Microcurrent-Mediated Modulation of Myofibroblasts for Cardiac Repair and Regeneration.

Cardiovascular diseases are a significant cause of illness and death worldwide, often resulting in myofibroblast differentiation, pathological remodeling, and fibrosis, characterized by excessive extracellular matrix protein deposition. Treatment options for cardiac fibrosis that can effectively target myofibroblast activation and ECM deposition are limited, necessitating an unmet need for new therapeutic approaches. In recent years, microcurrent therapy has demonstrated promising therapeutic effects, showcasing its translational potential in cardiac care. This study therefore sought to investigate the effects of microcurrent therapy on cardiac myofibroblasts, aiming to unravel its potential as a treatment for cardiac fibrosis and heart failure. The experimental design involved the differentiation of primary rat cardiac fibroblasts into myofibroblasts. Subsequently, these cells were subjected to microcurrent (MC) treatment at 1 and 2 µA/cm2 DC with and without polarity reversal. We then investigated the impact of microcurrent treatment on myofibroblast cell behavior, including protein and gene expression, by performing various assays and analyses comparing them to untreated myofibroblasts and cardiac fibroblasts. The application of microcurrents resulted in distinct transcriptional signatures and improved cellular processes. Gene expression analysis showed alterations in myofibroblast markers, extracellular matrix components, and pro-inflammatory cytokines. These observations show signs of microcurrent-mediated reversal of myofibroblast phenotype, possibly reducing cardiac fibrosis, and providing insights for cardiac tissue repair.

Depression, anxiety, and quality of life as predictors of rehospitalization in patients with chronic heart failure.

BACKGROUND: Chronic heart failure (CHF) is a severe condition, often co-occurring with depression and anxiety, that strongly affects the quality of life (QoL) in some patients. Conversely, depressive and anxiety symptoms are associated with a 2-3 fold increase in mortality risk and were shown to act independently of typical risk factors in CHF progression. The aim of this study was to examine the impact of depression, anxiety, and QoL on the occurrence of rehospitalization within one year after discharge in CHF patients. METHODS: 148 CHF patients were enrolled in a 10-center, prospective, observational study. All patients completed two questionnaires, the Hospital Anxiety and Depression Scale (HADS) and the Questionnaire Short Form Health Survey 36 (SF-36) at discharge timepoint. RESULTS: It was found that demographic and clinical characteristics are not associated with rehospitalization. Still, the levels of depression correlated with gender (p ≤ 0.027) and marital status (p ≤ 0.001), while the anxiety values ​​were dependent on the occurrence of chronic obstructive pulmonary disease (COPD). However, levels of depression (HADS-Depression) and anxiety (HADS-Anxiety) did not correlate with the risk of rehospitalization. Univariate logistic regression analysis results showed that rehospitalized patients had significantly lower levels of Bodily pain (BP, p = 0.014), Vitality (VT, p = 0.005), Social Functioning (SF, p = 0.007), and General Health (GH, p = 0.002). In the multivariate model, poor GH (OR 0.966, p = 0.005) remained a significant risk factor for rehospitalization, and poor General Health is singled out as the most reliable prognostic parameter for rehospitalization (AUC = 0.665, P = 0.002). CONCLUSION: Taken together, our results suggest that QoL assessment complements clinical prognostic markers to identify CHF patients at high risk for adverse events. CLINICAL TRIAL REGISTRATION: The study is registered under http://clinicaltrials.gov (NCT01501981, first posted on 30/12/2011), sponsored by Charité - Universitätsmedizin Berlin.

Sex Difference in Patients With Ischemic Heart Failure Undergoing Surgical Revascularization: Results From the STICH Trial (Surgical Treatment for Ischemic Heart Failure).

BACKGROUND: Female sex is conventionally considered a risk factor for coronary artery bypass grafting (CABG) and has been included as a poor prognostic factor in multiple cardiac operative risk evaluation scores. We aimed to investigate the association of sex and the long-term benefit of CABG in patients with ischemic left ventricular dysfunction enrolled in the prospective STICH trial (Surgical Treatment for Ischemic Heart Failure Study). METHODS: The STICH trial randomized 1212 patients (148 [12%] women and 1064 [88%] men) with coronary artery disease and left ventricular ejection fraction ≤35% to CABG+medical therapy (MED) versus MED alone. Long-term (10-year) outcomes with each treatment were compared according to sex. RESULTS: At baseline, women were older (63.4 versus 59.3 years; P=0.016) with higher body mass index (27.9 versus 26.7 kg/m2; P=0.001). Women had more coronary artery disease risk factors (diabetes mellitus, 55.4% versus 37.2%; hypertension, 70.9% versus 58.6%; hyperlipidemia, 70.3% versus 58.9%) except for smoking (13.5% versus 21.8%) and had lower rates of prior CABG (0% versus 3.4%; all P<0.05) than men. Moreover, women had higher New York Heart Association class (class III/IV, 66.2% versus 57.0%), lower 6-minute walk capacity (300 versus 350 m), and lower Kansas City Cardiomyopathy Questionnaire overall summary scores (51 versus 63; all P<0.05). Over 10 years of follow-up, all-cause mortality (49.0% versus 65.8%; adjusted hazard ratio, 0.67; 95% confidence interval, 0.52-0.86; P=0.002) and cardiovascular mortality (34.3% versus 52.3%; adjusted hazard ratio, 0.65; 95% confidence interval, 0.48-0.89; P=0.006) were significantly lower in women compared with men. With randomization to CABG+MED versus MED treatment, there was no significant interaction between sex and treatment group in all-cause mortality, cardiovascular mortality, or the composite of all-cause mortality or cardiovascular hospitalization (all P>0.05). In addition, surgical deaths were not statistically different (1.5% versus 5.1%; P=0.187) between sexes among patients randomized to CABG per protocol as initial treatment. CONCLUSIONS: Sex is not associated with the effect of CABG+MED versus MED on all-cause mortality, cardiovascular mortality, the composite of death or cardiovascular hospitalization, or surgical deaths in patients with ischemic left ventricular dysfunction. Thus, sex should not influence treatment decisions about CABG in these patients. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00023595.

Consecutive Observational Study to Validate EuroSCORE II Performances on a Single-Center, Contemporary Cardiac Surgical Cohort.

OBJECTIVE: To compare and validate the original EuroSCORE risk stratification models with the renewed EuroSCORE II model in a contemporary cardiac surgical practice. DESIGN: A consecutive observational study to validate EuroSCORE II performances, conducted as retrospective analysis of prospectively collected data. SETTING: A tertiary university institute for cardiovascular diseases. PARTICIPANTS: Adult patients undergoing cardiac surgery between January and December 2012. METHODS: One thousand eight hundred sixty-four consecutive patients were scored preoperatively using additive and logistic EuroSCORE as well as EuroSCORE II. The discriminative power of the EuroSCORE models was tested by calculating the area under the receiver operating characteristic curve (AUC). The calibration of the models was assessed by Hosmer-Lemeshow statistics and with observed-to-expected mortality ratio. MEASUREMENTS AND MAIN RESULTS: The in-hospital overall mortality was 3.65%, with predicted mortalities according to additive EuroSCORE, logistic EuroSCORE, and EuroSCORE II of 5.14%, 6.60%, and 3.51%, respectively. The observed-to-expected (O/E) mortality ratio confirmed good calibration for the entire cohort only for EuroSCORE II (1.05, 95% confidence interval 0.81 - 1.29). Hosmer-Lemeshow test confirmed overall good calibration only for additive EuroSCORE (p = 0.129). The EuroSCORE II confirmed very good discriminatory power for a prolonged intensive care unit (ICU) stay of>2 days and>5 days (AUCs>0.75). Acceptable discriminatory power was confirmed for a prolonged postoperative stay of>7 days and>12 days (AUCs>0.70). CONCLUSION: EuroSCORE II confirmed very good discriminatory capacity, good calibration ability (O/E mortality ratio), and good capability to predict prolonged ICU and postoperative stays in a contemporary patient cohort undergoing cardiac surgery.

Successful surgical aortic valve replacement in a patient with progeria.

The progeroid syndrome includes a group of rare, severe genetic disorders clinically characterized by premature physical ageing. Severe aortic stenosis has been described in progeria patients, but no previous surgical aortic valve replacement was reported. We describe a successful surgical aortic valve replacement combined with coronary artery bypass grafting in a progeria patient with severe aortic stenosis and a small aortic annulus.

On-line risk prediction models for acute type A aortic dissection surgery: validation of the German Registry of Acute Aortic Dissection Type A score and the European System for Cardiac Operative Risk Evaluation II.

OBJECTIVES: The German Registry of Acute Aortic Dissection Type A (GERAADA) on-line score calculator to predict 30-day mortality in patients undergoing surgery for acute type A aortic dissection (ATAAD) was recently launched. Using the European System for Cardiac Operative Risk Evaluation II (EuroSCORE II), it is also possible to predict operative mortality for the same type of surgery. The goal of our study was to validate the prediction accuracy of these 2 on-line risk prediction models. METHODS: Prospectively collected data for EuroSCORE II risk factors as well as all data for GERAADA scoring were extracted from an institutional database for 147 patients who underwent surgery for ATAAD between April 2018 and April 2021. The discriminative power was assessed using area under the receiver operating characteristic curve. The calibration of the models was tested by the Hosmer-Lemeshow statistics and by using the observed-to-expected (O/E) mortality ratio with the 95% confidence interval. RESULTS: The observed operative mortality was 14.3%. The mean predicted mortality rates for the GERAADA score and the EuroSCORE II were 15.6% and 10.6%, respectively. The EuroSCORE II discriminative power (area under the curve = 0.799) significantly outperformed the discriminatory power of the GERAADA score (area under the curve = 0.550). The Hosmer-Lemeshow statistics confirmed good calibration for both models (P-values of 0.49 and 0.29 for the GERAADA score and the EuroSCORE II, respectively). The O/E mortality ratio certified good calibration for both scores [GERAADA score (O/E ratio of 0.93, 95% confidence interval: 0.53-1.33); EuroSCORE II (O/E ratio of 1.35, 95% confidence interval: 0.77-1.93)]. CONCLUSIONS: The EuroSCORE II has better discriminative power for predicting operative mortality in ATAAD surgery than the GERAADA score. Both scores confirmed good calibration ability.

Cardio-microcurrent device for chronic heart failure: first-in-human clinical study.

AIMS: Most devices for treating ambulatory Class II and III heart failure are linked to electrical pulses. However, a steady electric potential gradient is also necessary for appropriate myocardial performance and may be disturbed by structural heart diseases. We investigated whether chronic application of electrical microcurrent to the heart is feasible and safe and improves cardiac performance. The results of this study should provide guidance for the design of a two-arm, randomized, controlled Phase II trial. METHODS AND RESULTS: This single-arm, non-randomized pilot study involved 10 patients (9 men; mean age, 62 ± 12 years) at two sites with 6 month follow-up. All patients had New York Heart Association (NYHA) Class III heart failure and non-ischaemic dilated cardiomyopathy, with left ventricular ejection fraction (LVEF) <35%. A device was surgically placed to deliver a constant microcurrent to the heart. The following tests were performed at baseline, at hospital discharge, and at six time points during follow-up: determination of LVEF and left ventricular end-diastolic/end-systolic diameter by echocardiography; the 6 min walk test; and assessment of NYHA classification and quality of life (36-Item Short-Form Health Survey questionnaire). Microcurrent application was feasible and safe; no device-related or treatment-related adverse events occurred. During follow-up, rapid and significant signal of efficacy (P < 0.005) was present with improvements in LVEF, left ventricular end-diastolic diameter, left ventricular end-systolic diameter, and distance walked. For eight patients, NYHA classification improved from Class III to Class I (for seven, as early as 14 days post-operatively); for one, to Class II; and for one, to Class II/III. 36-Item Short-Form Health Survey questionnaire scores also improved highly significantly. CONCLUSIONS: Chronic application of microcurrent to the heart is feasible and safe and leads to a rapid and lasting improvement in heart function and a near normalization of heart size within days. The NYHA classification and quality of life improve just as rapidly.

Six-minute walk distance after coronary artery bypass grafting compared with medical therapy in ischaemic cardiomyopathy.

Background: In patients with ischaemic left ventricular dysfunction, coronary artery bypass surgery (CABG) may decrease mortality, but it is not known whether CABG improves functional capacity. Objective: To determine whether CABG compared with medical therapy alone (MED) increases 6 min walk distance in patients with ischaemic left ventricular dysfunction and coronary artery disease amenable to revascularisation. Methods: The Surgical Treatment in Ischemic Heart disease trial randomised 1212 patients with ischaemic left ventricular dysfunction to CABG or MED. A 6 min walk distance test was performed both at baseline and at least one follow-up assessment at 4, 12, 24 and/or 36 months in 409 patients randomised to CABG and 466 to MED. Change in 6 min walk distance between baseline and follow-up were compared by treatment allocation. Results: 6 min walk distance at baseline for CABG was mean 340±117 m and for MED 339±118 m. Change in walk distance from baseline was similar for CABG and MED groups at 4 months (mean +38 vs +28 m), 12 months (+47 vs +36 m), 24 months (+31 vs +34 m) and 36 months (-7 vs +7 m), P>0.10 for all. Change in walk distance between CABG and MED groups over all assessments was also similar after adjusting for covariates and imputation for missing values (+8 m, 95% CI -7 to 23 m, P=0.29). Results were consistent for subgroups defined by angina, New York Heart Association class ≥3, left ventricular ejection fraction, baseline walk distance and geographic region. Conclusion: In patients with ischaemic left ventricular dysfunction CABG compared with MED alone is known to reduce mortality but is unlikely to result in a clinically significant improvement in functional capacity. Trial registration number: NCT00023595.

Radial artery vs saphenous vein graft used as the second conduit for surgical myocardial revascularization: long-term clinical follow-up.

BACKGROUND: There is ongoing debate regarding the efficacy of the radial artery (RA) as an aortocoronary conduit, with few solid data regarding long-term clinical results. We sought to determine if the use of the RA as the second arterial conduit, beside left internal thoracic artery (LITA), would improve long-term clinical outcome after CABG as compared to saphenous vein graft (SVG). METHODS: Between March 2001 and November 2003, 200 patients underwent isolated CABG and were randomized in 1:1 fashion to receive either LITA and RA grafts or LITA and SVGs. The primary end point was composite of cardiovascular mortality, non-fatal myocardial infarction and need for repeat myocardial revascularization (either surgical or percutaneous). RESULTS: There was no significant difference in absolute survival, with 12 deaths in each group during the study period (log rank = 0.01, p = 0.979). There were 3 and 2 cardiac deaths in RA and SVG groups, respectively. There was no difference in long-term clinical outcome between the groups (log rank = 0.450, p = 0.509). Eleven patients in RA group had one or more non-fatal events; 7 patients suffered a myocardial infarction, 9 patients underwent percutaneous coronary angioplasty, and 1 patient required redo coronary surgery. Likewise, 13 patients in SVG group had non-fatal event; 7 patients had myocardial infarction, 13 patients had percutaneous coronary intervention and 3 patients required redo coronary surgery. Angiograms were performed in 23 patients in RA group (patency rate 92 %) and 24 in SVG group (patency rate 86 %) (p = 0.67). CONCLUSION: In this small randomised study our data indicate that there is no difference in the 8 year clinical outcomes in relatively young patients between those having a RA or a saphenous vein graft used as a second conduit, beside LITA, for surgical myocardial revascularisation.

Severity of Remodeling, Myocardial Viability, and Survival in Ischemic LV Dysfunction After Surgical Revascularization.

OBJECTIVES: This study sought to test the hypothesis that end-systolic volume (ESV), as a marker of severity of left ventricular (LV) remodeling, influences the relationship between myocardial viability and survival in patients with coronary artery disease and LV systolic dysfunction. BACKGROUND: Retrospective studies of ischemic LV dysfunction suggest that the severity of LV remodeling determines whether myocardial viability predicts improved survival with surgical compared with medical therapy, with coronary artery bypass grafting (CABG) only benefitting patients with viable myocardium who have smaller ESV. However, this has not been tested prospectively. METHODS: Interactions of end-systolic volume index (ESVI), myocardial viability, and treatment with respect to survival were assessed in patients in the prospective randomized STICH (Comparison of Surgical and Medical Treatment for Congestive Heart Failure and Coronary Artery Disease) trial of CABG versus medical therapy who underwent viability assessment (n = 601; age 61 ± 9 years; ejection fraction ≤35%), with a median follow-up of 5.1 years. Median ESVI was 84 ml/m(2). Viability was assessed by single-photon emission computed tomography or dobutamine echocardiography using pre-specified criteria. RESULTS: Mortality was highest among patients with larger ESVI and nonviability (p < 0.001), but no interaction was observed between ESVI, viability status, and treatment assignment (p = 0.491). Specifically, the effect of CABG versus medical therapy in patients with viable myocardium and ESVI ≤84 ml/m(2) (hazard ratio [HR]: 0.85; 95% confidence interval [CI]: 0.56 to 1.29) was no different than in patients with viability and ESVI >84 ml/m(2) (HR: 0.87; 95% CI: 0.57 to 1.31). Other ESVI thresholds yielded similar results, including ESVI ≤60 ml/m(2) (HR: 0.87; 95% CI: 0.44 to 1.74). ESVI and viability assessed as continuous rather than dichotomous variables yielded similar results (p = 0.562). CONCLUSIONS: Among patients with ischemic cardiomyopathy, those with greater LV ESVI and no substantial viability had worse prognosis. However, the effect of CABG relative to medical therapy was not differentially influenced by the combination of these 2 factors. Lower ESVI did not identify patients in whom myocardial viability predicted better outcome with CABG relative to medical therapy. (Comparison of Surgical and Medical Treatment for Congestive Heart Failure and Coronary Artery Disease [STICH]; NCT00023595).

Cor triatriatum dexter and atrial septal defect in a 43-year-old woman.

Cor triatriatum dexter is a rare congenital heart anomaly in which a membrane divides the right atrium into 2 chambers. We report the case of a 43-year-old woman who had cor triatriatum dexter and a large atrial septal defect. During attempted percutaneous closure, the balloon disrupted the membrane and revealed that the defect had no inferior rim, precluding secure placement of an Amplatzer Septal Occluder. Surgical treatment subsequently proved to be successful. In patients with an incomplete membrane and a septal defect with well-defined rims, percutaneous treatment can be the first choice. In patients who have cor triatriatum dexter and unfavorable anatomic features or concomitant complex heart anomalies, open-heart surgery remains the gold standard for treatment.

Exercise capacity and mortality in patients with ischemic left ventricular dysfunction randomized to coronary artery bypass graft surgery or medical therapy: an analysis from the STICH trial (Surgical Treatment for Ischemic Heart Failure).

OBJECTIVES: The objective of this study was to assess the prognostic significance of exercise capacity in patients with ischemic left ventricular (LV) dysfunction eligible for coronary artery bypass graft surgery (CABG). BACKGROUND: Poor exercise capacity is associated with mortality, but it is not known how this influences the benefits and risks of CABG compared with medical therapy. METHODS: In an exploratory analysis, physical activity was assessed by questionnaire and 6-min walk test in 1,212 patients before randomization to CABG (n = 610) or medical management (n = 602) in the STICH (Surgical Treatment for Ischemic Heart Failure) trial. Mortality (n = 462) was compared by treatment allocation during 56 months (interquartile range: 48 to 68 months) of follow-up for subjects able (n = 682) and unable (n = 530) to walk 300 m in 6 min and with less (Physical Ability Score [PAS] >55, n = 749) and more (PAS ≤55, n = 433) limitation by dyspnea or fatigue. RESULTS: Compared with medical therapy, mortality was lower for patients randomized to CABG who walked ≥300 m (hazard ratio [HR]: 0.77; 95% confidence interval [CI]: 0.59 to 0.99; p = 0.038) and those with a PAS >55 (HR: 0.79; 95% CI: 0.62 to 1.01; p = 0.061). Patients unable to walk 300 m or with a PAS ≤55 had higher mortality during the first 60 days with CABG (HR: 3.24; 95% CI: 1.64 to 6.83; p = 0.002) and no significant benefit from CABG during total follow-up (HR: 0.95; 95% CI: 0.75 to 1.19; p = 0.626; interaction p = 0.167). CONCLUSIONS: These observations suggest that patients with ischemic left ventricular dysfunction and poor exercise capacity have increased early risk and similar 5-year mortality with CABG compared with medical therapy, whereas those with better exercise capacity have improved survival with CABG. (Comparison of Surgical and Medical Treatment for Congestive Heart Failure and Coronary Artery Disease [STICH]; NCT00023595).

Sex Difference in Patients with Ischemic Heart Failure Undergoing Surgical Revascularization: Results from the STICH Trial

BACKGROUND: Female sex is conventionally considered a risk factor for coronary artery bypass grafting (CABG) and has been included as a poor prognostic factor in multiple cardiac operative risk evaluation scores. We aimed to investigate the association of sex and the long-term benefit of CABG in patients with ischemic left ventricular (LV) dysfunction enrolled in the prospective Surgical Treatment for Ischemic Heart Failure Study (STICH) trial. METHODS: The STICH trial randomized 1212 patients [148 (12%) women and 1064 (88%) men] with CAD and LV ejection fraction (EF)≤ 35% to CABG + medical therapy (MED) versus MED alone. Long-term (10-year) outcomes with each treatment were compared according to sex. RESULTS: At baseline, women were older (63.4 vs 59.3, p=0.016) with higher BMI (27.9 vs 26.7, p=0.001). Women had more CAD risk factors (diabetes 55.4% vs 37.2%, hypertension 70.9% vs 58.6%, hyperlipidemia 70.3% vs 58.9%) except for smoking (13.5% vs 21.8%), and had lower rates of prior CABG (0% vs 3.4%, all p<0.05) than men. Moreover, women had higher New York Heart Association (NYHA) class (Class III/IV 66.2% vs 57.0%), lower 6-min walk capacity (300m vs 350m) and lower Kansas City Cardiomyopathy Questionnaire (KCCQ) overall summary scores (51 vs 63) (all p<0.05) than men. Moreover, women had higher New York Heart Association (NYHA) class (Class III/IV 66.2% vs 57.0%), lower 6-min walk capacity (300m vs 350m) and lower Kansas City Cardiomyopathy Questionnaire (KCCQ) overall summary scores (51 vs 63) (all p<0.05). Over 10-years of follow up, all- cause mortality (49.0% vs 65.8%, adjusted HR 0.67, CI 0.52­0.86, p=0.002) and CV mortality (34.3% vs 52.3%, adjusted HR 0.65, CI 0.48­0.89, p=0.006) were significantly lower in women compared to men. With randomization to CABG + MED vs. MED treatment, there was no significant interaction between sex and treatment group in all-cause mortality, CV mortality, or the composite of all-cause mortality or CV hospitalization (all p>0.05). In addition, surgical deaths were not statistically different (1.5% vs 5.1%, p=0.187) between sexes among patients randomized to CABG per protocol as initial treatment. CONCLUSIONS: Sex is not associated with the effect of CABG + MED vs. MED on all-cause mortality, CV mortality, the composite of death or CV hospitalization, or surgical deaths in patients with ischemic LV dysfunction. Thus, sex should not influence treatment decisions regarding CABG in these patients.