Consecutive-Day Ventricular and Atrial Cardiomyocyte Isolations from the Same Heart: Shifting the Cost–Benefit Balance of Cardiac Primary Cell Research

Freshly isolated primary cardiomyocytes (CM) are indispensable for cardiac research. Experimental CM research is generally incompatible with life of the donor animal, while human heart samples are usually small and scarce. CM isolation from animal hearts, traditionally performed by coronary artery perfusion of enzymes, liberates millions of cells from the heart. However, due to progressive cell remodeling following isolation, freshly isolated primary CM need to be used within 4–8 h post-isolation for most functional assays, meaning that the majority of cells is essentially wasted. In addition, coronary perfusion-based isolation cannot easily be applied to human tissue biopsies, and it does not straightforwardly allow for assessment of regional differences in CM function within the same heart. Here, we provide a method of multi-day CM isolation from one animal heart, yielding calcium-tolerant ventricular and atrial CM. This is based on cell isolation from cardiac tissue slices following repeated (usually overnight) storage of the tissue under conditions that prolong CM viability beyond the day of organ excision by two additional days. The maintenance of cells in their near-native microenvironment slows the otherwise rapid structural and functional decline seen in isolated CM during attempts for prolonged storage or culture. Multi-day slice-based CM isolation increases the amount of useful information gained per animal heart, improving reproducibility and reducing the number of experimental animals required in basic cardiac research. It also opens the doors to novel experimental designs, including exploring same-heart regional differences.

Coronary Interventions in Pediatric Congenital Heart Disease

Coronary artery lesions represent rare conditions in pediatric congenital heart disease and mainly include coronary artery stenoses (CAS) or coronary artery fistulae (CAF). Due to the small vessel size, pediatric percutaneous coronary interventions (PCI) are demanding and studies concerning long-term results are missing. In this retrospective study, we analyzed indications, procedural details, and post-procedural outcomes in pediatric patients who underwent PCI in our institution. For CAS treatment, procedural success was defined as efficient coronary revascularization with a significant improvement of coronary perfusion. CAF treatment was considered successful, when no residual shunt was detectable. From 1995 to 2020, 32 pediatric patients aged ≤ 18 years received interventional treatment for CAS (n = 24/32) or CAF (n = 8/32). Reasons for CAS were post-surgical (n = 15/24) or post-transplant (n = 9/24). Interventional treatment strategies included coronary angioplasty (20/43), stent placement (10/43), and a combination of both (13/43). In-hospital mortality occurred in 6/24 patients and late mortality in 5/24 patients leading to an overall 5-year survival of 62.5%. Early mortality mainly occurred due to post-ischemic myocardial failure. CAF occlusion was performed using coil embolization (n = 3), placement of vascular plugs (n = 3), a combination of both (n = 1), or a combination of coil embolization and a covered stent (n = 1). Treatment of coronary fistulae was successful in all patients with excellent post-procedural results and no follow-up death. PCI in pediatric patients with congenital heart disease can be performed safely and effectively. However, the overall 5-year survival probability of patients with CAS is reduced due to severe ischemic myocardial damage.

Case Report: Key Role of the Impella Device to Achieve Complete Revascularization in a Patient With Complex Multivessel Disease and Severely Depressed Left Ventricular Function

Background: Left ventricle (LV) assist devices may be required to stabilize hemodynamic status during complex, high-risk, and indicated procedures (CHIP). We present a case in which elective hemodynamic support with the Impella CP device was essential to achieve complete revascularization with PCI in a patient with complex multivessel disease and severely depressed LV function.Case Summary: A 45-year-old male with no previous history of cardiovascular disease presented to the emergency department for new onset exertional dyspnoea. Echocardiography showed severely depressed LV function (EF 27%) that was confirmed with cardiac magnetic resonance. Two chronic total occlusions (CTOs) of the proximal right coronary artery (RCA) and left circumflex coronary artery (LCx) were found at coronary angiography. After Heart Team evaluation, PCI with Impella hemodynamic support was planned. After crossing and predilating the CTO of the LCx, ventricular fibrillation (VF) occurred. No direct current (DC) shock was performed because the patient was conscious thanks to the support provided by the Impella pump. About 1 min later, spontaneous termination of VF occurred. Afterwards, the two CTOs were successfully treated with good result and no complications. Recovery of LV function was observed at discharge. At 9 months, the patient had no symptoms and echocardiography showed an EF of 60%.Discussion: In this complex high-risk patient, hemodynamic support was essential to allow successful PCI. It is remarkable that the patient remained conscious and hemodynamically stable during VF that spontaneously terminated after 1 min, likely because the Impella pump provided preserved coronary perfusion and LV unloading. This case confirms the pivotal role of Impella in supporting CHIP, particularly in patients with multivessel disease and depressed LV function.

108 Atrial fibrillation effects on coronary perfusion across the different myocardial layers: a computational analysis

Aims Atrial fibrillation (AF) patients may present ischaemic chest pain in the absence of classical obstructive coronary disease. Among the possible causes, the direct haemodynamic effect exerted by the irregular arrhythmia has not been studied in detail. Methods and results A computational fluid dynamics analysis was performed by means of a 1D-0D multiscale model of the entire human cardiovascular system, characterized by a detailed mathematical modelling of the coronary arteries and their downstream distal microcirculatory districts (subepicardial, midwall, and subendocardial layers). Three mean ventricular rates were simulated in both sinus rhythm (SR) and AF: 75, 100, 125 b.p.m. We conducted inter-layer and inter-frequency analysis of the ratio between mean beat-to-beat blood flow in AF compared to SR (Q¯AP/Q¯SR Inter-layer analysis showed that, for each simulated ventricular rate, Q¯AP/Q¯SR progressively decreased from the epicardial to the endocardial layer in the distal left coronary artery districts (P-values < 0.001 for both left anterior descending artery—LAD, and left circumflex artery—LCx), while this was not the case for the distal right coronary artery (RCA) district. Inter-frequency analysis showed that, focusing on each myocardial layer, Q¯AP/Q¯SR progressively worsened as the ventricular rates increased in all investigated microcirculatory districts (LAD, LCx, and RCA) (P-values < 0.001 for all layer-specific comparisons). Conclusions AF exerts direct haemodynamic consequences on the coronary microcirculation, causing a reduction in microvascular coronary flow particularly at higher ventricular rates; the most prominent reduction was seen in the subendocardial layers perfused by left coronary arteries (LAD and LCx).

Intra-aortic balloon pumps in cardiogenic shock: an overview

The intra-aortic balloon pump was first introduced for the treatment of cardiogenic shock. It is now the most commonly used form of circulatory support, despite disappointing findings from the intra-aortic balloon pump SHOCK II trial ( Thiele et al, 2012 ). Common placement is via the femoral artery into the aorta, with the tip of the balloon sitting below the left subclavian artery and the distal end above the renal arteries. The balloon is timed to inflate at the beginning of diastole augmenting coronary perfusion and deflate on the R wave just before systole, reducing the afterload. Patients who may be considered for intra-aortic balloon pump insertion are those experiencing ST elevation myocardial infarction or complex ischaemic disease and cardiogenic shock. Despite advances in catheter size and technology, potential complications include bleeding from the insertion site, limb ischaemia and compartment syndrome. Cardiovascular nurses require specialist knowledge and skills concerning balloon console technology, nursing care and potential complications.

Transmural Distribution of Coronary Perfusion and Myocardial Work Density Due to Alterations in Ventricular Loading, Geometry and Contractility

Myocardial supply changes to accommodate the variation of myocardial demand across the heart wall to maintain normal cardiac function. A computational framework that couples the systemic circulation of a left ventricular (LV) finite element model and coronary perfusion in a closed loop is developed to investigate the transmural distribution of the myocardial demand (work density) and supply (perfusion) ratio. Calibrated and validated against measurements of LV mechanics and coronary perfusion, the model is applied to investigate changes in the transmural distribution of passive coronary perfusion, myocardial work density, and their ratio in response to changes in LV contractility, preload, afterload, wall thickness, and cavity volume. The model predicts the following: (1) Total passive coronary flow varies from a minimum value at the endocardium to a maximum value at the epicardium transmurally that is consistent with the transmural distribution of IMP; (2) Total passive coronary flow at different transmural locations is increased with an increase in either contractility, afterload, or preload of the LV, whereas is reduced with an increase in wall thickness or cavity volume; (3) Myocardial work density at different transmural locations is increased transmurally with an increase in either contractility, afterload, preload or cavity volume of the LV, but is reduced with an increase in wall thickness; (4) Myocardial work density-perfusion mismatch ratio at different transmural locations is increased with an increase in contractility, preload, wall thickness or cavity volume of the LV, and the ratio is higher at the endocardium than the epicardium. These results suggest that an increase in either contractility, preload, wall thickness, or cavity volume of the LV can increase the vulnerability of the subendocardial region to ischemia.

Abstract 9160: Epinephrine-Dominant versus Non-Epinephrine Dominant Resuscitation for In-Hospital Cardiac Arrest

Introduction: Vasopressors are used during CPR to increase arterial resistance and aortic diastolic pressure, improving coronary perfusion and likelihood of ROSC. In comparison to epinephrine, vasopressin remains effective in an acidemic environment, has favorable cerebral perfusion, and does not directly increase myocardial oxygen demand. Studies comparing epinephrine and vasopressin report variable ROSC, survival, and neurological outcome. Most studies used few vasopressin doses and it is unclear whether greater vasopressin use leads to clinical benefit. Hypothesis: We hypothesized that a non-epinephrine dominant CPR approach with vasopressin would lead to greater ROSC than an epinephrine-dominant approach. Methods: This was a retrospective, single-center study conducted at an 800-bed academic medical center. All first cardiac arrests among adult inpatients between Jan 2018 and Mar 2021 were screened, and those with at least 2 vasopressor doses used were included. Patients who received epinephrine-dominant resuscitation (epinephrine-to-vasopressin dose ratio >2 or CPR using only epinephrine) were compared to patients who received a non-epinephrine dominant approach (epinephrine-to-vasopressin dose ratio ≤2). The incidence of ROSC was analyzed using a Chi-squared test where p <0.05 was considered significant. Secondary outcomes included survival to discharge with favorable neurologic outcome, survival to discharge, and Cerebral Performance Category scores. Results: Of 663 in-hospital cardiac arrests screened, 264 were included. Two hundred twenty-eight (86%) presented with PEA/asystole as the initial rhythm, and the most common etiologies were circulatory (41%) and respiratory (26%). The epinephrine-dominant arm achieved ROSC in 89 (66%) patients compared to 87 (67%) patients in the non-epinephrine dominant arm (RR 0.99, 95% CI 0.84-1.18, p=0.93). Survival to discharge was higher in the epinephrine-dominant arm (25% vs 15%, p=0.04). Conclusion: There was no difference in ROSC between epinephrine-dominant and non-epinephrine dominant resuscitation for adult in-hospital cardiac arrest. Future studies should examine the impact of non-epinephrine dominant CPR on long term neurologic outcomes.

Abstract 10911: Amplitude Spectral Area to Guide Shock and Epinephrine Delivery in a Swine Model of Ventricular Fibrillation and Closed-Chest Resuscitation

Introduction: VF accounts for ~30% of all sudden cardiac arrest episodes. VF signal analysis in the frequency domain - calculating the amplitude spectral area (AMSA) - can inform on the probability that an electrical shock could terminate VF followed by return of spontaneous circulation (ROSC). BLS guidelines require delivery of shocks every 2 min and epinephrine every 4 min. Yet, shocks often do not terminate VF and may injure the myocardium. We have previously reported that guiding the timing of shock delivery based on AMSA reduces myocardial injury and improves outcome. Epinephrine is given to increase the coronary perfusion pressure (CPP) and therefore myocardial blood flow but has detrimental effects on post-resuscitation myocardial function and possibly on neurological outcome. Hypothesis: Monitoring AMSA during CPR could be used not only to guide shock delivery but also to avoid administering epinephrine when AMSA predicts a high probability of shock success, reserving epinephrine when AMSA predicts a low probability of shock success and additional CPP increase might be helpful. Methods: In a swine model of electrically induced VF and mechanical chest compressions, two resuscitation protocols were compared in 8 pigs each: (1) A guidelines-driven (GD), delivering shocks and epinephrine guided by the current BLS protocol and (2) An AMSA-driven, delivering shocks and epinephrine guided by AMSA (ADSE). VF was untreated for 10 min and pigs that achieved ROSC were monitored for 240 min. Results: Compared to GD, ADSE was associated with a shorter time to ROSC (400±80 vs 569±16 sec, p=0.034) and higher survival rate at 240 minutes with borderline statistical significance (7/8 vs 3/8, p=0.059). ADSE required fewer shocks (3±2 vs 5±2, p=0.026) and received fewer doses of epinephrine (median [interquartile range], 1[1-1] vs 2[1.3-3], p=0.038). Conclusions: Resuscitation with the ADSE protocol was superior to the GD protocol resulting in a shorter time to ROSC with improved survival requiring fewer shocks and fewer epinephrine doses. The ADSE protocol represents a more tailored approach to resuscitation enabling delivery of resuscitation interventions with higher precision and consequently minimizing their associated adverse effects.

The effect of the head-up position on cardiopulmonary resuscitation: a systematic review and meta-analysis

Objective Experimental studies of head-up positioning (HUP) during cardiopulmonary resuscitation (CPR) have had some degree of conflicting published results. The current study aim was to analyze and reconcile those discrepancies in order to better clarify the effects of HUP CPR compared to conventional supine (SUP) CPR. Methods Three databases (PubMed, EMBASE and Cochrane Library) were searched comprehensively (from each respective database's inception to May 2021) for articles addressing HUP CPR. The primary outcome to be observed was cerebral perfusion pressure (CerPP), and secondary outcomes were mean intracranial pressure (ICP), mean arterial pressure (MAP), coronary perfusion pressure (CoPP) and frequencies of return of spontaneous circulation (ROSC). Results Seven key studies involving 131 animals were included for analysis. Compared to SUP CPR, CerPP (MD 10.37; 95% CI 7.11–13.64; p < 0.01; I2 = 58%) and CoPP (MD 7.56; 95% CI 1.84–13.27, p = 0.01; I2 = 75%) increased significantly with HUP CPR, while ICP (MD − 13.66; 95% CI − 18.6 to –8.71; p < 0.01; I2 = 96%) decreased significantly. Combining all study methodologies, there were no significant differences detected in MAP (MD − 1.63; 95% CI − 10.77–7.52; p = 0.73; I2 = 93%) or frequency of ROSC (RR 0.9; 95% CI 0.31–2.60; p = 0.84; I2 = 65%). However, in contrast to worse outcomes in studies using immediate elevation of the head in a reverse Trendelenburg position, study outcomes were significantly improved when HUP (head and chest only) was introduced in a steady, graduated manner following a brief period of basic CPR augmented by active compression–decompression (ACD) and impedance threshold (ITD) devices. Conclusion In experimental models, gradually elevating the head and chest following a brief interval of circulatory priming with ACD and ITD devices can enhance CoPP, lower ICP and improve CerPP significantly while maintaining MAP. This effect is immediate, remains sustained and is associated with improved outcomes.