Validation of Perioperative Troponin Levels for Predicting Postoperative Mortality and Long-Term Survival in Patients Undergoing Surgery for Hepatobiliary and Pancreatic Cancer.

Background: Hepatopancreato and biliary (HPB) tumors represent some of the leading cancer-related causes of death worldwide, with the majority of patients undergoing surgery in the context of a multimodal treatment strategy. Consequently, the implementation of an accurate risk stratification tool is crucial to facilitate informed consent, along with clinical decision making, and to compare surgical outcomes among different healthcare providers for either service evaluation or clinical audit. Perioperative troponin levels have been proposed as a feasible and easy-to-use tool in order to evaluate the risk of postoperative myocardial injury and 30-day mortality. The purpose of the present study is to validate the perioperative troponin levels as a prognostic factor regarding postoperative myocardial injury and 30-day mortality in Greek adult patients undergoing HPB surgery. Method: In total, 195 patients undergoing surgery performed by a single surgical team in a single tertiary hospital (2020-2022) were included. Perioperative levels of troponin before surgery and at 24 and 48 h postoperatively were assessed. Model accuracy was assessed by observed-to-expected (O:E) ratios, and area under the receiver operating characteristic curve (AUC). Survival at one year postoperatively was compared between patients with high and normal TnT levels at 24 h postoperatively. Results: Thirteen patients (6.6%) died within 30 days of surgery. TnT levels at 24 h postoperatively were associated with excellent discrimination and provided the best-performing calibration. Patients with normal TnT levels at 24 h postoperatively were associated with higher long-term survival compared to those with high TnT levels. Conclusions: TnT at 24 h postoperatively is an efficient risk assessment tool that should be implemented in the perioperative pathway of patients undergoing surgery for HPB cancer.

Cardiac rehabilitation after cardiac surgery: An important underutilized treatment strategy.

Physical inactivity remains in high levels after cardiac surgery, reaching up to 50%. Patients present a significant loss of functional capacity, with prominent muscle weakness after cardiac surgery due to anesthesia, surgical incision, duration of cardiopulmonary bypass, and mechanical ventilation that affects their quality of life. These complications, along with pulmonary complications after surgery, lead to extended intensive care unit (ICU) and hospital length of stay and significant mortality rates. Despite the well-known beneficial effects of cardiac rehabilitation, this treatment strategy still remains broadly underutilized in patients after cardiac surgery. Prehabilitation and ICU early mobilization have been both showed to be valid methods to improve exercise tolerance and muscle strength. Early mobilization should be adjusted to each patient's functional capacity with progressive exercise training, from passive mobilization to more active range of motion and resistance exercises. Cardiopulmonary exercise testing remains the gold standard for exercise capacity assessment and optimal prescription of aerobic exercise intensity. During the last decade, recent advances in healthcare technology have changed cardiac rehabilitation perspectives, leading to the future of cardiac rehabilitation. By incorporating artificial intelligence, simulation, telemedicine and virtual cardiac rehabilitation, cardiac surgery patients may improve adherence and compliance, targeting to reduced hospital readmissions and decreased healthcare costs.

Safety and effectiveness of neuromuscular electrical stimulation in cardiac surgery: A systematic review.

BACKGROUND: Lack of mobilization and prolonged stay in the intensive care unit (ICU) are major factors resulting in the development of ICU-acquired muscle weakness (ICUAW). ICUAW is a type of skeletal muscle dysfunction and a common complication of patients after cardiac surgery, and may be a risk factor for prolonged duration of mechanical ventilation, associated with a higher risk of readmission and higher mortality. Early mobilization in the ICU after cardiac surgery has been found to be low with a significant trend to increase over ICU stay and is also associated with a reduced duration of mechanical ventilation and ICU length of stay. Neuromuscular electrical stimulation (NMES) is an alternative modality of exercise in patients with muscle weakness. A major advantage of NMES is that it can be applied even in sedated patients in the ICU, a fact that might enhance early mobilization in these patients. AIM: To evaluate safety, feasibility and effectiveness of NMES on functional capacity and muscle strength in patients before and after cardiac surgery. METHODS: We performed a search on Pubmed, Physiotherapy Evidence Database (PEDro), Embase and CINAHL databases, selecting papers published between December 2012 and April 2023 and identified published randomized controlled trials (RCTs) that included implementation of NMES in patients before after cardiac surgery. RCTs were assessed for methodological rigor and risk of bias via the PEDro. The primary outcomes were safety and functional capacity and the secondary outcomes were muscle strength and function. RESULTS: Ten studies were included in our systematic review, resulting in 703 participants. Almost half of them performed NMES and the other half were included in the control group, treated with usual care. Nine studies investigated patients after cardiac surgery and 1 study before cardiac surgery. Functional capacity was assessed in 8 studies via 6MWT or other indices, and improved only in 1 study before and in 1 after cardiac surgery. Nine studies explored the effects of NMES on muscle strength and function and, most of them, found increase of muscle strength and improvement in muscle function after NMES. NMES was safe in all studies without any significant complication. CONCLUSION: NMES is safe, feasible and has beneficial effects on muscle strength and function in patients after cardiac surgery, but has no significant effect on functional capacity.

Intensive Care Unit Hyperglycemia After Cardiac Surgery: Risk Factors and Clinical Outcomes.

OBJECTIVES: Patients with hyperglycemia after cardiac surgery face increased morbidity and mortality due to postoperative complications. The main purpose of this study was to evaluate the incidence of postoperative hyperglycemia, the hyperglycemia risk factors, and its association with clinical outcomes in patients admitted to the cardiac surgery intensive care unit after cardiac surgery. DESIGN: Prospective, observational study. SETTING: Single-center hospital. PARTICIPANTS: Two hundred ten consecutive postoperative cardiac surgery patients admitted to the cardiac surgery intensive care unit. INTERVENTIONS: Patients' blood glucose levels were evaluated immediately after cardiac surgery and every 3 hours daily for 7 days or earlier upon discharge. Intravenous insulin was administered as per the institution's protocol. Perioperative predisposing risk factors for hyperglycemia and clinical outcomes were assessed. MEASUREMENTS AND MAIN RESULTS: Postoperative hyperglycemia, defined as glucose level ≥180 mg/dL, occurred in 30% of cardiac surgery patients. Diabetes mellitus (odds ratio [OR] 6.73; 95% CI [3.2-14.3]; p < 0.001), white blood cell count (OR 1.28; 95% CI [1.1-1.4]; p < 0.001), and EuroSCORE II (OR 1.20; 95% CI [1.1-1.4]; p = 0.004) emerged as independent prognostic factors for hyperglycemia. Moreover, patients with glucose ≥180 mg/dL had higher rates of acute kidney injury (34.9% v 18.9%, p = 0.013), longer duration of mechanical ventilation (959 v 720 min, p = 0.019), and sedation (711 v 574 min, p = 0.034), and higher levels of intensive care unit (ICU)-acquired weakness (14% v 5.5%, p = 0.027) and rate of multiorgan failure (6.3% v 0.7%, p = 0.02) compared with patients with glucose levels <180 mg/dL. CONCLUSIONS: In the intensive care unit, hyperglycemia occurs frequently in patients immediately after cardiac surgery. Diabetes, high EuroSCORE II, and preoperative leukocytosis are independent risk factors for postoperative hyperglycemia. Hyperglycemia is associated with worse clinical outcomes, including a higher rate of acute kidney injury and ICU-acquired weakness, greater duration of mechanical ventilation, and a higher rate of multiorgan failure.

Arrhythmias in Patients with Cardiac Amyloidosis: A Comprehensive Review on Clinical Management and Devices.

Cardiac amyloidosis (CA) is a rare but potentially life-threatening disease in which misfolded proteins accumulate in the cardiac wall tissue. Heart rhythm disorders in CA, including supraventricular arrhythmias, conduction system disturbances, or ventricular arrhythmias, play a major role in CA morbidity and mortality, and thus require supplementary management. Among them, AF is the most frequent arrhythmia during CA hospitalizations and is associated with significantly higher mortality, while ventricular arrhythmias are also common and are usually associated with poor prognosis. Early diagnosis of potential arrythmias could be performed through ECG, Holter monitoring, and/or electrophysiology study. Clinical management of these patients is quite significant, and it usually includes initiation of amiodarone and/or digoxin in patients with AF, potential electrical cardioversion, or ablation in specific patients with indication, as well as initiation of anticoagulants in all patients, independent of AF and CHADS-VASc score, for potential intracardiac thrombus. Moreover, identification of patients with conduction disorders that could benefit from prophylactic pacemaker implantation and/or CRT as well as identification of patients with life-threatening ventricular arrythmias that could benefit from ICD could both increase the survival rates of these patients and improve their quality of life.

Coronary Artery Aneurysms: Comprehensive Review and a Case Report of a Left Main Coronary Artery Aneurysm.

Coronary artery aneurysms (CAAs) are rare anatomical disorders of the coronary arteries. Atherosclerosis and Kawasaki disease are the principal causes of CCAs, while other causes including genetic factors, inflammatory arterial diseases, connective tissue disorders, endothelial damage after cocaine use, iatrogenic complications after interventions and infections, are also common among patients with CAAs. Although there is a variety of noninvasive methods including echocardiography, computed tomography, and magnetic resonance imaging, coronary angiography remains the gold standard diagnostic method. There is still no consensus about the most appropriate therapeutic strategy. Medical therapy including antiplatelets, anticoagulants, statins and ACEs are preferred either in patients with atherosclerosis, inflammatory status and stable CAAs, while percutaneous or surgery interventions are usually applied in patients with acute coronary syndrome due to a CAA culprit, obstructive coronary artery disease or large saccular aneurysms at a high risk of rupturing.

Lyophilized recombinant human brain natriuretic peptide: A promising therapy in patients with chronic heart failure.

Lyophilized recombinant brain natriuretic peptide (BNP) is an exogenous peptide synthesized by artificial recombination technology, with a similar structure and similar physiological effects with the endogenous natriuretic peptide secreted by the human body. It's main mechanism of action is to increase cyclic guanosine monophosphate by binding with its corresponding receptor in the body, regulating, thus, the imbalance of the vascular system and cardiac hemodynamics, improving the heart's pumping capacity, and inhibiting sympathetic excitability and myocardial remodeling. Moreover, it can promote mitochondrial metabolism and enhance the use of adenosine triphosphate in cardiomyocytes. In the present study, 102 chronic heart failure (HF) patients were randomly assigned to a control and an observation group consisting of 51 patients each. Patients of the control group were treated with standard HF therapy for 3 d including oral metoprolol tartrate tablets, spironolactone, and olmesartanate while patients of the observation group were administered the recombinant human BNP injection for the same time-period, plus the standard HF therapy. The recombinant human BNP group (observation group) demonstrated better physical, emotional, social, and economic scores, as well as cardiac and inflammatory biomarkers such as serum hypersensitive C-reactive protein, N-terminal pro BNP and troponin I levels, compared to the control group. Moreover, cardiac function was also improved, as left ventricular ejection fraction and stroke volume were significantly higher in the observation group than in the control group. Interestingly, adverse reactions were not different between the 2 groups. However, these results are not generalizable and the need of large multicenter randomized controlled trials examining the safety and efficacy of recombinant human BNP in HF patients is of major importance.

Spontaneous coronary artery dissection: A review of diagnostic methods and management strategies.

Spontaneous coronary artery dissection (SCAD) is a rare non-atherosclerotic cause of acute coronary syndromes defined as non-iatrogenic, non-traumatic separation of the coronary artery wall. The most common profile is a middle-aged woman between 44 and 53 years with few cardiovascular risk factors. SCAD is frequently linked with predisposing factors, such as postpartum, fibromuscular dysplasia or other vasculopathies, connective tissue disease and hormonal therapy, and it is often triggered by intense physical or emotional stress, sympathomimetic drugs, childbirth and activities increasing shear stress of the coronary artery walls. Patients with SCAD usually present at the emergency department with chest discomfort, chest pain, and rapid heartbeat or fluttery. During the last decades, the most common problem of SCAD was the lack of awareness about this condition which has led to significant underdiagnosis and misdiagnosis. However, modern imaging techniques such as optical coherence tomography, intravascular ultrasound, coronary angiography or magnetic resonance imaging have contributed to the early diagnosis of the disease. Treatment of SCAD remains controversial, especially during the last years, where invasive techniques are being used more often and in more emergent cardiac syndromes. Although conservative treatment combining aspirin and beta-blocker remains the recommended strategy in most cases, revascularization could also be suggested as a method of treatment in specific indications, but with a higher risk of complications. The prognosis of SCAD is usually good and long-term mortality seems to be low in these patients. Follow-up should be performed on a regular basis.

Cardioprotective Strategies from Cardiotoxicity in Cancer Patients: A Comprehensive Review.

Cardiotoxicity is a significant complication of chemotherapeutic agents in cancer patients. Cardiovascular incidents including LV dysfunction, heart failure (HF), severe arrhythmias, arterial hypertension, and death are associated with high morbidity and mortality. Risk stratification of cancer patients prior to initiation of chemotherapy is crucial, especially in high-risk patients for cardiotoxicity. The early identification and management of potential risk factors for cardiovascular side effects seems to contribute to the prevention or minimization of cardiotoxicity. Screening of cancer patients includes biomarkers such as cTnI and natriuretic peptide and imaging measurements such as LV function, global longitudinal strain, and cardiac MRI. Cardioprotective strategies have been investigated over the last two decades. These strategies for either primary or secondary prevention include medical therapy such as ACE inhibitors, ARBs, b-blockers, aldosterone antagonists, statins and dexrazoxane, physical therapy, and reduction of chemotherapeutic dosages. However, data regarding dosages, duration of medical therapy, and potential interactions with chemotherapeutic agents are still limited. Collaboration among oncologists, cardiologists, and cardio-oncologists could establish management cardioprotective strategies and approved follow-up protocols in patients with cancer receiving chemotherapy.

Practical Approaches to Build and Sustain a Cardio-Oncology Clinic.

The therapeutical advances in recent years in the field of oncology treatment have increased survival rates and improved the quality of life of oncology patients, thus turning cancer into a chronic disease. However, most of the new cancer treatments come at the expense of serious cardiovascular adverse events threatening the success story of these patients. The establishment of multidisciplinary medical teams to prevent, monitor, and treat cardiovascular diseases in cancer-treated patients is needed now more than ever. The aim of this narrative review is to demonstrate the existing knowledge and practical approaches on how to establish and maintain a cardio-oncology program for the rising number of patients who need it.

Cardiotoxicity of Non-Anthracycline Cancer Chemotherapy Agents.

Throughout the last decades, newly developed chemotherapeutic agents and immunotherapies that target signaling pathways have provided patients with better prognoses, improved their quality of life and increased survival rates, thus converting cancer to a stable chronic disease. However, non-anthracycline cancer chemotherapy agents and immunotherapies including human epidermal growth factor receptor 2 (HER2) inhibitors, vascular endothelial growth factor (VEGF) inhibitors, Bcr-Abl tyrosine-kinase inhibitors (TKI), proteasome inhibitors, immune checkpoint inhibitors and chimeric antigen receptor T cells (CAR-T cells) may cause cardiovascular toxicity events and complications that usually interrupt the continuation of an appropriate treatment regimen, which induces life-threatening risks or leads to long-term morbidity. Heart failure, cardiac arrythmias and cardiomyopathies are the most common cardiovascular events related to cardiotoxicity due to chemotherapy. Each patient should be carefully assessed and monitored before, during and after the administration of chemotherapy, to address any predisposing risk factors and the new onset of cardiotoxicity manifestations early and treat them appropriately. The development of novel anticancer agents that cause minimal cardiovascular toxicity events or novel agents that ameliorate the adverse effects of the existing anticancer agents could drastically change the field of cardio-oncology. The aim of this narrative review is to demonstrate new knowledge regarding the screening and diagnosis of non-anthracycline-induced cardiotoxicity and to propose protective measures that could be performed in order to achieve the delivery of optimal care.

Exercise training in heart transplantation.

Heart transplantation remains the gold standard in the treatment of end-stage heart failure (HF). Heart transplantation patients present lower exercise capacity due to cardiovascular and musculoskeletal alterations leading thus to poor quality of life and reduction in the ability of daily self-service. Impaired vascular function and diastolic dysfunction cause lower cardiac output while decreased skeletal muscle oxidative fibers, enzymes and capillarity cause arteriovenous oxygen difference, leading thus to decreased peak oxygen uptake in heart transplant recipients. Exercise training improves exercise capacity, cardiac and vascular endothelial function in heart transplant recipients. Pre-rehabilitation regular aerobic or combined exercise is beneficial for patients with end-stage HF awaiting heart transplantation in order to maintain a higher fitness level and reduce complications afterwards like intensive care unit acquired weakness or cardiac cachexia. All hospitalized patients after heart transplantation should be referred to early mobilization of skeletal muscles through kinesiotherapy of the upper and lower limbs and respiratory physiotherapy in order to prevent infections of the respiratory system prior to hospital discharge. Moreover, all heart transplant recipients after hospital discharge who have not already participated in an early cardiac rehabilitation program should be referred to a rehabilitation center by their health care provider. Although high intensity interval training seems to have more benefits than moderate intensity continuous training, especially in stable transplant patients, individualized training based on the abilities and needs of each patient still remains the most appropriate approach. Cardiac rehabilitation appears to be safe in heart transplant patients. However, long-term follow-up data is incomplete and, therefore, further high quality and adequately-powered studies are needed to demonstrate the long-term benefits of exercise training in this population.

A High-Cholesterol Diet Increases Toll-like Receptors and Other Harmful Factors in the Rabbit Myocardium: The Beneficial Effect of Statins.

BACKGROUND: A high-cholesterol diet (HCD) induces vascular atherosclerosis through vascular inflammatory and immunological processes via TLRs. The aim of this study is to investigate the mRNA expression of TLRs and other noxious biomarkers expressing inflammation, fibrosis, apoptosis, and cardiac dysfunction in the rabbit myocardium during (a) high-cholesterol diet (HCD), (b) normal diet resumption and (c) fluvastatin or rosuvastatin treatment. METHODS: Forty-eight male rabbits were randomly divided into eight groups (n = 6/group). In the first experiment, three groups were fed with HCD for 1, 2 and 3 months. In the second experiment, three groups were fed with HCD for 3 months, followed by normal chow for 1 month and administration of fluvastatin or rosuvastatin for 1 month. Control groups were fed with normal chow for 90 and 120 days. The whole myocardium was removed; total RNA was isolated from acquired samples, and polymerase chain reaction, reverse transcription PCR and quantitative real-time PCR were performed. RESULTS: mRNA of TLRs 2, 3, 4 and 8; interleukin-6; TNF-a; metalloproteinase-2; tissue inhibitor of metalloproteinase-1; tumor protein 53; cysteinyl aspartate specific proteinase-3; and brain natriuretic peptide (BNP) increased in HCD. Statins but not resumption of a normal diet decreased levels of these biomarkers and increased levels of antifibrotic factors. CONCLUSIONS: HCD increases the levels of TLRs; inflammatory, fibrotic and apoptotic factors; and BNP in the rabbit myocardium. Atherogenic diets adversely affect the myocardium at a molecular level and are reversed by statins.

Tissue-specific relaxin-2 is differentially associated with the presence/size of an arterial aneurysm and the severity of atherosclerotic disease in humans.

Circulating or tissue-related biomarkers are of clinical value for risk stratification in patients with abdominal aortic aneurysms. Relaxin-2 (RL2) has been linked to the presence and size of arterial aneurysms, and to the extent of atherosclerosis in human subjects. Here, we assessed the expression levels of RL2 in aneurysmal (AA, n = 16) and atherosclerotic (ATH, n = 22) arteries, and established the correlation between RL2 levels and the presence/size of AA and the clinical severity of atherosclerosis. The expression levels of metalloproteinases (MMPs) and endothelial nitric oxide synthetase (eNOS) were also detected for correlations with different phenotypes of atherosclerosis and AA. Temporal artery biopsy specimens (n = 6) and abdominal aortic tissues harvested from accident victims during autopsy (n = 10) were used as controls. Quantitative tissue biomarker analysis revealed that tissue-specific RL2 was increased in patients with larger or symptomatic AA compared to subjects with atherosclerotic disease and healthy controls. In situ RL2 levels were proportional to the size and the severity of aneurysmatic disease, and were substantially elevated in patients with symptomatic aneurysm of any diameter or asymptomatic aneurysm of a diameter >350% of that of the normal artery. In contrast, tissue RL2 was inversely associated with the clinical severity of atherosclerotic lesions. Correlation between RL2 and MMP2 was different between ATH1 and ATH2, depending on atherosclerosis grade. Overall, tissue RL2 is differentially associated with discrete phenotypes of arterial disease and might exert multipotent biological effects on vascular wall integrity and remodeling in human subjects.