The cerebral and cardiac effects of Norepinephrine in an experimental cardiac arrest model.

Introduction: Epinephrine has been the main drug recommended for decades during cardiopulmonary resuscitation (CPR). But epinephrine's ß-adrenergic effects might increase myocardial oxygen consumption and may cause arrythmias after ROSC. Norepinephrine has a weaker ß-adrenergic effect and could be useful during CPR. Studies on norepinephrine's effect on hemodynamic parameters and cerebral perfusion are scarce. This study aimed to assess norepinephrine's hemodynamic impact in an experimental model of cardiac arrest. Methods: After an initial dose study to determine the optimal dose, we conducted a prospective randomized study with 19 pigs. After 3 minutes of untreated ventricular fibrillation, animals received boluses of 0.5 mg Epinephrine (EPI) or 1 mg Norepinephrine (NE) every 5 minutes during CPR. Coronary perfusion pressure (CPP), carotid blood flow (CBF) and cerebral perfusion pressure (CePP) were evaluated. Results: At baseline, hemodynamic parameters did not differ between the two groups. During CPR, CPP and CBF were similar: 17.3 (12.8; 31.8) in the EPI group vs 16.0 (11.1; 37.7) in the NE group, p = 0.9 and 28.4 (22.0; 54.8) vs 30.8 (12.2; 56.3) respectively, p = 0.9. CePP was not significantly lower during resuscitation in the NE group compared to the EPI group: 12.2 (-8.2; 42.2) vs 7.8 (-2.0; 32.0) p = 0.4. Survival rate was low with only one animal in the EPI group and 2 in the NE group. Conclusion: Cerebral perfusion pressure, coronary perfusion pressure and carotid blood flow during CPR did not significantly differ between the norepinephrine group and the epinephrine group. Further investigations should evaluate different options such as a continuous NE infusion.

Left ventricular hemodynamics with veno-arterial extracorporeal membrane oxygenation.

BACKGROUND: There is considerable debate about the hemodynamic effects of veno-arterial extracorporeal membrane oxygenation (VA-ECMO). AIMS: To evaluate the changes in left ventricular (LV) function, volumes, and work in patients treated with VA-ECMO using invasive LV catheterization and three-dimensional echocardiographic volumes. METHODS: Patients on VA-ECMO underwent invasive hemodynamic evaluation due to concerns regarding candidacy for decannulation. Hemodynamic parameters were reported as means±standard deviations or medians (interquartile ranges) after evaluating for normality. Paired comparisons were done to evaluate hemodynamics at the baseline (highest) and lowest tolerated levels of VA-ECMO support. RESULTS: Twenty patients aged 52.3 ± 15.8 years were included. All patients received VA-ECMO for refractory cardiogenic shock (5/20 SCAI stage D, 15/20 SCAI stage E). At 3.0 (2.0, 4.0) days after VA-ECMO cannulation, the baseline LV ejection fraction was 20% (15%, 27%). The baseline and lowest VA-ECMO flows were 4.0 ± 0.6 and 1.5 ± 0.6 L/min, respectively. Compared to the lowest flow, full VA-ECMO support reduced LV end-diastolic volume [109 ± 81 versus 134 ± 93 mL, p = 0.001], LV end-diastolic pressure (14 ± 9 vs. 19 ± 9 mmHg, p < 0.001), LV stroke work (1858 ± 1413 vs. 2550 ± 1486 mL*mmHg, p = 0.002), and LV pressure-volume area (PVA) (4507 ± 1910 vs. 5193 ± 2388, p = 0.03) respectively. Mean arterial pressure was stable at the highest and lowest flows (80 ± 16 vs. 75 ± 14, respectively; p = 0.08) but arterial elastance was higher at the highest VA-ECMO flow (4.9 ± 2.2 vs lowest flow 2.7 ± 1.6; p < 0.001). CONCLUSIONS: High flow VA-ECMO support significantly reduced LV end-diastolic pressure, end-diastolic volume, stroke work, and PVA compared to minimal support. The Ea was higher and MAP was stable or minimally elevated on high flow.

Association between cardiopulmonary resuscitation duration and survival after out-of-hospital cardiac arrest according: a first nationwide study in France.

OBJECTIVE: Determining whether to pursue or terminate resuscitation efforts remains one of the biggest challenges of cardiopulmonary resuscitation (CPR). No ideal cut-off duration has been recommended and the association between CPR duration and survival is still unclear for out-of-hospital cardiac arrest (OHCA). The aim of this study was to assess the association between CPR duration and 30-day survival after OHCA with favorable neurological outcomes according to initial rhythm. METHODS: This was an observational, retrospective analysis of the French national multicentric registry on cardiac arrest, RéAC. The primary endpoint was neurologically intact 30-day survival according to initial rhythm. RESULTS: 20,628 patients were included. For non-shockable rhythms, the dynamic probability of 30-day survival with a Cerebral Performance Category (CPC) of 1 or 2 was less than 1% after 25 min of CPR. CPR duration over 10 min was not associated with 30-day survival with CPC of 1 or 2 (adjusted OR: 1.67; CI 95% 0.95-2.94). For shockable rhythms, the dynamic probability of 30-day survival with a CPC score of 1 or 2, was less than 1% after 54 min of CPR. CPR duration of 21-25 min was still associated with 30-day survival and 30-day survival with a CPC of 1 or 2 (adjusted OR: 2.77; CI 95% 2.16-3.57 and adjusted OR: 1.82; CI 95% 1.06-3.13, respectively). CONCLUSIONS: Survival decreased rapidly with increasing CPR duration, especially for non-shockable rhythms. Pursuing CPR after 25 min may be futile for patients presenting a non-shockable rhythm. On the other hand, shockable rhythms might benefit from prolonged CPR.

Cerebral hemodynamic effects of head-up CPR in a porcine model.

AIM: To assess the hemodynamic effects of head elevation on cerebral perfusion during cardiopulmonary resuscitation (CPR) in a porcine model of cardiac arrest. METHODS: VF was induced in eight 65 kg pigs that were treated with CPR after five minutes of no flow. Mean arterial pressure (MAP) was measured at the descending thoracic aorta. Internal carotid artery blood flow (CBF) was measured with an ultrasound probe. Cerebral perfusion pressure (CerPP) was calculated in two ways (CerPPICAP and CerPPreported) using the same intracranial pressure (ICP) measurement. CePPreported was calculated as MAP-ICP. CerPPICAP was calculated by using intracranial arterial pressure (ICAP) - ICP. The animals were switched between head up (HUP) and supine (SUP) CPR every five minutes for a total of twenty minutes of resuscitation. RESULTS: MAP and coronary perfusion pressure measurements were similar in both CPR positions (p = 0.36 and p = 0.1, respectively). ICP was significantly lower in the HUP CPR group (14.7 ± 1 mm Hg vs 26.9 ± 1 mm Hg, p < 0.001) as was ICAP (30.1 ± 2 mm Hg vs 42.6 ± 1 mmHg, p < 0.001). The proportional decrease in ICP and ICAP resulted in similar CerPPICAP comparing HUP and SUPCPR (p = 0.7). CBF was significantly lower during HUPCPR when compared to SUPCPR (58.5 ± 3 ml/min vs 78 ± 4 ml/min, p < 0.001). A higher CerPPreported was found during the HUP compared to SUP-CPR, when MAP was used (36.6 ± 2 mm Hg vs 23 ± 2 mm Hg, p < 0.001) without correcting for the hydrostatic pressure drop. CONCLUSION: HUP did not affect cerebral perfusion pressure and it significantly decreased internal carotid blood flow.

Case Report: Correlation between pulmonary capillary wedge pressure and left-ventricular diastolic pressure during treatment with veno-arterial extracorporeal membrane oxygenation.

Background: Pulmonary capillary wedge pressure (PCWP) is often used as a surrogate for left-ventricular end-diastolic pressure in patients (LVEDP) who are on veno-arterial extracorporeal membrane oxygenation (V-A ECMO) support for cardiogenic shock and cardiac arrest. However, the correlation between PCWP and LVEDP is not clear in the setting of V-A ECMO usage. We sought to evaluate this correlation in this case series. Methods: Patients were referred to our cardiac catheterization laboratory for invasive hemodynamic studies to assess their readiness for VA-ECMO decannulation. All patients underwent simultaneous left and right heart catheterization. Using standard techniques, we measured PCWP and LVEDP simultaneously. Continuous variables were reported as medians with interquartile ranges. The correlation between PCWP and LVEDP was evaluated using simple linear regression and reported as R2. Results: Four patients underwent invasive hemodynamic studies 4 (2.5, 7) days after VA-ECMO cannulation. All four patients had suffered in-hospital cardiac arrest and had been put on VA-ECMO. At the baseline level of VA-ECMO flow of 4.1 (3.8, 4.4) L/min, the median LVEDP and PCWP were 6 (4, 7.5) mmHg and 12 (6.5, 16) mmHg, respectively. At the lowest level of VA-ECMO flow of 1.9 (1.6, 2.0) L/min, the median LVEDP and PCWP was 13.5 (8.5, 16) mmHg and 15 (13, 18) mmHg, respectively. There was a poor correlation between the simultaneously measured PCWP and LVEDP (R2 = 0.03, p = 0.66). Conclusions: The PCWP may not correlate well with LVEDP in patients treated with VA-ECMO, particularly at high levels of VA-ECMO support.

Impact of age on survival for patients receiving ECPR for refractory out-of-hospital VT/VF cardiac arrest.

BACKGROUND: Extracorporeal cardiopulmonary resuscitation (ECPR) has been shown to improve neurologically favorable survival for patients with refractory ventricular tachycardia (VT)/ventricular fibrillation (VF) out-of-hospital cardiac arrest. Prior studies of the impact of age on outcomes in ECPR have demonstrated mixed results and we aim to investigate this relationship. METHODS: Patients treated with ECPR at the University of Minnesota Medical Center for refractory out-of-hospital VT/VF arrest from December 2015 to February 2023 were included. The primary endpoints included neurologically favorable survival to discharge. A receiver operating characteristic curve was used to determine an optimal predictive age limit with the highest accuracy for neurologically favorable survival. RESULTS: 391 consecutive patients were included: 22% (n = 86) were female and the mean age was 56.9 ± 11.8 years. Age was independently associated with neurologically favorable survival to discharge, with a 30% decrease in survival with every 10-year increase in age (OR 0.7 (0.57-0.87), p = 0.001. Among those with neurologically favorable survival to discharge, older patients had longer length of hospital stay compared to younger age groups (p = 0.002) while patients who failed to achieve neurologically favorable survival to discharge had similar length of stay independent of age (p = 0.51). CONCLUSIONS: Age is associated with neurologically favorable survival to discharge for patients receiving ECPR for refractory out-of-the-hospital VT/VF cardiac arrest. However, with a survival rate of 23% in the oldest age group, caution should be used when choosing age criteria for patient selection.

The Minnesota first-responder AED project: Aiming to increase survival in out-of-hospital cardiac arrest.

There are 350,000 out-of-hospital cardiac arrest (OHCA) cases annually in the United States of America. Using automated external defibrillators (AEDs) has increased survival in cardiac arrests (CA) with an initial shockable rhythm. Thus, guidelines recommend complete geographical coverage with AEDs. To fill in the gaps in Minnesota, the Center for Resuscitation Medicine at the University of Minnesota raised an $18.8 million grant from the Helmsley Charitable Trust to supply law enforcement first responders with AEDs and, thus, increase survival rates after OHCA by reducing the time to first shock. This report elaborates on the decision-making, fundraising, and logistic strategy required to reach statewide AED coverage. Methods: The baseline need for AEDs was analyzed using a questionnaire sent out to state law enforcement agencies, state patrols, city and county agencies, and tribal agencies in 2021. Furthermore, OHCA cases of 2021 were reviewed. The combination of this information led to an action plan to equip and train all agencies throughout the state's eight regions with AEDs. Results: The electronic survey was initially sent out to 358 agencies. The initial response rate was 77% (n = 276). This resulted in a total need of 8300 AEDs to be deployed over three years (2022-2025). As of 2023, over 4769 AEDs have been distributed, covering 237 sites. Conclusion: By equipping first responders with AED systems, the Center for Resuscitation Medicine aims to shorten the gap in statewide AED coverage, thus increasing the chances of survival after OHCA.

Left rib fractures during cardiopulmonary resuscitation are associated with hemodynamic variations in a pig model of cardiac arrest.

Background: Chest compressions (CC) are the cornerstone of cardiopulmonary resuscitation (CPR). But CC are also known to cause injuries, specifically rib fractures. The effects of such fractures have not been examined yet. This study aimed to investigate hemodynamic effects of rib fractures during mechanical CPR in a porcine model of cardiac arrest (CA). Methods: We conducted a retrospective hemodynamic study in 31 pigs that underwent mechanical CC. Animals were divided into three groups based on the location of rib fractures: No Broken Ribs group (n = 11), Left Broken Ribs group (n = 13), and Right Broken Ribs group (n = 7). Hemodynamic measurements were taken at 10 seconds before and 10, 30, and 60 seconds after rib fractures. Results: Baseline hemodynamic parameters did not differ between the three groups. Systolic aortic pressure was overall higher in the Left Broken Ribs group than in the No Broken Ribs group at 10, 30, and 60 seconds after rib fracture (p = 0.02, 0.01, and 0.006, respectively). The Left Broken Ribs group had a significantly higher right atrial pressure compared to the No Broken Rib group after rib fracture (p = 0.02, 0.01, and 0.03, respectively). There was no significant difference for any parameter for the Right Broken Ribs group, when compared to the No Broken Ribs group. Conclusion: An increase in main hemodynamic parameters was observed after left rib fractures while right broken ribs were not associated with any change in hemodynamic parameters. Reporting fractures and their location seems worthwhile for future experimental studies.

Long-term outcomes after minimal right lateral thoracotomy for the resection of cardiac tumors.

OBJECTIVES: Cardiac tumors are a rare and heterogeneous entity, with a cumulative incidence of up to 0.02%. This study aimed to investigate one of the largest patient cohorts for long-term outcomes after minimally-invasive cardiac surgery using right-anterior thoracotomy and femoral cardiopulmonary bypass (CPB) cannulation. METHODS: Between 2009 and 2021, patients who underwent minimally-invasive cardiac tumor removal at our department were included. The diagnosis was confirmed postoperatively by (immune-) histopathological analysis. Preoperative baseline characteristics, intraoperative data, and long-term survival were analyzed. RESULTS: Between 2009 and 2021, 183 consecutive patients underwent surgery for a cardiac tumor at our department. Of these, n = 74 (40%) were operated on using a minimally-invasive approach. The majority, n = 73 (98.6%), had a benign cardiac tumor, and 1 (1.4%) had a malignant cardiac tumor. The mean age was 60 ± 14 years, and n = 45 (61%) of patients were female. The largest group of tumors was myxoma (n = 62; 84%). Tumors were predominantly located in the left atrium in 89% (n = 66). CPB-time was 97 ± 36min and aortic cross-clamp time 43 ± 24 min s. The mean hospital stay was 9.7 ± 4.5 days. The perioperative mortality was 0%, and all-cause mortality after ten years was 4.1%. CONCLUSION: Minimally-invasive tumor excision is feasible and safe, predominantly in benign cardiac tumors, even in combination with concurrent procedures. Patients who require cardiac tumor removal should be evaluated for minimally-invasive cardiac surgery at a specialized center, as it is highly effective and associated with good long-term survival.

The impact of BMI on arrest characteristics and survival of patients with out-of-hospital cardiac arrest treated with extracorporeal cardiopulmonary resuscitation.

AIM: To assess the impact of body mass index (BMI) on survival to hospital discharge of patients presenting with refractory ventricular fibrillation treated with extracorporeal cardiopulmonary resuscitation. We hypothesize that due to limitations in pre-hospital care delivery, people with high BMI have worse survival after prolonged resuscitation and ECPR. METHODS: This study is a retrospective single-centre study that included patients suffering refractory VT/VF OHCA from December 2015 to October 2021 and had a BMI calculated at hospital admission. We compared the baseline characteristics and survival between patients with obesity (>30 kg/m2) and those without (≤30 kg/m2). RESULTS: Two-hundred eighty-three patients were included in this study, and two-hundred twenty-four required mechanical support with veno-arterial extracorporeal cardiopulmonary membrane oxygenation (VA ECMO). Patients with BMI > 30 (n = 133) had significantly prolonged CPR duration compared to their peers with BMI ≤ 30 kg/m2 (n = 150) and were significantly more likely to require support with VA ECMO (85.7% vs 73.3%, p = 0.015). Survival to hospital discharge was significantly higher in patients with BMI ≤ 30 kg/m2 (48% vs. 29.3%, p < 0.001). BMI was an independent predictor of mortality in a multivariable logistic regression analysis. The four-year mortality rate was low and not significantly different between the two groups (p = 0.32). CONCLUSION: ECPR yields clinically meaningful long-term survival in patients with BMI > 30 kg/m2. However, the resuscitation time is significantly prolonged, and the overall survival significantly lower compared to patients with BMI ≤ 30 kg/m2. ECPR should, therefore, not be withheld for this population, but faster transport to an ECMO capable centre is mandated to improve survival to hospital discharge.

The impact of levosimendan on survival and weaning from ECMO after extracorporeal cardiopulmonary resuscitation.

OBJECTIVES: Extracorporeal cardiopulmonary resuscitation (eCPR) is increasingly used due to its beneficial outcomes and results compared to conventional CPR. After cardiac arrest, the overall ejection fraction is severely impaired; thus, weaning from ECMO is often prolonged or impossible. We hypothesized that early application of levosimendan in these patients facilitates ECMO weaning and survival. METHODS: From 2016 until 2020, patients who underwent eCPR after cardiac arrest at our institution were analyzed retrospectively and divided into two groups: patients who received levosimendan during ICU stay (n = 24) and those who did not receive levosimendan (n = 84) and analyzed for outcome parameters. Furthermore, we used propensity-score matching and multinomial regression analysis to show the effect of levosimendan on outcome parameters. RESULTS: Overall, in-hospital mortality was significantly lower in the group which received levosimendan (28% vs. 88%, p ≤ 0.01), and ECMO weaning was more feasible in patients who received levosimendan (88% vs. 20%, p ≤ 0.01). CPR duration until ECMO cannulation was significantly shorter in the levosimendan group (44 + 26 vs. 65 + 28, p = 0.002); interestingly, the rate of mechanical chest compressions before ECMO cannulation was lower in the levosimendan group (50% vs. 69%, p = 0.005). CONCLUSION: In patients after cardiac arrest treated with eCPR, levosimendan seems to contribute to higher success rates of ECMO weaning, potentially due to a short to mid-term increase in inotropy. Also, the survival after levosimendan application was higher than patients who did not receive levosimendan.

Updates on the Global Prevalence and Etiology of Constrictive Pericarditis: A Systematic Review.

Constrictive pericarditis is a rare disease with poorly understood epidemiology. A systematic literature search was adopted to assess the region- and period-specific traits of constrictive pericarditis through Pubmed, EMBASE, and Scopus. Case reports and studies including less than 20 patients were excluded. The risk of bias was assessed through the Study Quality Assessment Tools developed by the National Heart Lung Blood Institute by 4 reviewers. Patient demographics, disease etiology, and mortality were the primary assessed outcomes. One hundred thirty studies with 11,325 patients have been included in this systematic review and meta-analysis. The age at diagnosis of constrictive pericarditis has markedly increased after 1990. Patients from Africa and Asia are considerably younger compared with those from Europe and North America. Moreover, there are differences in etiology, as tuberculosis remains the dominant cause of constrictive pericarditis in Africa and Asia but has been surpassed by history of previous chest surgery in North America and Europe. The human immunodeficiency virus affects 29.1% of patients from Africa diagnosed with constrictive pericarditis, a feature that is not observed on any other continent. The early mortality rate after hospitalization has improved. The variances of age at diagnosis and etiology of constrictive pericarditis should be considered by the clinician during the work-up of cardiac and pericardial diseases. An underlying human immunodeficiency virus infection complicates a significant portion of constrictive pericarditis cases in Africa. Early mortality has improved across the world but remains high.

Initial hospital length of stay and long-term survival of patients successfully resuscitated using extracorporeal cardiopulmonary resuscitation for refractory out-of-hospital cardiac arrest.

AIMS: The long-term outcomes of patients treated with extracorporeal cardiopulmonary resuscitation (ECPR) for refractory ventricular tachycardia/ventricular fibrillation (VT/VF) out-of-hospital cardiac arrest (OHCA) remain poorly defined. The purpose of this study was to describe the hospital length of stay and long-term survival of patients who were successfully rescued with ECPR after refractory VT/VF OHCA. METHODS AND RESULTS: In this retrospective cohort study, the length of index admission and long-term survival of patients treated with ECPR after OHCA at a single centre were evaluated. In a sensitivity analysis, survival of patients managed with left ventricular assist device (LVAD) implantation or heart transplantation during the same period was also evaluated. Between 1 January 2016 and 12 January 2020, 193 patients were transferred for ECPR considerations and 160 underwent peripheral veno-arterial extracorporeal membrane oxygenation cannulation. Of these, 54 (33.7%) survived the index admission. These survivors required a median 16 days of intensive care and 24 days total hospital stay. The median follow-up time of the survivors was 1216 (683, 1461) days. Of all, 79.6 and 72.2% were alive at 1 and 4 years, respectively. Most deaths within the first year occurred among the patients requiring discharge to a long-term acute care facility. Overall survival rates at 4 years were similar in the ECPR and LVAD cohorts (P = 0.30) but were significantly higher for transplant recipients (P < 0.001). CONCLUSION: This data suggest that the lengthy index hospitalization required to manage OHCA patients with ECPR is rewarded by excellent long-term clinical outcomes in an expert ECPR programme.

Long-Term Survival and Quality of Life in Non-Surgical Adult Patients Supported with Veno-Arterial Extracorporeal Oxygenation.

BACKGROUND: The use of veno-arterial extracorporeal membrane oxygenation (VA ECMO) for hemodynamic support is on the rise. Not much is known about the impact of extracorporeal membrane oxygenation (ECMO) and its complications on long-term survival and quality of life. METHODS: In this single-center, cross-sectional study, we evaluated the survival and quality of life in patients treated with VA ECMO between May 2009 and July 2019. Follow-up was conducted between November 2019 and January 2020. RESULTS: Overall, 118 patients were evaluated in this study. Of the 37 patients who were alive at hospital discharge, 32 answered the EuroQol-5 dimensional-5-level questionnaire (EQ-5D-5L). For patients discharged alive from the hospital, mean survival was 8.1 years, 8.4 years for cardiogenic shock, and 5.0 years for patients with refractory cardiac arrest. EQ-5D-5L index value of ECMO survivors was not significantly different from the general age-matched population. Neurologic complications and major bleeding during index hospitalization limit long-term quality of life. CONCLUSIONS: Patients treated with VA ECMO have high in-hospital mortality, with extracorporeal membrane oxygenation cardio-pulmonary resuscitation patients being at higher risk of early death. However, once discharged from the hospital, most patients remain alive with a reasonable quality of life.

Carotid ultrasonography improves residual risk stratification in guidelines-defined high cardiovascular risk patients.

AIMS: The clinical value of carotid atherosclerosis markers for residual risk stratification in high atherosclerotic cardiovascular disease (ASCVD) risk patients is not established. We aimed to derive and validate optimal values of markers of carotid subclinical atherosclerosis improving risk stratification in guidelines-defined high ASCVD risk patients. METHODS AND RESULTS: We consecutively analysed high or very high ASCVD risk patients from a cardiovascular (CV) prevention registry (n = 751, derivation cohort) and from the Atherosclerosis Risk in Communities (ARIC) study (n = 2,897, validation cohort). Baseline ASCVD risk was defined using the 2021 European Society of Cardiology guidelines (clinical ESCrisk). Intima-media thickness excluding plaque, average maximal (avg.maxWT), maximal wall thickness (maxWT) and number of sites with carotid plaque were assessed. As primary endpoint of the study was defined the composite of cardiac death, acute myocardial infarction and revascularization after a median of 3.4 years in both cohorts and additionally for 16.7 years in the ARIC cohort. RESULTS: MaxWT > 2.00 mm and avg.maxWT > 1.39 mm provided incremental prognostic value, improved discrimination and correctly reclassified risk over the clinical ESCrisk both in the derivation and the validation cohort (P < 0.05 for net reclassification index, integrated discrimination index and Delta Harrell's C index). MaxWT < 0.9 mm predicted very low probability of CV events (negative predictive value = 97% and 92% in the derivation and validation cohort, respectively). These findings were additionally confirmed for very long-term events in the validation cohort. CONCLUSION: Integration of carotid ultrasonography in guidelines-defined risk stratification may identify patients at very high-risk in need for further residual risk reduction or at very low probability for events.

Differential Effects of Reperfusion on Cardiac Mitochondrial Subpopulations in a Preclinical Porcine Model of Acute Myocardial Infarction.

Acute myocardial infarction (AMI) leads to localized cardiac ischemia and can be fatal if untreated. Despite being treatable, the threat of ischemia-reperfusion (IR) injury remains high. Mitochondria are central to both propagation and mitigation of IR injury, and cardiac mitochondria are categorized into two major subtypes-subsarcolemmal and interfibrillar mitochondria (SSM and IFM, respectively). We hypothesized that, in our pre-clinical porcine model of AMI, SSM and IFM are differentially affected by reperfusion. AMI was induced in female pigs by balloon occlusion of the left anterior descending artery for 45 min, followed by 4 h of reperfusion. At the end of reperfusion, animals were euthanized. Cardiac SSM and IFM from the affected ischemic area and a nearby non-ischemic area were isolated to compare mitochondrial function using substrates targeting mitochondrial electron transport chain complexes I and II. Despite detecting overall significant differences in mitochondrial function including yield, mitochondrial S3 and S4 respirations, and calcium retention, consistent individual functional differences in the two mitochondrial subpopulations were not observed, both between the two mitochondrial subtypes, as well as between the ischemic and non-ischemic tissue. Nonetheless, this study describes the mitochondrial subtype response within the initial few hours of reperfusion in a clinically relevant model of AMI, which provides valuable information needed to develop novel mitochondrially targeted therapies for AMI.

Enhancing cardiac arrest survival with extracorporeal cardiopulmonary resuscitation: insights into the process of death.

Extracorporeal cardiopulmonary resuscitation (ECPR) is an emerging method of cardiopulmonary resuscitation to improve outcomes from cardiac arrest. This approach targets patients with out-of-hospital cardiac arrest previously unresponsive and refractory to standard treatment, combining approximately 1 h of standard CPR followed by venoarterial extracorporeal membrane oxygenation (VA-ECMO) and coronary artery revascularization. Despite its relatively new emergence for the treatment of cardiac arrest, the approach is grounded in a vast body of preclinical and clinical data that demonstrate significantly improved survival and neurological outcomes despite unprecedented, prolonged periods of CPR. In this review, we detail the principles behind VA-ECMO-facilitated resuscitation, contemporary clinical approaches with outcomes, and address the emerging new understanding of the process of death and capability for neurological recovery.

Coronary artery disease burden relation with the presentation of acute cardiac events and ventricular fibrillation.

OBJECTIVES: Evaluate the differences in coronary artery disease (CAD) burden between patients with ischemic resuscitated, ischemic refractory VT/VF OHCA events and N/STEMI. BACKGROUND: Refractory out-of-hospital cardiac arrest patients presenting with initial shockable rhythms (VT/VF OHCA) have the highest mortality among patients with acute cardiac events. No predictors of VT/VF OHCA refractoriness have been identified. METHODS: A retrospective cohort design was used to assess baseline characteristics, clinical outcomes, and the angiographic severity of disease among patients with VT/VF OHCA undergoing emergent coronary angiography at the University of Minnesota Medical Center. The Gensini score was calculated for all patients to assess the angiographic burden of CAD. For patients with ischemia-related cardiac arrest, outcomes were further compared to an independent non-OHCA population presenting with N/STEMI. RESULTS: During the study period, 538 patients were admitted after VT/VF OHCA. Among them, 305 presented with resuscitated, and 233 with refractory VT/VF. 66% of resuscitated and 70% of refractory VT/VF had an underlying, angiographically documented, ischemic etiology. Ischemic resuscitated and refractory VT/VF had significant differences in Gensini score, (80.7 ± 3.6 and 127.6 ± 7.1, respectively, p < 0.001) and survival (77.3% and 30.0%, respectively, p < 0.001). Both groups had a higher CAD burden and worse survival than the non-OHCA N/STEMI population (360 patients). Ischemic refractory VT/VF was significantly more likely to present with chronic total occlusion in comparison to both N/STEMI and ischemic resuscitated VT/VF. CONCLUSION: Ischemia-related, refractory VT/VF OHCA has a higher burden of CAD and the presence of CTOs compared to resuscitated VT/VF OHCA and N/STEMI.

The relationship between telomere length and putative markers of vascular ageing: A systematic review and meta-analysis.

Accelerated biological aging contributes to the evolution of cardiovascular disease. However, its influence on subclinical organ damage remains unclear. Leukocyte telomere length (LTL) is emerging as a marker of biological cardiovascular aging. We performed a systematic review and meta-analysis to assess the association between LTL and measures of end-organ damage. PubMed, Medline, Embase, Cinahl Plus, ClinicalTrials.gov, and grey literature databases were searched for studies that assessed the association of LTL with arterial pulse wave velocity (aPWV), carotid intima-media thickness (cIMT), left ventricular mass (LVM or LVMI), renal outcomes, coronary artery calcium (CAC) and presence of carotid plaques. In a sample of 7256 patients, we found that cIMT (pooled correlation coefficient (r) = -0.249; 95 %CI -0.37, -0.128) and aPWV (pooled r = -0.194; 95 % CI -0.290, -0.100) inversely correlate with LTL. Compared to aPWV, cIMT had a stronger correlation with LTL. Patients without carotid plaques had longer telomeres than patients with carotid plaques. Quantitative analyses documented LTL association with renal outcomes and CAC, but not with LVM/LVMI. Among measures of end-organ damage, cIMT and aPWV provide the most accurate information on the contribution of biological aging to the process of vascular remodeling/damage.