Using a Mock Circulatory Loop as a Regulatory Science Tool to Simulate Different Heart Failure Conditions.

Mechanical circulatory support (MCS) device therapy is one of the primary treatment options for end-stage heart failure (HF), whereby a mechanical pump is integrated with the failing heart to maintain adequate tissue perfusion. The ISO 14708-5:2020 standard prescribes generic guidelines for nonclinical device evaluation and system performance testing of MCS devices using a mock circulatory loop (MCL). However, the utility of MCLs in premarket regulatory submissions of MCS devices is ambiguous, and the specific disease states that the device is intended to treat are not usually simulated. Hence, we aim to outline the potential of MCLs as a valuable regulatory science tool for characterizing MCS device systems by adequately representing target clinical-use HF conditions on the bench. Target pathophysiologic hemodynamics of HF conditions (i.e., cardiogenic shock (CS), left ventricular (LV) hypertrophy secondary to hypertension, and coronary artery disease), along with a healthy adult at rest and a healthy adult during exercise are provided as recommended test conditions. The conditions are characterized based on LV, aorta, and left atrium pressures using recommended cardiac hemodynamic indices such as systolic, diastolic, and mean arterial pressure, mean cardiac output (CO), cardiac cycle time, and systemic vascular resistance. This study is a first step toward standardizing MCLs to generate well-defined target HF conditions used to evaluate MCS devices.

Left Ventricular Unloading in Extracorporeal Membrane Oxygenation: A Clinical Perspective Derived from Basic Cardiovascular Physiology.

PURPOSE OF REVIEW: To present an abridged overview of the literature and pathophysiological background of adjunct interventional left ventricular unloading strategies during veno-arterial extracorporeal membrane oxygenation (V-A ECMO). From a clinical perspective, the mechanistic complexity of such combined mechanical circulatory support often requires in-depth physiological reasoning at the bedside, which remains a cornerstone of daily practice for optimal patient-specific V-A ECMO care. RECENT FINDINGS: Recent conventional clinical trials have not convincingly shown the superiority of V-A ECMO in acute myocardial infarction complicated by cardiogenic shock as compared with medical therapy alone. Though, it has repeatedly been reported that the addition of interventional left ventricular unloading to V-A ECMO may improve clinical outcome. Novel approaches such as registry-based adaptive platform trials and computational physiological modeling are now introduced to inform clinicians by aiming to better account for patient-specific variation and complexity inherent to V-A ECMO and have raised a widespread interest. To provide modern high-quality V-A ECMO care, it remains essential to understand the patient's pathophysiology and the intricate interaction of an individual patient with extracorporeal circulatory support devices. Innovative clinical trial design and computational modeling approaches carry great potential towards advanced clinical decision support in ECMO and related critical care.

Incidence and predictors of acute limb ischemia in acute myocardial infarction complicated by cardiogenic shock.

OBJECTIVE: To describe the incidence and predictors of acute limb ischemia (ALI) in patients with acute myocardial infarction (AMI) complicated by cardiogenic shock (CS). METHODS: Patients with index hospitalizations for AMI complicated by cardiogenic shock from 2016 to 2019 in the US National Readmission Database were identified. We evaluated the incidence of ALI and its associated mortality, length of stay, and cost of hospitalization. We used multivariable logistic regression to determine independent predictors of ALI in this population. RESULTS: A total of 84,615 patients had AMI complicated by cardiogenic shock and 1302 (1.54%) developed ALI. The rates of ALI increased from 1.29% in 2016 to 1.66% in 2019 (P ≤ .002). The use of microaxial mechanical circulatory support increased from 2.25% in 2016 to 13.36% in 2019 (P = .0001). The major predictors of ALI included peripheral arterial disease (odds ratio [OR], 7.34; 95% confidence interval [CI], 6.12-8.81), venoarterial extracorporeal membrane oxygenation (OR, 4.40; 95% CI, 3.19-6.07), and microaxial mechanical circulatory support (OR, 3.12; 95% CI, 2.74-3.55). ALI in patients with cardiogenic shock was associated higher mortality (39.20% vs 33.53%; P ≤ .0001). CONCLUSIONS: This nationwide observational study shows that ALI is an important complication of AMI with cardiogenic shock. This complication is associated with higher mortality. In addition to peripheral artery disease, the use of mechanical circulatory devices was associated with significantly higher rates of ALI.

Unmasking of a significant left main stenosis in a patient with high left ventricular pressures.

As identification of left main (LM) stenoses has prognostic and therapeutic relevance, a precise anatomic and/or functional characterization of angiographically intermediate LM stenoses, by using intravascular ultrasound (IVUS) and fractional flow reserve (FFR) respectively, is crucial (1). However, increased left ventricular (LV) pressures might affect FFR measurements (2). Here we describe the case of a patient with chronic coronary syndrome and severe LV dysfunction in whom coronary angiography revealed an intermediate LM stenosis and catheterization identified an increased LV end-diastolic pressure. FFR measurement showed disproportionally higher FFR values compared with the minimal luminal area assessed by IVUS. When cardiac output was artificially augmented by using Impella for assisting percutaneous coronary intervention, the value of FFR measurement turned out proportional to what expected for the degree of anatomical stenosis. This discrepancy between anatomic and functional measurement may be a sign of coronary autoregulation dysfunction and therefore could help to identify high-risk patients in whom the use of a mechanical support device is more beneficial during percutaneous revascularization.

Kidney replacement therapy in pediatric patients on mechanical circulatory support: challenges for the pediatric nephrologist.

The use of mechanical circulatory support (MCS) therapies in children with medically refractory cardiac failure has increased over the past two decades. With the growing experience and expertise, MCS is currently offered as a bridge to recovery or heart transplantation and in some cases even as destination therapy. Acute kidney injury (AKI) is common in patients with end-stage heart failure (ESHF). When severe AKI develops requiring kidney replacement therapy (KRT), these patients present unique challenges for the pediatric nephrology team. The use of KRT has not been adequately described in children with ESHF on the newer MCS. We also present original case series data from our center experience. The purpose of this review is to familiarize the reader with the current MCS technologies, approach to their selection, how they interact when combined with current KRT circuits, and distinguish similarities and differences. We will attempt to highlight the distinctive features of each technology, specifically focusing on growing trends in use of continuous-flow ventricular assist devices (CF-VAD) as it poses additional challenges to the pediatric nephrologist.

ANMCO POSITION PAPER: Role of intra-aortic balloon pump in patients with acute advanced heart failure and cardiogenic shock.

The treatment of patients with advanced acute heart failure is still challenging. Intra-aortic balloon pump (IABP) has widely been used in the management of patients with cardiogenic shock. However, according to international guidelines, its routinary use in patients with cardiogenic shock is not recommended. This recommendation is derived from the results of the IABP-SHOCK II trial, which demonstrated that IABP does not reduce all-cause mortality in patients with acute myocardial infarction and cardiogenic shock. The present position paper, released by the Italian Association of Hospital Cardiologists, reviews the available data derived from clinical studies. It also provides practical recommendations for the optimal use of IABP in the treatment of cardiogenic shock and advanced acute heart failure.

Mechanical Circulatory Support: a Comprehensive Review With a Focus on Women.

PURPOSE OF THE REVIEW: The purpose of this review is to analyze the evidence for use of mechanical circulatory support (MCS) with a focus on women, namely, intra-aortic balloon pump (IABP), Impella, ventricular assist devices (VAD), and extracorporeal membrane oxygenation (ECMO). RECENT FINDINGS: There is paucity of data examining management options for cardiogenic shock (CS) in women specifically. In published data, although only a minority of MCS recipients (33%) were women, there is a trend toward even lower use in women relative to men over time. Women presenting with CS tend to have a higher risk profile including older age, greater comorbidities, higher Society of Cardiothoracic Surgery (STS) mortality scores, more hypotension and index vasopressor requirements, and longer duration of CS. Overall, women receiving mechanical support suffer increased bleeding and vascular complications and have higher 30-day readmission rates. The incidence of cardiogenic shock (CS) has been rising at a higher rate in women compared to men. Women in CS tend to present with an overall higher risk profile including older age, greater burden of medical comorbidities, more hypotension and index vasopressor requirements, higher STS mortality scores, and more out-of-hospital cardiac arrest. After adjusting for comorbidities and traditional cardiovascular risk factors, mortality remained higher in younger women compared to men of similar age. In spite of these facts, evidence points to the underutilization of support devices in eligible female patients. Higher complication rates, such as vascular complications requiring surgery and bleeding requiring transfusion, may be deterring factors that limit the use of MCS and hinderoperator confidence and experience with devices in women. This suggests that future research should address the sex disparities in outcomes of contemporary MCS practices.

Platelet Mapping by Thromboelastography and Whole Blood Aggregometry in Adult Patients Supported by Mechanical Circulatory Support Device on Aspirin Therapy.

Patients on mechanical circulatory support (MCS) devices are placed on aspirin and may require platelet function testing (PFT) to monitor the adequacy of therapy. Routine laboratory PFT is performed using whole blood aggregation (WBA) which typically has a long turnaround time (4-5 hours) and may not be readily available. By contrast, platelet mapping by thromboelastography (TPM) can provide results within 45 minutes. The objective of this study was to compare the results of TPM with WBA. We compared platelet mapping maximal amplitude (MA) by TPM with that of arachidonic acid (AA) to WBA with AA by impedance. We analyzed paired samples where both TPM and WBA were available. Of 45 paired samples, 34 were from 29 MCS patients and 11 were from non-MCS patients. When applying institutional interpretation guidelines with an MAActivator cutoff of ≤40 mm, WBAAA vs TPM MAAA in non-MCS and MCS patients correlated well with an accuracy of 100 and 94.4%, respectively. MAActivator >40 had poor correlation with an accuracy of 37.5%. Irrespective of MAActivator value, TPM AA inhibition expressed in percent of inhibition had poor accuracy. When used with proper guidelines for interpretation, specifically when MAActivator ≤ 40 mm, TPM is a suitable and reliable test to use for MCS patients on aspirin.

Circulatory Mechanotherapeutics: Moving with the Force.

PURPOSE OF REVIEW: This review describes the current state of advancements in mechanical circulatory support (MCS) devices with significantly improved hemodynamic performance and decreased adverse events. Novel considerations for future MCS designs that impart spiral flow regimes will be detailed. RECENT FINDINGS: Significant challenges in MCS device use have included size reduction, premature pump mechanical bearing failure, acquired bleeding disorders, and vascular complications related to high shear forces and jetting. Some of these problems have been improved upon, such as the use of magnetically levitated impellers and hydrodynamic bearings. The relative simplicity of continuous flow pumps has also enabled their miniaturization, portability, and reduced energy consumption. Recent studies by our group demonstrated that spiral forms of flow possess hemodynamically beneficial attributes at the MCS outflow cannula and aorta interface, reducing jet impact, organizing streamlines, and thereby improving endothelial function through wall shear stress modulation. Despite MCS design improvements, they are far from perfect. Induced spiral fluid modulation may help address the known flow-mediated disturbances in vascular mechanobiology.

Case Report: Disparate flow in HeartMate II patient with extensive left ventricle repair.

This case study reports the operative management of a 63-year-old male patient following implantation of the HeartMate II (HMII) left ventricular assist device (LVAD), with a non-compliant left ventricle (LV) and a reduced right ventricular (RV) end-diastolic volume. Intraoperatively, the patient had a thin, fragile LV wall with laminated clot; a ventricular septal defect was encountered during removal of the clot. Along with an aortic valve repair, the LV and the septum were reconstructed with multiple bovine pericardium patches, thus, moderately reducing the RV and LV stroke volume. A difference in cardiac output via a Swan-Ganz catheter (approximately 1.5 l/min) was observed as opposed to the HMII's estimated flow. The result was later replicated and verified ITALIC! in vitrovia the Donovan Mock Circulation System (DMCS), where about 2 l/min lower flow on the HMII system was observed. In conclusion, the HMII flow rate displayed can be inaccurate and should only be used for trending.

Implantation of short-term biventricular assist device (BiVAD) using the CentriMag™ system: the Manchester technique.

Biventricular assist devices (BiVADs) using the CentriMag™ system are being used increasingly as a form of short-term mechanical circulatory support for the treatment of acute cardiogenic shock from any aetiology. They can be used as a bridge to decision, recovery or transplantation. BiVADs are associated with better clinical outcomes when compared to veno-arterial (VA) extracorporeal membrane oxygenator (ECMO) systems. In this paper, we describe a safe and reproducible method of BiVAD implantation using the CentriMag™ system at our institution.

Effectiveness of mechanical circulatory support devices in reversing pulmonary hypertension among heart transplant candidates: A systematic review.

BACKGROUND: Pulmonary hypertension (PH) poses a significant challenge in the selection of candidates for heart transplantation, impacting their eligibility and post-transplant outcomes. Mechanical circulatory support (MCS) devices, particularly left ventricular assist devices (LVADs), have emerged as a therapeutic option to manage PH in this patient population. This systematic review aims to evaluate the effectiveness of MCS devices in reversing fixed pulmonary hypertension in heart transplant candidates. METHODS: A comprehensive literature search was conducted across multiple databases, including PubMed, Scopus, and Web of Science, to identify studies that evaluated the effectiveness of MCS devices in reversing fixed pulmonary hypertension in heart transplant candidates. Data on pulmonary vascular resistance, PH reversal, heart transplant eligibility, and post-transplant outcomes were extracted and synthesized. RESULTS: The review included studies that demonstrated the potential of MCS devices, especially LVADs, to significantly reduce pulmonary vascular resistance and reverse fixed pulmonary hypertension in heart transplant candidates. These findings suggest that MCS devices can improve transplant eligibility and may positively impact post-transplant survival rates. However, the literature also indicates a need for further comparative studies to optimize MCS device selection and treatment protocols. CONCLUSION: MCS devices, particularly LVADs, play a crucial role in the management of fixed pulmonary hypertension in heart transplant candidates, improving their eligibility for transplantation and potentially enhancing post-transplant outcomes. Future research should focus on comparative effectiveness studies to guide clinical decision-making and optimize patient care in this challenging clinical scenario.

Integrated cardiothoracic team approach for complex lung transplantation procedures in Japan-current status and future direction.

The first lung transplant procedure in the world was performed in 1983, while in Japan that was first accomplished in 1998. Over the following 25 years, lung transplantation has become a viable treatment option for Japanese patients with a variety of end-stage lung diseases. Seventy cadaveric-donor lung (41 single, 29 bilateral), 11 bilateral living-donor lobar lung, and three heart-lung transplants have been performed with use of an integrated cardiothoracic team approach at medical facilities associated with Osaka University. Extremely advanced clinical and surgical skill sets are required to complete a lung transplant procedure, including surgical knowledge and techniques, as well as management of cardiovascular surgery, especially in regard to mechanical circulatory support (MCS), vascular anastomosis in difficult cases, and concomitant cardiac surgery. We have found that a collaborative effort by general thoracic and cardiac surgeons is an important key for success with lung transplantation. Complex lung transplant surgery and management in Japan are performed by use of an integrated cardiothoracic team approach, which has led to a synergistic impact on successful lung transplantation cases by capitalizing greatly on the experiences, techniques, and expertise of cardiac and thoracic experts. The present review is focused on the role of cardiac surgeons from the viewpoint of our experience with these cases.

Extracorporeal Membrane Oxygenation (VA-ECMO) in Management of Cardiogenic Shock.

Cardiogenic shock is a critical condition of low cardiac output resulting in insufficient systemic perfusion and end-organ dysfunction. Though significant advances have been achieved in reperfusion therapy and mechanical circulatory support, cardiogenic shock continues to be a life-threatening condition associated with a high rate of complications and excessively high patient mortality, reported to be between 35% and 50%. Extracorporeal membrane oxygenation can provide full cardiopulmonary support, has been increasingly used in the last two decades, and can be used to restore systemic end-organ hypoperfusion. However, a paucity of randomized controlled trials in combination with high complication and mortality rates suggest the need for more research to better define its efficacy, safety, and optimal patient selection. In this review, we provide an updated review on VA-ECMO, with an emphasis on its application in cardiogenic shock, including indications and contraindications, expected hemodynamic and echocardiographic findings, recommendations for weaning, complications, and outcomes. Furthermore, specific emphasis will be devoted to the two published randomized controlled trials recently presented in this setting.

Role of Genetic Polymorphisms in the Development of Complications in Patients with Implanted Left Ventricular Assist Devices: HeartWare, HeartMate II, and HeartMate 3.

Left ventricular assist device (LVAD) implantation is one of the mechanical circulatory support (MCS) treatments for advanced heart failure (HF) patients. MCS has emerged as a lifesaving therapy that improves patients' quality of life. However, MCS remains limited by a paradoxical coagulopathy accompanied by thrombosis and bleeding. The mechanisms of MCS thrombosis are increasingly being defined, but MCS-related bleeding, which is related to shear-mediated alteration of platelet function, remains poorly understood. Complications might develop due to the high non-physiological shear stress in the device and as a consequence of individual variability in response to the antithrombotic therapy. Thromboelastography (TEG) and genotyping of gene polymorphisms that are involved in the coagulation cascade and in the metabolism of the antithrombotic therapy might be valuable sources of information for the reduction of complication development. The aim of the study was to identify genetic factors related to the development of device complications according to the implanted LVAD type. We compared the clinical and genetic data of HF patients (n = 98) with/without complications with three types of implanted devices: HeartWare HVAD (HW), HeartMate II (HMII), and HeartMate 3 (HM3). rs9923231 in VKORC1 (95%CI -6.28-0.22, p = 0.04) and rs5918 in ITGB3 genes (95%CI 0.003-4.36, p = 0.05) showed significant association with the TEG coagulation index parameter, which identified hyper- and hypo-coagulation states. The wild genotype of rs5918 in the ITGB3 gene prevailed in patients implanted with HM3 devices, which developed fewer complications than with HMII (p = 0.04). Individual genetic information could be useful in the management of patients with HF and the implantation of MCS to reduce the development of complications.

A case report of giant cell myocarditis complicated by severe heart failure: the value of early endomyocardial biopsy and mechanical circulatory support.

Background: Giant cell myocarditis (GCM) is a rare, probably underdiagnosed and potentially fatal disease in young and middle-aged patients. Disease progression is often rapid, and life-threatening arrhythmias and cardiogenic shock due to progressive left ventricular failure are among the most feared complications. Although cardiac biomarkers and multimodality imaging are used as initial diagnostic tests in most patients, endomyocardial biopsy (EMB) is often required for a definitive diagnosis. However, there are still gaps in our knowledge in terms of the etiology, early diagnosis, management and prognosis of GCM. Case Description: We present the case of a male patient in his early 50s admitted to Haukeland University Hospital with fulminant GCM. He had no significant medical history in the past apart from hypertension, and presented to hospital in cardiogenic shock after a few weeks of progressive shortness of breath. Rapid initiation of methylprednisolone had an immediate effect on reducing myocardial inflammation, and sustained treatment with a combination of immunosuppressive agents along with optimal heart failure medications led to complete recovery of the heart function and clinical remission over several years. The case study highlights the urgency of an early EMB, access to mechanical circulatory support (MCS) and the efficacy of immunosuppressive treatment and optimal medical management for heart failure. Finally, our review of the literature also provides an updated guidance on the contemporary management of GCM patients. Conclusions: Accurate and early diagnosis with EMB in patients with GCM are crucial for better outcomes. Rapid initiation of methylprednisolone reduces myocardial inflammation and the risk of death. Sustained treatment with a combination of immunosuppressive agents together with optimal heart failure medications are essential for myocardial recovery and long-term stabilization. The use of MCS is the cornerstone in the management of GCM with a clear survival benefit.

A case of COVID-19-associated fulminant myocarditis successfully treated with mechanical circulatory support.

A 49-year-old man, who had not been vaccinated against COVID-19 visited the hospital for fever and cough, and a PCR test for COVID-19 was positive on the Day X. Initially, there was no decrease in oxygen saturation and the patient was under observation as a mild case without medication. Five days after the onset (Day X + 5), chest pain appeared. Electrocardiogram showed widespread ST-segment elevation, and blood tests showed high levels of troponin I. However, given that there was no stenotic lesion on coronary computed tomography, myocarditis was suspected, and he was transferred to our hospital on the Day X + 6. We started treatment with lemdesivir and dexamethasone. On the Day X + 7, the patient developed decreased left ventricular ejection fraction, hypotension, and hyperlactatemia. We decided that mechanical circulatory support was necessary and an Impella 5.0 was inserted under ventilator management. The patient was successfully weaned from the Impella 5.0 on the Day X + 17, was transferred to the general ward on the Day X + 24, continued rehabilitation, and was discharged home on the Day X + 39 with no heart failure symptoms. In this case, we performed daily bedside echocardiography and chose the Impella 5.0 instead of extra corporeal membrane oxygenation (ECMO) because there were no findings of severe pneumonia or right heart failure. The Impella 5.0 device was inserted via an axillary artery approach, given that it provides more assisted flow than the Impella CP inserted through the inguinal route. Furthermore, early rehabilitation was possible due to the lack of restriction of the lower body.

Mechanical circulatory support in ventricular arrhythmias.

In atrial and ventricular tachyarrhythmias, reduced time for ventricular filling and loss of atrial contribution lead to a significant reduction in cardiac output, resulting in cardiogenic shock. This may also occur during catheter ablation in 11% of overall procedures and is associated with increased mortality. Managing cardiogenic shock and (supra) ventricular arrhythmias is particularly challenging. Inotropic support may exacerbate tachyarrhythmias or accelerate heart rate; antiarrhythmic drugs often come with negative inotropic effects, and electrical reconversions may risk worsening circulatory failure or even cardiac arrest. The drop in native cardiac output during an arrhythmic storm can be partly covered by the insertion of percutaneous mechanical circulatory support (MCS) devices guaranteeing end-organ perfusion. This provides physicians a time window of stability to investigate the underlying cause of arrhythmia and allow proper therapeutic interventions (e.g., percutaneous coronary intervention and catheter ablation). Temporary MCS can be used in the case of overt hemodynamic decompensation or as a "preemptive strategy" to avoid circulatory instability during interventional cardiology procedures in high-risk patients. Despite the increasing use of MCS in cardiogenic shock and during catheter ablation procedures, the recommendation level is still low, considering the lack of large observational studies and randomized clinical trials. Therefore, the evidence on the timing and the kinds of MCS devices has also scarcely been investigated. In the current review, we discuss the available evidence in the literature and gaps in knowledge on the use of MCS devices in the setting of ventricular arrhythmias and arrhythmic storms, including a specific focus on pathophysiology and related therapies.

Pre- and post-operative mechanical circulatory support in surgical repair of post-acute myocardial infarction mechanical complications.

The outcomes of patients with acute myocardial infarctions (AMI) have significantly improved with advances in early reperfusion strategies; however, patients with massive infarcts or those who do not receive timely revascularization may develop mechanical complications of AMI. The most common mechanical complications are ventricular septal rupture (VSR), acute mitral regurgitation (MR) due to papillary muscle rupture, and free-wall rupture. Each complication is associated with a high risk of morbidity and mortality, and requires a multidisciplinary approach for prompt diagnosis and hemodynamic stabilization. Surgery is the mainstay of therapy but is associated with poor outcomes if performed too early during the treatment course for VSR or if performed too late with MR and free wall rupture. Optimal timing for surgery in combination with temporary circulatory support may be a feasible strategy for better results.

A multidisciplinary approach for the emergency care of patients with left ventricular assist devices: A practical guide.

The use of a left ventricular assist device (LVAD) as a bridge-to-transplantation or destination therapy to support cardiac function in patients with end-stage heart failure (HF) is increasing in all developed countries. However, the expertise needed to implant and manage patients referred for LVAD treatment is limited to a few reference centers, which are often located far from the patient's home. Although patients undergoing LVAD implantation should be permanently referred to the LVAD center for the management and follow-up of the device also after implantation, they would refer to the local healthcare service for routine assistance and urgent health issues related to the device or generic devices. Therefore, every clinician, from a bigger to a smaller center, should be prepared to manage LVAD carriers and the possible risks associated with LVAD management. Particularly, emergency treatment of patients with LVAD differs slightly from conventional emergency protocols and requires specific knowledge and a multidisciplinary approach to avoid ineffective treatment or dangerous consequences. This review aims to provide a standard protocol for managing emergency and urgency in patients with LVAD, elucidating the role of each healthcare professional and emphasizing the importance of collaboration between the emergency department, in-hospital ward, and LVAD reference center, as well as algorithms designed to ensure timely, adequate, and effective treatment to patients with LVAD.