Elevated Cardiac Biomarkers Research Articles

Cardiovascular immune-related adverse events: Evaluation, diagnosis and management.

Cardiotoxicities are associated with immune checkpoint inhibitor (ICI) therapy. Recent case series and retrospective studies have shown that cardiac immune‐related adverse events (irAEs) are rare but potentially fatal complications of immunotherapy, with various underlying risk factors such as combinations of different ICIs. High mortality rates and overreactive inflammation have been observed with ICI‐associated cardiotoxicities, highlighting the necessity of baseline and serial evaluations and the identification and management of cardiac irAEs as early as possible. The clinical presentations of irAEs range from asymptomatic cardiac biomarker elevation, myocarditis and pericardial diseases to heart failure and mild to fatal arrhythmia. Troponin measurement and electrocardiogram are sensitive initial tests, whereas cardiac magnetic resonance imaging and endomyocardial biopsy are both gold standard components of the diagnostic criteria. Close monitoring and timely consultation with a cardiologist are important for the diagnosis of ICI‐related cardiotoxicities, with decisions of stopping or rechallenging ICIs and strategies to manage heart injuries. Treatment principles are made according to risk stratifications. The first‐line medication is glucocorticoids of various doses, and the second‐line immunosuppression includes intravenous immunoglobin, antithymocyte globulin and other immunosuppressants, which are recommended in life‐threatening cases or in cases of resistance/no response to steroids.

Periprocedural elevated myocardial biomarkers and clinical outcomes following elective percutaneous coronary intervention: a comprehensive dose-response meta-analysis of 44,972 patients from 24 prospective studies.

The optimal cut-off value of isolated cardiac biomarker elevation for defining prognostically important percutaneous coronary intervention (PCI)-related myocardial injury is not known. We performed a meta-analysis to evaluate the dose-response relationship between isolated cardiac biomarker elevations and the risk of all-cause mortality following elective PCI. Twenty-four prospective studies (44,972 patients) were included. Patients with an isolated elevation of cardiac biomarkers had an increased risk of all-cause mortality when compared to those with no elevations (cardiac troponin I: odds ratio [OR] 1.42, 95% confidence interval [CI]: 1.19-1.69; creatine kinase-MB isoenzyme [CK-MB]: OR 1.43, 95% CI: 1.19-1.70). For the dose-response analysis, elevations of cardiac troponin I >3x or CK-MB >1x the 99th percentile upper reference limit (URL) were associated with increased mortality (cardiac troponin I: OR 1.51, 95% CI: 1.05-2.17; CK-MB: OR 1.25, 95% CI: 1.05-1.48). The pooled OR of mortality for each 3xURL increment of cardiac troponin I or CK-MB was 1.33 (95% CI: 1.15-1.53) and 1.38 (95% CI: 1.30-1.47). We found that a positive dose-response relationship between isolated cardiac troponin I and CK-MB with all-cause mortality and elevated cardiac troponin I >3x or CK-MB >1x the 99th percentile URL was associated with an increased risk of mortality.

Cardiac biomarkers for the detection of cardiotoxicity in childhood cancer-a meta-analysis.

AimsChildhood cancer therapy is associated with a significant risk of therapy‐related cardiotoxicity. This meta‐analysis aims to evaluate cardiac biomarkers for the detection of cancer therapy‐related left ventricular (LV) dysfunction in childhood cancer patients.Methods and resultsPubMed, Cochrane Library, Wiley Library, and Web of Science were screened for studies investigating brain natriuretic peptide (BNP)/N‐terminal proBNP (NT‐proBNP) or cardiac troponin in childhood cancer patients. The odds ratios (OR) for elevation of cardiac biomarkers and association with LV dysfunction were calculated using a random‐effects model. Data from 27 studies with 1651 subjects were included. BNP/NT‐proBNP levels were higher post‐treatment compared with controls or pre‐treatment values [standardized mean difference = 1.0; 95% confidence interval (CI) = 0.6–1.4; n = 320; P < 0.001]. LV dysfunction was present in 11.76% of included patients, and risk for LV dysfunction was increased in patients with elevated BNP/NT‐proBNP (OR = 7.1; 95% CI = 2.0–25.5; n = 350; P = 0.003). The sensitivity of BNP/NT‐proBNP for the detection of LV dysfunction was 33.3%, and the specificity was 91.5%. Sensitivity increased when selecting for studies that assessed patients < 5 years after anthracycline exposure and for studies including high cumulative anthracycline doses. Anthracycline chemotherapy was associated with an increased frequency of elevated troponin (OR = 3.7; 95% CI = 2.1–6.5; n = 348; P < 0.001). The available evidence on the association between elevated troponin and LV dysfunction was insufficient for an adequate analysis. In five included studies, the frequency of LV dysfunction was not increased in patients with elevated troponin (OR = 2.5; 95% CI = 0.5–13.2; n = 179; P = 0.53).ConclusionsBNP/NT‐proBNP is associated with cardiotoxicity in paediatric cancer patients receiving anthracycline therapy, but owing to low sensitivity, BNP/NT‐proBNP has to be evaluated in the context of further parameters including clinical assessment and echocardiography. Future studies are needed to determine whether troponin serves as a marker for cardiotoxicity in children. Standardized recommendations for the application of cardiac biomarkers in children undergoing cardiotoxic cancer therapy may benefit management and clinical outcome.

Coronary Artery Spasms Mimicking Acute ST-Elevation Myocardial Infarction in Dengue Haemorrhagic Fever

Dengue is an arboviral febrile illness endemic in many tropical and subtropical regions with frequent epidemics. Although most cases are self-limiting, progression into dengue haemorrhagic fever can have dire outcomes. The course can also be complicated by infrequent occurrence of unusual clinical manifestations which are increasingly recognized. We describe the case of a 16-year-old previously healthy girl diagnosed with dengue, who went on to develop severe ischaemic-type central chest pain towards the end of the critical phase of dengue haemorrhagic fever. Urgent investigation revealed acute ST-segment elevations in the high lateral leads of a surface electrocardiogram which completely reverted to normal within 2 hours, associated with elevated cardiac biomarkers but normal findings on transthoracic 2D echocardiography. She was managed with high-dose statins, nitrates, and pain relievers and made an uneventful recovery without any further episodes. The possible explanation for the presentation was focal myocarditis leading to coronary artery spasms.

Significant association of SYNTAX score on release of cardiac biomarkers in uncomplicated post-revascularization procedures among patients with stable multivessel disease

This study investigated the relationship between angiographic complexities of coronary artery disease (CAD) assessed by SYNTAX Score synergy between percutaneous coronary intervention with taxus and cardiac surgery score (SYNTAX Score) and cardiac biomarker elevation after revascularization procedures.This is a post-hoc analysis of the medicine, angioplasty or surgery study V study of patients with stable CAD. High-sensitivity troponin 1 (hs-TnI) and creatinine kinase-muscle/brain (CK-MB) were assessed before and after cardiovascular procedures. Baselines SYNTAX Scores (SXScores) were calculated by blinded investigators to patient characteristics.Of the 202 patients studied, the mean SXScore was 21.25 ± 9.24; 40.10 ± 7.09 in the high SXScore group and 19.06 ± 6.61 in low/mid SXscore group (P < .0001). Positive correlations existed between SXScore and median peaks after procedural hs-TnI (r = 0.18, P = .009) and CK-MB (r = 0.24, P = .001) levels. In patients with high SXScores (≥33), the median peaks of post-procedural hs-TnI (P = .034)and CK-MB (P = .004) levels were higher than in low/mid SXScore group (<33).The release of hs-TnI at 6 (P = .002), 12 (P = .008), and 24 hours (P = .039) was higher in high SXScore group than in low/mid SXscore group (<33) as was the release of CK-MB at 6 (P < .0001), 12 (P < .0001), 24 (P = .001), 36 (P = .007), 48 (P = .008), and 72 hours (P = .023). After multivariable analysis, high SXScore was a significant independent predictor of release of CK-MB and hs-TnI peaks higher than the median.The increase in release of cardiac biomarkers was significantly associated with the extent of atherosclerosis identified by the SYNTAX Score.

Myocardite aiguë auto-immune secondaire à une maladie de Basedow : à propos d’un cas

IntroductionInteractions between heart and thyroid are strong. Main cardiac complications of Graves’ disease are supra-ventricular tachycardia or high output cardiac failure, without real myocardial involvement. ObservationA 40-year-old man with history of refractory Graves’ disease was hospitalized for an acute chest pain with elevated cardiac biomarkers and normal coronarography. Acute myocarditis was confirmed by cardiac MRI. We found no evidence for an infectious etiology. We retained the hypothesis of acute autoimmune myocarditis in the context of active Graves’ disease. ConclusionAcute myocarditis is an exceptional complication of Graves’ disease, with most likely an autoimmune mechanism. Possible occurrence of fulminant rhythmic or hemodynamic complications justify minimal cardiological check-up before introducing beta blockers.

Racial Differences in Malignant Left Ventricular Hypertrophy and Incidence of Heart Failure: A Multicohort Study.

A malignant subphenotype of left ventricular hypertrophy (LVH) has been described, in which minimal elevations in cardiac biomarkers identify individuals with LVH at high risk for developing heart failure (HF). We tested the hypothesis that a higher prevalence of malignant LVH among blacks may contribute to racial disparities in HF risk. Participants (n=15 710) without prevalent cardiovascular disease were pooled from 3 population-based cohort studies, the ARIC Study (Atherosclerosis Risk in Communities), the DHS (Dallas Heart Study), and the MESA (Multi-Ethnic Study of Atherosclerosis). Participants were classified into 3 groups: those without ECG-LVH, those with ECG-LVH and normal biomarkers (hs-cTnT (high sensitivity cardiac troponin-T) <6 ng/L and NT-proBNP (N-terminal pro-B-type natriuretic peptide) <100 pg/mL), and those with ECG-LVH and abnormal levels of either biomarker (malignant LVH). The outcome was incident HF. Over the 10-year follow-up period, HF occurred in 512 (3.3%) participants, with 5.2% in black men, 3.8% in white men, 3.2% in black women, and 2.2% in white women. The prevalence of malignant LVH was 3-fold higher among black men and women versus white men and women. Compared with participants without LVH, the adjusted hazard ratio for HF was 2.8 (95% CI, 2.1-3.5) in those with malignant LVH and 0.9 (95% CI, 0.6-1.5) in those with LVH and normal biomarkers, with similar findings in each race/sex subgroup. Mediation analyses indicated that 33% of excess hazard for HF among black men and 11% of the excess hazard among black women was explained by the higher prevalence of malignant LVH in blacks. Of black men who developed HF, 30.8% had malignant LVH at baseline, with a corresponding population attributable fraction of 0.21. The proportion of HF cases occurring among those with malignant LVH, and the corresponding population attributable fraction, were intermediate and similar among black women and white men and lowest among white women. A higher prevalence of malignant LVH may in part explain the higher risk of HF among blacks versus whites. Strategies to prevent development or attenuate risk associated with malignant LVH should be investigated as a strategy to lower HF risk and mitigate racial disparities.

Using the SYNTAX score to predict myocardial injury early after on-pump coronary artery bypass surgery: a single-centre experience analysis.

IntroductionMarked isolated elevation of cardiac biomarkers (CK-MB, cardiac troponin I, heart-type fatty acid binding protein, hFABP) within 48 hours after coronary artery bypass surgery (CABG), even in the absence of electrocardiographic/angiographic evidence of myocardial infarction (MI), indicates prognostically significant cardiac procedural myocardial injury. There are no data exploring the relationship between the complexity of coronary atherosclerotic burden and early post-CABG myocardial injury.AimTo analyse correlations and predictive strength of the SYNTAX score (SS) for early myocardial injury after on-pump CABG.Material and methodsOne hundred and twenty consecutive patients undergoing CABG were included in the analysis. We obtained data on demographics, medical history, cardiovascular risk factors and echocardiography. Cardiac biomarkers were assessed at 6 hours after CABG. Multivariate linear regression analysis was performed to evaluate independent variables correlated with cardiac biomarkers.ResultsThe most significant predictor for myocardial injury was SS, strongly correlated with the rise of all cardiac biomarkers (p < 0.001). Hypertension and creatinine clearance were associated with cTnI and hFABP. Diabetes was corelated with hFABP. In a multivariate analysis including all significant predictors, SS remained an independent predictor for myocardial injury, strongly associated with hFABP (p < 0.001, OR = 5.79, 95% CI: 3.59–7.98), cTnI (p < 0.001, OR = 6.49, 95% CI: 4.78–8.20), but not with CK-MB (95% CI: 0.61–1.07).ConclusionsDefining myocardial injury as elevation of cardiac biomarkers between normal values and the cut-off for MI has a tremendous clinical significance as patients maintain high negative prognostic rates. SS could be used to predict post-operative rise of cardiac biomarkers, the correlation between SS and myocardial injury being very solid.

Early prescription of direct oral anticoagulants for acute intermediate-high risk pulmonary embolism

The use of direct oral anticoagulants (DOACs) for the early treatment of intermediate-high risk pulmonary embolism (PE) is poorly described. The aims of the present study were to describe clinical patterns and associated risk of adverse events between early and late DOAC prescription after admission for intermediate-high risk PE. We used a prospective regional multicenter registry including all consecutive hemodynamically stable PE patients stratified as intermediate-high risk with right heart strain on cardiac imaging and elevation of cardiac biomarkers. Early DOAC group was defined as a prescription < 72 h after admission, and late DOAC group was defined as a prescription between 72 h and 7 days. Efficacy and safety outcomes were evaluated at 30 days and 6 months. Among 477 patients admitted with an intermediate-high risk PE between 10/2012 and 12/2017, 209 patients were treated with DOACs within the acute phase: early DOAC group was composed of 68 patients (32.5%) and late DOAC group of 141 patients (67.8%). There was no significant difference in baseline characteristics between groups. The rates of efficacy and safety outcomes were similar between patients who were treated early with a DOAC and those who received a late strategy with a prolonged heparin lead-in. Hospital length of stay was shorter in the early DOAC group (6.0 ± 3.6 days vs. 8.2 ± 6.8 days, P = 0.01). Our results might suggest that, if a DOAC is selected for intermediate-high risk PE treatment, it could be prescribed early after admission.

P1688 Rare cause of acute heart failure in patient with scleroderma

Abstract A 32-year old female patient, known to have scleroderma, presented with symptoms of recurrent attacks of palpitations, dyspnea (NYHA class III) &amp; dizziness for 3 days before presentation. No chest pain or syncope. Physical examination at presentation revealed hemodynamic instability (BP: 80/50 mmHg, HR: 200 bpm/ regular thready pulse with fine bilateral basal chest crackles. ECG revealed ventricular tachycardia (figure 1), so electrical cardioversion was immediately done upon which the reverted to multifocal atrial tachycardia with RBBB and restoration of hemodynamics and disappearance of chest crackles. She also had thickening of the fingertips’ skin, amputated tip of the right middle finger with severe associated Raynaud’s phenomenon, skin tightness of both upper and lower limbs, Buccal buckling with limited mouth opening (figure 2 and 3). Renal function and serum electrolytes were normal with elevated troponin I, creatine kinase and CK-MB serum levels. Echocardiogram showed mild concentric LV hypertrophy with normal internal dimensions and severely impaired systolic function (EF∼ 20%) with severe global hypokinesia . The RV was also dilated and impaired (TAPSE∼8 mm). Mild pericardial effusion with no chamber collapse (Figure 4, 5 and 6). Coronary angiography revealed normal epicardial coronaries. Echocardiography one month prior to presentation revealed normal LV dimensions, preserved systolic function and mild diastolic dysfunction with no resting wall motion abnormalities, upper normal RV size with preserved RV systolic function and mild elevation of pulmonary artery systolic pressure. The presence of new acute biventricular failure in the absence of CAD and elevated cardiac biomarkers are highly suggestive of acute myocarditis. Medical therapy included loop diuretics, angiotensin-converting-enzyme inhibitor, beta-blocker and aldosterone receptor antagonist. She was discharged in NYHA I-II, with normal cardiac enzymes and left ventricle ejection fraction of 30% and resolution of the pericardial effusion. Discussion Scleroderma is rarely present with impaired LV contractility but more commonly presented with diastolic dysfunction (in up to 40% of cases) (1,2). This case was presented with acute myopericarditis with severe biventricular systolic dysfunction which is very rare with scleroderma and only mentioned in few case studies, so no consensus on specific treatment. Few patients with myocarditis and scleroderma were treated with immunosuppressants along with diuretics, beta-blockers, and ACE inhibitors with most of them showed improvement clinically with recovery of systolic function after 12 months of follow up (3). We noted improvement of patient symptoms within few days of diuretics, beta-blockers, Aldosterone antagonists and ACE inhibitors. This case had baseline conduction abnormalities (RBBB with multifocal atrial tachycardia) which could be present in up to 20% of cases (4). Abstract P1688 Figure.

Direktni oralni antikoagulansi - novo poglavlje u antikoagulantnoj terapiji

Thromboembolic events are the leading cause of morbidity and mortality worldwide. From the second half of the 20th century, vitamin K antagonists (VKAs), warfarin and acenocoumarol, were the only anticoagulants taken orally. The major reform in anticoagulation therapy was made by the advent of direct oral anticoagulants (DOACs), about 10 years ago. Direct thrombin inhibitor (dabigatran) and direct inhibitors of factor Xa (rivaroxaban, apixaban, edoxaban, and betrixaban) have demonstrated favorable risk/benefit ratio. Compared to warfarin, DOACs are associated with a predictable pharmacokinetic profile, lower severe bleeding complications, particularly intracranial hemorrhages, and minimal drug interactions. Moreover, DOACs achieve a rapid onset of action and have shown comparable efficacy with warfarin and low molecular weight heparin (LMWH) in clinical trials. As a result, DOACs are now replacing VKAs and LMWH for many indications including stroke and systemic embolism prevention in nonvalvular atrial fibrillation, prevention, and treatment of venous thromboembolism and thromboprophylaxis following total knee/hip replacement surgery. In addition, rivaroxaban (in combination with aspirin alone or aspirin and clopidogrel) is used in the prevention of atherothrombotic events following acute coronary syndrome with elevated cardiac biomarkers. In case of severe bleeding complications under DOACs treatment, antidotes are available; idarucizumab for dabigatran reversal and andexanet alfa for rivaroxaban and apixaban.

Electrocardiogram and Echocardiographic Findings of COVID-19 Patients in Makati Medical Center

BACKGROUND Echocardiography and electrocardiogram may prove useful in the care of COVID-19 patients but there is limited data postulating their usefulness in this disease. OBJECTIVE To determine electrocardiographic and echocardiographic findings among COVID-19 patients in Makati Medical Center. METHODS A retrospective single center analytical study involving adult Reverse transcription polymerase chain reaction (RT-PCR) confirmed COVID-19 positive patients admitted in Makati Medical Center from March to April 16, 2020. These patients had more than one electrocardiogram (ECG) result and a 2D echocardiography done during their admission. The initial and repeat ECGs during the course of hospital stay were obtained to determine if there were changes in ECG. On the other hand, echocardiographic investigations were confined to studies of left and right ventricular systolic function. RESULTS In the initial ECG findings, the most common abnormalities observed were QT prolongation (39.39%), ischemic changes (15.15%), and fascicular blocks (12.12%). During the course of admission, the most common were still QT prolongation (39.39%) and ischemic changes (13.64%), with the additional observation of further prolongation in QT from baseline (24.24%). For the echocardiographic findings, the right and left systolic functions were preserved in majority of the patients. No significant difference was noted in the electrogram and echocardiographic findings between survivor and non-survivors. CONCLUSION Majority of patients had abnormal ECG at baseline with further worsening during the course of confinement. Almost all abnormalities were related to QT prolongation. Though most patients had elevated cardiac biomarkers, only few patients had notable abnormalities in left and right ventricular function. Keywords COVID 19, Electrocardiogram, 2D Echocardiography

Rosuvastatin and simvastatin attenuate cisplatin-induced cardiotoxicity via disruption of endoplasmic reticulum stress-mediated apoptotic death in rats: targeting ER-Chaperone GRP78 and Calpain-1 pathways

Cisplatin (CP) is a powerful antineoplastic chemotherapeutic agent with broad-spectrum properties. Acute and cumulative cardiotoxicity are major limiting factors for CP therapy. Various pathogenic pathways have been suggested to CP-induced cardiotoxicity; oxidative damage, ER stress, and programmed cell death/apoptosis. The present study aimed to assess the signaling mechanisms related to the advantageous effects of rosuvastatin (RSV) and simvastatin (SMV) against CP-related cardiac ER stress dependent apoptotic death in rats. Acute cardiotoxicity was induced by a single dose of CP (10 mg/kg, i.p.) on the 10th day of the experiment. RSV (10 mg/ kg/day) and SMV (10 mg/kg/day) were orally administered for 15 days. CP-treated rats showed significant alterations in electrocardiographic recordings and elevation in serum cardiac function biomarkers; troponin T content, lactate dehydrogenase and creatine kinase-MB levels as well as boost in the cardiac oxidative stress biomarkers. In addition, CP exposure resulted in GRP78 induction; an ER stress and elevation marker at calpain-1 content as well as activation of activated caspase-3 (ACASP3) and caspase-12 were reflected on CP-triggered apoptosis evidenced by elevation in the Bax/Bcl-2 ratio. However, RSV and SMV administration mitigate those adverse CP effects. Statins administration prominently alleviated CP-induced cardiac abnormalities exerting improvement in the ECG pattern and cardiac enzyme biomarkers. Interestingly, statins; RSV and SMV, disrupted CP-induced ER stress and the consequent apoptotic cell death evidenced by downregulation of ER-chaperone GRP78, calpain-1, ACASP3 and caspase-12 as well as decline in the Bax/Bcl-2 ratio. From all the previous findings, it can be suggested that statins namely; RSV and SMV, play protective role against CP-induced cardiac injury by regulating ER stress-mediated apoptotic pathways.

Cardiac troponin I as a cardiac biomarker has prognostic and predictive value for poor survival in Egyptian buffalo calves with foot-and-mouth disease.

Background and Aim:Foot-and-mouth disease (FMD) causes huge economic losses in Egypt due to reductions in the production of red meat, milk, and milk by-products and can also lead to myocarditis in young animals. The aim of our study was to evaluate cardiac biomarkers, in particular cardiac troponin I (cTnI), and to reveal the relations of cardiac biomarkers with poor survival in FMD-infected Egyptian buffalo calves.Materials and Methods:Forty-two Egyptian buffalo calves were included in this study. The calves were divided into 12 apparently healthy control calves and 30 calves clinically diagnosed with FMD during a disease outbreak in Menofia and Behera Governorates, Egypt. The diseased calves were divided, according to age, into 13 calves <3 months old and 17 calves between 3 and 6 months old. The animals were examined clinically and subjected to analysis of cardiac biomarkers.Results:Biochemical analysis revealed significant elevations of cardiac biomarkers, especially creatine kinase myocardial band (CK-MB), lactate dehydrogenase (LDH), alanine aminotransferase (ALT), aspartate aminotransferase (AST), cardiac troponin T (cTnT), and cardiac troponin I (cTnI) in FMD-infected calves in comparison with control calves. There was a significant association between cTnI and poor survival in infected calves.Conclusion:Cardiac biomarkers could be used as a rapid method for diagnosis of myocarditis induced by FMD in Egyptian buffalo calves. In addition, cTnI is a very sensitive and accurate tool for determining myocardial cell damage in the earlier stages of the disease and a good predictor of poor survival in calves.

Insulin-like growth factor-1 levels predict myocardial injury and infarction after elective percutaneous coronary intervention: an optical coherence tomography study.

IntroductionPeriprocedural myocardial necrosis, which can range from a low level elevation of cardiac biomarkers to a large myocardial infarction (MI), is a common complication after percutaneous coronary intervention (PCI).AimWe hypothesized that insulin-like growth factor-1 (IGF-1) levels may play a protective role in myocardial injury after coronary stent placement and aimed to investigate the relationship between IGF-1 levels and plaque characteristics assessed by optical coherence tomography (OCT).Material and methodsBetween May 2015 and December 2015 we prospectively enrolled 74 patients with stable angina pectoris in whom single de novo coronary artery stenosis was present. PCI was performed according to standard methods. OCT was applied to all patients. TnT was analyzed at admission, before PCI and at 6, 12, 24 and 48 h after PCI. Serum IGF-1 was measured prior to PCI.ResultsA total of 25 (33.7%) patients had periprocedural myocardial injury or type 4a myocardial infarction, and 49 (66.2%) patients had no events. IGF-1 level and reference intimal thickness, medial thickness, and plaque fibrous cap thickness in OCT had strong correlations (r = 0.88, 0.80 and 0.88 respectively, p < 0.001). IGF-1 was an independent predictor of periprocedural myocardial injury or type 4a MI in univariate (OR = 0.929, 95% CI: 0.895–0.964, p < 0.001) and multivariate regression analysis (OR = 0.757, 95% CI: 0.575–0.998, p = 0.04). Based on ROC analysis, the best cut-off value of IGF-1 for predicting periprocedural myocardial injury or type 4a myocardial infarction was 144.5 ng/ml, with a maximum sensitivity of 88% and specificity of 77.6% (AUC = 0.80, 95% CI: 0.69–0.88, p < 0.0001).ConclusionsThe results from this study indicate that low IGF-1 levels are associated with plaque instability assessed by OCT. Low IGF-1 levels may identify patients who are at increased risk for periprocedural myocardial injury/infarction.

Increased Myocardial Stiffness in Patients With High-Risk Left Ventricular Hypertrophy: The Hallmark of Stage-B Heart Failure With Preserved Ejection Fraction.

Individuals with left ventricular hypertrophy (LVH) and elevated cardiac biomarkers in middle age are at high risk for the development of heart failure with preserved ejection fraction (HFpEF). However, it is unknown what the pathophysiological underpinnings of this high-risk state may be. We tested the hypothesis that patients with LVH and elevated cardiac biomarkers would demonstrate elevated left ventricular (LV) myocardial stiffness in comparison with healthy controls as a key marker for future HFpEF. Forty-six patients with LVH (LV septum >11 mm) and elevated cardiac biomarkers (N-terminal pro-B-type natriuretic peptide [>40 pg/mL] or troponin T [>0.6 pg/mL]) were recruited, along with 61 age- and sex-matched (by cohort) healthy controls. To define LV pressure-volume relationships, right heart catheterization and 3-dimensional echocardiography were performed while preload was manipulated using lower body negative pressure and rapid saline infusion. There were significant differences in body size, blood pressure, and baseline pulmonary capillary wedge pressure between groups (eg, pulmonary capillary wedge pressure: LVH, 13.4±2.7 versus control, 11.7±1.7 mm Hg, P<0.0001). The LV was less distensible in LVH than in controls (smaller volume for the same filling pressure). When preload was expressed as transmural filling pressure (pulmonary capillary wedge pressure - right atrial pressure), LV myocardial stiffness was nearly 30% greater in LVH than in controls (LVH stiffness constant, 0.053±0.027 versus controls, 0.042±0.020, P=0.028). LV myocardial stiffness in patients with LVH and elevated biomarkers (stage-B HFpEF) is greater than in age- and sex-matched controls and thus appears to represent a transitional state from a normal healthy heart to HFpEF. Although the LV myocardial stiffness of patients with LVH is greater than that of healthy controls at this early stage, further studies are required to clarify whether interventions such as exercise training to improve LV compliance may prevent the full manifestation of the HFpEF syndrome in these high-risk individuals. URL: https://www.clinicaltrials.gov. Unique identifiers: NCT03476785 and NCT02039154.

Coronary Sinus Filling Time as a Predictor of Coronary Microvascular Obstruction and Future Cardiovascular Events after Elective Left Anterior Descending Artery Stenting

Abstract Objective The main objective of this article is to study the usefulness of coronary sinus filling time (CSFT) as a predictor of coronary microvascular obstruction (CMVO) and future cardiovascular (CV) events after percutaneous coronary intervention (PCI) for left anterior descending (LAD) in stable coronary artery disease patients. Materials and Methods We analyzed 50 patients with stable angina who underwent elective PCI for single LAD significant stenosis. After stent deployment, coronary sinus was visualized in left anterior oblique 40 degree cranial 30 degree views, CSFT, and corrected thrombolysis in myocardial infarction frame count (cTFC) calculated from frame count. Post-procedure electrocardiographic changes noted and cardiac biomarker creatine phosphokinase and creatine phosphokinase-myocardial band levels estimated, and follow-up was done for 6 months. Patients classified into two groups: Group 1 with major adverse cardiac events (MACE) and Group 2 (without MACE). CSFT and cTFC measurements were compared among the two groups. Results Out of 50 patients who were recruited in the study, Group 1 comprises 20 patients, and Group 2 comprises 30 patients. Among the Group 1, 40% were females, while in Group 2, they were 16%. Group 1 showed high CSFT values compared to Group 2, and such are post-procedure ST, T changes (90% in Group 1, 20% in Group 2), cardiac biomarkers elevation (80% in Group 1, 23.3% in Group 2). At 6 months follow-up ejection fraction was lower in Group 1 (31.8 ± 6.4%) compared with Group 2 (58.8 ± 5.8%) at p &lt; 0.0001, and angina (85%) versus (20%). Mean CSFT was significantly more in Group 1 (5.77 ±0.75s) compared with Group 2 (4.61 ± 0.55s) at p &lt; 0.0001. With respect to cTFC, no significant differences were seen between the two groups (p &lt; 0.5628). Receiver operating characteristic curve analysis showed CSFT of &gt; 5.2s was the best cutoff value to differentiate the two groups. Conclusion CSFT significantly prolonged in patients with adverse cardiac events, and it may be used as a simple and quantitative predictor of CMVO and future CV events after elective PCI.

Atrial fibrillation is frequent but does not affect risk stratification in pulmonary embolism.

Although prior studies indicate a high prevalence of atrial fibrillation (AF) in patients with pulmonary embolism (PE), the exact prevalence and prognostic impact are unknown. We aimed to investigate the prevalence, risk factors and prognostic impact of AF on risk stratification, in-hospital adverse outcomes and mortality in 528 consecutive PE patients enrolled in a single-centre registry between 09/2008 and 09/2017. Overall, 52 patients (9.8%) had known AF and 57 (10.8%) presented with AF on admission; of those, 34 (59.6%) were newly diagnosed with AF. Compared to patients with no AF, overt hyperthyroidism was associated with newly diagnosed AF (OR 7.89 [2.99-20.86]), whilst cardiovascular risk comorbidities were more frequently observed in patients with known AF. Patients with AF on admission had more comorbidities, presented more frequently with tachycardia and elevated cardiac biomarkers and were hence stratified to higher risk classes. However, AF on admission had no impact on in-hospital adverse outcome (8.3%) and in-hospital mortality (4.5%). In multivariate logistic regression analyses corrected for AF on admission, NT-proBNP and troponin elevation as well as higher risk classes in risk assessment models remained independent predictors of an in-hospital adverse outcome. Atrial fibrillation is a frequent finding in PE, affecting more than 10% of patients. However, AF was not associated with a higher risk of in-hospital adverse outcomes and did not affect the prognostic performance of risk assessment strategies. Thus, our data support the use of risk stratification tools for patients with acute PE irrespective of the heart rhythm on admission.

Estimated Glomerular Filtration Rate, Activation of Cardiac Biomarkers and Long-Term Cardiovascular Outcomes: A Population-Based Cohort

ObjectiveTo classify subjects in a general population per their renal function and characterize the cardiac biomarker levels, left ventricular function and cardiovascular outcomes over a 10.2 year follow-up period (interquartile range, 5.1–11.4 years). MethodsThis was a retrospective review of a population-based random sample of residents aged ≥45 years. Data were collected between January 1, 1997, and December 31, 2000. One thousand nine hundred eighty-one individuals were classified based on estimated glomerular filtration rate (eGFR) into group I (>90 mL/min/1.73 m2), group II (60 to 89 mL/min/1.73 m2) and group III (<60 mL/min/1.73 m2; chronic kidney disease [CKD]). Age/sex-adjusted baseline characteristics, tertiles of N-terminal pro B-type natriuretic peptide (NT-proBNP) and high-sensitivity troponin T (hs-TnT) and their interactions with eGFR were examined. Outcomes measured included incident myocardial infarction (MI), congestive heart failure, stroke, and all-cause mortality. ResultsEight hundred nineteen patients were classified as group I, 1036 as group II, and 126 of 1981 (6.4%) as group III or CKD. Subjects in group III were older and had a higher incidence of hypertension, diabetes, and MI at baseline. Over a 10.2-year follow-up period, CKD was associated with an increased risk of MI (hazard ratio, 1.95; 95% CI, 1.2-3.14; P=.006) and composite cardiovascular outcomes including MI, congestive heart failure, stroke, and all-cause mortality (hazard ratio, 1.38; 95% CI, 1.05-1.83 ;P=.02). Subjects with NT-proBNP or hs-TnT in the third tertile were at greater risk of cardiovascular events without significant interactions between eGFR and levels of NT-proBNP and hs-TnT. ConclusionSubjects with CKD had significantly elevated cardiac biomarkers and were at an increased risk of MI and adverse cardiovascular events. This warrants future studies to investigate whether these cardiac biomarkers could identify high-risk CKD patients for aggressive management of cardiovascular risk factors.

78-Year-Old Woman With Intermittent Chest Pain and Palpitations

78-Year-Old Woman With Intermittent Chest Pain and Palpitations