Severe Early Graft Dysfunction Post-Heart Transplantation: Two Clinical Trajectories and Diastolic Perfusion Pressure as a Predictor of Mechanical Circulatory Support.

BACKGROUND: Severe early graft dysfunction (EGD) is defined by mechanical circulatory support (MCS) <24 hours of heart transplantation (HT). We classified severe EGD based on timing of post-HT MCS: 'Immediate' intra-operative vs 'Delayed' post-operative MCS (after admission into intensive care unit (ICU) from operating theatre). We hypothesised that (i) risk factors and clinical course differ between 'Immediate' and 'Delayed' MCS; and (ii) diastolic perfusion pressure (DPP=diastolic blood pressure-central venous pressure) and Norepinephrine equivalents (NE=sum of vasopressor doses), as measures of vasoplegia are related to 'Delayed' MCS. METHODS: Two-centre study of 216 consecutive patients who underwent HT. Recipient, donor, vasopressor doses and hemodynamic data at T0 and T6 (on admission and 6 hours after admission into ICU) were collected. RESULTS: Of the 216 patients, 67 patients had severe EGD ('Immediate' MCS: n=43, 'Delayed' MCS: n=24). The likelihood of 'immediate' MCS but not 'delayed' MCS increased with increasing warm ischemic and cardiopulmonary bypass times on multinomial regression analysis with 'no MCS' as the referent group. One-year mortality was highest in 'Immediate' MCS vs 'no MCS' and 'delayed' MCS (34.9% vs 3.4% and 8% respectively, P<0.001). Of the patients who had no immediate post-transplant MCS, DPP and NE at T6 were independently associated with subsequent 'delayed' MCS'. Sensitivity and specificity of NE ≥0.2mcg/kg/min for 'Delayed' MCS were 71% and 81%. Sensitivity and specificity of DPP of ≥40mmHg for No MCS were 83% and 74%. The discriminatory value of systemic vascular resistance for 'Delayed' MCS was poor. CONCLUSION: Risk factors and one-year survival differed significantly between 'Immediate' and 'Delayed' post-HT MCS. The latter is related to lower DPP and higher NE, which is consistent with vasoplegia as the dominant pathophysiology.

Multimodality imaging for the evaluation and management of patients with long-term (durable) left ventricular assist devices A Clinical Consensus Statement of the European Association of Cardiovascular Imaging (EACVI) of the ESC.

Left ventricular assist devices (LVADs) are gaining increasing importance as therapeutic strategy in advanced heart failure (HF), not only as bridge to recovery or to transplant, but also as destination therapy. Even though long-term LVADs are considered a precious resource to expand the treatment options and improve clinical outcome these patients, these are limited by peri-operative and post-operative complications, such as device-related infections, haemocompatibility-related events, device mispositioning and right ventricular failure. For this reason, a precise pre-operative, peri-operative and post-operative evaluation of these patients is crucial for the selection of LVADs candidates and the management LVADs recipients. The use of different imaging modalities offers important information to complete the study of patients with LVADs in each phase of their assessment, with peculiar advantages/disadvantages, ideal application and reference parameters for each modality. This clinical consensus statement sought to guide the use of multimodality imaging for the evaluation of patients with advanced HF undergoing LVADs implantation.

Antifungal prophylaxis against invasive Candida and Aspergillus infection in adult heart transplant recipients: protocol for a systematic review and meta-analysis.

INTRODUCTION: Invasive fungal infections (IFI) can contribute to increased mortality and morbidity rates after heart transplant in adults. The most common causes are Aspergillus and Candida species. There is uncertainty on how effective antifungal prophylaxis is against Candida spp infections and limited guidance on the prevention of Aspergillus spp infections. This systematic review and meta-analysis will assess the literature to see if antifungal prophylaxis reduces the incidence of IFI after heart transplant in adults. METHODS AND ANALYSIS: This systematic review protocol follows the Preferred Reporting Items for Systematic reviews and Meta Analysis guidelines. A systematic search of the Cochrane Library, Web of Science, Scopus, Embase, MEDLINE, and Proquest databases will be undertaken. Reference lists of retrieved publications and conference abstracts will also be searched. Title, abstract and full-text screening will be undertaken by two reviewers. Discrepancies will be resolved by a third reviewer. Studies with paediatric patients, multi-organ transplants, or patients with a second heart transplant will be excluded, along with those who do not have clear definitions and diagnostic criteria for IFI. Risk of bias will be assessed using the Cochrane Risk of Bias 2 tool and the Risk of Bias in Non-randomised Studies of Interventions tool. A meta-analysis will be carried out, but if studies are not deemed to be sufficiently similar, only a narrative synthesis will be undertaken. ETHICS AND DISSEMINATION: Ethical approval is not required for this systematic review as primary data will not be collected. The results of the review will be disseminated through publication in an academic journal and scientific conferences. PROSPERO REGISTRATION NUMBER: CRD42024516588.

Cardiogenic shock trajectories: is the Society for Cardiovascular Angiography and Interventions definition the right one?

PURPOSE OF REVIEW: We review the current Society for Cardiovascular Angiography and Interventions (SCAI) cardiogenic shock classification system and consider alternatives or iterations that may enhance our current descriptions of cardiogenic shock trajectory. RECENT FINDINGS: Several studies have identified the potential prognostic value of serial SCAI stage re-assessment, usually within the first 24 h of shock onset, to predict deterioration and clinical outcomes across shock causes. In parallel, numerous registry-based analyses support the utility of a more precise assessment of the macrocirculation and microcirculation, leveraging invasive haemodynamics, imaging and additional laboratory and clinical markers. The emergence of machine learning and artificial intelligence capabilities offers the opportunity to integrate multimodal data into high fidelity, real-time metrics to more precisely define trajectory and inform our therapeutic decision making. SUMMARY: Whilst the SCAI staging system remains a pivotal tool in cardiogenic shock assessment, communication and reassessment, it is vital that the sophistication with which we measure and assess shock trajectory evolves in parallel our understanding of the complexity and variability of clinical course and clinical outcomes.

Development of a quality of life measure for left ventricular assist device recipients using a mixed methods approach.

BACKGROUND: Left ventricular assist device (LVAD) recipients report symptom improvement but find adjusting to life with the LVAD challenging. These challenges are unique, and existing patient-reported outcome measures (PROMs) do not reflect their experiences. This study aimed to develop a culturally relevant quality of life PROM for use with LVAD recipients in future research, design evolutions and clinical practice. METHODS: A three-stage mixed-methods approach was used to develop a PROM: stage 1 included group concept mapping (GCM); stage 2 semi-structured qualitative interviews were conducted with 11 LVAD recipients and 10 clinicians, and a questionnaire was developed using a conceptual framework; and stage 3 used exploratory psychometric analysis of the PROM data using Rasch measurement theory. This paper presents stages 2 and 3. RESULTS: The conceptual framework consisted of four key concepts, including general health, life with the LVAD, equipment and clothing and emotional impact. Statements from interviews and GCM were used to create items for the LVAD quality of life (LVAD-QoL). Cognitive interviews tested face validity and participant comprehension. Forty-nine participants were recruited from three UK transplant centres. PROM data were collected and analysed using Rasch analysis. Four items displayed misfit; dependency between item sets was the biggest issue (57/485 pairwise differences). After restructuring and dealing with item misfit, the LVAD-QoL conformed to the Rasch model, supporting the psychometric properties and quality of the LVAD-QoL. CONCLUSIONS: Using a mixed-methods approach ensured the development of a robust and psychometrically sound tool for research, design evolution and clinical practice with LVAD recipients.

The management of heart failure cardiogenic shock: an international RAND appropriateness panel.

BACKGROUND: Observational data suggest that the subset of patients with heart failure related CS (HF-CS) now predominate critical care admissions for CS. There are no dedicated HF-CS randomised control trials completed to date which reliably inform clinical practice or clinical guidelines. We sought to identify aspects of HF-CS care where both consensus and uncertainty may exist to guide clinical practice and future clinical trial design, with a specific focus on HF-CS due to acute decompensated chronic HF. METHODS: A 16-person multi-disciplinary panel comprising of international experts was assembled. A modified RAND/University of California, Los Angeles, appropriateness methodology was used. A survey comprising of 34 statements was completed. Participants anonymously rated the appropriateness of each statement on a scale of 1 to 9 (1-3 as inappropriate, 4-6 as uncertain and as 7-9 appropriate). RESULTS: Of the 34 statements, 20 were rated as appropriate and 14 were rated as inappropriate. Uncertainty existed across all three domains: the initial assessment and management of HF-CS; escalation to temporary Mechanical Circulatory Support (tMCS); and weaning from tMCS in HF-CS. Significant disagreement between experts (deemed present when the disagreement index exceeded 1) was only identified when deliberating the utility of thoracic ultrasound in the immediate management of HF-CS. CONCLUSION: This study has highlighted several areas of practice where large-scale prospective registries and clinical trials in the HF-CS population are urgently needed to reliably inform clinical practice and the synthesis of future societal HF-CS guidelines.

Derivation of Stroke Volume from Pulmonary Artery Pressures.

INTRODUCTION: Intermittent cardiac output (CO) studies using thermodilution are considered the gold standard. We have developed a stroke volume (SV) calculator from pulmonary pulse pressure (PP) to allow continuous monitoring of SV and CO from PP. METHODS: Hemodynamic data on 169 patients following orthotopic heart transplantation were used to compare our calculator-derived SV (and SV index, or SVi) against thermodilution-derived SV on admission into intensive care unit immediately following heart transplantation (T0) and 6 h after admission (T6). RESULTS: The calculated SV correlated with thermodilution-derived SV T0 (r = 0.920, p < 0.001, coefficient of 0.539 and the constant of 2.06). The median calculator SV, adjusted for coefficient and constant, was 48.4 ml (37.7, 60.7), comparable to the median thermodilution-derived SV 47.9 ml (37.5, 61.0), p = 0.737 with acceptable agreement on Bland-Altman plots. The thermodilution-derived SVi was 28.1 ml (19.7, 38.7) and adjusted calculator-derived SVi 28.9 ml (19.7, 39.9), p = 0.781. At T6, median thermodilution-derived SVi was 27.7 ml (19.5, 35.9) compared to the calculator-derived SVi median of 26.1 ml (17.7, 37.7), p = 0.203. CONCLUSIONS: Changes in PP can be used to track changes in SV using this calculator. Changes in PP may be used to assess response to treatment in the early post-operative period.

Hemodynamic management of cardiogenic shock in the intensive care unit.

Hemodynamic derangements are defining features of cardiogenic shock. Randomized clinical trials have examined the efficacy of various therapeutic interventions, from percutaneous coronary intervention to inotropes and mechanical circulatory support (MCS). However, hemodynamic management in cardiogenic shock has not been well-studied. This State-of-the-Art review will provide a framework for hemodynamic management in cardiogenic shock, including a description of the 4 therapeutic phases from initial 'Rescue' to 'Optimization', 'Stabilization' and 'de-Escalation or Exit therapy' (R-O-S-E), phenotyping and phenotype-guided tailoring of pharmacological and MCS support, to achieve hemodynamic and therapeutic goals. Finally, the premises that form the basis for clinical management and the hypotheses for randomized controlled trials will be discussed, with a view to the future direction of cardiogenic shock.

Pulmonary artery wave intensity analysis in pulmonary hypertension associated with heart failure and reduced left ventricular ejection fraction.

Wave intensity analysis (WIA) uses simultaneous changes in pressure and flow velocity to determine wave energy, type, and timing of traveling waves in the circulation. In this study, we characterized wave propagation in the pulmonary artery in patients with pulmonary hypertension associated with left-sided heart disease (PHLHD) and the effects of dobutamine. During right heart catheterization, pressure and velocity data were acquired using a dual-tipped pressure and Doppler flow sensor wire (Combowire; Phillips Volcano), and processed offline using customized Matlab software (MathWorks). Patients with low cardiac output underwent dobutamine challenge. Twenty patients with PHLHD (all heart failure with reduced left ventricular ejection fraction) were studied. Right ventricular systole produced a forward compression wave (FCW), followed by a forward decompression wave (FDW) during diastole. Wave reflection manifesting as backward compression wave (BCW) following the FCW was observed in 14 patients. Compared to patients without BCW, patients with BCW had higher mean pulmonary artery pressure (28.7 ± 6.12 vs. 38.6 ± 6.5 mmHg, p = 0.005), and lower pulmonary arterial capacitance (PAC: 2.88 ± 1.75 vs. 1.73 ± 1.16, p = 0.002). Pulmonary vascular resistance was comparable. Mean pulmonary artery pressure of 34.5 mmHg (area under the curve [AUC]: 0.881) and PAC of 2.29 mL/mmHg (AUC: 0.833) predicted BCW. The magnitude of the FCW increased with dobutamine (n = 11) and correlated with pulmonary artery wedge pressure. Wave reflection in PHLHD is more likely at higher pulmonary artery pressures and lower PAC and the magnitude of reflected waves correlated with pulmonary artery wedge pressure. Dobutamine increased FCW but did not affect wave reflection.

A novel 'shunt fraction' method to derive native cardiac output during liberation from central VA ECMO.

The Fick principle is an established method to quantify intracardiac shunts. The Fick principle has also found utility in the practice of extracorporeal membrane oxygenation (ECMO). This report describes a novel 'shunt fraction' method to calculate intrinsic cardiac output in central (right atrial-to-aorta) ECMO. The physiological basis of this 'shunt fraction' method is described, followed by the case presentation that details the clinical application of this method of quantifying intrinsic cardiac output to guide weaning and liberation from central VA ECMO.

Consensus statements from the International Society for Heart and Lung Transplantation consensus conference: Heart failure-related cardiogenic shock.

The last decade has brought tremendous interest in the problem of cardiogenic shock. However, the mortality rate of this syndrome approaches 50%, and other than prompt myocardial revascularization, there have been no treatments proven to improve the survival of these patients. The bulk of studies have been in patients with acute myocardial infarction, and there is little evidence to guide the clinician in those patients with heart failure cardiogenic shock (HF-CS). An International Society for Heart and Lung Transplant consensus conference was organized to better define, diagnose, and manage HF-CS. There were 54 participants (advanced heart failure and interventional cardiologists, cardiothoracic surgeons, critical care cardiologists, intensivists, pharmacists, and allied health professionals) with vast clinical and published experience in CS, representing 42 centers worldwide. This consensus report summarizes the results of a premeeting survey answered by participants and the breakout sessions where predefined clinical issues were discussed to achieve consensus in the absence of robust data. Key issues discussed include systems for CS management, including the "hub-and-spoke" model vs a tier-based network, minimum levels of data to communicate when considering transfer, disciplines that should be involved in a "shock team," goals for mechanical circulatory support device selection, and optimal flow on such devices. Overall, the document provides expert consensus on some important issues facing practitioners managing HF-CS. It is hoped that this will clarify areas where consensus has been reached and stimulate future research and registries to provide insight regarding other crucial knowledge gaps.

The History of Extracorporeal Membrane Oxygenation and the Development of Extracorporeal Membrane Oxygenation Anticoagulation.

Extracorporeal membrane oxygenation (ECMO) was first started for humans in early 1970s by Robert Bartlett. Since its inception, there have been numerous challenges with extracorporeal circulation, such as coagulation and platelet activation, followed by consumption of coagulation factors and platelets, and biocompatibility of tubing, pump, and oxygenator. Unfractionated heparin (heparin hereafter) has historically been the defacto anticoagulant until recently. Also, coagulation monitoring was mainly based on bedside activated clotting time and activated partial thromboplastin time. In the past 50 years, the technology of ECMO has advanced tremendously, and thus, the survival rate has improved significantly. The indication for ECMO has also expanded. Among these are clinical conditions such as postcardiopulmonary bypass, sepsis, ECMO cardiopulmonary resuscitation, and even severe coronavirus disease 2019 (COVID-19). Not surprisingly, the number of ECMO cases has increased according to the Extracorporeal Life Support Organization Registry and prolonged ECMO support has become more prevalent. It is not uncommon for patients with COVID-19 to be on ECMO support for more than 1 year until recovery or lung transplant. With that being said, complications of bleeding, thrombosis, clot formation in the circuit, and intravascular hemolysis still remain and continue to be major challenges. Here, several clinical ECMO experts, including the "Father of ECMO"-Dr. Robert Bartlett, describe the history and advances of ECMO.

A systematic review and physiology of pulmonary artery pulsatility index in left ventricular assist device therapy.

OBJECTIVES: Right heart failure (RHF) is a major complication following left ventricular assist device (LVAD) implantation. Pulmonary artery pulsatility index (PAPi) has been evaluated as a haemodynamic marker for RHF, but PAPi is dependent on pulmonary vascular resistance (PVR). We conducted a systematic review to assess the relationship between PAPi and RHF and death in patients undergoing LVAD implantation and examined the relationship between PAPi cut-off and PVR. METHODS: We searched PubMed, EMBASE, CENTRAL and manually screened retrieved references to identify all clinical studies reporting PAPi in adult patients with a durable LVAD. Eligibility criteria were prespecified and 2 reviewers independently screened and extracted data; the Newcastle-Ottawa Scale was used to assess quality of non-randomized studies. This study was prospectively registered on PROSPERO (CRD42021259009). RESULTS: From 283 unique records, we identified 16 studies reporting haemodynamic assessment in 20 634 adult patients with an implanted durable LVAD. Only 2 studies reported on mortality and in both, a lower PAPi was significantly associated with death. Fifteen studies reported RHF data and, in 10 studies, a lower PAPi was significantly associated with RHF. Six studies reported on PAPi cut-offs ranging from 0.88 to 3.3; and the cut-offs were directly related to PVR (r = 0.6613, P = 0.019). CONCLUSIONS: Lower PAPi was associated with RHF and death following LVAD implantation, but a single PAPi cut-off cannot be defined, as it is dependent on PVR.

Phenotyping and Hemodynamic Assessment in Cardiogenic Shock: From Physiology to Clinical Application.

There is growing interest in invasive hemodynamic assessment in cardiogenic shock, primarily due to the widespread adoption of mechanical circulatory support (MCS). Invasive hemodynamic assessment is central to two aspects of cardiogenic shock management: (1) the phenotyping of cardiogenic shock, and (2) the assessment of response to therapy. Phenotyping of cardiogenic shock serves to guide timely therapeutic intervention, and the assessment of hemodynamic response to therapy directs the escalation or de-escalation of therapy, including MCS. This review aims to discuss these two aspects of hemodynamic assessment in cardiogenic shock. Firstly, the physiologic underpinnings of a phenotyping schema, and the implication of the cardiogenic shock phenotype on the MCS strategy in cardiogenic shock will be discussed. Secondly, the concept of cardiac power output and 'effective' oxygen delivery will be discussed in relation to hemodynamic response to therapy in cardiogenic shock.

Proportional pulmonary pulse pressure: A new index to assess response to veno-arterial extracorporeal membrane oxygenation.

BACKGROUND: Based on theoretical physiology, the ratio of pulmonary artery pulse pressure to mean pulmonary pressure (PP-MPAP), termed proportional pulmonary pulse pressure, provides a measure of coupling between the right ventricle and the pulmonary circulation. This study tested the hypothesis that lower PP-MPAP ratio was associated with left ventricular (LV) distension in patients with cardiogenic shock who underwent extracorporeal life support (ECLS). METHODS: This is a retrospective observational single-centre study of 22 patients with cardiogenic shock who underwent ECLS as the primary support modality without and with LV distension and Impella unloading. The relationship between post-support PP-MPAP and 12-hour lactate clearance was also assessed. RESULTS: Of the 22 patients: 10 patients underwent additional Impella unloading due to LV distension (Group 1) and 12 patients on ECLS only without LV distension (Group 2). As predicted by the theoretical model, PP-MPAP on ECLS dropped in Group 1 (pre-Impella) from 0.473 ± 0.067 to 0.372 ± 0.087, p < 0.001; but increased in Group 2 patients without LV distension (0.518 ± 0.070 to 0.549 ± 0.072, p = 0.002). Impella support in Group 1 increased PP-MPAP (0.372 ± 0.087 to 0.615 ± 0.094, p < 0.001). On multiple regression analysis, post-support PP-MPAP was significantly associated with 12-hour lactate clearance. CONCLUSION: Changes in PP-MPAP is associated hemodynamic response to ECLS and 12-hour lactate clearance. This simple parameter may guide therapeutic optimization in cardiogenic shock and ECLS.