Recovery Of Myocardial Function Research Articles

The impact of chronic alcohol overuse on right ventricular myocardial strain

Abstract Background The mechanisms and detail effects of alcohol cardiac toxicity are not clear. Purpose We aimed, to evaluate the relationship between the consumed alcohol dose and severity of right ventricle (RV) myocardial injury in patients overusing alcohol. Methods We collected a group of patients chronically overusing alcohol (ALC- alcohol overusers) and matched to them control group of abstainers (CG-control group). Clinical and echocardiography data have been obtained and statistical analysis performed. RV strain data were obtained from free wall (RVGS). Strain data were presented as absolute values. Results Group with available and feasible data of RV function consisted of 53 ALC patients, 75% men, 50±12 years old, and 33 controls CG, 69% men. Alcohol unit (AU – 10 gram of pure ethanol) consumed per week (AUW) was 21 (12–44) in ALC and 0 (0–0) in CG, P<0.001. The mean time of alcoholism amounted 20 (10–26) years. RVGS was: 20±7% in ALC vs. 24±3% in CG, P=0.001. In ALC, RV middle segment strain (RVmid) was 22±8% vs. 24±3%, P=0.01 and RV apical segment strain (RVapx) was 17±7 vs. 22±3, P=0.0002, see Table. No significant differences were detected for RV diameter, TAPSE and RVS', see Table. Moreover, univariate analysis showed significant positive correlation between free time (FT- time between last alcohol ingestion and echocardiography examination) and RVGS (rho = 0.36, P=0.01) as well as between FT and global longitudinal left ventricle strain (LVGS) (rho = 0.33, P=0.01), whereas TAPSE and RVS' did not show this relationship (rho = 0.30, P=0.41 and rho = 0.21, P=0.14, respectively). See Figure for RVGS. Conclusions Chronic alcohol overuse was associated with significant worsening of RV function expressed by absolute values of RVGS and RV middle and apical segment strains, offering novel quantitative parameter for reflecting early, often subclinical, impairment of RV function. RVGS and LVGS (contrary to TAPSE and RVS') reflected also myocardial function recovery after alcohol intake cessation proportionally to the elapsed abstinence time. Funding Acknowledgement Type of funding sources: None. Table 1Figure 1

Association between myocardial wall thickness and left ventricular functional recovery after catheter ablation of atrial fibrillation in patients with reduced ejection fraction

Abstract Background Catheter ablation of atrial fibrillation (AFCA) is an effective treatment to develop left ventricular (LV) functional recovery. However, the degree of recovery differs between individuals due to the different extent of myocardial fibrosis and scarring. Purpose To examine whether pre-ablation LV wall thickness (WT) and its regional heterogeneity predict LV functional recovery after AFCA in patients with LV systolic dysfunction. Methods Of 3682 consecutive patients who underwent first-time AFCA between January 2012 and September 2020 in our institution, 174 (age, 63±10 years; male, 83%; ischemic cardiomyopathy, 14%) with a baseline LV ejection fraction (LVEF) of <40% were retrospectively evaluated. They were subjected to 256-slice MDCT scanning at baseline and 3 months after AFCA. Baseline WT was evaluated by 16-segment model. Mean and standard deviation (SD) of 16 regional WT were calculated in both end-systolic and end-diastolic phase. Results LVEF significantly improved from 30±7% to 57±17% (p<0.001) after AFCA. Increase in LVEF (delta-LVEF) was positively correlated with baseline end-diastolic WT (r=0.31, p<0.001) and negatively correlated with SD of end-systolic WT (r=−0.21, p=0.007). Independent of WT measurements, delta-LVEF was negatively correlated with LV end-diastolic volume (r=−0.42, p<0.001). We created a scoring system to predict the degree of wall motion recovery using the median value of the 3 variables; assigned 1 point each for end-diastolic WT >7.4mm, SD of end-systolic WT <1.61mm, and LV end-diastolic volume <125ml. The model successfully predicted improvement in LVEF after AFCA (0 point (N=13) vs. 1 point (N=72) vs. 2–3 point (N=89), 11±16% vs. 20±17% vs. 33±12%, p<0.001). Conclusion Myocardial WT and its regional heterogeneity as well as LV end-diastolic volume predicted functional recovery after AFCA in patients with reduced LVEF. Funding Acknowledgement Type of funding sources: None.

Myocardial Contractile Function Recovery, Systemic Inflammation, and Prognosis in Takotsubo Syndrome.

Myocardial Contractile Function Recovery, Systemic Inflammation, and Prognosis in Takotsubo Syndrome.

Peripartum Cardiomyopathy. Medical Support Strategy

Peripartum cardiomyopathy (PPCM) is an idiopathic myocardial insufficiency that occurs in the absence of any diagnosed heart disease during the last month of pregnancy or during the first 5 months after delivery.
 The aim. To improve immediate and long-term maternal outcomes in patients with PPCM by establishing an optimal strategy for its diagnosis, treatment, delivery and medical support during the postpartum period.
 Materials and methods. The article presents the experience of multidisciplinary medical care for 11 pregnant wo-men and postpartum women with dilated cardiomyopathy (DCM) on the basis of the National Amosov Institute of Cardio-vascular Surgery and the Institute of Pediatrics, Obstetrics and Gynecology named after acad. O. M. Lukianova of NAMS of Ukraine. After the differential diagnosis, 8 women were defined as patients with PPCM, and 3 women had family history of the disease (DCM in relatives). All the patients were examined according to the protocol using the history, examination, and instrumental and laboratory findings.
 Results. After in-hospital treatment there was an increase in the left ventricular ejection fraction (LVEF) in the group of patients with PPCM from 28.3 ± 9.3% to 37.6 ± 7.6% and a decrease in end-diastolic volume (EDV) from 196.7 ± 47.7 ml to 181.3 ± 59.7 ml, end-systolic volume (ESV) from 104.25 ± 33.3 ml to 94.2 ± 35.1 ml. In four cases, patients with severe left ventricular (LV) dysfunction underwent urgent preterm Cesarean section in the second trimester of pregnancy. There were no early maternal losses, there were two perinatal losses of extremely premature infants (16 and 27 weeks of gesta-tion). In the follow-up period (23.5 ± 11.6 months), LVEF further increased up to 42.9 ± 8.4% and EDV and ESV decreased up to 170.1 ± 49.5 and 82.7 ± 40.6 ml, respectively. In 7 (87.5%) patients with PPCM, a significant improvement in clini-cal condition and pumping function of the heart was registered at the time of discharge from the hospital, and there was further improvement in the indicators for another 12 months, but complete recovery of cardiac function was achieved only in 3 (37.5%) patients. In patients from the group of family type DCM, complete recovery of LV myocardial function was not observed in any of the 3 studied cases.
 The article discusses the timing of the occurrence and diagnosis of PPCM, the main clinical, instrumental and labora-tory signs of the pathology, methods of cardiological, cardiosurgical and obstetric support of such pregnant women.
 Conclusions. The terms of the onset of PPCM manifestations may be wider (earlier) according to our observations and should be the subject of further research. The strategy of medical care for pregnant women doesn’t particularly depend on the type of DCM. However, obstetric tactics aimed at early delivery of a patient with PPCM with severe myocardial insufficiency are feasible in combination with interruption of lactation and in most cases allow to achieve compensation of circulation and partial recovery of LV function. Prescription of bromocriptine for this purpose seems appropriate. The use of repeated courses of levosimendan in patients with PPCM is feasible and helps to improve the LV function in the early postpartum period.

New Insight Into the Cardioprotective Effects of Allium ursinum L. Extract Against Myocardial Ischemia-Reperfusion Injury.

This study aimed to estimate the effects of increasing doses of Allium ursinum methanol extract on cardiac ischemia/reperfusion injury (I/R) with a special emphasis on the role of oxidative stress. Fifty rats were randomly divided into five groups (10 animals per group) depending on the applied treatment as follows: sham, rats who drank only tap water for 28 days and hearts were retrogradely perfused for 80 min without I/R injury, I/R, rats who drank only tap water for 28 days and hearts were exposed to ex vivo I/R injury and rats who consumed increasing doses of A. ursinum 125, 250, and 500 mg/kg for 28 days before I/R injury. Hearts from all rats were isolated and retrogradely perfused according to the Langendorff technique. Parameters of oxidative stress were spectrophotometrically measured in blood, coronary venous effluent, and heart tissue samples. Intake of wild garlic extract for 28 days significantly contributed to the recovery of cardiac function, which was reflected through preserved cardiac contractility, systolic function, and coronary vasodilatory response after ischemia. Also, wild garlic extract showed the potential to modulate the systemic redox balance and stood out as a powerful antioxidant. The highest dose led to the most efficient decrease in cardiac oxidative stress and improve recovery of myocardial function after I/R injury. We might conclude that wild garlic possesses a significant role in cardioprotection and strong antioxidant activity, which implicates the possibility of its use alone in the prevention or as adjuvant antioxidant therapy in cardiovascular diseases (CVD).

Long-Term High-Fat Diet Inhibits the Recovery of Myocardial Mitochondrial Function After Chronic Hypoxia Reoxygenation in Rats.

Yan, Jun, Kang Song, Sisi Zhou, and Ri-Li Ge. Long-term high-fat diet inhibits the recovery of myocardial mitochondrial function after chronic hypoxia reoxygenation in rats. High Alt Med Biol. 22:327-334, 2021. Aims: A high-fat diet (HFD) is associated with cardiovascular diseases and mitochondrial dysfunction. Obesity incidence is low at high altitudes, but the impact of HFD, which is closely associated with obesity at high altitudes, and the effects of reoxygenation on the heart are unclear. In this study, we investigated the effects of long-term HFD consumption on mitochondrial function in the myocardium after chronic hypoxia reoxygenation. Main Methods: Sprague-Dawley rats were randomized into the following six groups: normoxia groups, including a control group and HFD group; chronic hypoxia groups, including a normal chow diet (CH-CD) group and an HFD (CH-HFD) group; and hypoxic-reoxygenated (HR) groups, including a hypoxia-reoxygenation normal chow diet (HR-CD) group and a hypoxia-reoxygenation HFD (HR-HFD) group. All rats were euthanized in this study. Results: We found that chronic hypoxia aggravated myocardial mitochondrial dysfunction. The Flameng score (in which the higher the score, the more severe the mitochondrial damage) was used to assess the extent of mitochondrial structural damage. Compared with the control group and HFD group, the Flameng scores of the CH-CD and CH-HFD groups were significantly increased, respectively [1.260 ± 0.063 vs. 0.68 ± 0.05 (p < 0.05); 2.03 ± 0.07 vs. 1.48 ± 0.05 (p < 0.05)]. Moreover, progressive reoxygenation facilitated the recovery of myocardial mitochondrial function; this process was inhibited by long-term HFD. After reoxygenation, the Flameng scores in the HR-CD group became comparable to those in the CH-CD group [0.86 ± 0.05 vs. 1.26 ± 0.06 (p < 0.05)]. However, no significant changes were observed in the Flameng score between the HR-HFD and CH-HFD groups. Significance: Long-term HFD consumption inhibits myocardial mitochondrial function after reoxygenation. This finding may be helpful for the prevention and control of risk factors related to cardiovascular diseases in plateau residents.

Extracorporeal membrane oxygenation for multisystem inflammatory syndrome in children.

Early reports suggested that pediatric COVID-19 cases were less severe in children. Most children requiring intensive care admission in these reports had underlying medical conditions. Shortly after the surge of adult COVID-19 cases in Detroit, Michigan, previously healthy children began to present with shock with multiorgan dysfunction, elevated inflammatory markers, and physical exam findings with features of Kawasaki disease. This disease process was later called multisystem inflammatory syndrome in children (MIS-C.) In this case series, we describe three previously healthy children who presented with severe manifestations of MIS-C, including cardiogenic shock and profound systemic inflammation. These children developed severely depressed myocardial function with end-organ injury and were cannulated to veno-arterial extracorporeal membrane oxygenation (VA-ECMO) due to cardiogenic shock with arrhythmia. All three children improved with VA-ECMO support and anti-inflammatory treatment. All had complete recovery of myocardial function at discharge and 6-month follow-up with no significant morbidity.

Increased expression of inactive rhomboid protein 2 in circulating monocytes after acute myocardial infarction

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Deutsche Forschungsgemeinschaft (DFG; Sachbeihilfe HE6092/2) DGK (Deutsche Gesellschaft für Kardiologie) Otto-Hess-Promotionsstipendium Purpose Tumor necrosis factor-alpha (TNF-α) levels in the blood increase in the course of an acute myocardial infarction (AMI) and TNF-α is involved in the impaired recovery of myocardial function following AMI. The interaction of inactive rhomboid protein 2 (iRhom2) with the TNF-α converting enzyme (TACE) is required for the proper shedding of TNF-α from the cell surface of immune cells. We hypothesized, that iRhom2 expression increases in circulating monocytes of patients following AMI. Methods Circulating monocytes were MACS-sorted from peripheral blood of 50 patients with AMI (NSTEMI, n = 16; STEMI n = 34) at the day of admission (day 1) and 3 days after admission. 50 patients with chronic coronary syndrome (CCS) were recruited as control. mRNA was isolated from sorted monocytes and expression levels of iRhom2, TACE and TNF-α were evaluated by real-time RT-PCR. TNF-α protein levels were assessed in the serum. Levels of circulating classical, intermediate and non-classical monocyte subsets were determined by flow cytometry. Results There was a significant increase of iRhom2 mRNA expression levels in monocytes (by 14%, p = 0.012), levels of circulating intermediate monocytes (p &amp;lt; 0.001), and TNF-α serum levels (p &amp;lt; 0.001) at day 3 following AMI compared to day 1 reaching levels similar to those observed in CCS patients. In contrast, TNF-α and TACE mRNA expression in circulating monocytes did not differ between day 1 and 3 following AMI. iRhom2 mRNA expression in monocytes on day 3 following AMI correlated with TACE mRNA expression in monocytes (r = 0.72, p &amp;lt; 0.001), TNF-α serum levels (r = 0.33, p = 0.019), and levels of circulating intermediate monocytes (r = 0.37, p = 0.009). Conclusions Following AMI, iRhom2 expression in circulating monocytes increases in parallel to serum levels of TNF-α and levels of circulating intermediate monocytes. These findings suggest that iRhom2 contributes to inflammation following AMI and thus may serve as a potential therapeutic target.

Myocardial function recovery interventional assessment and surgical pump removal

Myocardial function recovery interventional assessment and surgical pump removal

The Position of the Heart During Normothermic Ex Situ Heart Perfusion is an Important Factor in Preservation and Recovery of Myocardial Function.

Ex situ heart perfusion (ESHP) is being investigated as a method for the continuous preservation of the myocardium in a semiphysiologic state for subsequent transplantation. Most methods of ESHP position the isolated heart in a hanging (H) state, representing a considerable departure from the in vivo anatomical positioning of the heart and may negatively affect the functional preservation of the heart. In the current study, cardiac functional and metabolic parameters were assessed in healthy pig hearts, perfused for 12 hours, in either an H, or supported (S) position, either in nonworking mode (NWM) or working mode (WM). The cardiac function was best preserved in the S position hearts in WM (median 11 hour cardiac index (CI)/1 hour CI%: working mode perfusion in supported position = 94.77% versus nonworking mode perfusion in supported position = 62.80%, working mode perfusion in H position = 36.18%, nonworking mode perfusion in H position = 9.75%; p < 0.001). Delivery of pyruvate bolus significantly improved the function in S groups, however, only partially reversed myocardial dysfunction in the H heart groups. The hearts perfused ex situ in a semianatomical S position and in physiologic WM had better functional preservation and recovery than the H hearts in non-S position. Optimizing the positional support for the ex situ-perfused hearts may improve myocardial preservation during ESHP.

An early echocardiographic prediction for functional myocardial recovery after ST elevation myocardial infarction.

Goals Discrimination of the time course of functional recovery in early period following ST elevation myocardial infarction (STEMI) has prognostic importance. This study aims to establish the ability of the combined systolic-diastolic index (E / (Ea x Sa), for differentiating recoverable myocardium or persistent non-viability in subjects with STEMI.Material and methods 77 patients with first acute STEMI were enrolled to the study. Serial transthoracic echocardiography (TTE) examinations were performed at the time of the admission (immediately after reperfusion), hospital discharge (5±1 days) and control examination (30±2 days). To assess the association between E / (Ea×Sa) index and myocardial recovery, two categories (Transient stunning and persistent non-viability) were defined on basis of improvement of left ventricle ejection fraction (LV EF) (Improvement was defined as an increase more than 10 % in LV EF at day 30 compared to baseline).Results 55 patients (71.4 %) had improvement of LV EF and 24 patients (28.6 %) had no recovery of systolic function (30 days LV EF 48.78±6.1 vs. 39.31±8.1 %, p=0.01). The E / (Ea×Sa) index were significantly higher in the "non-viability" than in stunning group on predischarge and 1 month (1.61±0.64 vs 1.25±0.43, p=0.01 and 1.33±0.25 vs 1.14±0.21, p=0.01, respectively). The change in the E / (Ea×Sa) index in early period (within 5±1 days) was higher in the stunning group (26 %) compared to non-viability group (15 %) (p=0.033). E / (Ea×Sa) index was found to be a significant predictor of myocardial recovery in multivariable logistic regression (OR 0.91, 95 % CI 0.83-0.98, p=0.001). Roc curve showed that the cutoff value of E / (Ea×Sa) index is 1.29 with 73 % of sensitivity and 61 % of specificity (AUC: 0.71, p=0.01, CI: 0.54-0.89).Conclusions Our findings suggest that E / (Ea×Sa) index is a strong predictor of functional recovery; the odds of recovery decreases as E / (Ea×Sa) index value increases.

Experience with a standardized protocol to predict successful explantation of left ventricular assist devices

ObjectivePatients with a continuous-flow left ventricular assist device may show recovery of myocardial function with unloading. Identifying candidates for and predicting clinical and hemodynamic stability after left ventricular assist device explantation remain challenging. MethodsRetrospective analysis of patients who underwent evaluation for left ventricular assist device explantation following a standardized protocol from January 2016 to March 2020. Patients who met screening criteria underwent echocardiography under “baseline,” “minimal net flow,” and “pump stop” conditions. If the protocol criteria were met, right heart catheterization with left ventricular assist device stoppage and occlusion of the outflow graft with a balloon catheter were performed. In patients with pulmonary capillary wedge pressure less than 16 mm Hg, explantation was performed under “pump stop” conditions. ResultsA total of 544 patients were screened. Of these, 57 (10.5%) underwent a total of 73 echocardiography under “baseline” “minimal net flow” and “pump stop” conditions and 46 underwent left ventricular assist device stoppage and occlusion of the outflow graft with balloon catheter maneuvers. Complications during the procedure were rare. Ultimately, 21 patients (3.9%) underwent explantation. The left ventricular ejection fraction at baseline was 55.5% ± 6.5%. The mean pulmonary capillary wedge pressure was 8.1 ± 2.6 mm Hg and increased to 10.7 ± 2.9 mm Hg under left ventricular assist device stoppage and occlusion of the outflow graft with a balloon catheter. A nonischemic cause of cardiomyopathy was more likely to be found in patients who underwent explantation (20/21 patients [95%], P = .020). The survival 1 year after explantation was 95.2%, with 1 death occurring 222 days after left ventricular assist device explantation. At follow-up (median 24.9 months [interquartile range, 16.4-43.1 months]), patients were in New York Heart Association class 1 (61.9%), 2 (28.6%), and 3 (9.5%). ConclusionsOur 4-year experience with a standardized protocol for left ventricular assist device explantation showed a low rate of adverse events. If all criteria are met, explantation can be performed safely and with an excellent survival and functional class.

Use of biventricular assist devices for acute heart failure after orthotopic liver transplantation: a case report

Presenter: Anushi Shah MD | Massachusetts General Hospital Background: Medical co-morbidities in liver transplantation augment surgical risk. We present this case report of a patient with immediate post-operative biventricular failure following liver transplant requiring veno-arterial extracorporeal membrane oxygenation (VA ECMO) and subsequent conversion to minimally invasive biventricular assist devices for cardiac recovery and new graft preservation. Methods: 66-year-old male decompensated alcoholic cirrhotic (MELD-Na 38) on the liver transplant waitlist had a pre-operative ECHO showing no evidence of overt valvular or coronary disease, ejection fraction (EF) 65%. He underwent an liver transplant on veno-venous bypass, our institutional standard procedure. Transesophageal echocardiography (TEE) pre-reperfusion showed normal biventricular function and at the end of the case showed an EF approximately 10-16% with biventricular dysfunction and severe mitral regurgitation requiring epinephrine, norepinephrine, vasopressin and ionotropic support. Due to continued poor perfusion and poor biventricular function in the ICU post-operatively, the patient was placed on VA ECMO for temporary stabilization and subsequent biventricular support using an Impella® 5.5 (Abiomed, Danvers MA) left ventricular assist device (LVAD) via axillary artery graft and a Protek-Duo (CardiacAssist Inc, Pittsburgh PA) percutaneous right ventricular assist device (RVAD) via the right internal jugular vein. Results: Over the course of post-operative days (POD) 3-11, the patient was weaned off pressors, extubated with close monitoring of liver function (Figure 1). Serial transthoracic echocardiography recovery of myocardial function. RVAD and LVAD were removed on POD 8 and POD 13, respectively. The liver graft function was maintained throughout. Serial TTE post mechanical support removal showed his EF had improved to 52%. Conclusion: This is the first report of minimally invasive biventricular support devices used for acute cardiogenic shock status post liver transplantation. We hypothesized that myocardial stress in the setting of the patient’s history of alcohol abuse was the contributing factors of acute global pump failure. A multidisciplinary team approach to prompt mechanical support ensured preservation of liver graft while allowing for cardiac recovery.

Identifying Patients With a Higher Potential for Recovery Post Left Ventricular Assist Device: A Single-Center Experience.

Background: Few patients with a left ventricular assist device (LVAD) achieve functional myocardial recovery to the point of LVAD explantation. The aim of this study was to highlight some of the hemodynamic and echocardiographic parameters we observed in patients who recovered.Methods: We conducted a retrospective analysis of 7 patients who received the HeartMate II LVAD (Abbott) at Temple Heart and Vascular Institute and subsequently underwent successful explantation following myocardial recovery. We compared baseline characteristics, echocardiographic data, and hemodynamic data.Results: Baseline characteristics of the cohort were as follows: age 51.6 ± 12.0 years, 57.1% male, 42.9% with nonischemic cardiomyopathy, and mean duration of LVAD support of 10.6 months. Comparison of echocardiographic and hemodynamic data (preimplant vs preexplant) revealed the following: left ventricular ejection fraction (%) was 12.8 ± 6.9 vs 52.8 ± 8.1 (P=0.0001), right atrial pressure (mmHg) was 12.3 ± 3.4 vs 5.0 ± 4.0 (P=0.022), mean pulmonary artery pressure (mmHg) was 36.0 ± 7.8 vs 15.4 ± 7.1 (P=0.01), cardiac output (L/min) was 3.6 ± 1.3 vs 5.5 ± 1.8 (P=0.004), and cardiac index (L/min/m2) was 1.8 ± 0.5 vs 2.7 ± 0.7 (P=0.008). Mean LVAD-free survival was 49.1 months. Results were consistent in both ischemic and nonischemic LVAD explants.Conclusion: A potential for LVAD explantation exists in patients with both ischemic and nonischemic cardiomyopathy. Myocardial recovery may be more likely among young patients with nonischemic cardiomyopathy and patients with recently diagnosed ischemic cardiomyopathy. Future prospective studies are needed.

Abstract 17186: Molecular Mechanisms Underlying Sex-Related Differences in Mitochondrial Response to Myocardial Ischemia/Reperfusion

Introduction: Cardiac dysfunction adversely impacts patient outcomes following surgically induced myocardial ischemia/reperfusion (I/R). Maintaining mitochondrial activity is crucial to reducing myocardial I/R. Inflammation and oxidative stress triggered by I/R impair mitochondria. Our group has shown sex differences in myocardial functional recovery after I/R. Here, we determined whether sex disparity in mitochondrial response to inflammatory mediator - TNFα and to reactive oxygen species - H 2 O 2 is responsible for sex differences in cardiac dysfunction. Given the key role of mitochondrial connexin43 (Cx43) in cardiac protection initiated by ischemic preconditioning, we also investigated the implication of Cx43 in sex-related mitochondrial response. Methods: Cardiomyocytes (male &amp; female; C57BL/6 &amp; doxycycline inducible Tnnt2-controlled Cx43 knockout) were subjected to simulated I/R (20’ I/60’ R), TNFα (10ng/ml), or H 2 O 2 (50 μM), +/- 17β-estradiol (E2).Mitochondrial membrane potential (ΔΨm) analyzed by JC1 red to JC1 green fluorescence intensity ratio (Fig. A) and mitochondrial respiration capacity by Seahorse XF Cell Mito Stress Test were determined.Cx43 was assessed in mitochondria by Western blots and Immunoelectron microscopy. Results: Improved ΔΨm (Fig. B) and preserved mitochondrial respiratory capacity were observed in female cardiomyocytes than in male ones following simulated I/R, TNFα, or H 2 O 2 .E2 restored mitochondrial activity in cardiomyocytes (Fig. C, D). In addition, E2 increased Cx43 content and phosphorylation in cardiac mitochondria. Ablation of cardiac Cx43 abolished E2-mediated mitochondrial protection during TNFα or H 2 O 2 challenge (Fig. E). Conclusions: Female cardiomyocytes were more resistant to I/R, TNFα, or H 2 O 2 stimulation than age-matched males, with greater protective role of mitochondrial Cx43 in female hearts. E2 usage regulated mitochondrial Cx43 and preserved cardiac mitochondrial performance.

Reduced effects of cardiac extracorporeal shock wave therapy on angiogenesis and myocardial function recovery in patients with end-stage coronary artery and renal diseases

BackgroundGrowing evidence have shown cardiac extracorporeal shock wave therapy (ESWT) improve clinical symptoms and left ventricular ejection fraction (LVEF) for patients with end-stage diffuse coronary artery disease (EnD-CAD) unsuitable for coronary interventions. However, little is known whether cardiac ESWT remains effective on symptomatic relief and improvement of LVEF for the EnD-CAD patients with end-stage renal disease (ESRD). MethodsThis was a small-scale prospective study. Between August 2016 and January 2019, a total of 16 subjects received cardiac ESWT for their EnD-CAD. They were divided into two groups according to ESRD or not, i.e., EnD-CAD group (n = 8) and EnD-CAD/ESRD group (n = 8). Clinical symptoms including angina and dyspnea, levels of circulating endothelial progenitor cells (EPC), LVEF, and adverse events were regularly followed up for one year to compare safety and efficacy of cardiac ESWT between the EnD-CAD patients with or without ESRD. ResultsAll participants tolerated cardiac ESWT without any relevant side effects such as skin allergic reaction, local redness/tenderness or cardiac arrhythmia. There were similar baseline comorbidities and clinical features between two groups, but the EnD-CAD/ESRD group had significantly higher serum potassium level as well as lower renal function and lipid profile (all p-values <0.03). After cardiac ESWT, the patients in both groups had significant improvement in angina and dyspnea at 1 year (all p-values <0.03). However, the EnD-CAD/ESRD group did not have increase in either circulating EPC levels or LVEF at 6 months (mean change in LVEF: −4.00% ± 8.32%, p = 1.000). In contrast, the EnD-CAD group had gradually improving levels of circulating EPC surface markers and increased LV systolic function (mean change in LVEF: +4.87% ± 8.76%, p = 0.092). Notably, patients in the EnD-CAD/ESRD group suffered from high incidental clinical adverse events before and after enrollment into the ESWT study (75% vs. 25%, p = 0.132). ConclusionAlthough cardiac ESWT provided improvement of clinical symptoms in the EnD-CAD patients, its long-term effects on the angiogenesis and LVEF were reduced for those high-risk patients with concomitant EnD-CAD and ESRD. Trial registrationnone.

Left ventricular wall stress is associated with myocardial functional recovery in patients with severe aortic stenosis and systolic dysfunction undergoing transcatheter aortic valve replacement

Left ventricular wall stress is associated with myocardial functional recovery in patients with severe aortic stenosis and systolic dysfunction undergoing transcatheter aortic valve replacement

Exosomes from SIRT1-Overexpressing ADSCs Restore Cardiac Function by Improving Angiogenic Function of EPCs

Acute myocardial infarction (AMI) is one of the leading causes of mortality in cardiovascular diseases. The aim of this study was to investigate whether exosomes from Sirtuin 1 (SIRT1)-overexpressing adipose-derived stem cells (ADSCs) had a protective effect on AMI. The expression of C-X-C chemokine receptor type 7 (CXCR7) was significantly downregulated in peripheral blood endothelial progenitor cells (EPCs) from AMI patients (AMI-EPCs) compared with that in healthy donors, which coincided with impaired tube formation. The exosomes from SIRT1 overexpression in ADSCs (ADSCs-SIRT1-Exos) increased the expression of C-X-C motif chemokine 12 (CXCL12) and nuclear factor E2 related factor 2 (Nrf2) in AMI-EPCs, which promoted migration and tube formation of AMI-EPCs, and overexpression of CXCR7 helped AMI-EPCs to restore the function of cell migration and tube formation. Moreover, CXCR7 was downregulated in the myocardium of AMI mice, and knockout of CXCR7 exacerbated AMI-induced impairment of cardiovascular function. Injection of ADSCs-SIRT1-Exos increased the survival and promoted the recovery of myocardial function with reduced infarct size and post-AMI left ventricular remodeling, induced vasculogenesis, and decreased AMI-induced myocardial inflammation. These findings showed that ADSCs-SIRT1-Exos may recruit EPCs to the repair area and that this recruitment may be mediated by Nrf2/CXCL12/CXCR7 signaling.

Concise Review: Harnessing iPSC-derived Cells for Ischemic Heart Disease Treatment.

Ischemic heart disease (IHD) is one of the most common cardiovascular diseases and is the leading cause of death worldwide. Stem cell therapy is a promising strategy to promote cardiac regeneration and myocardial function recovery. Recently, the generation of human induced pluripotent cells (hiPSCs) and their differentiation into cardiomyocytes and vascular cells offer an unprecedented opportunity for the IHD treatment. This review briefly summarizes hiPSCs and their differentiation, and presents the recent advances in hiPSC injection, engineered cardiac patch fabrication, and the application of hiPSC derived extracellular vesicle. Current challenges and further perspectives are also discussed to understand current risks and concerns, identify potential solutions, and direct future clinical trials and applications.

Update on Weaning from Veno-Arterial Extracorporeal Membrane Oxygenation.

Venoarterial extracorporeal membrane oxygenation (VA-ECMO) provides temporary cardiac and respiratory support and has emerged as an established salvage intervention for patients with hemodynamic compromise or shock. It is thereby used as a bridge to recovery, bridge to permanent ventricular assist devices, bridge to transplantation, or bridge to decision. However, weaning from VA-ECMO differs between centers, and information about standardized weaning protocols are rare. Given the high mortality of patients undergoing VA-ECMO treatment, it is all the more important to answer the many questions still remaining unresolved in this field Standardized algorithms are recommended to optimize the weaning process and determine whether the VA-ECMO can be safely removed. Successful weaning as a multifactorial process requires sufficient recovery of myocardial and end-organ function. The patient should be considered hemodynamically stable, although left ventricular function often remains impaired during and after weaning. Echocardiographic and invasive hemodynamic monitoring seem to be indispensable when evaluating biventricular recovery and in determining whether the VA-ECMO can be weaned successfully or not, whereas cardiac biomarkers may not be useful in stratifying those who will recover. This review summarizes the strategies of weaning of VA-ECMO and discusses predictors of successful and poor weaning outcome.