Mechanical Circulatory Support Therapy Research Articles

Validation of the HeartMate 3 survival risk score in a large left ventricular assist device center.

The HeartMate 3 survival risk score was recently validated in the Multicenter study Of MagLev Technology in Patients Undergoing Mechanical Circulatory Support Therapy with HeartMate 3 to predict patient-specific survival in HeartMate 3 left ventricular assist device candidates. The HeartMate 3 survival risk score stratifies individuals into tertiles according to survival probability. We performed a single-center retrospective review of all HeartMate 3 left ventricular assist device recipients between September 2017 and August 2022. Baseline characteristics were collected from the electronic medical records. HeartMate 3 survival risk scores were calculated for all eligible patients. One- and 2-year Kaplan-Meier survival analyses were conducted. A univariate and multivariable Cox regression model was used to identify predictors. A total of 181 patients were included in this final analysis. The median age was 62years, 83% were male, and 26% were Interagency Registry for Mechanically Assisted Circulatory Support Profile 1. The mean HeartMate 3 survival risk score for the entire cohort was 2.66±0.66. Two-year survivals in the high, average, and low survival groups were 93.5%±3.2%, 81.6%±7.4%, and 82.0%±6.6%, respectively. As a continuous variable, the unadjusted HeartMate 3 survival risk score was a significant predictor of mortality (hazard ratio, 2.20; 95% CI, 1.08-4.45; P=.029). The areas under the curve were 0.70 and 0.66 at 1 and 2years, respectively. We were unable to demonstrate the discriminatory ability of the HeartMate 3 survival risk score using the original stratification, but we found significantly increased survival in the high survival group using a binary cutoff (hazard ratio, 4.8; 95% CI, 1.01-20.9; P=.038). The unadjusted HeartMate 3 survival risk score was associated with postimplant survival in patients outside of the Multicenter study Of MagLev Technology in Patients Undergoing Mechanical Circulatory Support Therapy with HeartMate 3 but did not remain an independent predictor after adjusting for ischemic etiology and severe diabetes. The HeartMate 3 survival risk score was able to identify patients at high survival using a binary cutoff, but we were unable to demonstrate its discriminatory ability among the previously published risk tertiles.

Artificial Intelligence Approaches for Predicting the Risks of Durable Mechanical Circulatory Support Therapy and Cardiac Transplantation.

Background: The use of AI-driven technologies in probing big data to generate better risk prediction models has been an ongoing and expanding area of investigation. The AI-driven models may perform better as compared to linear models; however, more investigations are needed in this area to refine their predictability and applicability to the field of durable MCS and cardiac transplantation. Methods: A literature review was carried out using Google Scholar/PubMed from 2000 to 2023. Results: This review defines the knowledge gaps and describes different AI-driven approaches that may be used to further our understanding. Conclusions: The limitations of current models are due to missing data, data imbalances, and the uneven distribution of variables in the datasets from which the models are derived. There is an urgent need for predictive models that can integrate a large number of clinical variables from multicenter data to account for the variability in patient characteristics that influence patient selection, outcomes, and survival for both durable MCS and HT; this may be fulfilled by AI-driven risk prediction models.

Lower vs Higher Oxygenation Target and Days Alive Without Life Support in COVID-19

Supplemental oxygen is ubiquitously used in patients with COVID-19 and severe hypoxemia, but a lower dose may be beneficial. To assess the effects of targeting a Pao2 of 60 mm Hg vs 90 mm Hg in patients with COVID-19 and severe hypoxemia in the intensive care unit (ICU). Multicenter randomized clinical trial including 726 adults with COVID-19 receiving at least 10 L/min of oxygen or mechanical ventilation in 11 ICUs in Europe from August 2020 to March 2023. The trial was prematurely stopped prior to outcome assessment due to slow enrollment. End of 90-day follow-up was June 1, 2023. Patients were randomized 1:1 to a Pao2 of 60 mm Hg (lower oxygenation group; n = 365) or 90 mm Hg (higher oxygenation group; n = 361) for up to 90 days in the ICU. The primary outcome was the number of days alive without life support (mechanical ventilation, circulatory support, or kidney replacement therapy) at 90 days. Secondary outcomes included mortality, proportion of patients with serious adverse events, and number of days alive and out of hospital, all at 90 days. Of 726 randomized patients, primary outcome data were available for 697 (351 in the lower oxygenation group and 346 in the higher oxygenation group). Median age was 66 years, and 495 patients (68%) were male. At 90 days, the median number of days alive without life support was 80.0 days (IQR, 9.0-89.0 days) in the lower oxygenation group and 72.0 days (IQR, 2.0-88.0 days) in the higher oxygenation group (P = .009 by van Elteren test; supplemental bootstrapped adjusted mean difference, 5.8 days [95% CI, 0.2-11.5 days]; P = .04). Mortality at 90 days was 30.2% in the lower oxygenation group and 34.7% in the higher oxygenation group (risk ratio, 0.86 [98.6% CI, 0.66-1.13]; P = .18). There were no statistically significant differences in proportion of patients with serious adverse events or in number of days alive and out of hospital. In adult ICU patients with COVID-19 and severe hypoxemia, targeting a Pao2 of 60 mm Hg resulted in more days alive without life support in 90 days than targeting a Pao2 of 90 mm Hg. ClinicalTrials.gov Identifier: NCT04425031.

Ventricular assist device using a thoracotomy-based implant technique: Multi-Center Implantation of the HeartMate 3 in Subjects With Heart Failure Using Surgical Techniques Other Than Full Median Sternotomy (HM3 SWIFT)

ObjectivesThe HeartMate 3 (Abbott) left ventricular assist device provides substantial improvement in long-term morbidity and mortality in patients with advanced heart failure. The Implantation of the HeartMate 3 in Subjects With Heart Failure Using Surgical Techniques Other Than Full Median Sternotomy study compares thoracotomy-based implantation clinical outcomes with standard median sternotomy. MethodsWe conducted a prospective, multicenter, single-arm study in patients eligible for HeartMate 3 implantation with thoracotomy-based surgical technique (bilateral thoracotomy or partial upper sternotomy with left thoracotomy). The composite primary end point was survival free of disabling stroke (modified Rankin score >3), or reoperation to remove or replace a malfunctioning device, or conversion to median sternotomy at 6-months postimplant (elective transplants were treated as a success). The primary end point (noninferiority, −15% margin) was assessed with >90% power compared with a propensity score-matched cohort (ratio 1:2) derived from the Multi-Center Study of MagLev Technology in Patients Undergoing Mechanical Circulatory Support Therapy With HeartMate 3 continued access protocol. ResultsThe study enrolled 102 patients between December 2020 and July 2022 in the thoracotomy-based arm at 23 North American centers. Follow-up concluded in December 2022. In the Implantation of the HeartMate 3 in Subjects With Heart Failure Using Surgical Techniques Other Than Full Median Sternotomy study group, noninferiority criteria was met (absolute between-group difference, −1.2%; Farrington Manning lower 1-sided 95% CI, −9.3%; P < .0025) and event-free survival was not different (85.0% vs 86.2%; hazard ratio, 1.01; 95% CI, 0.58-2.10). Length of stay with thoracotomy-based implant was longer (median, 20 vs 17 days; P = .03). No differences were observed for blood product utilization, adverse events (including right heart failure), functional status, and quality of life between cohorts. ConclusionsThoracotomy-based implantation of the HeartMate 3 left ventricular assist device is noninferior to implantation via standard full sternotomy. This study supports thoracotomy-based implantation as an additional standard for surgical implantation of the HeartMate 3 left ventricular assist device.

Real-Time Detection of Circulating Thrombi in an Extracorporeal Circuit Using Doppler Ultrasound: In-Vitro Proof of Concept Study.

Thromboembolic stroke continues to be by far the most common severe adverse event in patients supported with mechanical circulatory assist devices. Feasibility of using Doppler ultrasound to detect circulating thrombi in an extracorporeal circuit was investigated. A mock extracorporeal circulatory loop of uncoated cardiopulmonary bypass tubing and a roller pump was setup. A Doppler bubble counter was used to monitor the mean ultrasound backscatter signal (MUBS). The study involved two sets of experiments. In Scenario 1, the circuit was sequentially primed with human blood components, and the MUBS was measured. In Scenario 2, the circuit was primed with heparinized fresh porcine blood, and the MUBS was measured. Fresh blood clots (diameter <1,000 microns, 1,000-5,000 microns, >5,000 microns) were injected into the circuit followed by protamine administration. In Scenario 1 (n = 3), human platelets produced a baseline MUBS of 1.5 to 3.5 volts/s. Addition of packed human red blood cells increased the baseline backscatter to 17 to 21 volts/s. Addition of fresh frozen plasma did not change the baseline backscatter. In Scenario 2 (n = 5), the blood-primed circuit produced a steady baseline MUBS. Injection of the clots resulted in abrupt and transient increase (range: 3-30 volts/s) of the baseline MUBS. Protamine administration resulted in a sustained increase of MUBS followed by circuit thrombosis. Doppler ultrasound may be used for real-time detection of circulating solid microemboli in the extracorporeal circuit. This technology could potentially be used to design safety systems that can reduce the risk of thromboembolic stroke associated with mechanical circulatory support therapy.

Extracorporeal Carbon Dioxide Removal to De-escalate Venovenous Extracorporeal Membrane Oxygenation in Severe COVID-19 Acute Respiratory Distress Syndrome

In a subset of patients with COVID-19 acute respiratory distress syndrome (ARDS), there is a need for extracorporeal membrane oxygenation (ECMO) for pulmonary support. The primary extracorporeal support tool for severe COVID-19 ARDS is venovenous (VV) ECMO; however, after hypoxemic respiratory failure resolves, many patients experience refractory residual hypercarbic respiratory failure. Extracorporeal carbon dioxide removal (ECCO2R) for isolated hypercarbic type II respiratory failure can be used in select cases to deescalate patients from VV ECMO while the lung recovers the ability to exchange CO2. The objective of this study was to describe the authors' experience in using ECCO2R as a bridge from VV ECMO. Hemolung Respiratory Assist System (RAS) is a commercially available (ECCO2R) device, and the United States Food and Drug Administration accelerated its use under its Emergency Use Authorization for the treatment of refractory hypercarbic respiratory failure in COVID-19-induced ARDS. This created an environment in which selected and targeted mechanical circulatory support therapy for refractory hypercarbic respiratory failure could be addressed. This retrospective study describes the application of Hemolung RAS as a VV ECMO deescalation platform to treat refractory hypercarbic respiratory failure after the resolution of hypoxemic COVID-19 ARDS. A quaternary-care academic medical center, single institution. Patients with refractory hypercarbic respiratory failure after COVID-19 ARDS who were previously supported with VV ECMO. Twenty-one patients were placed on ECCO2R after VV ECMO for COVID-19 ARDS. Seventeen patients successfully were transitioned to ECCO2R and then decannulated; 3 patients required reescalation to VV ECMO secondary to hypercapnic respiratory failure, and 1 patient died while on ECCO2R. Five (23.8%) of the 21 patients were transitioned off of VV ECMO to ECCO2R, with a compliance of <20 (mL/cmH2O). Of these patients, 3 with low compliance were reescalated to VV ECMO. Extracorporeal carbon dioxide removal can be used to continue supportive methods for patients with refractory type 2 hypercarbic respiratory failure after COVID-19 ARDS for patients previously on VV ECMO. Patients with low compliance have a higher rate of reescalation to VV ECMO.

Clinical practice guideline for the diagnosis and treatment of cardiorenal syndrome (2023 Edition)

The guideline was co-authored by a working group composed of multidisciplinary experts in nephrology, cardiology, critical care medicine, and evidence-based medicine. It focused on eight clinical issues concerning prediction, diagnosis and assessment of cardiorenal syndrome, prevention, treatment of drugs and their selection, mechanical circulatory support and blood purification therapy, heart and/or kidney transplantation, treatment of major complications, multidisciplinary combination therapy, and special diagnosis and treatment in children and pregnant women, mainly based on evidence-based evidence of cardiorenal syndrome, heart failure and chronic kidney disease. Meanwhile, the domestic and foreign clinical guidelines in related fields were referenced to put forward recommendations. The present guideline aims to guide and standardize the clinical practice of diagnosis, prevention, treatment and management of cardiorenal syndrome, promote the development of clinical trials, and improve the level of prevention, treatment and scientific research.

Clinical Outcomes With a Fully Magnetically Levitated Left Ventricular Assist Device Among Women and Men

BackgroundLeft ventricular assist devices (LVADs) are underused among women with advanced heart failure, but reasons remain unclear. Outcomes in women compared with men with contemporary fully magnetically levitated LVADs remain uncertain. ObjectivesThe authors examined differences in characteristics, 2-year outcomes, and risk for key adverse events among women and men. MethodsIn 2,200 HeartMate3 (HM3) (Abbott Cardiovascular) LVAD recipients in the MOMENTUM 3 study (Multicenter Study of MagLev Technology in Patients Undergoing Mechanical Circulatory Support Therapy with HeartMate 3), survival free of disabling stroke or reoperation to replace or remove a malfunctioning pump at 2 years was analyzed between women and men. Other outcomes included overall 2-year survival, adverse events, and functional measures. ResultsWomen comprised 20.4% (n = 448 of 2,200) of the study population and were younger, with nonischemic cardiomyopathy, and more often were Black persons compared with men. The primary endpoint (women 79.4% vs men 75.5% (adjusted [a]HR: 0.96 [95% CI: 0.75-1.24]; P = 0.66) or survival at 2 years (women 82.4% vs men 80.2%; aHR: 1.06 [95% CI: 0.81-1.40]; P = 0.66) was no different. Women had an increased rate of stroke (adjusted incidence rate ratio [aIRR]: 1.52 [95% CI: 1.09-2.11]; P = 0.012), major bleeding (aIRR: 1.28 [95% CI: 1.15-1.42]; P < 0.0001) and infection (aIRR 1.14 [95% CI: 1.03-1.55]; P = 0.01), but these differences were not seen among older (>65 years) patients. Both groups had similar gains in 6-minute walk distance and quality-of-life measurements. ConclusionsThere were no differences in the primary composite endpoint or overall survival in women compared with men at 2 years of support. Reasons underlying increase in hemocompatibility-related events and infection-related morbidity in younger women deserves further study. (MOMENTUM 3 IDE [HM3], NCT02224755; MOMENTUM 3 Continued Access Protocol [MOMENTUM 3 CAP], NCT02892955)

Fulminant Myocarditis Associated With Parvovirus B19 and Epstein-Barr Virus Coinfection

Abstract Parvovirus B19 (PVB19) and Epstein-Barr virus (EBV) commonly cause infection worldwide, with most persons infected during childhood. Their disease courses are usually mild and brief; however, PVB19 and EBV have been implicated as etiologies of viral myocarditis. We report a case of PVB19 and EBV coinfection associated with fulminant lymphocytic myocarditis. We address the implications of the case, including the differential diagnosis, immunomodulatory treatment considerations, and evidence for the pathologic roles of PVB19, EBV, and coinfection in myocarditis. Although the pathogenic roles of PVB19 or EBV alone in myocarditis are not well established, coinfection of PVB19 and EBV may unlock their pathogenic roles causing fulminant myocarditis. Treatment with steroids and intravenous immunoglobulin G in a patient with rapid clinical deterioration despite the presence of active infection on endomyocardial biopsy by polymerase chain reaction can result in a safe and quick recovery of fulminant viral myocarditis. Early and aggressive intervention, including both mechanical circulatory support and immunomodulatory therapy, may be key to improved outcomes in cases of fulminant myocarditis.

SHOCK4: Utilizing Mechanical Circulatory Support and Immunomodulation for the Management of Fulminant Lymphocytic Myocarditis: Case Series

Purpose: Five consecutive patients with biopsy-proven lymphocytic myocarditis (LM) presented to our medical center with cardiogenic shock (CS) requiring Mechanical Circulatory Support (MCS) and Immunomodulatory therapy. We present our experience and highlight the variability of presentation and management strategies. Methods: Five consecutive patients presented to our center between 3/1/2022 and 12/1/2022 with acute onset ventricular dysfunction and CS (Table). One had an out-of-hospital cardiac arrest. Due to the fulminant presentation and lack of typical risk factors, there was high clinical suspicion for myocarditis. One patient had positive influenza A testing. Results: All patients were managed acutely with VA-ECMO with or without left ventricular ventilation. All patients underwent an endomyocardial biopsy which showed virus-negative LM. Immunomodulatory therapy strategies varied among patients. Our initial approach was Methylprednisolone for 3 days and IVIG for all. Moreover, for those with a slower rate of recovery, or continued high inflammatory markers, plasmapharesis was utilized in addition to prolonged prednisone and/or azathioprine courses (Table). Of the five subjects, two had myocardial recovery, one developed chronic myocarditis, one developed chronic heart failure, and one required a durable LVAD. Conclusion: Lymphocytic myocarditis is a rare inflammatory disorder of the heart characterized by mononuclear cellular infiltrate and ventricular dysfunction. Fulminant myocarditis is characterized by CS or cardiac arrest. Prompt diagnosis is critical because the prognosis and recovery are better than with nonspecific histological findings or giant cell myocarditis (1,2). Our series and others have demonstrated MCS key role in decreasing mortality while treating the myocardial consequences of inflammatory injury (5-7). While viral infections are the most common cause found in 30-40% of cases (1,3,4), only one patient in our series had an influenza A infection, and none had positive viral testing on the biopsy. We found no consistent history of COVID-19 infection or vaccination among the patients. There is no consensus on the best strategy for immunomodulatory therapy, and more extensive studies with long-term outcomes are needed.

BIO19: Patient-Specific Econotherapeutic Closed-Clinician/Engineer-in-the-loop Framework for VAD Physiological Control

Background: Mechanical circulatory support therapy essentially restricts patients to the hospital. Numerous clinical publications and national/international presentations indicate the need for early patient discharge, both from a quality of life and economic viewpoint. An alternative strategy is to look at providing time-appropriate VAD support to temporize patients for transplantation or other definitive therapy. However, current VAD systems do not possess high-level feedback control targeting therapy-specific objectives. Current Controllers (i) operate in open-loop fixed-average-speed mode (do not adjust to match physiological demand or cardiac function) and (ii) have minimal ability to assess and respond to adverse events. Therefore, our group is embarking on developing an Intelligent VAD ControllerTM (iVC™) with advanced, modern features that address the deficits of prevailing technologies. Methods: As an initial step towards the design of an Intelligent VAD ControllerTM (iVC™), we developed an Econotherapeutic framework based on concepts of modern control theory, inter-operator communication (Kanban Method), and industrial supply-demand management (Tanpin-Kanri System). The design inputs included considerations for 1. collaboration of clinician and engineer; 2. patient-specific therapeutic goals; 3. fusion of multiple control objectives; 4. non-invasive monitoring of the patient and hardware, and 5. considerations of the financial/resource cost. From the perspective of a control problem, we extend the engineering theory behind its implementation by including, in our framework, the therapy and healthcare protocols to the control problem as constraints. Results: The resulting Econotherapeutic framework is depicted schematically in Figures 1 and 2 below. Figure 1 outlines the framework’s architecture, which includes two sub-frameworks: Therapeutic and Economical. The outlines of the framework’s functions are provided to optimize patient-specific therapy and follow-up and the economic burden of care and control. Figure 2 outlines the inter-operator communication (inspired by Kanban Methods) protocols that form the basis for the framework in terms of roles and responsibilities, design aspects of the control, and implementation steps (including support). The framework addresses the design inputs with the outlines mentioned in Figure 1 as to what the framework addresses, with the implementation of the framework specific to a patient carried out by the protocols outlined in Figure 2. Conclusion: A VAD closed-loop physiological control is, in essence, a multi-disciplinary optimization problem driven by both medical and engineering considerations. The econotherapeutic framework derived above provides a framework for developing an iVC. We will now proceed to develop, in conjunction with clinicians, the possible details of the framework and, using The PediaFlowTM Pediatric VAD, conduct feasibility studies of the iVC that tests the framework.Figure 1. Architecture of the Econotherapeutic FrameworkFigure 2. The Design, Management and Monitoring Communication protocols of the Econotherapeutic Framework for iVC for every individual patient.

Therapeutic limitation in cardiogenic shock: lessons learnt from the Altshock-2 registry

Abstract Funding Acknowledgements Type of funding sources: None. Background Mortality from cardiogenic shock (CS) shows great disparities (1). This evidence reflects variations in access to care and medical practice, related to the lack of clear guidelines for appropriate patient selection for mechanical circulatory support (MCS) application. In this regard, the results of most trials or meta-analyses were neutral on survival, and the costs in terms of patient morbidity/mortality are high and unproven (2). Accordingly, a judicious use of MCS is crucial for an adequate resource allocation and to avoid futility. Purpose To characterize trends in use of support devices and compare outcomes between CS patients included in a contemporary national Cardiac Intensive Care Units (CICUs) registry, treated or not with MCS. Methods 324 sequential patients admitted with CS at a CICUs network between March 2020 and August 2022 were identified. We categorized patients according to treatment with MCS (n=204; 63%) and medical therapy (n=120; 37%). We investigated differences in clinical, laboratory, hemodynamics, echocardiographic and prognostic scores on admission, at 24-hours and at discharge. In-hospital outcome and mid-term survival were described for each treatment cohort. Comparison of continuous variables was performed using Student’s t-test. For categorical variables, the χ2 statistic was used. Results CS was a complication of acute myocardial infarction in 141 patients (44%) and of acute on chronic heart failure in 124 patients (38%); 58 patients (18%) presented with other diagnosis. In MCS cohort, we reported more advanced Society for Cardiovascular Angiography and Interventions (SCAI) shock stages and MCS implantation was more prevalent within 24-hours in SCAI C (48,6% on admission; 51,2% at 24-hours). In-hospital mortality did not differ between the two groups (38% in MCS and 37% in medically treated patients, p=0,874). Chronic kidney disease (OR 2.1, 95%CI 1.2-3.5, p=0,009), elevated lactates and SCAI stage at 24-hours (OR and 95%CI were, respectively, 3.45, 1.99-5.97 and 3.67, 2.46-5.47, p&amp;lt;0,001) emerged as major independent predictors of in-hospital mortality in MCS subgroup. A significant protective association persisted for those monitored with pulmonary artery catheter (OR 0.61, 95%CI 0.51-0.92, p=0.001). Among the 196 patients evaluated at mid-term follow up MCS treatment had not markedly improved cumulative survival compared to medical treatment (51,9% in MCS subgroup versus 55,6% in medical therapy, p=0,806). Palliative care team was rarely engaged (14% in MCS cohort vs 27% in medical therapy, p=0,83). Conclusions In this nation-wide study, mortality in MCS patients was high and no statistically significant difference on in-hospital and mid-term survival emerged between patients receiving MCS compared to medical therapy. Hence, a prompt and constant risk-stratification is mandatory to exclude patients too sick to derive any benefits from invasive therapies, avoiding futility.

Lactate versus Phosphate as Biomarkers to Aid Mechanical Circulatory Support Decisions in Patients with Out-of-Hospital Cardiac Arrest and Return of Spontaneous Circulation.

Identifying patients who may benefit from mechanical circulatory support (MCS) after out-of-hospital cardiac arrest (OHCA) and return of spontaneous circulation (ROSC) remains challenging; thus, a search for helpful biomarkers is warranted. We aimed to evaluate phosphate and lactate levels on admission regarding their associations with survival with and without MCS. In 224 OHCA patients who achieved ROSC, the initial phosphate and lactate levels were investigated to discriminate in-hospital mortality by receiver operating characteristic (ROC) curves. According to the Youden Index (YI) from the respective ROC, the groups were risk stratified by both biomarkers, and 30-day mortality was analyzed in patients with and without MCS. Within the entire collective, MCS was not associated with a better chance of survival. Both phosphate and lactate level elevations showed good yet comparable discriminations to predict mortality (areas under the curve: 0.80 vs. 0.79, p = 0.74). In patients with initial phosphate values > 2.2 mmol/L (>YI), 30-day mortality within the MCS cohort was lower (HR 2.3, 95% CI: 1.4-3.7; p = 0.0037). In patients with lower phosphate levels and groups stratified by lactate, 30-day mortality was similar in patients with and without MCS. We found a significant association between survival and MCS therapy in patients with phosphate levels above 2.2 mmol/L (Youden Index), and a similar discrimination of patient overall survival by lactate and phosphate. Prospective studies should assess the possible independent prognostic value of phosphate and its clearance for MCS efficiency.

Understanding COVID-19-related myocarditis: pathophysiology, diagnosis, and treatment strategies.

Coronavirus disease 2019 (COVID-19) disease has infected nearly 600 million people, resulting in > 6 million deaths, with many of them dying from cardiovascular diseases. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is caused by a combination of the virus surface spike protein and the human angiotensin-converting enzyme 2 (ACE2) receptor. In addition to being highly expressed in the lungs, ACE2 is widely distributed in the heart, mainly in myocardial cells and pericytes. Like other types of viruses, SARS-CoV-2 can cause myocarditis after infecting the myocardial tissue, which is attributed to the direct damage of the virus and uncontrolled inflammatory reactions. Patients with chest tightness, palpitation, abnormal electrocardiogram, and cardiac troponin elevation, should be suspected of myocarditis within 1-3 weeks of COVID-19 infection. When the hemodynamics change rapidly, fulminant myocarditis should be suspected. Cardiac ultrasound, myocardial biopsy, cytokine detection, cardiac magnetic resonance imaging, 18F-fluorodeoxyglucose positron emission tomography, and other examination methods can assist in the diagnosis. Although scientists and clinicians have made concerted efforts to seek treatment and prevention measures, there are no clear recommendations for the treatment of COVID-19-related myocarditis. For most cases of common myocarditis, general symptomatic and supportive treatments are used. For COVID-19-related fulminant myocarditis, it is emphasized to achieve "early identification, early diagnosis, early prediction, and early treatment" based on the "life support-based comprehensive treatment regimen." Mechanical circulatory support therapy can rest the heart, which is a cure for symptoms, and immune regulation therapy can control the inflammatory storms which is a cure for the disease. Furthermore, complications of COVID-19-related myocarditis, such as arrhythmia, thrombosis, and infection, should be actively treated. Herein, we summarized the incidence rate, manifestations, and diagnosis of COVID-19-related myocarditis and discussed in detail the treatment of COVID-19-related myocarditis, especially the treatment strategy of fulminant myocarditis.

Presentation and Outcomes of Patients With Preoperative Critical Illness Undergoing Cardiac Surgery

BackgroundLittle is known about the prevalence and post-surgical outcomes associated with cardiac intensive care unit (CICU) therapeutics among CICU patients referred for cardiac surgery. ObjectivesThe purpose of this study was to investigate the clinical characteristics and outcomes of CICU patients referred for cardiac surgery from the intensive care unit. MethodsWe analyzed characteristics and outcomes of CICU admissions referred from the CICU for cardiac surgery during 2017 to 2020 across 29 centers. The primary outcome was in-hospital mortality. ResultsAmong 10,321 CICU admissions, 887 (8.6%) underwent cardiac surgery, including 406 (46%) coronary artery bypass graftings, 201 (23%) transplants or ventricular assist devices, 171 (19%) valve surgeries, and 109 (12%) other procedures. Common indications for CICU admission included shock (33.5%) and respiratory insufficiency (24.9%). Preoperative CICU therapies included vasoactive therapy in 52.2%, mechanical circulatory support in 35.9%, renal replacement in 8.2%, mechanical ventilation in 35.7%, and 17.5% with high-flow nasal cannula or noninvasive positive pressure ventilation. In-hospital mortality was 11.7% among all CICU admissions and 9.1% among patients treated with cardiac surgery. After multivariable adjustment, pre-op mechanical circulatory support and renal replacement therapy were associated with mortality, while respiratory support and vasoactive therapy were not. ConclusionsNearly 1 in 12 contemporary CICU patients receive cardiac surgery. Despite high preoperative disease severity, CICU admissions undergoing cardiac surgery had a comparable mortality rate to CICU patients overall; highlighting the ability of clinicians to select higher acuity patients with a reasonable perioperative risk.

The convergent cavopulmonary connection: A novel and efficient configuration of Fontan to accommodate mechanical support

ObjectiveThe current total cavopulmonary connection Fontan has competing inflows and outflows, creating hemodynamic inefficiencies that contribute to Fontan failure and complicate placement and efficiency of mechanical circulatory support. We propose a novel convergent cavopulmonary connection (CCPC) Fontan design to create a single, converged venous outflow to the pulmonary arteries, thus increasing efficiency and mechanical circulatory support access. We then evaluate the feasibility and hemodynamic performance of the CCPC in various patient sizes using computational fluid dynamic assessments of computer-aided designs. MethodsCardiac magnetic resonance imaging data from 12 patients with single ventricle (10 total cavopulmonary connection, 2 Glenn) physiology (body surface area, 0.5-2.0 m2) were segmented to create 3-dimensional replicas of all thoracic structures. Surgically feasible CCPC shapes within constraints of anatomy were created using iterative computational fluid dynamic and clinician input. Designs varied based on superior and inferior vena cava conduit sizes, coronal attachment height, coronal entry angle, and axial entry angle of the superior vena cava to the inferior vena cava. CCPC designs were optimized based on efficiency (indexed power loss), risk of arteriovenous malformations (hepatic flow distribution), and risk of flow stasis (% nonphysiologic wall shear stress). ResultsAll CCPC designs met hemodynamic performance thresholds for indexed power loss and hepatic flow distribution. CCPC designs showed improvements in reducing % nonphysiologic wall shear stress and balancing HFD. ConclusionsCCPC is physiologically and surgically feasible in various patient sizes using validated computational fluid dynamic models. CCPC configuration has analogous indexed power loss, hepatic flow distribution, and % nonphysiologic wall shear stress compared with total cavopulmonary connection, and the single inflow and outflow may ease mechanical circulatory support therapies. Further studies are required for design optimization and mechanical circulatory support institution.

Biventricular assist devices and total artificial heart: Strategies and outcomes.

In contrast to the advanced development of the left ventricular assist device (LVAD) therapy for advanced heart failure, the mechanical circulatory support (MCS) with biventricular assist device (BVAD) and total artificial heart (TAH) options remain challenging. The treatment strategy of BVAD and TAH therapy largely depends on the support duration. For example, an extracorporeal centrifugal pump, typically referred to as a temporary surgical extracorporeal right ventricular assist device, is implanted for the short term with acute right ventricular failure following LVAD implantation. Meanwhile, off-label use of a durable implantable LVAD is a strategy for long-term right ventricular support. Hence, this review focuses on the current treatment strategies and clinical outcomes based on each ventricle support duration. In addition, the issue of heart failure post-heart transplantation (post-HT) is explored. We will discuss MCS therapy options for post-HT recipients.

Prediction of Survival After Implantation of a Fully Magnetically Levitated Left Ventricular Assist Device

BackgroundClinical trials inform on average efficacy, but individualized risk assessments for outcome prediction are important in guiding treatment implementation. ObjectivesThe authors developed and validated a patient-specific risk score to predict survival at 1 and 2 years after HeartMate 3 (HM3) left ventricular assist device (LVAD) implantation. MethodsThe MOMENTUM 3 (Multicenter Study of MagLev Technology in Patients Undergoing Mechanical Circulatory Support Therapy with HeartMate 3) trial includes 2,200 HM3 LVAD patients in the pivotal trial and Continued Access Protocol study (2014-2018). The authors randomly assigned all patients to a derivation cohort (n = 1,540) or validation cohort (n = 660). Univariate mortality predictors were screened for potential model inclusion, stepwise selection was used to build the multivariable Cox proportional hazards regression model, and performance (discrimination and calibration) was evaluated. ResultsAge, prior cardiac surgery (coronary artery bypass grafting [CABG] or valve procedure), lower serum sodium, higher blood urea nitrogen (BUN), small left ventricular size, and right atrial pressure-to-pulmonary capillary wedge pressure (RAP/PCWP) ratio >0.6 were significant risk factors for mortality. Receiver-operating characteristic (ROC) analysis in the validation cohort demonstrated an area under the curve (AUC) of 0.76 (95% CI: 0.70-0.81) at 1 year and 0.71 (95% CI: 0.66-0.77) at 2 years. Calibration between predicted and observed survival of the risk quintiles was high, with Pearson correlation coefficients of 0.986 and 0.994 at 1 and 2 years, respectively. Patients were successfully stratified into tertiles with higher-than-average, average, and lower-than-average survival, and observed mortality risk increased by 2-fold from one tertile to the next. ConclusionsA practical, easy-to-use HM3 Survival Risk Score with 6 components was developed to accurately predict 1- and 2-year survival after HM3 LVAD implantation. The survival risk score can be used to provide individual survival estimates to facilitate shared decision making when considering HM3 LVAD therapy. (MOMENTUM 3 Trial Portfolio; NCT02224755, NCT02892955)

Impact of left ventricular ejection fraction on mortality and use of mechanical circulatory support in non-ischaemic cardiogenic shock

Abstract Background Evidence in non-ischaemic cardiogenic shock (CS), especially regarding prognostic markers and use of mechanical circulatory support (MCS), is scarce. Aim The aim of this study was to evaluate left ventricular ejection fraction (LVEF) as a prognostic marker as well as a factor to guide the use of MCS in non-ischaemic CS. Methods In this international observational study, patients with non-ischaemic CS (e.g. caused by severe de-novo or acute on chronic heart failure; but not by acute myocardial infarction) treated with or without MCS from 18 tertiary-care centers in five countries were enrolled. Cox regression models adjusted for age, sex, SCAI class, lactate, prior resuscitation, mechanical ventilation and pH were fitted to evaluate the association between LVEF and 30-day mortality as well as the interaction between MCS use, LVEF and 30-day mortality. Results A total of 807 patients were enrolled, of whom 387 (47,9%) were treated with and 418 (52.1%) without MCS; mean age was 63 [interquartile range (IQR) 51.5–72) years, 601 (74.5%) were male, 486 (60.2%) had acute on chronic heart failure, 221 (32.7%) had an ischaemic cardiomyopathy and 277 (34.5%) had prior cardiac arrest. The baseline LVEF was 20 (IQR 15–30) % and baseline lactate was 4.9 (IQR 2.6–8.5) mmol/l. There was no significant association between LVEF and 30-day mortality risk [hazard ratio (HR) 0.95, 95% confidence interval (CI) 0.74–1.22 if LVEF was considered as a continuous variable; HR 1.09, 95% CI 0.83–1.44 if LVEF was considered as a categorical variable with ≤20% vs. &amp;gt;20%]. However, there was a significant interaction between MCS use and LVEF, indicating a lower 30-day mortality risk with MCS use in patients with a depressed LVEF (HR 0.74, 95% CI 0.52–1.05, interaction-p = 0.04). Conclusion In this retrospective, multicenter, international study of patients with non-ischaemic CS, LVEF was not a predictor of 30-day mortality risk. However, we observed a significant interaction between MCS use and LVEF, indicating a lower morality risk with MCS use only in patients with a depressed LVEF. This provides rationale to use LVEF as a parameter to guide MCS therapy in non-ischaemic CS, and calls for a randomized trial on this topic. Funding Acknowledgement Type of funding sources: None.

Impact of the elevated angiopoietin-2 levels during Impella support on the short-term prognosis.

Elevated serum angiopoietin-2 levels in patients with acute myocardial infarction-related cardiogenic shock with and without intra-aortic balloon pump as well as acute decompensated heart failure are associated with short-term mortality. However, its prognostic impact in patients with cardiogenic shock supported by Impella-incorporated mechanical circulatory support (MCS) remains unknown. Patients who received temporary MCS (Impella alone or Impella and veno-arterial extracorporeal membrane oxygenation) in our institute between August 2018 and January 2022 were included in this prospective study. The serum levels of angiopoietin-2 were measured just before and following the initiation of temporary MCS therapy. Association between the levels of serum angiopoietin-2 and 30-day mortality was investigated. A total of 38 patients (median 72years old, 63% men) were included. The median levels of serum angiopoetin-2 tended to decrease from baseline to 4days following the initiation of temporary MCS from 5.2 (3.3, 10.5)ng/mL to 4.8 (2.7, 6.8)ng/mL (p = 0.132). A higher angiopoietin-2 (> 6.8ng/mL) following the initiation of temporary MCS was associated with higher 30-day mortality (89.7% versus 44.4%, p = 0.0048) with an odds ratio 18.946 (95% confidence interval 1.624-218.695, p = 0.018) adjusted for potential confounders. A higher serum angiopoietin-2 level following the initiation of Impella-incorporated temporary MCS, instead of baseline angiopoetin-2 level, was associated with higher short-term mortality.