Author Correction: Cardiovascular, hematological and neurosensory impact of COVID-19 and variants.

Correction to: European Review for Medical and Pharmacological Sciences 2021; 25 (8): 3350-3364-DOI: 10.26355/eurrev_202104_25747-PMID: 33928623, published online 30 April, 2021. After publication, the authors requested to correct the Acknowledgements of the above-mentioned article. There are amendments to this paper. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/25747.

Cardiovascular, hematological and neurosensory impact of COVID-19 and variants.

OBJECTIVE: The purpose of this article was to review our clinical experience with COVID-19 patients observed in the Cardiovascular Division of Pompidou Hospital (University of Paris, France) and the Department of Neurology of the Eastern Piedmont University (Novara, Italy), related to the impact on the cardiovascular, hematological, and neurologic systems and sense organs. PATIENTS AND METHODS: We sought to characterize cardiovascular, hematological, and neurosensory manifestations in patients with COVID-19 and variants. Special attention was given to initial signs and symptoms to facilitate early diagnosis and therapy. Indications of ECMO (extracorporeal membrane oxygenation) for cardiorespiratory support were evaluated. RESULTS: Preliminary neurosensorial symptoms, such as anosmia and dysgeusia, are useful for diagnosis, patient isolation, and treatment. Early angiohematological acro-ischemic syndrome includes hand and foot cyanosis, Raynaud digital ischemia phenomenon, skin bullae, and dry gangrene. This was associated with neoangiogenesis, vasculitis, and vessel thrombosis related to immune dysregulation, resulting from "cytokine storm syndrome". The most dangerous complication is disseminated intravascular coagulation, with mortality risks for both children and adults. CONCLUSIONS: COVID-19 is a prothrombotic disease with unique global lethality. A strong inflammatory response to viral infection severely affects cardiovascular and neurological systems, as well as respiratory, immune, and hematological systems. Rapid identification of acro-ischemic syndrome permits the treatment of disseminated intravascular coagulation complications. Early sensorial symptoms, such as gustatory and olfactory loss, are useful for COVID-19 diagnosis. New variants of SARS-CoV-2 are emerging, principally from United Kingdom, South Africa, and Brazil. These variants seem to spread more easily and quickly, which may lead to more cases of COVID.

Use of arginine-glycine-aspartic acid adhesion peptides coupled with a new collagen scaffold to engineer a myocardium-like tissue graft.

BACKGROUND: Cardiac tissue engineering might be useful in treatment of diseased myocardium or cardiac malformations. The creation of functional, biocompatible contractile tissues, however, remains challenging. We hypothesized that coupling of arginine-glycine-aspartic acid-serine (RGD+) adhesion peptides would improve cardiomyocyte viability and differentiation and contractile performance of collagen-cell scaffolds. METHODS: Clinically approved collagen scaffolds were functionalized with RGD+ cells and seeded with cardiomyocytes. Contractile performance, cardiomyocyte viability and differentiation were analyzed at days 1 and 8 and/or after culture for 1 month. RESULTS: The method used for the RGD+ cell-collagen scaffold coupling enabled the following features: high coupling yields and complete washout of excess reagent and by-products with no need for chromatography; spectroscopic quantification of RGD+ coupling; a spacer arm of 36 A, a length reported as optimal for RGD+-peptide presentation and favorable for integrin-receptor clustering and subsequent activation. Isotonic and isometric mechanical parameters, either spontaneous or electrostimulated, exhibited good performance in RGD+ constructs. Cell number and viability was increased in RGD+ scaffolds, and we saw good organization of cell contractile apparatus with occurrence of cross-striation. CONCLUSIONS: We report a novel method of engineering a highly effective collagen-cell scaffold based on RGD+ peptides cross-linked to a clinically approved collagen matrix. The main advantages were cell contractile performance, cardiomyocyte viability and differentiation.

Angiogenesis without functional outcome after mononuclear stem cell transplant in a doxorubicin-induced dilated myocardiopathy murine model.

OBJECTIVES: Cell transplantation is considered a novel approach in the treatment of myocardiopathy. The objective of this study was to evaluate the effects of autologous mononuclear stem cell therapy in doxorubicin-induced dilated myocardiopathy by conducting both functional and histopathologic analysis. METHODS: Seventy male rats were doxorubicin injected intraperitoneally for 2 weeks. At 1 month, the animals that had demonstrated left ventricular ejection fractions less than 40% were randomly divided into a mononuclear stem cell group and controls. Mononuclear stem cells were isolated. All animals underwent echocardiographic study: baseline, pre-cell therapy, and at 1 month post-cell therapy, and analyzed by the nonparametric Mann-Whitney test. Transplants were performed by subepicardial injections. Standard staining was performed. RESULTS: Twenty-three animals were randomly treated: mononuclear stem cell and control groups, with 11 rats completing the study. Cell viability was 85%. Mononuclear stem cells (n=5; 5x106 cells /300 microL medium) and control (n=6; 300 microL medium) were used. The resulting left ventricular ejection fraction in the cell therapy group was not significantly different compared with controls (p=0.54). New vessels were demonstrated in the subepicardial region. CONCLUSIONS: Autologous mononuclear stem cell therapy was not functionally effective in doxorubicin-induced dilated myocardiopathy in the animal model under study with the experimental conditions, despite occurrence of angiogenic activity.

Mesothelial cell transplantation in myocardial infarction.

Mesothelial cells (MCs) are accessible in human patients by excision and digestion of epiploon or from peritoneal fluid or lavage. MCs are easy to culture to obtain large quantities in vitro and they can be genetically modified with interesting therapeutic genes. The important potential of MCs in tissue engineering has been shown during epiplooplasty to different organs and also in creating artificial blood conduits. MC of epicardium is probably the precursor of coronary arteries during embryogenesis. MCs secrete a broad spectrum of angiogenic cytokines, growth factors and extracellular matrix, which could be useful for repairing damaged tissues. MCs are transitional mesodermal-derived cells and considered as progenitor stem cell, have similar morphological and functional properties with endothelial cells and conserve properties of transdifferentiation. MC therapy in myocardial infarction induced neoangiogenesis in infarcted scar and preserved heart function. In conclusion, a potential therapeutic strategy would be to implant or re-implant genetically modified MCs in post-infarction injury to enhance tissue repair and healing. Imparting therapeutic target genes such as angiogenic genes would also be useful for inducing neovascularization.

Left ventricular reconstruction after resection of a large fibroma.

Cardiac fibromas are rare tumors that are histologically benign but potentially lethal because of their location. The prognosis is related to complete resection. We report the case of a 15-year-old boy who, 1 year after partial excision of a large fibroma, underwent successful complete resection through a conventional surgical approach with left ventricular reconstruction.

Cellular therapy reverses myocardial dysfunction.

OBJECTIVES: Cellular cardiomyoplasty refers to the implantation of autologous skeletal muscle cells into the myocardium to reinforce its structure and function. In this study a reproducible method for the creation of a myocardial lesion was developed. The functional benefit of cell implantation was evaluated by 2-dimensional echocardiography for global contraction and color kinesis echocardiography, which allows the precise assessment of the regional contraction. METHODS: A left ventricular intramyocardial injection with snake cardiotoxin was carried out on a sheep model to induce a well-delineated transmural lesion. Three weeks later, the lesion was assessed by echocardiography. Thereafter, autologous skeletal muscle cells or culture media (control) were injected into the lesion. Two months after cell implantation, the myocardial contraction was again evaluated by echocardiography and the implanted cells were analyzed by a fast myosin heavy chain antibody. RESULTS: 1. The snake cardiotoxin produced a well-delineated transmural lesion in all animals. 2. Echocardiographic studies showed a significant improvement in global and regional left ventricular function in cell-treated sheep. 3. Histologic analyses demonstrated satellite cell survival at the periphery of the lesions. CONCLUSION: Satellite cells implanted in a cardiotoxin-induced myocardial lesion survived for a 2-month period and were associated with a significant functional improvement of both local and global contraction.

LD-PACE II: a new cardiomyostimulator for cardiac bioassist.

The LD-PACE II was designed for use in cardiomyoplasty, aortomyoplasty, and skeletal muscle ventricles. All parameters specified as programmable can be changed in a noninvasive manner (using a programming interface wand connected to a computer using the Windows 95/98 environment). Two new functions may be very useful clinically, based on experimental research. 1. Work-rest regimen. The LD-PACE II is able to deliver alternating periods of muscle contractions and rest. Work and rest periods may be programmed independently between 1 and 120 minutes in increments of 1 minute. The work-rest regimen may be useful clinically if muscle contractions are needed for cardiac assist postoperatively. 2. Night/day regimen. This feature allows for a change in the ratio of muscle contractions according to a patient's activity level. During the day the cardiosynchronization ratio may be set from 1:1 to 1:4, and during the night it may be set for 1:8 to 1:16. This allows the muscle to have a long rest period, prevents overuse, and prolongs battery life. These two new features make this cardiomyostimulator very attractive for cardiomyoplasty in particular. The addition of the work-rest and night-day regimens allow the muscle to rest for periods during the day to prevent overuse, subsequent damage, and potential atrophy.

[Utilization of aortomyoplasty as a biological pumping system]. / Utilisation de l'aortomyoplastie comme système biologique de contrepulsion.

Aortomyoplasty is a surgical technique of constructing a neo-ventricle on the ascending or descending aorta with the latissimus dorsi muscle. This is electrically stimulated to contract during diastole, thereby creating a system of chronic, haemo-compatible aortic pumping. Long-term experimental studies have shown increases in cardiac output (from 3.6 to 5.5 l/min), decreases in peripheral resistances (from 1574 to 1134 dyne.sec.cm-5) and increases in indices of subendocardial viability (DPTI/TTI: 1.1 to 1.4). These experimental studies have been confirmed by the initial clinical results. To date, world experience includes thirty-six patients. With cardiomyoplasty, aortomyoplasty is a new arm in the therapeutic arsenal against severe cardiac failure by providing a new system of chronic circulatory assistance which is implantable and biocompatible.

Is 10 minutes the optimum immersion time in 0.6% glutaraldehyde for human pericardium?

BACKGROUND AND AIM OF THE STUDY: Pericardial fixation with 0.6% glutaraldehyde is usually assessed by measuring the shrinkage temperature of the tissue: the higher the shrinkage temperature, the greater the degree of cross-linking induced between collagen molecules. Animal pericardium studies have shown maximum response to be obtained after brief immersion (10 min). Our aim was to evaluate the effect of glutaraldehyde immersion time on shrinkage temperature of human pericardium which, to our knowledge, has not yet been studied. METHODS: Pericardial strips were harvested from 40 patients undergoing cardiac surgery. Time of immersion in glutaraldehyde ranged from 3 min to 6 months. Fresh untreated human pericardium samples were used as controls. The relationship between shrinkage temperature and time of treatment with glutaraldehyde was studied using a regression analysis. RESULTS: Glutaraldehyde treatment of pericardial tissues caused an increase in shrinkage temperature that was related biphasically to the time of immersion in glutaraldehyde. Mathematical expression of this curve permitted glutaraldehyde immersion time to be evaluated in relation to the degree of optimal shrinkage temperature. The time required for optimal fixation with glutaraldehyde, as measured by shrinkage temperature, was 100+/-0.77 min. CONCLUSION: Our results suggested that a 10-min exposure to glutaraldehyde was insufficient for 'correct' fixation of human pericardium. Inadequate glutaraldehyde exposure of human pericardium may explain mid and long-term failures reported with this tissue in cardiac surgery.

[Metaplasia of aortic tissue into tracheal tissue. Surgical perspectives]. / Métaplasie de tissu aortique en tissu trachéal. Perspectives chirurgicales.

Tracheal reconstruction after extensive resection remains an unsolved surgical problem. Numerous attempts have been made using tracheal grafts or prosthetic conduits with disappointing results. In this study, we propose a new alternative using an aortic autograft as tracheal substitute. In a first series of experiments, a half circumference of two rings was replaced with an autologous carotid artery patch. In a second series, a complete segment of trachea was replaced with an autologous aortic graft supported by an endoluminal tracheal stent. No dehiscence or stenosis was observed. Microscopic examinations at 3 and 6 months showed the replacement of the aortic tissue by tracheal tissue comprising neoformation of cartilage and mucociliary or non-keratinizing metaplastic polystratified squamous epithelium. Although these results need to be confirmed by a larger series of experiments, they showed that a vascular tissue placed in a different environment with a different function can be submitted to a metaplastic transformation which tends to restore a normal structure adapted to its new function. These remarkable findings offer new perspectives in tracheal reconstruction in human.

Model of complete separation of the hepatic veins from the systemic venous system.

BACKGROUND: In patients undergoing a Fontan operation, partial diversion of the hepatic veins to the pulmonary venous atrium has been tried with various techniques. They failed because of the development of intrahepatic collaterals leading to an unacceptable right-to-left shunting. We postulate that to avoid the formation of intrahepatic collaterals, the totality of the liver has to be drained into the same pressure compartment. We have designed a model of cavopulmonary anastomosis in which a prosthetic conduit reproduces an azygos continuation, associated with the diversion of the totality of the hepatic venous return. This article reports on the early hemodynamics and the fate of the separation of the two venous compartments in long-term survivors. METHODS: Eighteen goats were operated on; the pulmonary artery and hepatic vein pressures were recorded. During month 2, an opacification of the inferior vena cava and the cavopulmonary connection was performed. Between months 6 and 14, another opacification was performed, together with pressure recording at both ends of the conduit. RESULTS: Postoperatively the pulmonary artery pressure was pulsatile with a mean of 10 mm Hg and the hepatic vein pressure was 0 mm Hg. The first angiogram showed patent tubes with fast progression of the contrast. Throughout the inferior vena cava injection, there was no opacification of the portal or hepatic veins. The late study showed a narrowed conduit in all animals. During the injection, a collateral was injected, feeding into the inferior mesenteric vein. No collateral circulation could be seen draining directly into the liver. The median gradient between the two ends of the conduit was 11 mm Hg. CONCLUSIONS: The isolation of the entire hepatic venous drainage is feasible and efficient for the separation of two pressure compartments. No intrahepatic collaterals are observed with this model at short- or long-term follow-up. The separation of the hepatic venous drainage should persist without collateral circulation as long as the inferior vena cava pressure stays at the levels observed in Fontan circulation.

[Left ventricular reconstruction after excision of a large fibroma]. / Reconstruction ventriculaire gauche après exérèse d'un volumineux fibrome.

The authors report the case of a 15 year old boy with a large left ventricular fibroma discovered after a series of syncopal episodes due to obstruction to ejection. The first attempt to remove the fibroma in Columbia was only partially successful. In view of the risk of death associated with this type of tumour, it was decided to offer the patient complete excision after a full morphological and functional evaluation of myocardial function and the consequences of the tumour on mitral valve function and on the coronary circulation. The operation was performed under cardiopulmonary bypass and aortic clamping by conventional surgery, associated with reconstruction of the cardiac free wall with a large patch of autologous pericardium which was necessary to avoid cardiac transplantation, the ultimate sanction in this indication.

[The pericardium: a heterogeneous tissue. Anatomic and morphometric considerations]. / Le péricarde: un tissu hétérogène. Considérations anatomiques et morphométriques.

BACKGROUND AND AIMS OF THE STUDY: Short-term glutaraldehyde fixed autologous pericardium is widely used in cardiac valve repair or in autologous pericardial bioprosthesis construction. The thinner the tissue, the better the fixation. The aim of this study was to determine thickness and useful surface area of pericardium in relation to harvesting site using a digital thickness counter (0.01 mm precision). Parietal pericardium fragments were obtained from the pericardial sac of six fresh cadavers (group I). In the other groups, pericardial strips (80 x 30 mm) were obtained from patients undergoing surgery: group II patients (n = 5 females) and group III (n = 10 males) were non-cardiomegalic (cardiothoracic ratio (CTR) < 0.5)), while group IV patients (n = 5) were all cardiomegalic (CTR > 0.5). Results were reported on a coloric scale according to measurement position. In group I, mean surface area was 93 +/- 18 cm2, and thickness gradually increased from 0.1 to 0.6 mm, maximally on the diaphragm, along the left heart side. In other groups, a gradual increase in thickness was identified towards the diaphragmatic zone. Significant differences in tissue thickness appear as a result of cardiomegaly, but are not related to the sex of the patients. Pericardium taken from the right anterior aspect of the pericardial sac in patients without cardiomegaly is the most appropriate tissue for valve reconstructive surgery, due to its thin nature and hence better fixation properties.

Autologous pericardial patch harvesting site for cardiac valve repair: anatomic and morphometric considerations.

BACKGROUND AND AIMS OF THE STUDY: Short-term glutaraldehyde-fixed autologous pericardium is widely used in cardiac valve repair or in autologous pericardial bioprosthesis construction. The thinner the tissue, the better the fixation. The aim of this study was to determine thickness and useful surface area of pericardium in relation to harvesting site using a digital thickness counter (0.01 mm precision). METHODS: Parietal pericardium fragments were obtained from the pericardial sac of six fresh cadavers (group I). In the other groups, pericardial strips (80 x 30 mm) were obtained from patients undergoing surgery: group II patients (n = 5 females) and group III (n = 10 males) were non-cardiomegalic (cardiothoracic ratio (CTR)<0.5), while group IV patients (n = 5) were all cardiomegalic (CTR >0.5). RESULTS: Results were reported on a coloric scale according to measurement position. In group I, mean surface area was 93+/-18 cm2, and thickness gradually increased from 0.1 to 0.6 mm, maximally on the diaphragm, along the left heart side. In other groups, a gradual increase in thickness was identified towards the diaphragmatic zone. Significant differences in tissue thickness appear as a result of cardiomegaly, but are not related to the sex of the patients. CONCLUSIONS: Pericardium taken from the right anterior aspect of the pericardial sac in patients without cardiomegaly is the most appropriate tissue for valve reconstructive surgery, due to its thin nature and hence better fixation properties.

Does glutaraldehyde induce calcification of bioprosthetic tissues?

BACKGROUND: Glutaraldehyde has been said to be responsible in part for the calcification of glutaraldehyde-treated tissues after implantation in animals or humans. We investigated whether the origin of the tissue, autologous or heterologous, could have a more prominent role in the process of calcification. METHODS: Three-month-old sheep received sheep pericardial samples (n = 133) and human pericardial samples (n = 123) implanted subcutaneously. Samples were treated with 0.6% glutaraldehyde for 5, 10, or 20 minutes or 7 days and then rinsed thoroughly before implantation. Samples were then retrieved after 3 months. Calcium content was assessed by spectrophometry. RESULTS: The results show a low calcium content in the autologous group (mean 1.14+/-2.07) and a high calcium content in the heterologous group (mean 38.97+/-26). These results were the same regardless of the duration of the treatment. CONCLUSIONS: Glutaraldehyde treatment (0.6%) does not play a significant role in the calcification of glutaraldehyde-treated tissue regardless of the origin, autologous or heterologous, of the tissue. Glutaraldehyde-treated autologous tissues are associated with an incidence of calcification lower than heterologous tissues.

Dynamic cardiomyoplasty: clinical follow-up at 12 years.

OBJECTIVE: The purpose of this study is to evaluate the long-term outcome of dynamic cardiomyoplasty. This surgical technique was conceived to assist the failing heart. The many proposed mechanisms of action of cardiomyoplasty are: (1) systolic assist; (2) limitation of ventricular dilation; (3) reduction of ventricular wall stress (sparing effect); (4) ventricular remodeling with an active girdling effect; (5) angiogenesis; and (6) a neurohumoral effect. METHODS: We investigated 95 patients in our hospital undergoing this procedure due to severe chronic heart failure, refractory to optimal medical treatment. Patients had a mean age of 51 +/- 12 years. The etiology of heart failure was ischemic 55%, idiopathic 34%, ventricular tumor 6%, and other 5%. The mean follow-up was 44 months. RESULTS: The mean New York Heart Association (NYHA) functional class improved postoperatively from 3.2 to 1.8. Average radioisotopic left ventricular (LV) ejection fraction increased from 17 +/- 5 to 27 +/- 4% (P < 0.05). Stroke volume index increased from 32 +/- 7 to 43 +/- 8 ml/beat per m2 (P < 0.05). The heart size remained stable over the long term. Following cardiomyoplasty, the number of hospitalizations due to congestive heart failure was reduced to 0.4 hospitalizations/patient per year (preoperative: 2.5, P < 0.05). Computed tomography scans showed at long term a preserved latissimus dorsi muscle structure in 84% of patients. Survival probability at 7 years is 54%. Six patients underwent heart transplant after cardiomyoplasty (mean delay: 25 months), due to the natural evolution of their underlying heart disease. There were no specific technical difficulties. CONCLUSIONS: Clinically, this procedure reverses heart failure, improves functional class and ameliorates quality of life. The latissimus dorsi muscle histological structure is maintained at long-term, when postoperative electrostimulation is performed, avoiding excessive stimulation. Cardiomyoplasty may delay or prevent the progression of heart failure and the indication of cardiac transplantation.

Retrospective risk analysis for early heart-related death after cardiomyoplasty. The Worldwide Cardiomyoplasty Group.

BACKGROUND: Dynamic cardiomyoplasty is an evolving treatment for heart failure that uses an electrically stimulated latissimus dorsi muscle wrapped around the heart to improve cardiac function. Preoperative patient characteristics and deaths after cardiomyoplasty have been recorded during the past 5 years in a cumulative database representing worldwide experience of 42 medical centers. METHODS: Statistical models of hazards (monthly death rates) were used to identify risk factors for transiently increased risk of cardiovascular mortality within 2 months after cardiomyoplasty. RESULTS: Actuarial survival (n = 261) was 88%, 80%, and 76% at 1, 3, and 6 months after cardiomyoplasty, respectively. The peak hazard of 6% dying per month occurred during the first month after the surgical procedure. Lower ejection fraction, increased number of major coronary arteries with > or = 70% stenotic lesions, and lower chronotropic responses during exercise were independent risk factors for the transient increase in early cardiovascular mortality. Early risk of cardiovascular mortality was significantly reduced as centers gained experience with more than 3 patients. CONCLUSION: Early survival after cardiomyoplasty has improved with experience and might be reduced further by preoperative assessments that identify patients at highest risk.

Study of muscular and ventricular function in dynamic cardiomyoplasty: a ten-year follow-up.

BACKGROUND: The basic physiologic principle underlying cardiomyoplasty is long-term electrostimulation of a latissimus dorsi muscle (LDM) wrapped around the heart to obtain a phasic activity that could be integrated with ventricular kinetics. The aim of cardiomyoplasty is to prolong survival and to improve the quality of life of patients with severe chronic and irreversible myocardial failure by improving systolic contraction and correcting diastolic dysfunction. METHODS: To evaluate the long-term outcome of cardiomyoplasty, we investigated 82 patients electively undergoing this procedure in-our hospital. All patients had severe chronic heart failure that did not respond to optimal medical treatment. Patients had a mean age of 50 +/- 12 years (84% males). The cause of heart failure was ischemic (55%), idiopathic cardiomyopathy (34%), ventricular tumor (6%), and other (5%). The mean follow-up was 4.3 years. RESULTS: The mean New York Heart Association functional class improved after operation from 3.2 to 1.8. Average radioisotopic left ventricular ejection fraction increased from 17% +/- 6% to 28% +/- 3% (p < 0.05). Stroke volume index increased from 35 +/- 9 to 46 +/- 8 ml/beat/m2 (p < 0.05). The heart size remained stable at long term (evaluated by echo and computed tomography scanning). After cardiomyoplasty the number of successive hospitalizations resulting from congestive heart failure was reduced to 0.4 hospitalizations/patient/year (before operation 2.5, p < 0.05). Computed tomography scans showed at long-term a preserved LDM structure in 82% of patients who underwent operation. Survival probability at 7 years was 54% for the totality of patients, and 66% for patients who underwent operation in New York Heart Association functional class 3. Five patients underwent heart transplantation after cardiomyoplasty (mean delay 29 months), principally as a result of the natural evolution of their underlying heart disease, without major technical difficulties. CONCLUSIONS: Our 10-year clinical experience demonstrates that cardiomyoplasty increases ejection fraction, improves functional class, and ameliorates quality of life. Ventricular volumes and diameters remain stable long term. LDM structure is maintained long term if electrostimulation is performed avoiding excessive myostimulation. Patient selection is the most important determinant for early and late outcome. Late death in patients undergoing cardiomyoplasty is principally due to sudden death. Our future aim is to incorporate a cardioverter-defibrillator in the cardiomyostimulator, thus improving long-term results. Cardiomyoplasty may delay or prevent end-stage heart failure and the need for heart transplantation.