Ventricular Unloading Research Articles

Thrombocytopenia with Impella: Not a HIT.

Key Points The Impella percutaneous microaxial ventricular assist device provides significant ventricular unloading, but at the cost of increased major bleeding, hemolysis, and thrombocytopenia. The present study shows that nearly all patients develop thrombocytopenia within 7 days of Impella insertion with 81% having a >50% decrease. Platelet recovery occurs following device removal. Recognition of Impella‐related thrombocytopenia can reduce the concern for heparin‐induced thrombocytopenia and avoid the potential risks of direct thrombin inhibitors.

Timing of Active Left Ventricular Unloading in Patients on Venoarterial Extracorporeal Membrane Oxygenation Therapy

BackgroundIt is currently unclear if active left ventricular (LV) unloading should be used as a primary treatment strategy or as a bailout in patients with cardiogenic shock (CS) treated with venoarterial extracorporeal membrane oxygenation (VA-ECMO). ObjectivesThis study sought to evaluate the association between timing of active LV unloading and implantation of VA-ECMO with outcomes of patients with CS. MethodsData from 421 patients with CS treated with VA-ECMO and active LV unloading at 18 tertiary care centers in 4 countries were analyzed. Patients were stratified by timing of device implantation in early vs delayed active LV unloading (defined by implantation before up to 2 hours after VA-ECMO). Adjusted Cox and logistic regression models were fitted to evaluate the association between early active LV unloading and 30-day mortality as well as successful weaning from ventilation. ResultsOverall, 310 (73.6%) patients with CS were treated with early active LV unloading. Early active LV unloading was associated with a lower 30-day mortality risk (HR: 0.64; 95% CI: 0.46-0.88) and a higher likelihood of successful weaning from ventilation (OR: 2.17; 95% CI: 1.19-3.93) but not with more complications. Importantly, the relative mortality risk increased and the likelihood of successful weaning from ventilation decreased almost proportionally with the time interval between VA-ECMO implantation and (delayed) initiation of active LV unloading. ConclusionsThis exploratory study lends support to the use of early active LV unloading in CS patients on VA-ECMO, although the findings need to be validated in a randomized controlled trial.

Three Cases of LMT-STEMI with Cardiogenic Shock Under ECPELLA Support with Different Levels of Left Ventricular Unloading

Acute myocardial infarction with cardiogenic shock (AMICS) has an extremely high mortality rate, despite the development of early reperfusion strategies and intensive cardiovascular care medicine. In most cases, residual damage to the left ventricular (LV) damage induces refractory heart failure, even after successful salvage from cardiac arrest and shock conditions in the acute phase. We herein report three cases of AMICS that were supported by a combination of veno-arterial extracorporeal membrane oxygenation (VA-ECMO) and the Impella percutaneous microaxial heart pump, collectively referred to as ECPELLA. The first case was supported by an Impella CP pump prior to percutaneous coronary intervention (PCI), followed by ECPELLA. After PCI, the Impella was upgraded to an Impella 5.0. However, the LV function did not recover [LV ejection fraction (LVEF) 24%], and the patient died due to intestinal ischemia. The second case was supported by VA-ECMO prior to PCI, followed by ECPELLA. The LV function did not recover (LVEF 25%), and the patient was transferred to the ventricular assist device/heart transplant center. The third case received ECPELLA prior to PCI. The patient was successfully weaned from VA-ECMO and Impella support. The LVEF recovered to 39%, and the patient was discharged from the hospital on day 47. Although all three patients were supported by ECPELLA in the acute phase, the LV load during PCI differed markedly among the three cases. ECPELLA, which provides sufficient systemic perfusion with total LV unloading, may contribute to myocardial protection in AMICS.

Impella Support for Surgical Ventricular Septal Defect Repair.

Acute postinfarct ventricular septal defect (VSD) is associated with high mortality due to a combination of cardiogenic shock and a complex repair in recently infarcted fragile myocardium. 1 Although the Impella heart pump is established as support for cardiogenic shock, it is relatively contraindicated in postinfarct VSD because of potential right-to-left shunt or stroke due to VSD tissue-related embolus. On autopsy, early repair is technically difficult due to tissue friability and as a result, 38% of surgically repaired patients have evidence of recurrent interventricular septal rupture. 2 Delayed surgical repair (>7 days) is associated with superior survival-54% after 7 days versus 18% prior-but hemodynamic instability may prevent delay. 3 Case reports have shown successful early left ventricular unloading with Impella patients with acute postinfarct VSD before surgical repair. 4,5 We discuss our algorithm for pre-repair Impella support in which we stratify pre-repair support based on the Qp/Qs ratio. For VSD with Qp/Qs >2.5, we use a preoperative Impella heart pump and have not demonstrated reversal in the left-to-right shunt on echocardiography and/or stroke. Our findings are consistent with theoretical models of unloading as demonstrated by shifts in pressure-volume loops. 6.

Effect of Left Ventricular Unloading by Pump Speed Adjustment on Myocardial Flow in Continuous-flow Left Ventricular Assist Device Patients.

Resting myocardial blood flow (MBF) and myocardial flow reserve (MFR) are reduced in heart failure (HF) patients supported by pulsatile left ventricular assist devices (LVADs). The effect of continuous-flow (CF) physiology on these parameters is underexplored in CF-LVAD patients. We investigated the impact of CF-LVADs on resting MBF and MFR under two left ventricular (LV) loading conditions. Nine HeartMate II patients (42 ± 12 years, 100% male) on support for 370 ± 281 days were enrolled. Results were compared with 9 HF patients (58 ± 13 years, 67% male, LV ejection fraction 27 ± 9%) and 10 healthy volunteers (56 ± 10 years, 20% male). CF-LVAD patients underwent transthoracic echocardiography with ramp study. MBF and MFR were measured utilizing positron emission/computed tomography imaging under two LV loading conditions: "high-speed" (HS), promoting aortic valve (AV) closure and LV unloading; "low-speed" (LS), promoting AV opening and LV loading. Global resting MBF was similar in HS, LS, HF, and healthy: 0.8 ± 0.3, 0.7 ± 0.3, 0.7 ± 0.1, 0.9 ± 0.2 ml/min/g, respectively; p = NS. HS global MFR was reduced compared with LS and HF: 1.6 ± 0.6 versus 1.9 ± 0.5, p = 0.004; 1.6 ± 0.6 versus 2.4 ± 0.5, p = 0.01, respectively. HS regional MFR was reduced compared with LS in the left anterior descending (1.7 ± 0.7 vs. 2.0 ± 0.6, p = 0.027) and left circumflex (1.8 ± 0.7 vs. 2.2 ± 0.9, p = 0.008), but not in right coronary artery (1.7 ± 0.7 vs. 1.7 ± 0.6, p = 0.76). Resting MBF is preserved among CF-LVAD patients and is similar to HF and healthy. Promoting LV ventricular unloading with higher speed was associated with lower global and regional left coronary MFR, while right coronary MFR did not change.

Key questions about aortic insufficiency in patients with durable left ventricular assist devices.

The development of the latest generation of durable left ventricular assist devices (LVAD) drastically decreased adverse events such as pump thrombosis or disabling strokes. However, time-related complications such as aortic insufficiency (AI) continue to impair outcomes following durable LVAD implantation, especially in the context of long-term therapy. Up to one-quarter of patients with durable LVAD develop moderate or severe AI at 1 year and its incidence increases with the duration of support. The continuous regurgitant flow within the left ventricle can compromise left ventricular unloading, increase filling pressures, decrease forward flow and can thus lead to organ hypoperfusion and heart failure. This review aims to give an overview of the epidemiology, pathophysiology, and clinical consequences of AI in patients with durable LVAD.

Tricuspid surgery at the time of LVAD implant: A critique.

Tricuspid regurgitation (TR) is a common finding in patients with end stage heart failure referred for implantation of left ventricular assist devices. While functional TR frequently resolves after left ventricular unloading, patients with residual and progressive TR demonstrate increased rates of RV dysfunction and poor survival. Criteria for intervention on the tricuspid valve have focused on the degree of tricuspid annular dilatation and the severity of tricuspid regurgitant volume. The surgical decision making regarding intervention on the tricuspid valve remains obscure and historical cohort data cannot distinguish cause from effect.

Cardiac fibroblasts and mechanosensation in heart development, health and disease.

The term 'mechanosensation' describes the capacity of cells to translate mechanical stimuli into the coordinated regulation of intracellular signals, cellular function, gene expression and epigenetic programming. This capacity is related not only to the sensitivity of thecells to tissue motion, but also to the decryption of tissue geometric arrangement and mechanical properties. The cardiac stroma, composed of fibroblasts, has been historically considered a mechanically passive component of the heart. However, the latest research suggests that the mechanical functions of these cells are an active and necessary component of the developmental biology programme of the heart that is involved in myocardial growth and homeostasis, and a crucial determinant of cardiac repair and disease. In this Review, we discuss the general concept of cell mechanosensation and force generation as potent regulators in heart development and pathology, and describe the integration of mechanical and biohumoral pathways predisposing the heart to fibrosis and failure. Next, we address the use of 3D culture systems to integrate tissue mechanics to mimic cardiac remodelling. Finally, we highlight the potential of mechanotherapeutic strategies, including pharmacological treatment and device-mediated left ventricular unloading, to reverse remodelling in the failing heart.

Abstract 12589: Left Ventricular Unloading Preserves Ventricular Function and Reduces New-Onset Atrial Fibrillation in Patients With Acute Myocardial Infarction Complicated by Cardiogenic Shock

Introduction: Left ventricular (LV) unloading by percutaneous ventricular assist device (pVAD) reduces myocardial workload and oxygen consumption and provides a new concept for improving outcome for acute myocardial infarction complicated with cardiogenic shock (AMI-CS). AMI results in reduced LV ejection fraction and left atrium remodeling, and increased the incidence of atrial fibrillation. The aim of this study is to investigate the effectiveness of LV unloading by pVAD in terms of mid-term mortality, LV function, and the incidence of atrial fibrillation. Methods: We retrospectively reviewed AMI-CS patients who were admitted to our hospital between July 2014 and December 2021. We investigated patient demographics and baseline characteristics, mid-term clinical outcome, re-admission rate as well as new-onset atrial fibrillation compared between the patients supported with pVAD and without pVAD group during 180-day follow-up. Results: A total of 82 AMI-CS patients treated with pVAD (n=54) or without pVAD (n=28) were analyzed. Mean age was 70±15 years old and 56 patients were male. Door to balloon time (110±56min vs. 91±53min, p=0.33) and Peak CK-MB (471.8±338mg/dl vs. 486.0±545mg/dl, p=0.43) were similar in both groups. During the 180-days follow-up, 23 patients died and 12 patients were re-hospitalized for heart failure (HF). New-onset atrial fibrillation occurred in 16 patients, which was significantly less frequent in pVAD group (11% vs. 36%. p=0.016). Between baseline and 180-days follow-up period, changes of LV ejection fraction (16% vs. 6%, p=0.02) and NT-proBNP (-28% vs. -5%, p=0.03) were significantly higher in pVAD group. There was no significant difference in 180-day all-cause mortality (28% vs. 29%, p=1.0) between the two groups. Multivariate logistic regression showed new-onset atrial fibrillation was independently associated with an increased risk of HF readmission (hazard ratio 2.63, 95% confidence interval 1.91-3.57; p=0.01). Conclusion: pVAD support preserves LV function following ventricular unloading and reduces new-onset atrial fibrillation, which might be contributed to the improvement of mid-term outcome.

Interventricular-Septal Output While Supported on Left Ventricular Assist Device Therapy.

The effects of left ventricular unloading on septal function in patients with left ventricular assist devices (LVADs) have not been well characterized in vivo. The purpose of this study was to evaluate the relationship between markers of septal function with echocardiography in relationship to RV dysfunction and late RV failure after LVAD implantation. A retrospective study was conducted of patients supported on centrifugal-flow LVADs implanted over a 10-year period. Echocardiographic data were collected pre-operatively and up to 2 years after implantation. Interventricular septum (IVS) measurements were taken at end-systole and end-diastole. Interventricular-septal output (ISO) was calculated using the formula: (IVSs-IVSd)×heart rate. A total of 110 patients were included. An immediate and sustained reduction in both lateral annulus systolic velocity (RVS') and TAPSE were observed after implant ( p < 0.0001). However, ISO gradually decreased over time ( p < 0.0001). While ISO was not predictive of late RV failure, a decrease in ISO by 25% or greater from pre-implant to hospital discharge was associated with late RV failure (OR 4.8; 95% CI, 1.4-16.5; p = 0.012) even after adjusting for relevant clinical variables ( p ≤ 0.01 for each model). RV function is known to be influenced by mechanical ventricular interdependence and we demonstrate that measurement of ISO may be a useful marker in assessing RV dysfunction and predicting RV failure in patients following LVAD implantation.

Initial clinical validation of a hybrid in silico-in vitro cardiorespiratory simulator for comprehensive testing of mechanical circulatory support systems.

Simulators are expected to assume a prominent role in the process of design—development and testing of cardiovascular medical devices. For this purpose, simulators should capture the complexity of human cardiorespiratory physiology in a realistic way. High fidelity simulations of pathophysiology do not only allow to test the medical device itself, but also to advance practically relevant monitoring and control features while the device acts under realistic conditions. We propose a physiologically controlled cardiorespiratory simulator developed in a mixed in silico-in vitro simulation environment. As inherent to this approach, most of the physiological model complexity is implemented in silico while the in vitro system acts as an interface to connect a medical device. As case scenarios, severe heart failure was modeled, at rest and at exercise and as medical device a left ventricular assist device (LVAD) was connected to the simulator. As initial validation, the simulator output was compared against clinical data from chronic heart failure patients supported by an LVAD, that underwent different levels of exercise tests with concomitant increase in LVAD speed. Simulations were conducted reproducing the same protocol as applied in patients, in terms of exercise intensity and related LVAD speed titration. Results show that the simulator allows to capture the principal parameters of the main adaptative cardiovascular and respiratory processes within the human body occurring from rest to exercise. The simulated functional interaction with the LVAD is comparable to the one clinically observed concerning ventricular unloading, cardiac output, and pump flow. Overall, the proposed simulation system offers a high fidelity in silico-in vitro representation of the human cardiorespiratory pathophysiology. It can be used as a test bench to comprehensively analyze the performance of physically connected medical devices simulating clinically realistic, critical scenarios, thus aiding in the future the development of physiologically responding, patient-adjustable medical devices. Further validation studies will be conducted to assess the performance of the simulator in other pathophysiological conditions.

Patients with fulminant myocarditis supported with veno-arterial extracorporeal membrane oxygenation: a systematic review and meta-analysis of short-term mortality and impact of risk factors.

Fulminant myocarditis (FM) may lead to cardiogenic shock requiring veno-arterial extracorporeal membrane oxygenation (VA-ECMO). Results of effectiveness studies of VA-ECMO have been contradictory. We evaluated the aggregate short-term mortality after VA-ECMO and predictive factors in patients with FM. We systematically searched in electronic databases (February 2022) to identify studies evaluating short-term mortality (defined as mortality at 30 days or in-hospital) after VA-ECMO support for FM. We included studies with 5 or more patients published after 2009. We assessed the quality of the evidence using the QUIPS and GRADE tools. Mortality was pooled using random effect models. We performed meta-regression to explore heterogeneity based on a priori defined factors. We included 54 observational studies encompassing 2388 FM patients supported with VA-ECMO. Median age was 41 years (25th to 75th percentile 37–47), and 50% were female. The pooled short-term mortality was 35% (95% CI 29–40%, I2 = 69%; moderate certainty). By meta-regression, studies with younger populations showed lower mortality. Female sex, receiving a biopsy, cardiac arrest, left ventricular unloading, and earlier recruitment time frame, did not explain heterogeneity. These results remained consistent regardless of continent and the risk of bias category. In individual studies, low pH value, high lactate, absence of functional cardiac recovery on ECMO, increased burden of malignant arrhythmia, high peak coronary markers, and IVIG use were identified as independent predictors of mortality. When conventional therapies have failed, especially in younger patients, cardiopulmonary support with VA-ECMO should be considered in the treatment of severe FM. Supplementary InformationThe online version contains supplementary material available at 10.1007/s10741-022-10277-z.

Timing of active left ventricular unloading in patients with cardiogenic shock on veno-arterial extracorporeal membrane oxygenation therapy

Abstract Aim To evaluate the impact of timing of active left ventricular (LV) unloading in relation to veno-arterial extracorporeal membrane oxygenation (VA-ECMO) implantation on outcomes of patients with cardiogenic shock (CS). Methods and results Data from 421 patients with CS treated with active LV unloading on top of VA-ECMO at 18 tertiary-care centers in 4 countries were collected. Only patients in whom both devices were implanted within 24 hours of each other were considered and patients were stratified by timing of device implantation in early vs. delayed active LV unloading (e.g. active LV unloading before vs. after VA-ECMO). Cox and logistic regression models (adjusted for age, sex, lactate, cardiopulmonary resuscitation (CPR), VA-ECMO assisted CPR and enrollment center) were fitted to evaluate the association between early active LV unloading and 30-day mortality as well as several safety outcomes. Overall, 310 (73.6%) patients were treated with early active LV unloading. Early active LV unloading was associated with a lower 30-day mortality risk (hazard ratio 0.63, 95% confidence interval 0.46–0.87) and a higher likelihood of weaning from mechanical ventilation (odds ratio 1.25, 95% confidence interval 1.03–1.52), but not with more complications. Importantly, postponing active LV unloading in these patients was associated with higher mortality risk (Figure 1), and lower likelihood of successful weaning from mechanical ventilation. Conclusion This exploratory study lends support to the use of early active LV unloading in CS patients on VA-ECMO as a primary treatment strategy, as opposed to a bail-out approach. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Unrestricted research grant from Abiomed

Gender differences with the use of percutaneous left ventricular assist device in cardiogenic shock patients – results from the Dresden Impella Registry

Abstract Background Cardiogenic shock (CS) is a state of end-organ hypoperfusion due to cardiac output failure and is characterized by high mortality. Percutaneous left ventricular assist devices (pLVAD), like the Impella® system, support the left ventricular function and provide a sufficient oxygen supply to all tissues, which might improve outcome. In the current study, we investigated gender-specific differences in a large, propensity score matched cohort of patients receiving an Impella CP® in CS. Beside all-cause mortality, we focused on requirement of hemodialysis and surrogate parameters like development of systemic inflammatory response syndrome (SIRS), or sepsis, which is known to be associated with enhanced morbidity and mortality. Methods The Dresden Impella Registry is an ongoing registry including more than 650 patients since 2014. Among, a total of 95 female and 237 male patients received an Impella CP® in CS. Two groups of similar sample size (n=60) resulted after propensity score matching. A logistic regression model was used for adjustment of the baseline characteristics (nearest neighbor matching). Kaplan-Meier curves at 30, 180 and 365 days as well as clinical, laboratory and hemodynamic parameters were compared between male and female patients. Results The propensity score matched cohorts showed a well balancing without significant differences between baseline characteristics. At time of admission, female patients were 68.9±1.8 years old, male patients 67.2±1.5 years. A cardiopulmonary resuscitation (CPR) before pLVAD was performed in 53.3% in both groups. The comparison of mean arterial pressure, norepinephrine and dobutamine dosage showed no differences initially and in course. The left ventricular ejection fraction did not differ between both cohorts (♀ 28.6±2.3% vs. ♂ 26.7±1.7%, p=0.885). The duration of left ventricular unloading was 44.1±6.5 h among female patients and 56.0±7.3 h among male patients (p=0.119). The all-cause mortality showed no difference at 30, 180, and 365 d (30 d: ♀ 61.7±6.3% vs. ♂ 56.7±6.4%, p=0.349; 180 d: ♀ 73.3±5.7% vs. ♂ 68.3±6.0%, p=0.312; 365 d: ♀ 76.7±5.5% vs. ♂ 70.0±5.9%, p=0.312). However, hemodialysis was less frequently required in female patients (♀ 28.3% vs. ♂ 45.8%, p=0.049). The duration of hemodialysis did not differ between the groups (♀ 123.9±57.8 h vs. ♂ 108.1±56.3 h, p=0.744). Furthermore, occurrence of SIRS and sepsis were less frequently observed in female patients (SIRS ♀ 45.0% vs. ♂ 75.0%, p=0.042; sepsis ♀ 43.3% vs. ♂ 62.7%, p=0.034). Conclusion All-cause mortality showed no gender-specific differences in a well-balanced propensity score matched analysis of CS patients receiving LV-unloading with a pLVAD. However, females had a decreased requirement of hemodialysis and a less frequent occurrence of SIRS and sepsis. Further studies are needed to investigate whether these differences might improve outcome in larger cohorts. Funding Acknowledgement Type of funding sources: None.

Left ventricular unloading with Impella versus IABP in patients on VA-ECMO for cardiogenic shock

Abstract Background Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) use for circulatory support in shock is limited by increased left ventricular afterload. Impella and intra-aortic balloon pump (IABP) can be used in conjunction with VA-ECMO to help unload the left ventricle. Data comparing the two strategies are limited. Purpose We performed a systematic review and meta-analysis of published data to compare outcomes of patients with shock supported by VA-ECMO in conjunction with Impella versus IABP. Methods We conducted a search of Medline, Embase, and Cochrane databases to identify studies comparing the use of Impella versus IABP in patients on VA-ECMO. The primary outcome of interest was all-cause mortality (in-hospital or 30-day). Secondary outcomes included transition to destination therapy with left ventricular assist device (LVAD) or transplant, stroke, need for continuous renal replacement therapy (CRRT), bleeding, and hemolysis. Risk ratios (RR) with 95% confidence interval and the heterogeneity statistic I2 were reported for each outcome. Results Six observational studies with a total of 629 patients were included in the analysis. Of these, 205 (33%) and 424 (67%) patients were supported by Impella and IABP respectively, in addition to VA-ECMO. All six studies reported the primary outcome. No difference was observed in all-cause mortality between VA-ECMO with Impella and VA-ECMO with IABP (RR 1.02 [0.74–1.40], I2=74%). Similar rates were observed for transition to LVAD or transplant (RR 0.75 [0.45–1.27], I2=0%), stroke (RR 1.50 [0.80–2.83], I2=0%), and need for CRRT (RR 1.04 [0.82–1.32], I2=0%). However, use of VA-ECMO with Impella was associated with a higher risk of bleeding (RR 1.91 [1.28–2.86], I2=68%) and hemolysis (RR 4.61 [1.24–17.17], I2=66%) as compared with use of VA-ECMO with IABP. Conclusion In patients with shock requiring VA-ECMO, concurrent use of Impella and IABP had similar risk of mortality, transition to LVAD/transplant, stroke, and need for CRRT. However, Impella use was associated with higher risk of bleeding and hemolysis. Randomized trials are needed to identify the optimal strategy for left ventricular unloading in patients with cardiogenic shock on VA-ECMO. Funding Acknowledgement Type of funding sources: None.

Biology of myocardial recovery in advanced heart failure with long-term mechanical support.

Cardiac remodeling is an adaptive, compensatory biological process following an initial insult to the myocardium that gradually becomes maladaptive and causes clinical deterioration and chronic heart failure (HF). This biological process involves several pathophysiological adaptations at the genetic, molecular, cellular, and tissue levels. A growing body of clinical and translational investigations demonstrated that cardiac remodeling and chronic HF does not invariably result in a static, end-stage phenotype but can be at least partially reversed. One of the paradigms which shed some additional light on the breadth and limits of myocardial elasticity and plasticity is long term mechanical circulatory support (MCS) in advanced HF pediatric and adult patients. MCS by providing (a) ventricular mechanical unloading and (b) effective hemodynamic support to the periphery results in functional, structural, cellular and molecular changes, known as cardiac reverse remodeling. Herein, we analyze and synthesize the advances in our understanding of the biology of MCS-mediated reverse remodeling and myocardial recovery. The MCS investigational setting offers access to human tissue, providing an unparalleled opportunity in cardiovascular medicine to perform in-depth characterizations of myocardial biology and the associated molecular, cellular, and structural recovery signatures. These human tissue findings have triggered and effectively fueled a "bedside to bench and back" approach through a variety of knockout, inhibition or overexpression mechanistic investigations in vitro and in vivo using small animal models. These follow-up translational and basic science studies leveraging human tissue findings have unveiled mechanistic myocardial recovery pathways which are currently undergoing further testing for potential therapeutic drug development. Essentially, the field is advancing by extending the lessons learned from the MCS cardiac recovery investigational setting to develop therapies applicable to the greater, not end-stage, HF population. This review article focuses on the biological aspects of the MCS-mediated myocardial recovery and together with its companion review article, focused on the clinical aspects, they aim to provide a useful framework for clinicians and investigators.

Exercise oscillatory ventilation in patients with advanced heart failure with and without left ventricular assist device.

Exercise oscillatory ventilation (EOV), indicating pathological fluctuations on pulmonary arterial pressure, is associated with mortality in patients with heart failure (HF). Whether left ventricular assist device (LVAD)-induced ventricular unloading can reverse EOV and may prevent short-term rehospitalization has not been investigated. We performed a retrospective single-center in- and outpatient analysis of patients with (n=20, LVAD) and without (n=27, HF) circulatory support and reduced ejection fraction (EF, 22.8 ± 7.9%). The association of cardiopulmonary exercise testing (CPET) variables and 3 months-rehospitalization (3MR) as a primary outcome was analyzed. Furthermore, CPET variables were compared regarding the presence of EOV (+/-). Lower VO2peak (11.6 ± 4.9ml/kg/min vs. 14.4 ± 4.3ml/kg/min, p=0.039), lower increase of PETCO2 (CI=0.049-1.127; p=0.068), and higher VE/VCO2 (43.8 ± 9.5 vs. 38.3 ± 10.6; p=0.069) were associated with 3MR. Flattening of O2 pulse (CI=0.139-2.379; p=0.487) had no impact on 3MR. EOV was present in 59.5% (n=28/47) of patients, without a significant difference between LVAD and HF patients (p=0.959). Patients with HF/EOV+ demonstrated significantly lower VO2peak compared with HF/EOV- (p=0.039). LVAD/EOV+ displayed significantly lower EF (p=0.004) and fewer aortic valve opening than LVAD/EOV- (p=0.027). Lower VO2peak , but not EOV, was associated with 3MR. EOV occurred at a similar rate in LVAD and HF patients, which may illustrate insufficient unloading during exercise in chronic LVAD therapy and may contribute to the limited exercise capacity following LVAD implantation. Simultaneous CPET and right heart catheterization studies are needed to elucidate whether EOV may serve as a non-invasive predictor of insufficient LV unloading necessitating LVAD reprograming.

Invasive Real Time Biventricular Pressure-Volume Loops to Monitor Dynamic Changes in Cardiac Mechanoenergetics During Structural Heart Interventions: Design and Rationale of a Prospective Single-Center Study

BackgroundTranscatheter valvular interventions affect cardiac and hemodynamic physiology by changing ventricular (un-)loading and metabolic demand as reflected by cardiac mechanoenergetics. Real-time quantifications of these changes are scarce. Pressure-volume loop (PVL) monitoring appraises both load-dependent and load-independent compounds of cardiac physiology including myocardial work, ventricular unloading, and ventricular-vascular interactions. The primary objective is to describe changes in physiology induced by transcatheter valvular interventions using periprocedural invasive biventricular PVL monitoring. The study hypothesizes transcatheter valve interventions modify cardiac mechanoenergetics that translate into improved functional status at 1-month and 1-year follow-up. MethodsIn this single-center prospective study, invasive PVL analysis is performed in patients undergoing transcatheter aortic valve replacement or tricuspid or mitral transcatheter edge-to-edge repair. Clinical follow-up is per standard of care at 1 and 12 months. This study aims to include 75 transcatheter aortic valve replacement patients and 41 patients in both transcatheter edge-to-edge repair cohorts. ResultsThe primary outcome is the periprocedural change in stroke work, potential energy, and pressure-volume area (mmHg mL−1). The secondary outcomes comprise changes in a myriad of parameters obtained by PVL measurements, including ventricular volumes and pressures and the end-systolic elastance—effective arterial elastance ratio as a reflection of ventricular—vascular coupling. A secondary endpoint associates these periprocedural changes in cardiac mechanoenergetics with functional status at 1 month and 1 year. ConclusionsThis prospective study aims to elucidate the fundamental changes in cardiac and hemodynamic physiology during contemporary transcatheter valvular interventions.

Left Ventricular Unloading in Acute on Chronic Heart Failure: From Statements to Clinical Practice.

Cardiogenic shock remains a deadly complication of acute on chronic decompensated heart failure (ADHF-CS). Despite its increasing prevalence, it is incompletely understood and therefore often misdiagnosed in the early phase. Precise diagnosis of the underlying cause of CS is fundamental for undertaking the correct therapeutic strategy. Temporary mechanical circulatory support (tMCS) is the mainstay of management: identifying and selecting optimal patients through understanding of the hemodynamics and a prompt profiling and timing, is key for success. A recent statement from the American Heart Association provided pragmatic suggestions on tMCS device selection, escalation, and weaning strategies. However, several areas of uncertainty still remain in clinical practice. Accordingly, we present an overview of the main pitfalls that can occur during patients’ management with tMCS through a clinical case. This case illustrates the strict interdependency between left ventricular unloading and right ventricular dysfunction in the case of low filling pressures. Moreover, it further illustrates the pivotal role of stepwise escalation of therapy in a patient with an ADHF-CS and its peculiarities as compared to other forms of acute heart failure.

Rationale and Design of JenaMACS-Acute Hemodynamic Impact of Ventricular Unloading Using the Impella CP Assist Device in Patients with Cardiogenic Shock.

Introduction: Cardiogenic shock due to myocardial infarction or heart failure entails a reduction in end organ perfusion. Patients who cannot be stabilized with inotropes and who experience increasing circulatory failure are in need of an extracorporeal mechanical support system. Today, small, percutaneously implantable cardiac assist devices are available and might be a solution to reduce mortality and complications. A temporary, ventricular, continuous flow propeller pump using magnetic levitation (Impella®) has been approved for that purpose. Methods and Study Design: JenaMACS (Jena Mechanical Assist Circulatory Support) is a monocenter, proof-of-concept study to determine whether treatment with an Impella CP® leads to improvement of hemodynamic parameters in patients with cardiogenic shock requiring extracorporeal, hemodynamic support. The primary outcomes of JenaMACS are changes in hemodynamic parameters measured by pulmonary artery catheterization and changes in echocardiographic parameters of left and right heart function before and after Impella® implantation at different support levels after 24 h of support. Secondary outcome measures are hemodynamic and echocardiographic changes over time as well as clinical endpoints such as mortality or time to hemodynamic stabilization. Further, laboratory and clinical safety endpoints including severe bleeding, stroke, neurological outcome, peripheral ischemic complications and occurrence of sepsis will be assessed. JenaMACS addresses essential questions of extracorporeal, mechanical, cardiac support with an Impella CP® device in patients with cardiogenic shock. Knowledge of the acute and subacute hemodynamic and echocardiographic effects may help to optimize therapy and improve the outcome in those patients. Conclusion: The JenaMACS study will address essential questions of extracorporeal, mechanical, cardiac support with an Impella CP® assist device in patients with cardiogenic shock. Knowledge of the acute and subacute hemodynamic and echocardiographic effects may help to optimize therapy and may improve outcome in those patients. Ethics and Dissemination: The protocol was approved by the institutional review board and ethics committee of the University Hospital of Jena. Written informed consent will be obtained from all participants of the study. The results of this study will be published in a renowned international medical journal, irrespective of the outcomes of the study. Strengths and Limitations: JenaMACS is an innovative approach to characterize the effect of additional left ventricular mechanical unloading during cardiogenic shock via a minimally invasive cardiac assist system (Impella CP®) 24 h after onset and will provide valuable data for acute interventional strategies or future prospective trials. However, JenaMACS, due to its proof-of-concept design, is limited by its single center protocol, with a small sample size and without a comparison group.