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.

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.

Improved Survival With Extracorporeal Cardiopulmonary Resuscitation Despite Progressive Metabolic Derangement Associated With Prolonged Resuscitation.

BACKGROUND: The likelihood of neurologically favorable survival declines with prolonged resuscitation. However, the ability of extracorporeal cardiopulmonary resuscitation (ECPR) to modulate this decline is unknown. Our aim was to examine the effects of resuscitation duration on survival and metabolic profile in patients who undergo ECPR for refractory ventricular fibrillation/ventricular tachycardia out-of-hospital cardiac arrest. METHODS: We retrospectively evaluated survival in 160 consecutive adults with refractory ventricular fibrillation/ventricular tachycardia out-of-hospital cardiac arrest treated with the University of Minnesota (UMN) ECPR protocol (transport with ongoing cardiopulmonary resuscitation [CPR] to the cardiac catheterization laboratory for ECPR) compared with 654 adults who had received standard CPR in the amiodarone arm of the ALPS trial (Amiodarone, Lidocaine, or Placebo Study). We evaluated the metabolic changes and rate of survival in relation to duration of CPR in UMN-ECPR patients. RESULTS: Neurologically favorable survival was significantly higher in UMN-ECPR patients versus ALPS patients (33% versus 23%; P=0.01) overall. The mean duration of CPR was also significantly longer for UMN-ECPR patients versus ALPS patients (60 minutes versus 35 minutes; P<0.001). Analysis of the effect of CPR duration on neurologically favorable survival demonstrated significantly higher neurologically favorable survival for UMN-ECPR patients compared with ALPS patients at each CPR duration interval <60 minutes; however, longer CPR duration was associated with a progressive decline in neurologically favorable survival in both groups. All UMN-ECPR patients with 20 to 29 minutes of CPR (8 of 8) survived with neurologically favorable status compared with 24% (24 of 102) of ALPS patients with the same duration of CPR. There were no neurologically favorable survivors in the ALPS cohort with CPR ≥40 minutes, whereas neurologically favorable survival was 25% (9 of 36) for UMN-ECPR patients with 50 to 59 minutes of CPR and 19% with ≥60 minutes of CPR. Relative risk of mortality or poor neurological function was significantly reduced in UMN-ECPR patients with CPR duration ≥60 minutes. Significant metabolic changes included decline in pH, increased lactic acid and arterial partial pressure of carbon dioxide, and thickened left ventricular wall with prolonged professional CPR. CONCLUSIONS: ECPR was associated with improved neurologically favorable survival at all CPR durations <60 minutes despite severe progressive metabolic derangement. However, CPR duration remains a critical determinate of survival.

Advanced reperfusion strategies for patients with out-of-hospital cardiac arrest and refractory ventricular fibrillation (ARREST): a phase 2, single centre, open-label, randomised controlled trial.

BACKGROUND: Among patients with out-of-hospital cardiac arrest (OHCA) and ventricular fibrillation, more than half present with refractory ventricular fibrillation unresponsive to initial standard advanced cardiac life support (ACLS) treatment. We did the first randomised clinical trial in the USA of extracorporeal membrane oxygenation (ECMO)-facilitated resuscitation versus standard ACLS treatment in patients with OHCA and refractory ventricular fibrillation. METHODS: For this phase 2, single centre, open-label, adaptive, safety and efficacy randomised clinical trial, we included adults aged 18-75 years presenting to the University of Minnesota Medical Center (MN, USA) with OHCA and refractory ventricular fibrillation, no return of spontaneous circulation after three shocks, automated cardiopulmonary resuscitation with a Lund University Cardiac Arrest System, and estimated transfer time shorter than 30 min. Patients were randomly assigned to early ECMO-facilitated resuscitation or standard ACLS treatment on hospital arrival by use of a secure schedule generated with permuted blocks of randomly varying block sizes. Allocation concealment was achieved by use of a randomisation schedule that required scratching off an opaque layer to reveal assignment. The primary outcome was survival to hospital discharge. Secondary outcomes were safety, survival, and functional assessment at hospital discharge and at 3 months and 6 months after discharge. All analyses were done on an intention-to-treat basis. The study qualified for exception from informed consent (21 Code of Federal Regulations 50.24). The ARREST trial is registered with ClinicalTrials.gov, NCT03880565. FINDINGS: Between Aug 8, 2019, and June 14, 2020, 36 patients were assessed for inclusion. After exclusion of six patients, 30 were randomly assigned to standard ACLS treatment (n=15) or to early ECMO-facilitated resuscitation (n=15). One patient in the ECMO-facilitated resuscitation group withdrew from the study before discharge. The mean age was 59 years (range 36-73), and 25 (83%) of 30 patients were men. Survival to hospital discharge was observed in one (7%) of 15 patients (95% credible interval 1·6-30·2) in the standard ACLS treatment group versus six (43%) of 14 patients (21·3-67·7) in the early ECMO-facilitated resuscitation group (risk difference 36·2%, 3·7-59·2; posterior probability of ECMO superiority 0·9861). The study was terminated at the first preplanned interim analysis by the National Heart, Lung, and Blood Institute after unanimous recommendation from the Data Safety Monitoring Board after enrolling 30 patients because the posterior probability of ECMO superiority exceeded the prespecified monitoring boundary. Cumulative 6-month survival was significantly better in the early ECMO group than in the standard ACLS group. No unanticipated serious adverse events were observed. INTERPRETATION: Early ECMO-facilitated resuscitation for patients with OHCA and refractory ventricular fibrillation significantly improved survival to hospital discharge compared with standard ACLS treatment. FUNDING: National Heart, Lung, and Blood Institute.

The Evolving Role of the Cardiac Catheterization Laboratory in the Management of Patients With Out-of-Hospital Cardiac Arrest: A Scientific Statement From the American Heart Association.

Coronary artery disease is prevalent in different causes of out-of-hospital cardiac arrest (OHCA), especially in individuals presenting with shockable rhythms of ventricular fibrillation/pulseless ventricular tachycardia (VF/pVT). The purpose of this report is to review the known prevalence and potential importance of coronary artery disease in patients with OHCA and to describe the emerging paradigm of treatment with advanced perfusion/reperfusion techniques and their potential benefits on the basis of available evidence. Although randomized clinical trials are planned or ongoing, current scientific evidence rests principally on observational case series with their potential confounding selection bias. Among patients resuscitated from VF/pVT OHCA with ST-segment elevation on their postresuscitation ECG, the prevalence of coronary artery disease has been shown to be 70% to 85%. More than 90% of these patients have had successful percutaneous coronary intervention. Conversely, among patients resuscitated from VF/pVT OHCA without ST-segment elevation on their postresuscitation ECG, the prevalence of coronary artery disease has been shown to be 25% to 50%. For these patients, early access to the cardiac catheterization laboratory is associated with a 10% to 15% absolute higher functionally favorable survival rate compared with more conservative approaches of late or no access to the cardiac catheterization laboratory. In patients with VF/pVT OHCA refractory to standard treatment, a new treatment paradigm is also emerging that uses venoarterial extracorporeal membrane oxygenation to facilitate return of normal perfusion and to support further resuscitation efforts, including coronary angiography and percutaneous coronary intervention. The burden of coronary artery disease is high in this patient population, presumably causative in most patients. The strategy of venoarterial extracorporeal membrane oxygenation, coronary angiography, and percutaneous coronary intervention has resulted in functionally favorable survival rates ranging from 9% to 45% in observational studies in this patient population. Patients with VF/pVT should be considered at the highest severity in the continuum of acute coronary syndromes. These patients have a significant burden of coronary artery disease and acute coronary thrombotic events. Evidence from randomized trials will further define optimal clinical practice.

3-Dimensional printing to predict paravalvular regurgitation after transcatheter aortic valve replacement.

BACKGROUND: There is no effective method to predict paravalvular regurgitation prior to transcatheter aortic valve replacement (TAVR). METHODS: We retrospectively analyzed pre-TAVR computed tomography (CT) scans of 20 patients who underwent TAVR for severe, calcific aortic stenosis and subsequently printed 3-dimensional (3D) aortic root models of each patient. Models were printed using Ninjaflex thermoplastic polyurethane (TPU) (Ninjatek Manheim, PA) and TPU 95A (Ultimaker, Netherlands) on Ultimaker 3 Extended 3D printer (Ultimaker, Netherlands). The models were implanted at nominal pressure with same sized Sapien balloon-expandable frames (Edwards Lifesciences, CA) as received in-vivo. Ex-vivo implanted TAVR models (eTAVR) were scanned using Siemens SOMATOM flash dual source CT (Siemens, Malvern, PA) and then analyzed with Mimics software (Materialize NV, Leuven, Belgium) to evaluate relative stent appositions. eTAVR were then compared to post-TAVR echocardiograms for each patient to assess for correlations of identified and predicted paravalvular leak (PVL) locations. RESULTS: A total of 20 patients (70% male) were included in this study. The median age was 77.5 (74-83.5) years. Ten patients were characterized to elicit mild (9/10) or moderate (1/10) PVL, and 10 patients presented no PVL. In patients with echocardiographic PVL, eTAVR 3D model analyses correctly identified the site of PVL in 8/10 cases. In patients without echocardiographic PVL, eTAVR 3D model analyses correctly predicted the lack of PVL in 9/10 cases. CONCLUSION: 3D printing may help predict the potential locations of associated PVL post-TAVR, which may have implications for optimizing valve selection and sizing.

TIME Trial: Effect of Timing of Stem Cell Delivery Following ST-Elevation Myocardial Infarction on the Recovery of Global and Regional Left Ventricular Function: Final 2-Year Analysis.

RATIONALE: The TIME trial (Timing in Myocardial Infarction Evaluation) was the first cell therapy trial sufficiently powered to determine if timing of cell delivery after ST-segment-elevation myocardial infarction affects recovery of left ventricular (LV) function. OBJECTIVE: To report the 2-year clinical and cardiac magnetic resonance imaging results and their modification by microvascular obstruction. METHODS AND RESULTS: TIME was a randomized, double-blind, placebo-controlled trial comparing 150 million bone marrow mononuclear cells versus placebo in 120 patients with anterior ST-segment-elevation myocardial infarctions resulting in LV dysfunction. Primary end points included changes in global (LV ejection fraction) and regional (infarct and border zone) function. Secondary end points included changes in LV volumes, infarct size, and major adverse cardiac events. Here, we analyzed the continued trajectory of these measures out to 2 years and the influence of microvascular obstruction present at baseline on these long-term outcomes. At 2 years (n=85), LV ejection fraction was similar in the bone marrow mononuclear cells (48.7%) and placebo groups (51.6%) with no difference in regional LV function. Infarct size and LV mass decreased ≥30% in each group at 6 months and declined gradually to 2 years. LV volumes increased ≈10% at 6 months and remained stable to 2 years. Microvascular obstruction was present in 48 patients at baseline and was associated with significantly larger infarct size (56.5 versus 36.2 g), greater adverse LV remodeling, and marked reduction in LV ejection fraction recovery (0.2% versus 6.2%). CONCLUSIONS: In one of the longest serial cardiac magnetic resonance imaging analyses of patients with large anterior ST-segment-elevation myocardial infarctions, bone marrow mononuclear cells administration did not improve recovery of LV function over 2 years. Microvascular obstruction was associated with reduced recovery of LV function, greater adverse LV remodeling, and more device implantations. The use of cardiac magnetic resonance imaging leads to greater dropout of patients over time because of device implantation in patients with more severe LV dysfunction resulting in overestimation of clinical stability of the cohort. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00684021.

Extracorporeal cardiopulmonary resuscitation for cardiac arrest.

PURPOSE OF REVIEW: Extracorporeal cardiopulmonary resuscitation (ECPR) is a contemporary resuscitation approach that employs veno-arterial extracorporeal membrane oxygenation (VA-ECMO). This approach is increasingly used worldwide to mitigate the widespread hemodynamic and multiorgan dysfunction that accompanies cardiac arrest. RECENT FINDINGS: In this review, the physiology of VA-ECMO and ECPR, the role of ECPR in contemporary resuscitation care, the complications associated with ECPR and VA-ECMO usage, and intensive care considerations for this population are discussed. SUMMARY: ECPR offers a promising mechanism to mitigate multiorgan injury and allow time for the institution of supportive interventions required to effectively treat cardiac arrest. More prospective data in the context of extensive prehospital and hospital collaboration is needed to promote its successful use.

Evaluation of Cell Therapy on Exercise Performance and Limb Perfusion in Peripheral Artery Disease: The CCTRN PACE Trial (Patients With Intermittent Claudication Injected With ALDH Bright Cells).

BACKGROUND: Atherosclerotic peripheral artery disease affects 8% to 12% of Americans >65 years of age and is associated with a major decline in functional status, increased myocardial infarction and stroke rates, and increased risk of ischemic amputation. Current treatment strategies for claudication have limitations. PACE (Patients With Intermittent Claudication Injected With ALDH Bright Cells) is a National Heart, Lung, and Blood Institute-sponsored, randomized, double-blind, placebo-controlled, phase 2 exploratory clinical trial designed to assess the safety and efficacy of autologous bone marrow-derived aldehyde dehydrogenase bright (ALDHbr) cells in patients with peripheral artery disease and to explore associated claudication physiological mechanisms. METHODS: All participants, randomized 1:1 to receive ALDHbr cells or placebo, underwent bone marrow aspiration and isolation of ALDHbr cells, followed by 10 injections into the thigh and calf of the index leg. The coprimary end points were change from baseline to 6 months in peak walking time (PWT), collateral count, peak hyperemic popliteal flow, and capillary perfusion measured by magnetic resonance imaging, as well as safety. RESULTS: A total of 82 patients with claudication and infrainguinal peripheral artery disease were randomized at 9 sites, of whom 78 had analyzable data (57 male, 21 female patients; mean age, 66±9 years). The mean±SEM differences in the change over 6 months between study groups for PWT (0.9±0.8 minutes; 95% confidence interval [CI] -0.6 to 2.5; P=0.238), collateral count (0.9±0.6 arteries; 95% CI, -0.2 to 2.1; P=0.116), peak hyperemic popliteal flow (0.0±0.4 mL/s; 95% CI, -0.8 to 0.8; P=0.978), and capillary perfusion (-0.2±0.6%; 95% CI, -1.3 to 0.9; P=0.752) were not significant. In addition, there were no significant differences for the secondary end points, including quality-of-life measures. There were no adverse safety outcomes. Correlative relationships between magnetic resonance imaging measures and PWT were not significant. A post hoc exploratory analysis suggested that ALDHbr cell administration might be associated with an increase in the number of collateral arteries (1.5±0.7; 95% CI, 0.1-2.9; P=0.047) in participants with completely occluded femoral arteries. CONCLUSIONS: ALDHbr cell administration did not improve PWT or magnetic resonance outcomes, and the changes in PWT were not associated with the anatomic or physiological magnetic resonance imaging end points. Future peripheral artery disease cell therapy investigational trial design may be informed by new anatomic and perfusion insights. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01774097.

Management of left main coronary artery obstruction after transcatheter aortic valve replacement utilizing a periscope approach.

Coronary obstruction is a rare but potentially fatal complication of transcatheter aortic valve replacement (TAVR). It can result from native leaflet or stent frame obstruction of the coronary ostia. There are reports detailing the difficulty of percutaneous coronary intervention following TAVR, but none that describe a periscope approach to access the left main ostia in the presence of a braided nitinol frame. This report describes an alternative approach to access a coronary artery when the valve stent struts are prohibitive to equipment delivery.

Embolization of a complex coronary to pulmonary artery fistula using balloon assisted liquid embolic injection: A novel technique.

Complex Coronary artery to Pulmonary artery fistulas (CPFs) can be difficult to manage with embolization or ligation. An 88-year-old woman with exertional angina was found to have a complex precordial CPF, severe Mitral regurgitation, and Pulmonary Hypertension. CPF treatment was recommended prior to minimally invasive mitral valve replacement (to avoid postoperative myocardial ischemia from worsened steal). The CPF was supplied by multiple branches from the LAD and RCA, and formed a complex common varicosity with multiple drainage channels to the pulmonary artery. The CPF was treated by injecting a liquid embolic agent, Ethylene Vinyl Alcohol Copolymer (Onyx, Medtronic, MN), into two of the feeding arteries arising from the RCA through a Scepter C Dual lumen balloon micro catheter (Microvention, Aliso Viejo, CA. This resulted in complete obliteration of the fistula, and the patient subsequently underwent successful mitral valve replacement surgery.

Virtual reality to predict paravalvular leak in bicuspid severe aortic valve stenosis in transcatheter aortic valve implants.

OBJECTIVES: Severe aortic stenosis (AS) in bicuspid aortic valves (BAV) is associated with an increased risk of paravalvular leak (PVL) after a transcatheter aortic valve replacement (TAVR). Virtual reality (VR) has been shown to be an effective tool in surgical training, but its utility in clinical practice has not been studied. Here we present the first study to evaluate the use of VR simulation in pre-procedure planning and prediction of PVL in TAVR in patients with severe BAV AS. METHODS: Twenty-two patients with severe BAV AS undergoing TAVR between 2014 and 2018 at the University of Minnesota were included in the study. VR simulation of TAVR implants was performed and implants were analyzed for PVL. The primary endpoint was the percent circumference of valve malapposition in VR as compared to the severity of PVL on post-procedure echocardiography. RESULTS: The median age was 78.26 years (IQR 63.77-86.79) and 40.9% (n = 9) were female. Our VR model accurately predicted the presence and absence of PVL in all patients (17/17 and 5/5, respectively). The mean circumferential PVL was 3.73 % ± 7.71. The receiver operator characteristic curve showed an area under the curve of 0.83 (0.59-1.00, P = .03) for malapposition in the VR-TAVR simulated model. CONCLUSIONS: VR-TAVR implantation may predict PVL in severe BAV AS undergoing TAVR.

Transcatheter closure of a large post-myocardial infarction ventricular septal defect using the GORE cardioform ASD Occluder.

A 49-year-old man presented late with an anterior wall myocardial infarction (MI) status post-primary coronary intervention of the left anterior descending artery that resulted in no reflow of the vessel. The patient was transferred to our institution in cardiogenic shock.

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.

Effect of Combination of Balloon Pulmonary Angioplasty and Medical Therapy on Reverse Right Ventricular Remodeling and Hemodynamics in Chronic Thromboembolic Pulmonary Hypertension.

INTRODUCTION: Chronic thromboembolic pulmonary hypertension (CTEPH) is a progressive and debilitating disorder that results from incomplete resolution of vascular obstructions resulting in pulmonary hypertension. Surgical pulmonary thromboendarterectomy (PTE) is the treatment of choice for CTEPH. Unfortunately, many CTEPH patients are ineligible for PTE or do not have access to an expert surgical center. Medical therapy imparts important symptomatic and exercise benefits for CTEPH patients, but it does not extend survival. Balloon pulmonary angioplasty (BPA) is an emerging transcatheter approach that is both safe and efficacious. However, the potential synergy between upfront BPA and medical therapy treatment approaches in patients with inoperable CTEPH is unknown. Here, we evaluated how the combination of BPA and medical therapy compared to medical therapy alone in a newly established BPA program. METHODS: Twenty-one patients with inoperable or residual CTEPH were evaluated in this single-center observational study. Ten patients underwent upfront BPA and medical therapy while 11 patients were treated with medical therapy alone. Hemodynamic and echocardiographic assessments were performed at baseline and at least 1 month after completion of therapy. Continuous variables were compared using t-test or Mann-Whitney U-test. Categorical variables were analyzed with Chi squared and Fisher's exact test where appropriate. RESULTS: Combination therapy significantly reduced mean pulmonary arterial pressure (mPAP) and pulmonary vascular resistance (PVR), but medical therapy only significantly lowered PVR. Comprehensive echocardiographic analysis revealed a more robust reverse right ventricular (RV) remodeling effect and augmentation of RV function with combination therapy. At the end of study, the combination therapy group had lower mPAP and PVR and better RV function. Importantly, there were no significant adverse effects in patients treated with BPA. CONCLUSION: Combination therapy significantly improves hemodynamics and RV function in inoperable CTEPH while carrying an acceptable risk profile, even in a newly developed program. Further studies comparing upfront combination therapy to medical therapy with larger, long-term, and randomized approaches should be considered.

TAVR Beyond Fetal Viability: An Alternative to Preterm Delivery in Symptomatic Severe Aortic Stenosis.

A patient with structural valve degeneration of an aortic bioprosthesis with stenosis stage 3 underwent valve-in-valve transcatheter aortic valve replacement (TAVR) at 29 weeks with improvement. This is the first reported TAVR in the third trimester. TAVR may be an alternative to preterm delivery in cases of symptomatic aortic stenosis.

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.

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.

Effect of the use and timing of bone marrow mononuclear cell delivery on left ventricular function after acute myocardial infarction: the TIME randomized trial.

CONTEXT: While the delivery of cell therapy after ST-segment elevation myocardial infarction (STEMI) has been evaluated in previous clinical trials, the influence of the timing of cell delivery on the effect on left ventricular function has not been analyzed. OBJECTIVES: To determine the effect of intracoronary autologous bone marrow mononuclear cell (BMC) delivery after STEMI on recovery of global and regional left ventricular function and whether timing of BMC delivery (3 days vs 7 days after reperfusion) influences this effect. DESIGN, SETTING, AND PATIENTS: A randomized, 2 × 2 factorial, double-blind, placebo-controlled trial, Timing In Myocardial infarction Evaluation (TIME) enrolled 120 patients with left ventricular dysfunction (left ventricular ejection fraction [LVEF] ≤ 45%) after successful primary percutaneous coronary intervention (PCI) of anterior STEMI between July 17, 2008, and November 15, 2011, as part of the Cardiovascular Cell Therapy Research Network sponsored by the National Heart, Lung, and Blood Institute. INTERVENTIONS: Intracoronary infusion of 150 × 106 BMCs or placebo (randomized 2:1) within 12 hours of aspiration and cell processing administered at day 3 or day 7 (randomized 1:1) after treatment with PCI. MAIN OUTCOME MEASURES: The primary end points were change in global (LVEF) and regional (wall motion) left ventricular function in infarct and border zones at 6 months measured by cardiac magnetic resonance imaging and change in left ventricular function as affected by timing of treatment on day 3 vs day 7. The secondary end points included major adverse cardiovascular events as well as changes in left ventricular volumes and infarct size. RESULTS: The mean (SD) patient age was 56.9 (10.9) years and 87.5% of participants were male. At 6 months, there was no significant increase in LVEF for the BMC group (45.2% [95% CI, 42.8% to 47.6%] to 48.3% [95% CI, 45.3% to 51.3%) vs the placebo group (44.5% [95% CI, 41.0% to 48.0%] to 47.8% [95% CI, 43.4% to 52.2%]) (P = .96). There was no significant treatment effect on regional left ventricular function observed in either infarct or border zones. There were no significant differences in change in global left ventricular function for patients treated at day 3 (−0.9% [95% CI, −6.6% to 4.9%], P = .76) or day 7 (1.1% [95% CI, −4.7% to 6.9%], P = .70). The timing of treatment had no significant effect on regional left ventricular function recovery. Major adverse events were rare among all treatment groups. CONCLUSION: Among patients with STEMI treated with primary PCI, the administration of intracoronary BMCs at either 3 days or 7 days after the event had no significant effect on recovery of global or regional left ventricular function compared with placebo. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00684021.