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Bone marrow mononuclear cells (BMMCs) have been evaluated for their ability to improve cardiac repair and benefit patients with severe ischemic heart disease and heart failure. In our single-center trial in 2006-2011 we demonstrated the safety and efficacy of BMMCs injected intramyocardially in conjunction with coronary artery bypass surgery. The effect persisted in the follow-up study 5 years later. In this study, we investigated the efficacy of BMMC therapy beyond 10 years. A total of 18 patients (46%) died during over 10-years follow-up and 21 were contacted for participation. Late gadolinium enhancement cardiac magnetic resonance imaging (CMRI) and clinical evaluation were performed on 14 patients, seven from each group. CMRIs from the study baseline, 1-year and 5-years follow-ups were re-analyzed to enable comparison. The CMRI demonstrated a 2.1-fold larger reduction in the mass of late gadolinium enhancement values between the preoperative and the over 10-years follow-up, suggesting less scar or fibrosis after BMMC treatment (- 15.1%; 95% CI - 23 to - 6.7% vs. - 7.3%; 95% CI - 16 to 4.5%, p = 0.039), compared to placebo. No differences in mortality or morbidity were observed. Intramyocardially injected BMMCs may exert long-term benefits in patients with ischemic heart failure. This deserves further evaluation in patients who have received BMMCs in international clinical studies over two decades., (© 2024. The Author(s).)

Background: Penetrating cardiac injuries are rare but often fatal, with 16-55% mortality. We report a patient who suffered a non-fatal occupational cardiac injury., Case Presentation: A 47-year-old man was operating an ironworker machine. A thin 3-cm metal fragment catapulted from the machine piercing the chest wall and the right ventricular outflow tract (RVOT), burrowing into the interventricular septum (IVS). The patient remained hemodynamically stable and walked to the nearest hospital. ECG-gated computed tomography revealed the exact location of the fragment within the IVS, allowing for detailed preoperative planning. The fragment was removed through a sternotomy and an incision through the RVOT. The postoperative course was uneventful., Conclusions: This case underscores the value of detailed preoperative imaging and the wide spectrum of clinical scenarios of penetrating cardiac injuries., (© 2024. The Author(s).)

Cardiogenic growth factors play important roles in heart development. Placental growth factor (PLGF) has previously been reported to have angiogenic effects; however, its potential role in cardiogenesis has not yet been determined. We analyze single-cell RNA-sequencing data derived from human and primate embryonic hearts and find PLGF shows a biphasic expression pattern, as it is expressed specifically on ISL1 + second heart field progenitors at an earlier stage and on vascular smooth muscle cells (SMCs) and endothelial cells (ECs) at later stages. Using chemically modified mRNAs (modRNAs), we generate a panel of cardiogenic growth factors and test their effects on enhancing cardiomyocyte (CM) and EC induction during different stages of human embryonic stem cell (hESC) differentiations. We discover that only the application of PLGF modRNA at early time points of hESC-CM differentiation can increase both CM and EC production. Conversely, genetic deletion of PLGF reduces generation of CMs, SMCs and ECs in vitro. We also confirm in vivo beneficial effects of PLGF modRNA for development of human heart progenitor-derived cardiac muscle grafts on murine kidney capsules. Further, we identify the previously unrecognized PLGF-related transcriptional networks driven by EOMES and SOX17. These results shed light on the dual cardiomyogenic and vasculogenic effects of PLGF during heart development., (© 2023. Springer Nature Limited.)

Purpose: We evaluated the residual vascular and adipose tissue inflammation in patients with chronic coronary artery disease (CAD) using positron emission tomography (PET)., Methods: Our study population consisted of 98 patients with known CAD and 94 control subjects who had undergone 18 F-fluorodeoxyglucose ( 18 F-FDG) PET due to non-cardiac reasons. Aortic root and vena cava superior 18 F-FDG uptake were measured to obtain the aortic root target-to-background ratio (TBR). In addition, adipose tissue PET measurements were done in pericoronary, epicardial, subcutaneous, and thoracic adipose tissue. Adipose tissue TBR was calculated using the left atrium as a reference region. Data are presented as mean ± standard deviation or as median (interquartile range)., Results: The aortic root TBR was higher in CAD patients compared to control subjects, 1.68 (1.55-1.81) vs. 1.53 (1.43-1.64), p  < 0.001. Subcutaneous adipose tissue uptake was elevated in CAD patients 0.30 (0.24-0.35) vs. 0.27 (0.23-0.31), p  < 0.001. Metabolic activity of CAD patients and control subjects was comparable in the pericoronary (0.81 ± 0.18 vs. 0.80 ± 0.16, p  = 0.59), epicardial (0.53 ± 0.21 vs. 0.51 ± 0.18, p  = 0.38) and thoracic (0.31 ± 0.12 vs. 0.28 ± 0.12, p  = 0.21) adipose tissue regions. Aortic root or adipose tissue 18 F-FDG uptake was not associated with the common CAD risk factors, coronary calcium score, or aortic calcium score ( p value > 0.05)., Conclusion: Patients with a chronic CAD had a higher aortic root and subcutaneous adipose tissue 18 F-FDG uptake compared to control patients, which suggests residual inflammatory risk., Competing Interests: Competing InterestsValtteri Uusitalo had advisory board activity and lecture fees from Pfizer. Sini Toivonen, Miia Lehtinen, Peter Raivio, Juha Sinisalo and Antti Loimaala declare no conflict of interest., (© The Author(s) 2022.)

Background: Saphenous vein grafts (SVG) are the most commonly used conduits in coronary artery bypass grafting (CABG). Graft failure is observed in up to 50% of SVG at 10 years after surgery. Whether a difference in SVG patency rates exists between men and women remains unclear., Methods: We performed a study-level meta-analysis to evaluate sex-related differences in follow-up patency rates of SVG after CABG. A systematic literature search was conducted to identify studies on CABG that reported follow-up SVG patency rates in men and women. The primary outcome was SVG patency rates by sex at follow-up., Results: Seventeen studies totaling 8235 patients and 14,781 SVG grafts were included. There was no significant difference in follow-up SVG patency rates between men and women (incidence rate ratio 0.96, 95% confidence interval 0.90-1.03, p = .24), with mean angiographic follow-up of 33.5 months (standard deviation 29.2). Leave-one-out and cumulative analysis were consistent with the main analysis. We concluded that follow-up SVG patency rate is similar between men and women undergoing CABG., (© 2022 Wiley Periodicals LLC.)

Heart regeneration is an unmet clinical need, hampered by limited renewal of adult cardiomyocytes and fibrotic scarring. Pluripotent stem cell-based strategies are emerging, but unravelling cellular dynamics of host-graft crosstalk remains elusive. Here, by combining lineage tracing and single-cell transcriptomics in injured non-human primate heart biomimics, we uncover the coordinated action modes of human progenitor-mediated muscle repair. Chemoattraction via CXCL12/CXCR4 directs cellular migration to injury sites. Activated fibroblast repulsion targets fibrosis by SLIT2/ROBO1 guidance in organizing cytoskeletal dynamics. Ultimately, differentiation and electromechanical integration lead to functional restoration of damaged heart muscle. In vivo transplantation into acutely and chronically injured porcine hearts illustrated CXCR4-dependent homing, de novo formation of heart muscle, scar-volume reduction and prevention of heart failure progression. Concurrent endothelial differentiation contributed to graft neovascularization. Our study demonstrates that inherent developmental programmes within cardiac progenitors are sequentially activated in disease, enabling the cells to sense and counteract acute and chronic injury., (© 2022. The Author(s).)

Objectives: Frail patients with malnourishment due to an esophageal condition and dysphagia are often unamenable to safe surgery. Thus, in high-risk patients, less invasive techniques such as percutaneous endoscopic gastrostomy (PEG) are regarded as a safer choice. Nevertheless, as described here, PEG insertion can have rare serious complications. Materials and methods: We report the case of a frail patient with dysphagia due to a large Zenker's diverticulum and concomitant giant hiatal hernia. To improve her nutrinitional status before surgery she received a PEG after endoscopic repositioning of the hernia. Results: Within 48 hours after hernia repositioning and PEG insertion, a severe adverse event ensued: dislodgement of the PEG due to stomach reherniation. Conclusions: This case challenges the use of PEG as an only means for gastric fixation for hiatal hernia.

Background: The COVID-19 pandemic has disrupted all aspects of healthcare, including cardiothoracic surgery (CTS). We sought to determine the pandemic's impact on CTS trainees' educational experiences., Methods: A survey was developed and distributed to members of the Thoracic Surgery Residents Association and other international CTS trainees. Trainees were asked to evaluate their cumulative experiences and share their overall perceptions of how CTS training had been impacted during the earliest months of the COVID-19 pandemic (i.e., since March 01, 2020). Surveys were distributed and responses were recorded June 25-August 05, 2020. In total, 748 surveys were distributed and 166 responses were received (overall response rate 22.2%). Of these, 126 of 166 responses (75.9%) met inclusion criteria for final analysis., Results: Final responses analyzed included 45 of 126 (35.7%) United States (US) and 81 of 126 (64.3%) international trainees, including 101 of 126 (80.2%) senior and 25 of 126 (19.8%) junior trainees. Most respondents (76/126, 43.2%) lost over 1 week in the hospital due to the pandemic. Juniors (12/25, 48.0%) were more likely than seniors (20/101, 19.8%) to be reassigned to COVID-19-specific units (p < .01). Half of trainees (63/126) reported their case volumes were reduced by over 50%. US trainees (42/45, 93.3%) were more likely than international trainees (58/81, 71.6%) to report reduced operative case volumes (p < .01). Most trainees (104/126, 83%) believed their overall clinical acumen was not adversely impacted by the pandemic., Conclusions: CTS trainees in the United States and abroad have been significantly impacted by the COVID-19 pandemic, with time lost in the hospital, decreased operative experiences, less time on CTS services, and frequent reassignment to COVID-19-specific care settings., (© 2021 Wiley Periodicals LLC.)

Objectives: The increasing complexity of surgical patients and working time constraints represent challenges for training. In this study, the European Association for Cardio-Thoracic Surgery Residents' Committee aimed to evaluate satisfaction with current training programmes across Europe., Methods: We conducted an online survey between October 2018 and April 2019, completed by a total of 219 participants from 24 countries., Results: The average respondent was in the fourth or fifth year of training, mostly on a cardiac surgery pathway. Most trainees follow a 5-6-year programme, with a compulsory final certification exam, but no regular skills evaluation. Only a minority are expected to take the examination by the European Board of Cardiothoracic Surgery. Participants work on average 61.0 ± 13.1 h per week, including 27.1 ± 20.2 on-call. In total, only 19.7% confirmed the implementation of the European Working Time Directive, with 42.0% being unaware that European regulations existed. Having designated time for research was reported by 13.0%, despite 47.0% having a postgraduate degree. On average, respondents rated their satisfaction 7.9 out of 10, although 56.2% of participants were not satisfied with their training opportunities. We found an association between trainee satisfaction and regular skills evaluation, first operator experience and protected research time., Conclusions: On average, residents are satisfied with their training, despite significant disparities in the quality and structure of cardiothoracic surgery training across Europe. Areas for potential improvement include increasing structured feedback, research time integration and better working hours compliance. The development of European guidelines on training standards may support this., (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Background: Operative mortality after complete atrioventricular septal defect (cAVSD) repair has improved vastly. Less improvement has been demonstrated regarding late mortality and reoperation rates, however. There is evident lack of comprehensive population-based studies analyzing the history and progress of the ever-changing operative results., Methods: This is a 5-million population-based retrospective study of consecutive 388 cAVSD patients operated in Finland between 1962 and 2014. Data were collected using Children's Cardiac Surgical Registry of Children's Hospital at the Helsinki University Hospital, Finland. Mortality data and reoperation rates were analyzed on a decade-by-decade basis., Results: During the early era, overall mortality was 17.4%, operative mortality constituting 10.9%. The operative results have improved significantly over the decades, and eventually, the last decade showed no mortality. A total of 23 late deaths occurred; of these, 20 were directly heart-related. Half of the late mortality occurred during the first postoperative year. The only significant risk factor for overall mortality was an earlier decade of operation (p < 0.001). Reoperation rates have not decreased but slightly increased over decades (p = 0.621), and reoperations have been performed mainly during the first year after the primary operation. Actuarial freedom from left side atrioventricular valve reoperation at 15 years was 90.9%., Conclusions: There has been an outstanding improvement in surgical results through the years even though the general operative approach has remained the same. Rates of reoperation have not been declining, but the reoperations are dated to early childhood years. The improvement in results has been ongoing., (Copyright © 2019 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

The generation of human pluripotent stem cell (hPSC)-derived ventricular progenitors and their assembly into a 3-dimensional in vivo functional ventricular heart patch has remained an elusive goal. Herein, we report the generation of an enriched pool of hPSC-derived ventricular progenitors (HVPs), which can expand, differentiate, self-assemble, and mature into a functional ventricular patch in vivo without the aid of any gel or matrix. We documented a specific temporal window, in which the HVPs will engraft in vivo. On day 6 of differentiation, HVPs were enriched by depleting cells positive for pluripotency marker TRA-1-60 with magnetic-activated cell sorting (MACS), and 3 million sorted cells were sub-capsularly transplanted onto kidneys of NSG mice where, after 2 months, they formed a 7 mm × 3 mm × 4 mm myocardial patch resembling the ventricular wall. The graft acquired several features of maturation: expression of ventricular marker (MLC2v), desmosomes, appearance of T-tubule-like structures, and electrophysiological action potential signature consistent with maturation, all this in a non-cardiac environment. We further demonstrated that HVPs transplanted into un-injured hearts of NSG mice remain viable for up to 8 months. Moreover, transplantation of 2 million HVPs largely preserved myocardial contractile function following myocardial infarction. Taken together, our study reaffirms the promising idea of using progenitor cells for regenerative therapy., (Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: The atrial appendages are a tissue reservoir for cardiac stem cells. During on-pump coronary artery bypass graft (CABG) surgery, part of the right atrial appendage can be excised upon insertion of the right atrial cannula of the heart-lung machine. In the operating room, the removed tissue can be easily cut into micrografts for transplantation. This trial aims to assess the safety and feasibility of epicardial transplantation of atrial appendage micrografts in patients undergoing CABG surgery., Methods/design: Autologous cardiac micrografts are made from leftover right atrial appendage during CABG of 6 patients. Atrial appendage is mechanically processed to micrografts consisting of atrial appendage-derived cells (AADCs) and their extracellular matrix (ECM). The micrografts are epicardially transplanted in a fibrin gel and covered with a tissue-engineered ECM sheet. Parameters including echocardiography-reflecting cardiac insufficiency-are studied pre- and post-operatively as well as at 3 and 6 months of the follow-up. Cardiac functional magnetic resonance imaging is performed preoperatively and at 6-month follow-up. The primary outcome measures are patient safety in terms of hemodynamic and cardiac function over time and feasibility of therapy administration in a clinical setting. Secondary outcome measures are left ventricular wall thickness, change in the amount of myocardial scar tissue, changes in left ventricular ejection fraction, plasma concentrations of N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels, New York Heart Association class, days in hospital, and changes in the quality of life. Twenty patients undergoing routine CAGB surgery will be recruited to serve as a control group., Discussion: This study aims to address the surgical feasibility and patient safety of epicardially delivered atrial appendage micrografts during CABG surgery. Delivery of autologous micrografts and AADCs has potential applications for cell and cell-based gene therapies., Trial Registration: ClinicalTrials.gov Identifier: NCT02672163. Date of registration: 02.02.2016., Competing Interests: The AADC consortium has been focusing on the cell therapy as a treatment for heart failure for many years. Its knowledge is based on multidisciplinary cooperation between authorities and several previous studies in this field.The trial protocol has been evaluated and approved by the Surgical Ethics Committee of the Hospital District of Helsinki and Uusimaa (number 180/13/03/02/13). Informed and written consent to participate in the study will be obtained by the main researcher from all participants.Informed and written consent for publication will be obtained from all participants.The authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Aims: Single-photon emission computed tomography (SPECT) and positron emission tomography (PET) are suggested to improve clinical decision-making in ischaemic cardiomyopathy. Here, we present a unique cohort of patients who underwent nuclear medicine studies and cardiac magnetic resonance imaging (MRI) both before and 1 year after coronary artery bypass (CABG) surgery to assess benefit from surgery., Methods and Results: Before CABG, we applied three quantitative techniques using (18)F-fluorodeoxyglucose-PET and (99m)technetium-tetrofosmin-SPECT with a software tool to measure defects with hypoperfused but viable and non-viable myocardium in 15 patients. One method used solely PET, two others combined PET and SPECT at different thresholds. As a reference, we used change in left-ventricular (LV) function and volume by MRI. Preoperatively, ischaemic but viable areas detected by the method with a 10% threshold combining PET-SPECT and the PET-only method correlated significantly with preoperative regional wall thickening (WT; P = 0.03 and P = 0.005, respectively). When compared with global functional outcome (change in LV ejection fraction) and LV remodelling (change in end-diastolic volume) 1 year postoperatively, no correlation appeared with preoperative PET- or PET-SPECT-derived viable or non-viable tissue. Neither was any correlation observable between local change in WT and local preoperative defect size evaluated by any of these three methods., Conclusion: Preoperatively, PET and PET-SPECT with 10% threshold detected dysfunctional myocardium, but all analysis methods failed to predict 1-year functional outcome assessed by MRI. In patients with three-vessel disease and heart failure, SPECT perfusion and PET viability study results show substantial heterogeneity; this should be considered when selecting patients for revascularization., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.)

Background: Long-term results regarding treatment of chronic ischemic heart failure with bone marrow mononuclear cells (BMMCs) have been few. We received encouraging results at the 1-year follow-up of patients treated with combined coronary artery bypass grafting (CABG) and BMMCs, so we decided to extend the follow-up., Methods: The study patients had received injections of BMMCs or vehicle into the myocardial infarction border area during CABG in a randomized and double-blind manner. We could contact 36 of the 39 patients recruited for the original study. Pre-operatively and after an extended follow-up period, we performed magnetic resonance imaging, measured pro-B-type amino-terminal natriuretic peptide, reviewed patient records from the follow-up period, and determined current quality of life with the Medical Outcomes Study Short-Form 36 (SF-36) Health Survey., Results: The median follow-up time was 60.7 months (interquartile range [IQR], 45.1-72.6 months). No statistically significant difference was detected in change of pro-B-type amino-terminal natriuretic peptide values or in quality of life between groups. The median change in left ventricular ejection fraction was 4.9% (IQR, -2.1% to 12.3%) for controls and 3.9% (IQR, -5.2% to 10.2%) for the BMMC group (p = 0.647). Wall thickening in injected segments increased by a median of 17% (IQR, -5% to 30%) for controls and 15% (IQR, -12% to 19%) for BMMC patients (p = 0.434). Scar size in injected segments increased by a median of 2% (IQR, -7% to 19%) for controls but diminished for BMMC patients, with a median change of -17% (IQR, -30% to -6%; p = 0.011)., Conclusions: In the treatment of chronic ischemic heart failure, combining intramyocardial BMMC therapy with CABG fails to affect cardiac function but can sustainably reduce scar size, even in the long-term., (Copyright © 2015 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Objectives: We present here a sub-study of our prospective, randomized, double-blinded trial of bone marrow mononuclear cell (BMMC) transplantation with coronary artery bypass surgery (CABG) (ClinicalTrials.gov Identifier: NCT00418418), evaluating our secondary end-point concerning hospital stay as well as perioperative morbidity. Injecting a substantial amount of biologically active cells into a diseased myocardium inspires concerns for safety, a concern overlooked in previous trials., Methods: We evaluated the immediate perioperative effects of intramyocardial injection of autologous BMMCs combined with CABG. In a randomized double-blinded manner, 39 patients received injections either of BMMCs (n = 20) or of vehicle medium (n = 19). The patients' haemodynamics, arterial blood gases, systemic vein oxygen level, blood glucose, acid-base balance, lactate, haemoglobin, body temperature and diuresis, as well as medications needed, were recorded in the operating theatre and in the intensive care unit (ICU) every 4 h throughout the first postoperative 24 h., Results: No dissimilarities in these parameters were detectable. In the ICU, the median need for adrenaline was 0.0086 µg/kg/min (first quartile 0.0000, third quartile 0.0204) for controls and 0.0090 µg/kg/min (0.0000, 0.0353) for BMMC patients (P = 0.757); for noradrenaline, 0.0586 µg/kg/min (0.0180, 0.0888) for controls and 0.0279 µg/kg/min (0.0145, 0.0780) for BMMC patients (P = 0.405). The median stay at the ICU was 2 days for both groups (1, 2 for controls; 1, 3 for BMMCs; P = 0.967). Within the first postoperative day, one control patient had an elevated level of creatine kinase-myocardial band fraction mass (CK-MBm) up to >100 µg/l; no BMMC patient showed elevated CK-MBm levels (P = 0.474)., Conclusions: Both intramyocardial BMMC and placebo injections appear safe during surgery and immediate ICU stay after treatment of heart failure., (© The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Background: Bone marrow mononuclear cell (BMMC) transplantation for heart failure has shown inconsistent therapeutic efficacy., Methods: We enrolled 104 ischemic heart failure patients scheduled for coronary artery bypass surgery (CABG). After 4- to 12-week pharmacotherapy optimization, 39 patients with left ventricular ejection fraction (LVEF) of ≤45% received injections of BMMC or vehicle intra-operatively into the myocardial infarction border area in a randomized, double-blind manner., Results: The median number of cells injected was 8.4 × 10(8) (interquartile range [IQR]: 5.2 × 10(8) to 13.5 × 10(8)). We measured LV function and myocardial scar size by magnetic resonance imaging (MRI), and viability by positron emission tomography (PET) and single-photon emission computed tomography (SPECT), pre-operatively and after 1-year follow-up. LVEF, the pre-defined primary end-point measure, improved by a median of 5.6% in the control group (IQR 0.2 to 10.1) and by 4.8% in the BMMC group (IQR -0.5 to 8.2) (p = 0.59). Wall thickening in injected segments rose by a median of 4.5% among controls (IQR -18.1 to 23.9) and by 5.5% in the BMMC group (IQR -6.6 to 26.5) (p = 0.68). Changes in viability by PET and SPECT did not differ between groups. Myocardial scar size by MRI in injected segments rose by a median of 5.1% among controls (IQR -3.3 to 10.8), but fell by 13.1% in the BMMC group (IQR -21.4 to -6.5) (p = 0.0002)., Conclusions: BMMC therapy combined with CABG failed to improve LV systolic function, or viability, despite reducing myocardial scar size., (Copyright © 2014 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)