Takotsubo cardiomyopathy:Pathophysiology and role of cardiac biomarkers in differential diagnosis

Takotsubo cardiomyopathy(TC) is characterized by reversible ventricular dysfunction, not limited to the distribution of an epicardial coronary artery. A disease primarily afflicting post-menopausal women, it is frequently mistaken for acute anterior wall myocardial infarction. Alternatively called Stress Cardiomyopathy, physical or emotional triggers are identified in only three fourths of TC patients. Long considered a benign condition, recent findings suggest poor short term prognosis similar to acute coronary syndrome(ACS). Despite the widely recognized pathophysiological role of catecholamine excess, its diagnostic role is uncertain. TC is suspected based on typical wall motion abnormalities in ventriculogram or echocardiogram. Several additional electrocardiographic, laboratory and imaging parameters have been studied with the goal of clinical diagnosis of TC. While several clinical clues differentiate it from ACS, a clinical diagnosis is often elusive leading to avoidable cardiac catheterizations. Natriuretic peptides(NPs), a family of peptide hormones released primarily in response to myocardial stretch, play a significant role in pathophysiology, diagnosis as well as treatment of congestive heart failure. TC with its prominent ventricular dysfunction is associated with a significant elevation of NPs. NPs are elevated in ACS as well but the degree of elevation is typically lesser than in TC. Markers of myocardial injury such as troponin are usually elevated to a higher degree in ACS than in TC. This differential elevation of NPs and markers of myocardial injury may play a role in early clinical recognition of TC.

Level of Cardiac Biomarkers in Immediate Post-Operative Period after Off-Pump CABG and Its Comparison with On-Pump CABG: A Prospective Analytical Study

Background: Coronary artery bypass grafting (CABG) is an important modality of treatment for ischemic heart disease. Both off-pump and on-pump CABG have direct effect on the level cardiac biomarkers in the perioperative period. The use of cardiopulmonary bypass (CPB) and aortic cross-clamping may cause additive myocardial damage leading to further elevation of blood markers. The present study is aimed at measuring and comparing the cardiac biomarker levels in immediate post-operative period after on-pump CABG (ONCAB) and off-pump CABG (OPCAB). Methods: All the patients who underwent CABG from January 2015 to June 2016 on elective or emergency basis at Nilratan Sircar Medical College & Hospital have been included in the study. Total 106 patients were operated for CABG of which 75 patients were operated for OPCAB and 31 patients were operated for ONCAB. For the comparison of data the blood markers Troponin-T (Trop-T) and Creatine Kinase-MB (CK-MB) are measured during anesthesia before surgery, post-operatively after 1 hour, post-operatively after 4 hours and post-operatively after 20 hours. All recorded data are analyzed using standard statistical methods. Results: We found the markers are elevated immediately after surgery and gradually come down within 24 hours after surgery in both OPCAB and ONCAB groups. The elevation is more after ONCAB than OPCAB group in immediate post-operative period but the difference is not significant after 20 hours of surgery. Conclusion: Elevated levels of cardiac biomarkers in the immediate post-operative period indicate myocardial damage during surgery, especially after ONCAB in comparison to OPCAB. This may attribute to the better hemodynamic stability in the immediate post-operative period after OPCAB than ONCAB assuming comparable and adequate revascularization in patients of both groups. The avoidance of CPB and cross-clamp may explain better myocardial functioning immediately after OPCAB. But after 20 hours, the level of cardiac markers is comparable in both groups indicating little difference in post-operative recovery and long-term prognosis.

Release of Cardiac Biomarkers during a Cycling Race

Objectives: Over the past two decades, a large interest in cardiac marker elevations has developed in endurance sports events. The intense effort is not without risk. We aimed to see if the relatively cardiospecific biomarkers could show the damage on cardiac muscle cells. Methods: Fourteen cyclists were recruited for an international race (177 km). We studied different cardiac biomarkers, renal function markers and blood cytology. The subjects were submitted to three blood test: one before (T0), one just after (T1) and the last one 3 hours after the race (T3). Results: Blood cytology markers, namely erythrocytes, hemoglobin, hematocrit, and average hemoglobin concentration, were found to evolve in a similar way. Renal function markers, such as creatinin, cystatin C and uric acid, showed a post effort increase that might be related to renal blood flow depletion during exercise. Cardiac and muscular markers were all increased at T1. Conclusions: Physiological stress induced by an international cycling race certainly has consequences on cardiac muscle cells. Fortunately, those blood concentration variations are more representative of a transitional state, due to an imbalance created by an intense aerobic effort maintained during several hours, rather than an irreversible injury.

Prevalence of posttraumatic stress disorder following acute coronary syndrome and clinical characteristics of patients referred to cardiac rehabilitation

BACKGROUND Studies have demonstrated that patients who have experienced acute coronary syndrome(ACS)have an increased risk of developing posttraumatic stress disorder(PTSD)and experiencing worse survival outcomes than those who do not develop PTSD.Nevertheless,the prevalence rates of PTSD following ACS vary widely across studies,and it is noteworthy that in most cases,the diagnosis of PTSD was based on self-report symptom questionnaires,rather than being established by psychiatrists.Additionally,the individual characteristics of patients who develop PTSD after ACS can differ widely,making it difficult to identify any consistent patterns or predictors of the disorder.AIM To investigate the prevalence of PTSD among a large sample of patients undergoing cardiac rehabilitation(CR)after ACS,as well as their characteristics in comparison to a control group.METHODS The participants of this study are patients who have experienced ACS with or without undergoing percutaneous coronary intervention and are enrolled in a 3-wk CR program at the largest CR center in Croatia,the Special Hospital for Medical Rehabilitation Krapinske Toplice.Patient recruitment for the study took place over the course of one year,from January 1,2022,to December 31,2022,with a total of 504 participants.The expected average follow-up period for patients included in the study is about 18 mo,and currently ongoing.Using self-assessment questionnaire for PTSD criteria and clinical psychiatric interview,a group of patients with a PTSD diagnosis was identified.From the participants who do not have a PTSD diagnosis,patients who would match those with a PTSD diagnosis in terms of relevant clinical and medical stratification variables and during the same rehabilitation period were selected to enable comparability of the two groups.RESULTS A total of 507 patients who were enrolled in the CR program were approached to participate in the study.Three patients declined to participate in the study.The screening PTSD Checklist-Civilian Version questionnaire was completed by 504 patients.Out of the total sample of 504 patients,74.2%were men(n=374)and 25.8%were women(n=130).The mean age of all participants was 56.7 years(55.8 for men and 59.1 for women).Among the 504 participants who completed the screening questionnaire,80 met the cutoff criteria for the PTSD and qualified for further evaluation(15.9%).All 80 patients agreed to a psychiatric interview.Among them,51 patients(10.1%)were diagnosed with clinical PTSD by a psychiatrist according to Diagnostic and Statistical Manual of Mental Disorders criteria.Among the variables analyzed,there was a noticeable difference in the percentage of theoretical maximum achieved on exercise testing between the PTSD and non-PTSD groups.Non-PTSD group achieved a significantly higher percentage of their maximum compared to the PTSD group(P=0.035).CONCLUSION The preliminary results of the study indicate that a significant proportion of patients with PTSD induced by ACS are not receiving adequate treatment.Furthermore,the data suggest that these patients may exhibit reduced physical activity levels,which could be one of the possible underlying mechanisms in observed poor cardiovascular outcomes in this population.Identifying cardiac biomarkers is crucial for identifying patients at risk of developing PTSD and may derive benefits from personalized interventions based on the principles of precision medicine in multidisciplinary CR programs.

Cardiovascular impact of COVID-19 with a focus on children: A systematic review

BACKGROUND Since the beginning of the pandemic,coronavirus disease-2019(COVID-19)in children has shown milder cases and a better prognosis than adults.Although the respiratory tract is the primary target for severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),cardiovascular involvement is emerging as one of the most significant and life-threatening complications of SARS-CoV-2 infection in adults.AIM To summarize the current knowledge about the potential cardiovascular involvement in pediatric COVID-19 in order to give a perspective on how to take care of them during the current pandemic emergency.METHODS Multiple searches in MEDLINE,PubMed were performed using the search terms“COVID-19”or“SARS-CoV-2"were used in combination with“myocardial injury”or"arrhythmia"or“cardiovascular involvement”or"heart disease"or"congenital heart disease"or“pulmonary hypertension”or"long QT"or“cardiomyopathies”or“channelopathies”or"Multisystem inflammatory system"or"PMIS"or“MIS-C”or”Pediatric multisystem inflammatory syndrome"or"myocarditis"or"thromboembolism to identify articles published in English language from January 1st,2020 until July 31st,2020.The websites of World Health Organization,Centers for Disease control and Prevention,and the Johns Hopkins Coronavirus Resource Center were reviewed to provide up to date numbers and infection control recommendations.Reference lists from the articles were reviewed to identify additional pertinent articles.Retrieved manuscripts concerning the subject were reviewed by the authors,and the data were extracted using a standardized collection tool.Data were subsequently analyzed with descriptive statistics.For Pediatric multisystemic inflammatory syndrome temporally associated with COVID-19(PMIS),multiple meta-analyses were conducted to summarize the pooled mean proportion of different cardiovascular variables in this population in pseudo-cohorts of observed patients.RESULTS A total of 193 articles were included.Most publications used in this review were single case reports,small case series,and observational small-sized studies or literature reviews.The meta-analysis of 16 studies with size>10 patients and with complete data about cardiovascular involvement in children with PMIS showed that PMIS affects mostly previously healthy school-aged children and adolescents presenting with Kawasaki disease-like features and multiple organ failure with a focus on the heart,accounting for most cases of pediatric COVID-19 mortality.They frequently presented cardiogenic shock(53%),ECG alterations(27%),myocardial dysfunction(52%),and coronary artery dilation(15%).Most cases required PICU admission(75%)and inotropic support(57%),with the rare need for extracorporeal membrane oxygenation(4%).Almost all of these children wholly recovered in a few days,although rare deaths have been reported(2%).Out of PMIS cases we identified 10 articles reporting sporadic cases of myocarditis,pulmonary hypertension and cardiac arrythmias in previously healthy children.We also found another 10 studies reporting patients with preexisting heart diseases.Most cases consisted in children with severe COVID-19 infection with full recovery after intensive care support,but cases of death were also identified.The management of different cardiac conditions are provided based on current guidelines and expert panel recommendations.CONCLUSION There is still scarce data about the role of cardiovascular involvement in COVID-19 in children.Based on our review,children(previously healthy or with preexisting heart disease)with acute COVID-19 requiring hospital admission should undergo a cardiac workup and close cardiovascular monitoring to identify and treat timely life-threatening cardiac complications.

Prognostic value of elevated cardiac and inflammatory biomarkers in patients with severe COVID-19:a single-center,retrospective study

Background:The outbreak of coronavirus disease 2019(COVID-19)caused by severe acute respiratory syndrome coronavirus 2 in India has been declared a public health emergency.Many patients with COVID-19 experience cardiac injury.Patients with COVID-19 admitted to the intensive care unit(ICU)with acute myocardial injury showed increased high-sensitivity troponin levels.Abnormal troponin levels may indicate myocardial injury and are commonly associated with COVID-19.Methods:We conducted a retrospective observational study of 44 patients with severe COVID-19 in ICU during the second wave.The primary end point of our retrospective study was 28-day mortality,and the time of ICU admission was designated as day 0.We extracted and analyzed cardiac biomarkers,such as creatine kinase(CK),creatine kinase-MB(CK-MB),B-type natriuretic peptide(BNP),and high-sensitivity cardiac troponin I(hs-cTnI),and various inflammatory markers such as C-reactive protein(CRP)level,interleukin 6(IL-6),D-dimer,ferritin,lactate dehydrogenase,IL-6,and procalcitonin in patients with severe COVID-19 at ICU admission and 72 hours after ICU admission from our electronic medical record system.Results:The best cutoff of BNP were 326.8 and 398.5 pg/mL,CK were 195.95 and 180.12 U/L,CK-MB were 112.10 and 108.5 U/L,and hs-cTnI were 0.035 and 0.025 ng/mL,at ICU admission and 72 hours after ICU admission for predicting 28-day mortality among nonsurvivors.Conclusion:In patients with severe COVID-19,CK and hs-cTnI may be considered effective and valuable predictive cardiac biomarkers among nonsurvivors and predict poor prognosis.

Tako-tsubo cardiomyopathy

Tako-tsubo cardiomyopathy（TC） is a recently described acute cardiac syndrome, which the latest cardiomyopathy classification of the European Society of Cardiology describes as an unclassified cardiomyopathy. TC mimics acute myocardial infarction（AMI） and is characterised by ischaemic chest symptoms, an elevated electrocardiogram ST-segment, and moderately increased levels of cardiac disease markers. However, patients with TC have no coronary angiogram-detectable or non-obstructive coronary arterial disease（CAD）, and left ventriculography documents transient left apical and middle ventricular wall dysfunction. In this review, we describe TC and evaluate epidemiological, clinical and instrumental features, pathophysiological mechanisms, therapy and prognosis of this syndrome,with a view to raising awareness of the disease.

New Cutoff for High Sensitivity Troponin to Better Risk Stratify Patients with Non-ST Elevated Myocardial Infarction

Background: The diagnosis of Non-ST Elevated Myocardial Infarction (NSTEMI) is dependent on elevation of high sensitivity troponin (Hs-troponin). The current cutoff point for Hs-troponin is highly sensitive but not specific for obstructive coronary artery disease (CAD). This study aims to determine the best cutoff point for diagnosing CAD in patients presented with NSTEMI. Methods: Our study included all patients admitted as NSTEMI that underwent coronary angiography (CAG). They were grouped into two groups: A and B. Group A has obstructive CAD of 70% or more stenosis and group B with non-obstructive CAD. Patients were assessed for their demographics, clinical history, laboratory and imaging results. Using SPSS version 22, the pooled cohort of patients were analyzed at significant level < 0.05 and the data were tested for significant correlations between two predetermined groups. Results: Group A comprised 87.6% of the patients and both groups had a median age of 53 years. In Group A, 91% were males, 54% diabetics, 54% hypertensives, and median Hs-troponin was 145 ng/L. While in group B, 88% were males, 39% diabetics, 60% hypertensives, and median Hs-troponin was 54 ng/L. There was significant correlation between the two groups in the percentage of diabetes and median troponin level (p < 0.05). A ROC curve has identified a level of 127 ng/dL as the best cutoff of Hs-troponin in detecting obstructive CAD (p = 0.03). Interestingly, 60% of patients in group B had alternative diagnoses. Conclusion: Hs-troponin is sensitive but less specific for obstructive CAD. However, increasing its cutoff value will improve its specificity.

Troponin I biomarker as a strong prognostic factor for predicting COVID-19 mortality:A systematic review

BACKGROUND The increase in circulating Troponin-I in the blood of patients suffering coronavirus disease 2019(COVID-19)can be a strong prognostic factor for predicting disease poorer outcome.AIM To review the literatures to approve this claim systematically.METHODS Two blinded reviewers independently screened the titles and abstracts of the manuscripts using the keywords and deeply searching the databanks including PubMed,Scopus,Google Scholar,and Web of knowledge,followed by profoundly appraisement of the full texts to assess the inclusion appropriateness.RESULTS The manuscripts entered into our final assessment were categorized as the two groups including 10 manuscripts describing and comparing death and diseaserelated complications between the subgroups of patients with raised serum troponin level and those with normal ranges of this biomarker and 7 manuscripts comparing the mean level of serum troponin concentration across the survived and non-survived groups.Comparing outcome of COVID-19 disease in the groups with raised troponin level and normal level of this markers showed increased the likelihood of death[hazard ratio(HR)=4.967,P<0.001],acute respiratory distress syndrome(HR=5.914,P<0.001),acute kidney injury(HR=3.849,P<0.001),and intensive care unit(ICU)admission(HR=3.780,P<0.001)following raise of troponin.The pooled analysis showed significantly higher concentration of this marker in the survived group compared to non-survived group(weighted mean differences of 22.278,95%CI:15.647 to 28.927,P<0.001).CONCLUSION Raising troponin-I on admission can be linked to the increase risk for in-hospital death,acute respiratory distress syndrome,kidney injury,and ICU admission by 4.9,5.9,3.8,and 3.7 times as compared to those with initial normal troponin-I concentration.Thus,raising baseline value of troponin-I can be used as a prognostic factor for poor outcome of COVID-19.