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.

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.

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.

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.

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.

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.

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.

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.

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.

Living with a left ventricular assist device: Capturing recipients experiences using group concept mapping software.

BACKGROUND: Left ventricular assist device (LVAD) implantation significantly impacts on a recipient's symptoms and quality of life. Capturing their experiences and post implant journey is an important part of clinical practice, research and device design evolution. Patient reported outcome measures (PROMs) are a useful tool for capturing that experience. However, patient reported outcome measures need to reflect recipients' experiences. Discussions with a patient partner group found that none of the frequently used cardiology PROMs captured their unique experiences. AIMS: To capture the experiences and important issues for LVAD recipients. Develop a conceptual map of domains and items that should be reflected in patient reported outcomes. METHODS: Group concept mapping (GCM) web-based software was used to remotely capture and structure recipients' experiences across a wide geographical area. GCM is a semi-quantitative mixed method consisting of 3 stages: item generation, item sorting and rating (importance, relevance and frequency). Patient partners were involved in all aspects of the study design and development. RESULTS: 18 LVAD recipients consented to take part. 101 statements were generated and multi-dimensional scaling, and hierarchical cluster analysis identified 9 clusters. Cluster themes included: Activities, Partner/family support, Travel, Mental wellbeing, Equipment and clothing, Physical and cognitive limitations, LVAD Restrictions, LVAD Challenges and positive impact of the LVAD (LVAD Positives). LVAD Positives were scored highest across all the rating variables, e.g., frequency (2.85), relevance (2.44) and importance (2.21). Other domains rated high for importance included physical and cognitive limitations (2.19), LVAD restrictions (2.11), Partner/family support (2.02), and Equipment and clothing (2.01). CONCLUSION: Online GCM software facilitated the inclusion of geographically dispersed recipients and provided useful insights into the experiences of LVAD recipients. The conceptual framework identifies important domains and items that should be prioritised and included in patient reported outcomes in future research, LVAD design evolution, and clinical practice.

Prognostic value of right atrial pressure-corrected cardiac power index in cardiogenic shock.

AIM: The pulmonary artery catheter (PAC)-derived cardiac power index (CPI) has been found of prognostic value in cardiogenic shock (CS) patients. The original CPI equation included the right atrial pressure (RAP), accounting for heart filling pressure as a determinant of systolic myocardial work, but this term was subsequently omitted. We hypothesized that the original CPI formula (CPIRAP ) is superior to current CPI for risk stratification in CS. METHODS AND RESULTS: A single-centre cohort of 80 consecutive Society for Cardiovascular Angiography and Interventions (SCAI) B-D CS patients with available PAC records was included. Overall in-hospital mortality was 21.3%. Results showed CPIRAP to be the strongest haemodynamic predictor of in-hospital death (padj  = 0.038), outperforming CPI [area under the receiver operating characteristic (ROC) curves: 0.726 and 0.673, P-for-difference = 0.025]. When the population was stratified according to the identified CPIRAP (0.28 W/m2 ) and accepted CPI (0.32 W/m2 ) thresholds, the cohort with discordant indexes (low CPIRAP and high CPI) comprised a group of 13 patients featuring a congested phenotype with frequent right ventricle or biventricular involvement. In this group, in-hospital mortality was high (30.8%) similar to those with concordant low CPI and CPIRAP . CONCLUSION: Incorporating RAP in CPI calculation (CPIRAP ) improves the prognostic yield in patients with CS SCAI B-D. A cut-off of 0.28 W/m2 identifies patients at higher risk of in-hospital mortality. The improved prognostic value of CPIRAP may derive from identification of patients with more intravascular congestion who may experience substantial in-hospital mortality, uncaptured by the commonly used CPI equation.

How does protocolization improve outcomes in cardiogenic shock due to end-stage heart failure?

BACKGROUND: Protocolized team-based care has been shown to improve outcomes in cardiogenic shock (CS) in patients with end-stage heart failure (ESHF). This study tested the hypothesis that protocolized care improves survival by reducing multi-organ dysfunction prior to orthotopic heart transplantation (OHT) or durable left ventricular assist device (LVAD). METHODS: We developed a protocolized Recognize/rescue-Optimization-Stabilization-Exit/de-Escalation (ROSE) framework for CS due to ESHF. Six-month survival pre-ROSE (2014-2018) and post-ROSE (2018-2021) were compared. The Sequential Organ Failure Assessment (SOFA) score was calculated as a measure of multi-organ dysfunction pre-MCS and pre-"Exit" therapy (OHT, LVAD or recovery). RESULTS: 101 consecutive patients with CS due to ESHF who were deteriorating on inotropes (INTERMACS 1 or 2) were included (63 in Pre-ROSE and 38 in Post-ROSE). The proportions of patients who died on support (26 (41%) vs 11 (29%), p = 0.213) or bridged to "Exit" therapy were comparable between Pre- and Post-ROSE: OHT (28 (44%) vs 21 (55%), p = 0.292); durable LVAD (8 (13%) vs 5 (13%), p = 0.947); or recovery (1 (2%) vs 1 (3%), p = 0.715). SOFA score prior to "Exit" therapy was higher Pre-ROSE compared to Post-ROSE (4 (2-7) vs 2 (1-5), p = 0.012). Six-month survival from initial MCS (71% vs 41%, p = 0.004) and in patients who underwent "Exit" therapy (100% vs 71%, p = 0.001) were higher Post-ROSE vs Pre-ROSE, respectively. Higher pre-"Exit" SOFA score was associated with 6-month survival. None of the patients with Pre-"Exit" SOFA score ≥ 9 survived at 6 months. CONCLUSION: Protocolization of CS care in ESHF improved six-month survival by improving multi-organ dysfunction (SOFA score) prior to OHT and LVAD implant.

Outcomes of temporary mechanical circulatory support in cardiogenic shock due to end-stage heart failure.

Background: There are few reports of mechanical circulatory support (MCS) in patients with cardiogenic shock (CS) due to end-stage heart failure (ESHF). We evaluated our institutional MCS strategy and compared the outcomes of INTERMACS 1 and 2 patients with CS due to ESHF. Methods: Retrospective analysis of prospectively collected data (November 2014 to July 2019) from a single centre. ESHF was defined by a diagnosis of HF prior to presentation with CS. Other causes of CS (eg: acute myocardial infarction) were excluded. We compared the clinical course, complications and 90-day survival of patients with CS due to ESHF in INTERMACS profile 1 and 2. Results: We included 60 consecutive patients with CS due to ESHF Differences in baseline characteristics were consistent with the INTERMACS profiles. The duration of MCS was similar between INTERMACS 1 and 2 patients (14 (10-33) vs 15 (7-23) days, p = 0.439). There was no significant difference in the number of patients with complications that required intervention. Compared to INTERMACS 2, INTERMACS 1 patients had more organ dysfunction on support and significant lower 90-day survival (66% vs 34%, p = 0.016). Conclusion: Our temporary MCS strategy, including earlier intervention in patients with CS due to ESHF at INTERMACS 2 was associated with less organ dysfunction and better 90-day survival compared to INTERMACS 1 patients.