The left ventricular assist device 'skeleton man': case report-simple tools for skeletal muscle evaluation and very early aerobic/resistance/inspiratory training in cardiac cachexia.

Background: Skeletal muscle wasting (SMW) is highly prevalent in patients with heart failure (HF) at left ventricular assist device (LVAD) implantation and is associated with morbidity and mortality. At the same time, SMW is clinically under-recognized, while exercise training (ET) studies in weak LVAD patients are lacking. Case summary: A 60-year-old man with advanced HF, SMW, cardiac cachexia, and frailty was confined in bed for 6 months initially supported with intravenous inotropes and subsequently with an intra-aortic balloon pump. His frailty was recognized as an LVAD-responsive frailty, and patient was successfully implanted with a HeartWare (Medtronic). Post-surgery, patient was very weak, unable even to move in bed without assistance. We evaluated skeletal muscle using simple tools such as the Oxford scale, mid-thigh circumference, hand-held dynamometry, and maximum inspiratory pressure. Physical performance was assessed with the sit to stand test, gait speed test, pedal bike timing, and the 6 min walk test. On top of routine physiotherapy, patient underwent an 8-week modified aerobic/resistance/inspiratory (ARIS) ET programme at moderate intensity and showed significant improvements in skeletal muscle mass and strength and physical and functional capacity. Discussion: We want to emphasize the importance of skeletal muscle evaluation at LVAD implantation and the feasibility and effectiveness of early ARIS training in very weak patients.

Right heart failure with left ventricular assist devices: Preoperative, perioperative and postoperative management strategies. A clinical consensus statement of the Heart Failure Association (HFA) of the ESC.

Right heart failure (RHF) following implantation of a left ventricular assist device (LVAD) is a common and potentially serious condition with a wide spectrum of clinical presentations with an unfavourable effect on patient outcomes. Clinical scores that predict the occurrence of right ventricular (RV) failure have included multiple clinical, biochemical, imaging and haemodynamic parameters. However, unless the right ventricle is overtly dysfunctional with end-organ involvement, prediction of RHF post-LVAD implantation is, in most cases, difficult and inaccurate. For these reasons optimization of RV function in every patient is a reasonable practice aiming at preparing the right ventricle for a new and challenging haemodynamic environment after LVAD implantation. To this end, the institution of diuretics, inotropes and even temporary mechanical circulatory support may improve RV function, thereby preparing it for a better adaptation post-LVAD implantation. Furthermore, meticulous management of patients during the perioperative and immediate postoperative period should facilitate identification of RV failure refractory to medication. When RHF occurs late during chronic LVAD support, this is associated with worse long-term outcomes. Careful monitoring of RV function and characterization of the origination deficit should therefore continue throughout the patient's entire follow-up. Despite the useful information provided by the echocardiogram with respect to RV function, right heart catheterization frequently offers additional support for the assessment and optimization of RV function in LVAD-supported patients. In any patient candidate for LVAD therapy, evaluation and treatment of RV function and failure should be assessed in a multidimensional and multidisciplinary manner.

Advanced Heart Failure: Therapeutic Options and Challenges in the Evolving Field of Left Ventricular Assist Devices.

Heart Failure is a chronic and progressively deteriorating syndrome that has reached epidemic proportions worldwide. Improved outcomes have been achieved with novel drugs and devices. However, the number of patients refractory to conventional medical therapy is growing. These advanced heart failure patients suffer from severe symptoms and frequent hospitalizations and have a dismal prognosis, with a significant socioeconomic burden in health care systems. Patients in this group may be eligible for advanced heart failure therapies, including heart transplantation and chronic mechanical circulatory support with left ventricular assist devices (LVADs). Heart transplantation remains the treatment of choice for eligible candidates, but the number of transplants worldwide has reached a plateau and is limited by the shortage of donor organs and prolonged wait times. Therefore, LVADs have emerged as an effective and durable form of therapy, and they are currently being used as a bridge to heart transplant, destination lifetime therapy, and cardiac recovery in selected patients. Although this field is evolving rapidly, LVADs are not free of complications, making appropriate patient selection and management by experienced centers imperative for successful therapy. Here, we review current LVAD technology, indications for durable MCS therapy, and strategies for timely referral to advanced heart failure centers before irreversible end-organ abnormalities.

The Han:SPRD Rat: A Preclinical Model of Polycystic Kidney Disease.

Autosomal Dominant Polycystic Kidney Disease (ADPKD) stands as the most prevalent hereditary renal disorder in humans, ultimately culminating in end-stage kidney disease. Animal models carrying mutations associated with polycystic kidney disease have played an important role in the advancement of ADPKD research. The Han:SPRD rat model, carrying an R823W mutation in the Anks6 gene, is characterized by cyst formation and kidney enlargement. The mutated protein, named Samcystin, is localized in cilia of tubular epithelial cells and seems to be involved in cystogenesis. The homozygous Anks6 mutation leads to end-stage renal disease and death, making it a critical factor in kidney development and function. This review explores the utility of the Han:SPRD rat model, highlighting its phenotypic similarity to human ADPKD. Specifically, we discuss its role in preclinical trials and its importance for investigating the pathogenesis of the disease and developing new therapeutic approaches.

Machine Learning Multicenter Risk Model to Predict Right Ventricular Failure After Mechanical Circulatory Support: The STOP-RVF Score.

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.

Treatment Strategies and Outcomes of Right Ventricular Failure Post Left Ventricular Assist Device Implantation: An INTERMACS Analysis.

Right heart failure (RHF) management after left ventricular assist device (LVAD) implantation includes inotropes, right ventricular mechanical support, and heart transplantation. The purpose of this study is to compare different RHF treatment strategies in patients with a magnetically levitated centrifugal LVAD. A total of 6,632 Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) patients from 2013 to 2020 were included. Of which, 769 (69.6%) patients (group 1) were supported with inotropes (≥14 days post-LVAD implantation), 233 (21.1%) patients (group 2) were supported with temporary right ventricular assist device (RVAD) that was implanted during LVAD implant, 77 (7.0%) patients (group 3) with durable centrifugal RVAD implanted during the LVAD implant, and 26 (2.4%) patients (group 4) were supported with RVAD (temporary or permanent), which was implanted at a later stage. Groups 1 and 4 had higher survival rates in comparison with group 2 (hazard ratio [HR] = 0.513, 95% confidence intervals [CIs] = 0.402-0.655, p < 0.001, versus group 1) and group 3 (HR = 0.461, 95% CIs = 0.320-0.666, p < 0.001, versus group 1). Patients in group 3 showed higher heart transplantation rates at 12 and 36 months as compared with group 1 (40.4% and 46.6% vs. 21.9% and 37.4%, respectively), group 2 (40.4% and 46.6% vs. 25.8% and 39.3%, respectively), and group 4 (40.4% and 46.6% vs. 3.8% and 12.0%, respectively). Severe RHF post-LVAD is associated with poor survival. Patients with LVAD who during the perioperative period are in need of right ventricular temporary or durable mechanical circulatory support constitute a group at particular risk. Improvement of devices tailored for right ventricular support is mandatory for further evolution of the field.

Churg-Strauss syndrome-associated heart failure and left ventricular thrombosis.

We present a case of a 47-year-old woman with a history of asthma and mononeuritis who presented with shortness of breath and fatigue. Heart failure was diagnosed and echocardiography revealed large floating thrombi attached to the left ventricular walls. Cardiac magnetic resonance imaging showed evidence of myocarditis and angiitis. Blood count revealed eosinophilia. She was diagnosed with eosinophilic granulomatosis with polyangiitis or Churg-Strauss syndrome (CSS) according to recently updated criteria. Medical management with specific aetiology (anticoagulation or immunosuppression) and heart failure treatment resulted in clinical improvement. We further discuss the diagnostic approach of CSS with cardiovascular complications and therapeutic management.

Prospective Phenotyping of Right Ventricle Function Following Intra-Aortic Balloon Pump Counterpulsation in Left Ventricular Assist Device Candidates: Outcomes and Predictors of Response.

Intra-aortic balloon pump (IABP) may be applied to optimize advanced heart failure (AHF) patients and improve right ventricular (RV) function before left ventricular assist device (LVAD) implantation. We aimed to evaluate the outcome of this intervention and define RV response predictors. Decompensated AHF patients, not eligible for LVAD because of poor RV function, who required IABP for stabilization were enrolled. Echocardiography and invasive hemodynamics were serially applied to determine fulfillment of prespecified "LVAD eligibility RV function" criteria (right atrium pressure [RA] <12 mm Hg, pulmonary artery pulsatility index [PAPi] >2.00, RA/pulmonary capillary wedge pressure [PCWP] <0.67, RV strain <-14.0%). Right ventricular-free wall tissue was harvested to assess interstitial fibrosis. Eighteen patients (12 male), aged 38 ± 14 years were supported with IABP for 55 ± 51 (3-180) days. In 11 (61.1%), RV improved and fulfilled the prespecified criteria, while seven (38.9%) showed no substantial improvement. Histopathology revealed an inverse correlation between RV interstitial fibrosis and functional benefit following IABP: interstitial fibrosis correlated with post-IABP RA ( r = 0.63, p = 0.037), RA/PCWP ( r = 0.87, p = 0.001), PAPi ( r = -0.83, p = 0.003). Conclusively, IABP improves RV function in certain AHF patients facilitating successful LVAD implantation. Right ventricular interstitial fibrosis quantification may be applied to predict response and guide preoperative patient selection and optimization. http://links.lww.com/ASAIO/A995.

Inotropic therapy in patients with advanced heart failure. A clinical consensus statement from the Heart Failure Association of the European Society of Cardiology.

This clinical consensus statement reviews the use of inotropic support in patients with advanced heart failure. The current guidelines only support use of inotropes in the setting of acute decompensated heart failure with evidence of organ malperfusion or shock. However, inotropic support may be reasonable in other patients with advanced heart failure without acute severe decompensation. The clinical evidence supporting use of inotropes in these situations is reviewed. Particularly, patients with persistent congestion, systemic hypoperfusion, or advanced heart failure with need for palliation, and specific situations relevant to implantation of left ventricular assist devices or heart transplantation are discussed. Traditional and novel drugs with inotropic effects are discussed and use of guideline-directed therapy during inotropic support is reviewed. Finally, home inotropic therapy is described, and palliative care and end-of-life aspects are reviewed in relation to management of ongoing inotropic support (including guidance for maintenance and weaning of chronic inotropic therapy support).

Phenotype Characterization and Course of Patients With Arrhythmogenic Right Ventricular Cardiomyopathy and Biventricular Advanced Heart Failure: A Report of 3 Cases.

BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC) may be complicated by heart failure. Management of advanced heart failure in this context is challenging. METHODS: We reviewed our center's experience with advanced heart failure therapies in patients with ARVC. Three rapidly deteriorating patients with ARVC with biventricular heart failure were found. Their management and outcomes are presented. Data on ventricular fibrosis were available in 2 of them and are also included. RESULTS: The first patient underwent initially successful paracorporeal pulsatile biventricular assist device (BiVAD) implantation. However, a large ischemic stroke occurred 2 weeks later, and the patient died after 2 months. The second patient underwent urgent BiVAD implantation after extracorporeal membrane oxygenation support because of cardiogenic shock, but his course was complicated by multiorgan failure due to systemic infection and the patient died. The last patient, being at Interagency Registry for Mechanically Assisted Circulatory Support 3-4 profile, underwent heart transplant with uneventful recovery. Extensive fibrosis was present in both ventricles of 2 patients undergoing pathology examination. CONCLUSIONS: Patients with ARVC and advanced biventricular heart failure are characterized by extensive ventricular fibrosis and considerable risk, but data on their management are limited. Biventricular circulatory support is associated with suboptimal outcomes, and prioritization for heart transplant seems preferable.

LVAD as a Bridge to Remission from Advanced Heart Failure: Current Data and Opportunities for Improvement.

Left ventricular assist devices (LVADs) are an established treatment modality for advanced heart failure (HF). It has been shown that through volume and pressure unloading they can lead to significant functional and structural cardiac improvement, allowing LVAD support withdrawal in a subset of patients. In the first part of this review, we discuss the historical background, current evidence on the incidence and assessment of LVAD-mediated cardiac recovery, and out-comes including quality of life after LVAD support withdrawal. In the second part, we discuss current and future opportunities to promote LVAD-mediated reverse remodeling and improve our pathophysiological understanding of HF and recovery for the benefit of the greater HF population.

Right Heart Failure Following Left Ventricular Device Implantation: Natural History, Risk Factors, and Outcomes: An Analysis of the STS INTERMACS Database.

BACKGROUND: Our current understanding of right heart failure (RHF) post-left ventricular assist device (LVAD) is lacking. Recently, a new Interagency Registry for Mechanically Assisted Circulatory Support definition of RHF was introduced. Based on this definition, we investigated natural history, risk factors, and outcomes of post-LVAD RHF. METHODS: Patients implanted with continuous flow LVAD between June 2, 2014, and June 30, 2016 and registered in the Interagency Registry for Mechanically Assisted Circulatory Support/Society of Thoracic Surgeons Database were included. RHF incidence and predictors, and survival after RHF were assessed. The manifestations of RHF which were separately analyzed were elevated central venous pressure, peripheral edema, ascites, and use of inotropes. RESULTS: Among 5537 LVAD recipients (mean 57±13 years, 49% destination therapy, support 18.9 months) prevalence of 1-month RHF was 24%. Of these, RHF persisted at 12 months in 5.3%. In contrast, de novo RHF, first identified at 3 months, occurred in 5.1% and persisted at 12 months in 17% of these, and at 6 months occurred in 4.8% and persisted at 12 months in 25%. Higher preimplant blood urea nitrogen (ORs,1.03-1.09 per 5 mg/dL increase; P<0.0001), previous tricuspid valve repair/replacement (ORs, 2.01-10.09; P<0.001), severely depressed right ventricular systolic function (ORs,1.17-2.20; P=0.004); and centrifugal versus axial LVAD (ORs,1.15-1.78; P=0.001) represented risk factors for RHC incidence at 3 months. Patients with persistent RHF at 3 months had the lowest 2-year survival (57%) while patients with de novo RHF or RHF which resolved by 3 months had more favorable survival outcomes (75% and 78% at 2 years, respectively; P<0.001). CONCLUSIONS: RHF at 1 or 3 months post-LVAD was a common and frequently transient condition, which, if resolved, was associated with relatively favorable prognosis. Conversely, de novo, late RHF post-LVAD (>6 months) was more frequently a persistent disorder and associated with increased mortality. The 1-, 3-, and 6-month time points may be used for RHF assessment and risk stratification in LVAD recipients.

Circulating and Myocardial Cytokines Predict Cardiac Structural and Functional Improvement in Patients With Heart Failure Undergoing Mechanical Circulatory Support.

Background Recent prospective multicenter data from patients with advanced heart failure demonstrated that left ventricular assist device (LVAD) support combined with standard heart failure medications, induced significant cardiac structural and functional improvement, leading to high rates of LVAD weaning in selected patients. We investigated whether preintervention myocardial and systemic inflammatory burden could help identify the subset of patients with advanced heart failure prone to LVAD-mediated cardiac improvement to guide patient selection, treatment, and monitoring. Methods and Results Ninety-three patients requiring durable LVAD were prospectively enrolled. Myocardial tissue and blood were acquired during LVAD implantation, for measurement of inflammatory markers. Cardiac structural and functional improvement was prospectively assessed via serial echocardiography. Eleven percent of the patients showed significant reverse remodeling following LVAD support (ie, responders). Circulating tumor necrosis factor alpha, interleukin (IL)-4, IL-5, IL-6, IL-7, IL-13, and interferon gamma were lower in responders, compared with nonresponders (P<0.05, all comparisons). The myocardial tissue signal transducer and activator of transcription-3, an inflammatory response regulator, was less activated in responders (P=0.037). Guided by our tissue studies and a multivariable dichotomous regression analysis, we identified that low levels of circulating interferon gamma (odds ratio [OR], 0.06; 95% CI, 0.01-0.35) and tumor necrosis factor alpha (OR, 0.05; 95% CI, 0.00-0.43), independently predict cardiac improvement, creating a 2-cytokine model effectively predicting responders (area under the curve, 0.903; P<0.0001). Conclusions Baseline myocardial and systemic inflammatory burden inversely correlates with cardiac improvement following LVAD support. A circulating 2-cytokine model predicting significant reverse remodeling was identified, warranting further investigation as a practical preintervention tool in identifying patients prone to LVAD-mediated cardiac improvement and device weaning.

The effect of paracorporeal pulsatile biventricular assist devices on allosensitization in adults: A comparison with left ventricular assist devices.

Ventricular assist devices (VADs) have been associated with the development of anti-HLA antibodies ('allosensitization'), but data on devices providing biventricular support in adults are limited. We sought to characterize differences in anti-HLA antibody formation in adult patients receiving left- (LVAD) versus biventricular- (BiVAD) assist devices as bridge to transplantation (BTT) by retrospectively reviewing the records of adult patients who have undergone VAD implantation at our institution. We assessed 82 patients supported with a pulsatile-flow paracorporeal BiVAD and compared them with 40 patients receiving LVAD till 2018. Forty-eight (58.5%) of the BiVAD and 23 (57.5%) of the LVAD patients were eventually transplanted (p = 0.91) with an average time to transplantation 559 and 598 days, respectively (p = 0.73). Evidence of sensitization pre-VAD was found in 11.0% of the BiVAD patients and 15.0% of the LVAD ones (p = 0.53); these percentages rose to 43.9% (p < 0.001) and 40.0% (p = 0.01), respectively. The post-VAD sensitization status was not significantly different between the BiVAD and the LVAD group (p = 0.68). De novo sensitization was comparable between the two groups (p = 0.55). Post-transplantation outcomes regarding rejections and cardiac allograft vasculopathy were also similar. Conclusively, BiVAD- and LVAD- induced allosensitization do not appear to differ significantly.

Left ventricular deformation mechanics over time in patients with thalassemia major with and without iron overload.

BACKGROUND: Myocardial iron overload in patients with thalassemia major (TM) is one of the most important complications. The purpose of the study was to identify advanced echocardiography parameters for early identification of myocardial dysfunction during follow-up of patients with TM. METHODS: Forty TM patients who were 41 ± 5 years old were included in the study and divided into two groups according to cardiac magnetic resonance T2* results (Group 1: Τ2* > 25 ms, Group 2: Τ2* ≤ 25 ms). Liver T2* parameters were also measured. Conventional and deformational echocardiographic parameters were measured at baseline and approximately 2 years later. RESULTS: Thirty-two patients had Τ2* = 34 ± 4 ms (Group 1), and 8 had Τ2* = 17 ± 9 ms (Group 2). Blood consumption was 185 ± 60 and 199 ± 37 ml/kg/yr (p = 0.64), and liver T2* was 4 ± 5 and 17 ± 21 ms (p = 0.01) in Groups 1 and 2, respectively. At baseline, Group 1 had better left ventricular global longitudinal strain (GLS) (- 22 ± 3 vs. - 18 ± 5, p = 0.01) and similar left ventricular ejection fraction (LVEF) (62 ± 5% vs. 58 ± 10%, p = 0.086) than Group 2. At the 28 ± 11-month follow-up, LVEF, GLS, and T2* values in Group 1 (63 ± 3%, - 21 ± 3%, 34 ± 4 ms) and Group 2 (56 ± 11%, - 17 ± 4%, 17 ± 9 ms) did not change significantly compared to their corresponding baseline values. In 8 patients from Group 1, a worsening (> 15%) in LS (p = 0.001) was detected during follow-up, with a marginal reduction in LVEF. CONCLUSIONS: GLS seems to be an efficient echocardiographic parameter for detecting hemochromatosis-related cardiac dysfunction earlier than LVEF. It also seems to be affected by other factors (free radical oxygen, immunogenetic mechanisms or viral infections) in a minority of patients, underscoring the multifactorial etiology of cardiomyopathy.

Percutaneous Mechanical Unloading Simultaneously With Reperfusion Induces Increased Myocardial Salvage in Experimental Acute Myocardial Infarction.

BACKGROUND: Despite advances in reperfusion times, patients presenting with acute myocardial infarction carry an unacceptably high rate of mortality and morbidity. Mechanical unloading of the left ventricle (LV) has been suggested to reduce infarct size after acute myocardial infarction. Although prior studies have investigated LV unloading during ischemia with a delay in reperfusion, little is known about the optimal timing for LV unloading in the setting of acute myocardial infarction. METHODS: Studies were conducted in 17 adult Yorkshire swine weighing 67±5 kg. A coronary balloon was inflated in the mid left anterior descending for 60 minutes to induce a myocardial infarction. The coronary balloon was then deflated for 120 minutes (reperfusion). The animals were stratified into 3 groups: group 1 (control, reperfusion with no LV unloading, n=5), group 2 (LV unloading during ischemia with delayed reperfusion, n=6), and group 3 (simultaneous LV unloading and reperfusion, n=6). Staining the hearts with Evans blue and 2,3,5-triphenyltetrazolium chloride was used to identify the area at risk and the infarct area respectively. Infarct percent size was defined as the area of infarcted myocardium divided by the area at risk. RESULTS: Of the 3 groups, group 3 demonstrated significantly smaller infarct percent size compared with controls (54.7±20.3% versus 22.2±13.4%; P=0.03). Comparison between group 1 and group 2 did not reveal significant difference (54.7±20.3% versus 43.3±24.6%; P=0.19). CONCLUSIONS: In our large animal experimental model, simultaneous reperfusion and mechanical LV unloading yielded the smallest infarct size compared with no LV unloading or LV unloading with delayed reperfusion. In the context of prior studies showing benefit to unloading before reperfusion, these findings raise questions about how this strategy may be translated to humans.