7%; P = .42) and 3 months (35 ± 7% vs 35 ± 4%; P = .98) after removal of the devices for HT. TAH patients had undetectable haptoglobin in 96% of assessments, increased lactate dehydrogenase (1,128 ± 384 units/L), and detectable plasma free hemoglobin in 40% of measurements (21 ± 15 mg/dL). High sensitivity C-reactive protein (52 ± 50 mg/dL) was elevated, and reticulocyte production index was decreased (1.6 ± 0.6). CONCLUSIONS: Patients implanted with a TAH have persistent anemia that resolves only after HT. The association of hemolysis, ineffective erythropoiesis, and inflammation with the TAH warrants further study.
Subject(s)
Anemia/etiology , Heart Transplantation/adverse effects , Heart-Assist Devices/adverse effects , Adult , Aged , Anemia/blood , Anemia/physiopathology , C-Reactive Protein/metabolism , Erythropoietin/blood , Female , Heart Ventricles , Hematocrit , Hemolysis/physiology , Humans , Luminescent Measurements , Male , Middle Aged , Retrospective StudiesABSTRACT
PURPOSE OF REVIEW: Treatment options for late-stage biventricular heart failure are limited but include medical therapy with intravenous inotropes, biventricular assist devices (Bi-VADs) and the total artificial heart (TAH). In this manuscript, we review the indications, surgical techniques and outcomes for the TAH. RECENT FINDINGS: The TAH offers biventricular replacement, rather than 'assistance', as the device is placed orthotopically after excision of the entire ventricular myocardium and all four native valves. In contrast to patients with Bi-VADs, patients with the TAH have no postoperative inotrope requirements, arrhythmias or inflow/outflow cannulae-related complications. Additionally, patients participate in rehabilitation early after device placement and the development of a portable drive may facilitate hospital discharge in the USA. Furthermore, total heart replacement may be ideal for heart failure associated with unique anatomical and mechanical complications. SUMMARY: The TAH is an effective therapeutic option for the treatment of patients dying of heart failure who may not be suitable candidates for left ventricular assist devices.
Subject(s)
Heart Failure/surgery , Heart, Artificial , Female , Heart Failure/rehabilitation , Heart Ventricles/pathology , Hemodynamics , Humans , Male , Middle Aged , Physical Therapy ModalitiesABSTRACT
The medical community has seen an explosive rise in the utilization of implantable mechanical circulatory support devices for late-stage cardiomyopathy. Care for these complex patients requires a basic understanding of device physiology and potential complications. This review focuses on an algorithm that incorporates a careful clinical history and examination with diagnostic modalities for the evaluation of a patient who is failing therapy with a continuous-flow left ventricular assist device, as well as the general management and optimization of patients implanted with an artificial heart.
Subject(s)
Heart Failure/surgery , Heart, Artificial , Heart-Assist Devices , Algorithms , Heart Ventricles , HumansABSTRACT
Temporary mechanical circulatory support can be delivered through a variety of techniques, including percutaneous left ventricular assist devices, surgically implanted rotary pumps, and veno-arterial extracorporeal membrane oxygenation. However, limitations include the effects of high afterload, intravascular hemolysis, patient vascular anatomy, surgical morbidity, and limited patient mobility which can hinder patient recovery. We describe a series of patients managed with transapical left ventricular mechanical circulatory support using a dual lumen cannula for the management of cardiogenic shock as a bridge to recovery or definitive decision. This support strategy may represent an additional option in the care for patients with cardiogenic shock that can provide full temporary anterograde mechanical circulatory support while potentially improving patient mobility and minimizing device-related complications.
Subject(s)
Heart-Assist Devices , Shock, Cardiogenic , Humans , Shock, Cardiogenic/surgery , Shock, Cardiogenic/etiology , Cannula/adverse effects , Mobility Limitation , Heart-Assist Devices/adverse effects , Catheterization/adverse effectsSubject(s)
Cardiomyopathies/therapy , Heart-Assist Devices/adverse effects , Thrombosis/diagnostic imaging , Ultrasonography, Interventional , Ventricular Function, Left , Cardiomyopathies/diagnosis , Cardiomyopathies/physiopathology , Device Removal , Echocardiography, Doppler, Color , Echocardiography, Transesophageal , Female , Humans , Intraoperative Care , Middle Aged , Predictive Value of Tests , Reoperation , Thrombosis/etiology , Thrombosis/surgery , Treatment OutcomeABSTRACT
There is a dearth of information regarding the functional abilities of patients with the total artificial heart (TAH). Increased utilization of the TAH and patient discharge to home with the portable unit necessitates a shift in focus to quality of life, which includes quantifying and ultimately optimizing functional capacity. To date, only single-patient case studies have described the exercise response of the TAH patient. Fourteen patients with the TAH underwent cardiopulmonary exercise testing with concurrent analysis of TAH device function. All device settings remained fixed during testing. Peak oxygen consumption (VO2; 0.872 L/min [interquartile range (IQR) = 0.828-1.100 L/min]), percent predicted peak VO2 (36% [IQR = 32-42%]), and ventilatory anaerobic threshold (0.695 L/min [IQR = 0.542-0.845 L/min]) were markedly reduced in the TAH compared with predicted normal values. Determinants of VO2 using device-generated hemodynamics revealed a blunted cardiac output (+9% increase) and exaggerated oxygen extraction with exercise. Peak VO2 strongly correlated with resting (R = +0.548, p = 0.045), ventilatory anaerobic threshold (R = +0.780, p = 0.001), and peak exercise cardiac output (R = +0.672, p = 0.008). Patients with the TAH have significantly impaired exercise performance. The limitations to cardiopulmonary exercise testing performance appear to be related to limited ability of the pump to modulate output for activity and reduced oxygen carrying capacity.
Subject(s)
Exercise Tolerance/physiology , Exercise/physiology , Heart, Artificial , Adult , Cross-Sectional Studies , Female , Hemodynamics/physiology , Humans , Male , Middle Aged , Quality of LifeABSTRACT
More than 5 million Americans suffer from heart failure and more than 250,000 die annually. Cardiac surgery, as applied to advanced heart failure, has evolved significantly in the past 50 years. Current therapeutic interventions are focused on the appropriate assessment of myocardial dysfunction as a means to select the right patient for the appropriate procedure using state-of-the-art myocardial viability testing and metabolic testing to determine candidacy for conventional interventions, mechanical devices, or transplant. Advances in mechanical circulatory support with more efficient and less morbid ventricular assist devises offer the potential to change the trajectory of this growing epidemiologic dilemma.
Subject(s)
Heart Failure/surgery , Cardiac Surgical Procedures/methods , Cardiac Surgical Procedures/trends , Forecasting , Heart Transplantation , Heart, Artificial , HumansABSTRACT
Patients who received a total artificial heart (TAH) at Virginia Commonwealth University (VCU) between January 1, 2010 and December 31, 2011 were identified from the VCU Mechanical Circulatory Support Clinical Database. Retrospective data extraction from the medical records was performed from the time of TAH implantation until heart transplantation or death. Infections were classified as confirmed or suspected. Twenty-seven men and five women, mean age 49.5 years (range 24-68 years) received a TAH. The mean duration of TAH support was 225 days (range 1-1,334 days). Of the 32 patients, 4 (12.5%) died and 28 (87.5 %) underwent heart transplantation. Causes of death were pneumonia (n = 1), TAH malfunction (n = 1), refractory cardiogenic shock (n = 1), and respiratory failure (n = 1). Seventy documented and 13 suspected infections developed in 25 patients (78%). The most common sources of infection were urinary tract (n = 26), respiratory tract (n = 18), and bloodstream (n = 11). There were five pump infections and two driveline infections. The number of infections per patient ranged from 0 to 10. Sixteen different pathogens were identified; the most common were: Klebsiella pneumoniae (n = 15), coagulase-negative Staphylococci (n = 10), Enterococcus species (n = 9), and Enterobacter species (n = 8). Mortality directly attributable to infection was infrequent.
Subject(s)
Heart, Artificial/adverse effects , Infections/epidemiology , Infections/etiology , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Adult , Aged , Female , Humans , Male , Middle Aged , Retrospective Studies , Young AdultABSTRACT
Pulmonary hypertension (PH) among heart transplant recipients is associated with an increased risk of mortality. Pulmonary hemodynamics improves after left ventricular assist device (LVAD) implantation; however, the impact of PH before total artificial heart (TAH) implantation on posttransplant hemodynamics and survival is unknown. This is a single center retrospective study aimed to evaluate the impact of TAH implantation on posttransplant hemodynamics and mortality in two groups stratified according to severity of PH: high (≥3 Woods units [WU]) and low (<3 WU) baseline pulmonary vascular resistance (PVR). Hemodynamic data were obtained from right heart catheterization performed at baseline (before TAH) and posttransplant at 1 and 12 months. Patients in the high PVR group (n = 12) experienced improvement in PVR (baseline = 4.31 ± 0.7; 1-month = 1.69 ± 0.7, p < 0.001; 12-month = 48 ± 0.9, p < 0.001) and transpulmonary gradient (baseline = 15.8 ± 3.3; 1-month = 11.57 ± 5.0, p = 0.07; 12-month = 8.50 ± 4.0, p = 0.008) after transplantation, reaching similar values as the low PVR group at 12 months. The filling pressures improved in the high PVR group after heart transplantation (HT), but remained elevated. There was no significant difference in survival between the two groups at 12 months follow-up. Patients with high PVR who are bridged to transplant with TAH had improvement in PVR at 12 months after transplant, and the degree of PVR did not impact posttransplant survival.
Subject(s)
Heart Failure/surgery , Heart Transplantation , Heart, Artificial , Hypertension, Pulmonary/surgery , Adult , Heart Failure/physiopathology , Heart-Assist Devices , Hemodynamics , Humans , Hypertension, Pulmonary/etiology , Hypertension, Pulmonary/physiopathology , Male , Middle Aged , Retrospective StudiesABSTRACT
OBJECTIVES: This study investigated the mechanism of lead malfunction by monitoring lead parameters throughout left ventricular assist device (LVAD) implantation. BACKGROUND: Implantable cardioverter-defibrillator (ICD) lead malfunction can occur after LVAD implantation. METHODS: ICD lead data were prospectively evaluated during and after LVAD implantation and at 12 pre-specified intraoperative time points. RESULTS: We prospectively evaluated 32 patients with ICDs who underwent LVAD implantation, of whom 20 patients underwent serial testing at 12 intraoperative steps. Post-operative right ventricle (RV) sensing had decreased by >50% from baseline in 7 patients (22%), with RV sensing improving at 1 to 7 weeks in 2 patients (28.6%). Nine patients (28.1%) had >10-ohm (Ω) high-voltage (HV) impedance changes from baseline to final impedance. In all 5 patients with >50% decrease in RV sensing and all 7 patients with a >10-Ω HV impedance change who underwent intraoperative testing, changes were not detected until after weaning from cardiopulmonary bypass. Patients with decreased RV lead sensing >50% (n = 7) had lower glomerular filtration rates (48.7 ± 21.9 ml/min/1.73 m2 vs. 68.4 ± 22.5 ml/min/1.73 m2, respectively, p = 0.0489), were more likely to have undergone concomitant RVAD placement (42.9% vs. 0%, respectively, p = 0.0071), concomitant tricuspid valve surgery (57.1% vs. 16%, p = 0.0469), or to have had cardiac tamponade or unplanned return to the operating room (57.1% vs. 12%, p = 0.0258). CONCLUSIONS: ICD lead malfunction can occur following LVAD implantation but may improve over time. Intraoperative RV sensing and HV impedance changes were not detected until after weaning from cardiopulmonary bypass, suggesting the mechanism of RV lead malfunction may be related to LV unloading and concomitant leftward septal shift. A conservative approach is warranted in many patients with ICD parameter changes after LVAD implantation because parameter abnormalities may improve over time. (Implantable Cardioverter Defibrillator (ICD) Function During Ventricular Assist Device (VAD) Implantation; NCT01576562).
ABSTRACT
BACKGROUND: Mutations in KCNE2 have been linked to long-QT syndrome (LQT6), yet KCNE2 protein expression in the ventricle and its functional role in native channels are not clear. METHODS AND RESULTS: We detected KCNE2 protein in human, dog, and rat ventricles in Western blot experiments. Immunocytochemistry confirmed KCNE2 protein expression in ventricular myocytes. To explore the functional role of KCNE2, we studied how its expression was altered in 2 models of cardiac pathology and whether these alterations could help explain observed changes in the function of native channels, for which KCNE2 is a putative auxiliary (beta) subunit. In canine ventricle injured by coronary microembolizations, the rapid delayed rectifier current (I(Kr)) density was increased. Although the protein level of ERG (I(Kr) pore-forming, alpha, subunit) was not altered, the KCNE2 protein level was markedly reduced. These data are consistent with the effect of heterologously expressed KCNE2 on ERG and suggest that in canine ventricle, KCNE2 may associate with ERG and suppress its current amplitude. In aging rat ventricle, the pacemaker current (I(f)) density was increased. There was a significant increase in the KCNE2 protein level, whereas changes in the alpha-subunit (HCN2) were not significant. These data are consistent with the effect of heterologously expressed KCNE2 on HCN2 and suggest that in aging rat ventricle, KCNE2 may associate with HCN2 and enhance its current amplitude. CONCLUSIONS: KCNE2 protein is expressed in ventricles, and it can play diverse roles in ventricular electrical activity under (patho)physiological conditions.
Subject(s)
Heart Ventricles/metabolism , Potassium Channels, Voltage-Gated , Potassium Channels/physiology , Potassium/metabolism , Ventricular Remodeling/physiology , Aging/metabolism , Animals , COS Cells , Chlorocebus aethiops , Disease Models, Animal , Dogs , ERG1 Potassium Channel , Ether-A-Go-Go Potassium Channels , Heart Conduction System/physiopathology , Heart Ventricles/pathology , Humans , Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels , Ion Channels/metabolism , Ion Transport , Long QT Syndrome/metabolism , Macromolecular Substances , Male , Muscle Proteins/metabolism , Myocardial Ischemia/metabolism , Myocardium/metabolism , Potassium Channels/analysis , Potassium Channels/genetics , Potassium Channels/metabolism , Protein Subunits , Rats , Rats, Inbred SHR , Rats, Inbred WKY , Species Specificity , TransfectionABSTRACT
The total artificial heart (TAH) is a form of mechanical circulatory support in which the patient's native ventricles and valves are explanted and replaced by a pneumatically powered artificial heart. Currently, the TAH is approved for use in end-stage biventricular heart failure as a bridge to heart transplantation. However, with an increasing global burden of cardiovascular disease and congestive heart failure, the number of patients with end-stage heart failure awaiting heart transplantation now far exceeds the number of available hearts. As a result, the use of mechanical circulatory support, including the TAH and left ventricular assist device (LVAD), is growing exponentially. The LVAD is already widely used as destination therapy, and destination therapy for the TAH is under investigation. While most patients requiring mechanical circulatory support are effectively treated with LVADs, there is a subset of patients with concurrent right ventricular failure or major structural barriers to LVAD placement in whom TAH may be more appropriate. The history, indications, surgical implantation, post device management, outcomes, complications, and future direction of the TAH are discussed in this review.