Efficacy and Safety of Acoramidis in Transthyretin Amyloid Cardiomyopathy.

BACKGROUND: Transthyretin amyloid cardiomyopathy is characterized by the deposition of misfolded monomeric transthyretin (TTR) in the heart. Acoramidis is a high-affinity TTR stabilizer that acts to inhibit dissociation of tetrameric TTR and leads to more than 90% stabilization across the dosing interval as measured ex vivo. METHODS: In this phase 3, double-blind trial, we randomly assigned patients with transthyretin amyloid cardiomyopathy in a 2:1 ratio to receive acoramidis hydrochloride at a dose of 800 mg twice daily or matching placebo for 30 months. Efficacy was assessed in the patients who had an estimated glomerular filtration rate of at least 30 ml per minute per 1.73 m2 of body-surface area. The four-step primary hierarchical analysis included death from any cause, cardiovascular-related hospitalization, the change from baseline in the N-terminal pro-B-type natriuretic peptide (NT-proBNP) level, and the change from baseline in the 6-minute walk distance. We used the Finkelstein-Schoenfeld method to compare all potential pairs of patients within strata to generate a P value. Key secondary outcomes were death from any cause, the 6-minute walk distance, the score on the Kansas City Cardiomyopathy Questionnaire-Overall Summary, and the serum TTR level. RESULTS: A total of 632 patients underwent randomization. The primary analysis favored acoramidis over placebo (P<0.001); the corresponding win ratio was 1.8 (95% confidence interval [CI], 1.4 to 2.2), with 63.7% of pairwise comparisons favoring acoramidis and 35.9% favoring placebo. Together, death from any cause and cardiovascular-related hospitalization contributed more than half the wins and losses to the win ratio (58% of all pairwise comparisons); NT-proBNP pairwise comparisons yielded the highest ratio of wins to losses (23.3% vs. 7.0%). The overall incidence of adverse events was similar in the acoramidis group and the placebo group (98.1% and 97.6%, respectively); serious adverse events were reported in 54.6% and 64.9% of the patients. CONCLUSIONS: In patients with transthyretin amyloid cardiomyopathy, the receipt of acoramidis resulted in a significantly better four-step primary hierarchical outcome containing components of mortality, morbidity, and function than placebo. Adverse events were similar in the two groups. (Funded by BridgeBio Pharma; ATTRibute-CM ClinicalTrials.gov number, NCT03860935.).

[The role of cardiac biomarkers in perioperative risk evaluation of noncardiac surgery patients-A summary of the ESAIC guidelines 2023]. / Die Rolle von kardialen Biomarkern in der perioperativen Risikoevaluation von nichtkardiochirurgischen Patienten ­ eine Zusammenfassung der ESAIC-Leitlinie 2023.

BACKGROUND: The recently published ESAIC guidelines highlight the clinical value of cardiac troponins (cTn) and B­type natriuretic peptides (BNP) for risk assessment in patients undergoing noncardiac surgery. OBJECTIVE: Summary of the ESAIC guideline recommendations. MATERIAL AND METHODS: The evidence for the recommendations was extracted from studies that investigated the perioperative role of cTn and BNP as prognostic factors, for risk prediction and for therapeutic guidance. To collate this evidence 12 relevant endpoints as well as risk benefit analyses of systematic screening were considered to issue the strength of the recommendations. RESULTS: The body of evidence for these guidelines was based on 115 studies. The evidence varied significantly across the 12 predefined endpoints. Additionally, there was a gradient in evidence for the use of cTn and BNP as prognostic factors, for risk prediction and for therapeutic guidance. The guidelines issue a weak recommendation for the use of preoperative, postoperative and combined measurement of cTn as well as for preoperative BNP measurement to assess the prognosis. For risk prediction a weak recommendation was formulated for combined and postoperative cTn and preoperative BNP measurements. No recommendation could be given for the evidence on biomarkers as data were very limited. CONCLUSION: Both cTn and BNP can be used as prognostic factors or to predict the risk for selected endpoints. Therapeutic interventions should not be guided by cardiac biomarker levels.

Diagnostic accuracy of brain natriuretic peptide and N-terminal-pro brain natriuretic peptide to detect complications of cardiac transplantation in adults: A systematic review and meta-analysis.

BACKGROUND: We aimed to evaluate the utility of BNP and NT-proBNP in identifying adverse recipient outcomes following cardiac transplantation. METHODS: We searched MEDLINE (Ovid), Embase (Ovid), and the Cochrane Library from inception to February 2023. We included studies reporting associations between BNP or NT-proBNP and adverse outcomes following cardiac transplantation in adults. We calculated standardised mean differences (SMD) with 95% confidence intervals (CI); or confusion matrices with sensitivities and specificities. Where meta-analysis was inappropriate, studies were analysed descriptively. RESULTS: Thirty-two studies involving 2,297 cardiac transplantation recipients were included. We report no significant association between BNP or NT-proBNP and significant acute cellular rejection of grade 3A or higher (SMD 0.40, 95% CI -0.06-0.86) as defined by the latest 2004 International Society for Heart and Lung Transplantation Guidelines. We also report no strong associations between BNP or NT-proBNP and cardiac allograft vasculopathy or antibody mediated rejection. CONCLUSION: In isolation, serum BNP and NT-proBNP lack sufficient sensitivity and specificity to reliably predict adverse outcomes following cardiac transplantation.

Galectin-3 changes from admission to discharge and its prognostic value for in-hospital mortality in heart failure: A prospective observational study.

The aim of this study was to compare the levels of Galectin-3 (Gal-3) in heart failure patients at admission and discharge, and to evaluate the ability of Gal-3 at admission in predicting in-hospital mortality. A total of 111 patients were enrolled. Gal-3 and B-type natriuretic peptide (BNP) levels were measured at admission and discharge. Receiver operating characteristic analysis was used to determine the optimal cutoff values for Gal-3 and BNP, and logistic regression was used to assess the predictive ability of these biomarkers for in-hospital mortality. Gal-3 levels at discharge (24.08 ±â€…9.55) were significantly lower than those at admission (30.71 ±â€…11.22). The majority of patients (72.07%) experienced a decrease in Gal-3 levels, with a median reduction of 19.9% (interquartile range [IQR] 8.7-29.8). Gal-3 levels showed a weak correlation with BNP levels both at admission and discharge. Combining Gal-3 and BNP significantly improved the ability to predict in-hospital mortality, and including heart failure stage as a third predictor further improved the predictive accuracy. The optimal cutoff values for Gal-3 and BNP to predict in-hospital mortality were identified as 28.1 ng/mL and 1782.6 pg/mL, respectively, with moderate to good sensitivity and specificity. A median reduction of 19.9% of Gal-3 may indicate possibility to discharge. Our findings suggest that Gal-3 and BNP, when combined with heart failure stage, may be useful for predicting in-hospital mortality.

Galectin-3, Acute Kidney Injury and Myocardial Damage in Patients With Acute Heart Failure.

BACKGROUND: Galectin-3, a biomarker of inflammation and fibrosis, can be associated with renal and myocardial damage and dysfunction in patients with acute heart failure (AHF). METHODS AND RESULTS: We retrospectively analyzed 790 patients with AHF who were enrolled in the AKINESIS study. During hospitalization, patients with galectin-3 elevation (> 25.9 ng/mL) on admission more commonly had acute kidney injury (assessed by KDIGO criteria), renal tubular damage (peak urine neutrophil gelatinase-associated lipocalin [uNGAL] > 150 ng/dL) and myocardial injury (≥ 20% increase in the peak high-sensitivity cardiac troponin I [hs-cTnI] values compared to admission). They less commonly had ≥ 30% reduction in B-type natriuretic peptide from admission to last measured value. In multivariable linear regression analysis, galectin-3 was negatively associated with estimated glomerular filtration rate and positively associated with uNGAL and hs-cTnI. Higher galectin-3 was associated with renal replacement therapy, inotrope use and mortality during hospitalization. In univariable Cox regression analysis, higher galectin-3 was associated with increased risk for the composite of death or rehospitalization due to HF and death alone at 1 year. After multivariable adjustment, higher galectin-3 levels were associated only with death. CONCLUSIONS: In patients with AHF, higher galectin-3 values were associated with renal dysfunction, renal tubular damage and myocardial injury, and they predicted worse outcomes.

Carbohydrate antigen 125 combined with N-terminal pro-B-type natriuretic peptide in the prediction of acute heart failure following ST-elevation myocardial infarction.

The value of serum carbohydrate antigen 125 (CA125) combined with N-terminal pro-B-type natriuretic peptide (NT-proBNP) in the evaluation of acute heart failure (AHF) after ST-segment elevation myocardial infarction (STEMI) remains unclear. The aim of this study was to evaluate the efficacy of CA125 combined with NT-proBNP in predicting AHF following STEMI. A total of 233 patients with STEMI were evaluated, including 39 patients with Killip II-IV and 194 patients with Killip I. The optimal cutoff point for predicting AHF was determined by receiver operating characteristic (ROC) curve, and the independent predictors of AHF were evaluated by multiple logistic regression. According to the cutoff value, it was divided into three groups: C1 = CA125 < 13.20 and NT-proBNP < 2300 (n = 138); C2 = CA125 ≥ 13.20 or NT-proBNP ≥ 2300 (n = 59); C3 = CA125 ≥ 13.20 and NT-proBNP ≥ 2300 (n = 36). Differences between groups were compared by odds ratio (OR). The levels of CA125 and NT-proBNP in AHF group were higher than those in non-AHF group (19.90 vs 10.00, P < .001; 2980.00 vs 1029.50, P < .001, respectively). The optimal cutoff values of CA125 and NT-proBNP for predicting AHF were 13.20 and 2300, both of which were independent predictors of AHF. The incidence of AHF during hospitalization was highest in C3 (69.44%), middle in C2 (20.34%) and lowest in C1 (1.45%). After adjustment for clinical confounding variables, compared with C1: C2 (OR = 6.41, 95% CI: 1.22-33.84, P = .029), C3 (OR = 19.27, 95% CI: 3.12-118.92, P = .001). Elevated CA125 and NT-proBNP are independent predictors of AHF in STEMI patients, and their combination can improve the recognition efficiency.

Evaluación del grado de congestión clínica y hemodinámica como predictores de mortalidad en pacientes ambulatorios con insuficiencia cardíaca de edad avanzada / Assessment of clinical and hemodynamic congestion as predictors of mortality in elderly outpatients with heart failure

Introducción El objetivo del estudio fue evaluar si la exploración física y la determinación de la fracción N-terminal del propéptido natriurético cerebral pueden predecir un peor pronóstico en pacientes ambulatorios con insuficiencia cardíaca. Pacientes y métodos Estudio retrospectivo llevado a cabo entre 2010 y 2018, en 238 pacientes diagnosticados de insuficiencia cardíaca. Al inicio, se evaluó la presencia de crepitantes pulmonares y edema de miembros inferiores (congestión clínica) junto con la fracción N-terminal del propéptido natriurético cerebral≥1500pg/mL (congestión hemodinámica). Los pacientes se clasificaron en 4 grupos en función del patrón congestivo: sin congestión (G1) (n=50); con congestión clínica (G2) (n=43); con congestión hemodinámica (G3) (n=73) y con congestión clínica y hemodinámica (G4) (n=72). El objetivo primario fue la muerte por cualquier causa al año de seguimiento. Resultados Se analizaron un total de 238 pacientes, edad media 82 años, 61,8% mujeres, y 20,7% con fracción de eyección del ventrículo izquierdo reducida. Treinta pacientes (12,6%) fallecieron en el primer año de seguimiento. Después de ajustar por variables de confusión (sexo, alta hospitalaria reciente por insuficiencia cardíaca, filtrado glomerular estimado, y fracción de eyección del ventrículo izquierdo), el riesgo de muerte en cada grupo,al compararlos con el grupo de referencia G1, fue: G2, HR 4,121 (IC95% 1,131–15,019); G3, HR 2,511 (IC95% 1,007-6,263), y; G4, HR 7,418 (IC95% 1,630-33,763). Conclusión La congestión en pacientes ambulatorios con insuficiencia cardíaca se correlaciona con el pronóstico. Los pacientes con congestión clínica y hemodinámica tuvieron el mayor riesgo de muerte global al año (AU)

Introduction This work aims to evaluate whether a clinical examination and measurement of N-terminal pro-brain natriuretic peptide can predict poor prognosis in outpatients with heart failure. Patients and methods We carried out a retrospective study from 2010 to 2018 in 238 patients diagnosed with heart failure. At baseline, we evaluated the presence of pulmonary rales and bilateral leg edema (clinical congestion) together with N-terminal pro-brain natriuretic peptide≥1500 pg/mL (hemodynamic congestion). Patients were classified into 4 groups depending on their congestion pattern: no congestion (G1) (n=50); clinical congestion (G2) (n=43); hemodynamic congestion (G3) (n=73); and clinical and hemodynamic congestion (G4) (n=72). The primary outcome was all-cause mortality at one year of follow-up. Results A total of 238 patients were included. The mean age was 82 years, 61.8% were women, and 20.7% had reduced left ventricular ejection fraction. Thirty patients died in the first year of follow-up (12.6%). After controlling for confounding variables (sex, recent discharge for heart failure, estimated glomerular filtration rate, and left ventricular ejection fraction), the independent risk of death in each group compared to G1 as the reference group was: G2: HR 4.121 (95%CI 1.131-15.019); G3: HR 2.511 (95%CI 1.007-6.263); and G4: HR 7.418 (95%CI 1.630-33.763). Conclusion Congestion in outpatients with heart failure correlates with prognosis. Patients with both clinical and hemodynamic congestion had the highest risk of all-cause death at one year (AU)

Acetazolamide in Acute Decompensated Heart Failure with Volume Overload.

BACKGROUND: Whether acetazolamide, a carbonic anhydrase inhibitor that reduces proximal tubular sodium reabsorption, can improve the efficiency of loop diuretics, potentially leading to more and faster decongestion in patients with acute decompensated heart failure with volume overload, is unclear. METHODS: In this multicenter, parallel-group, double-blind, randomized, placebo-controlled trial, we assigned patients with acute decompensated heart failure, clinical signs of volume overload (i.e., edema, pleural effusion, or ascites), and an N-terminal pro-B-type natriuretic peptide level of more than 1000 pg per milliliter or a B-type natriuretic peptide level of more than 250 pg per milliliter to receive either intravenous acetazolamide (500 mg once daily) or placebo added to standardized intravenous loop diuretics (at a dose equivalent to twice the oral maintenance dose). Randomization was stratified according to the left ventricular ejection fraction (≤40% or >40%). The primary end point was successful decongestion, defined as the absence of signs of volume overload, within 3 days after randomization and without an indication for escalation of decongestive therapy. Secondary end points included a composite of death from any cause or rehospitalization for heart failure during 3 months of follow-up. Safety was also assessed. RESULTS: A total of 519 patients underwent randomization. Successful decongestion occurred in 108 of 256 patients (42.2%) in the acetazolamide group and in 79 of 259 (30.5%) in the placebo group (risk ratio, 1.46; 95% confidence interval [CI], 1.17 to 1.82; P<0.001). Death from any cause or rehospitalization for heart failure occurred in 76 of 256 patients (29.7%) in the acetazolamide group and in 72 of 259 patients (27.8%) in the placebo group (hazard ratio, 1.07; 95% CI, 0.78 to 1.48). Acetazolamide treatment was associated with higher cumulative urine output and natriuresis, findings consistent with better diuretic efficiency. The incidence of worsening kidney function, hypokalemia, hypotension, and adverse events was similar in the two groups. CONCLUSIONS: The addition of acetazolamide to loop diuretic therapy in patients with acute decompensated heart failure resulted in a greater incidence of successful decongestion. (Funded by the Belgian Health Care Knowledge Center; ADVOR ClinicalTrials.gov number, NCT03505788.).

Niveles plasmáticos de troponina T y de la fracción aminoterminal del propéptido natriurético cerebral y su relación con mortalidad en COVID-19 / Troponin-T and n-terminal pro-brain type natriuretic peptide plasma levels and its relationship with mortality in COVID-19

Introducción: El compromiso cardiovascular en la enfermedad por coronavirus 2019 (COVID-19) no necesariamente se presenta con los síntomas clásicos descriptos en la miocarditis. Es creciente la evidencia que demuestra compromiso cardiovascular subclínico en contexto de la intensa inflamación desatada, la tormenta de citocinas involucradas, el estado protrombótico basal y la disfunción endotelial consecuente. Nos propusimos analizar si la troponina T (TT) y la fracción amino-terminal del propéptido natriurético cerebral (NT-proBNP) determinada al momento de ingreso hospitalario se relacionan con la mortalidad durante la internación de estos pacientes. Material y métodos: Estudio analítico, observacional, de cohortes retrospectivas y corte transversal. Incluyó sujetos con COVID-19 internados por enfermedad moderada-severa, del 20 de marzo de 2020 al 15 de noviembre de 2020. Se analizaron las determinaciones de TT y NT-proBNP obtenidas en las primeras 24 horas de ingreso. Se consideró TT alterada si ≥ 0,014 ng/dL y NT-proBNP alterado si ≥ 300 pg/mL. Resultados: Se incluyeron 108 sujetos, 63,2% hombres, edad 51,5 años (59-43). El 28% ingreso a Unidad de Cuidados Intensivos (UCI) y el 25% falleció. El grupo de pacientes con TT elevada presentó mayor mortalidad (OR = 3,1; IC 95% = 1,10-8,85; p = 0,028) al igual que el grupo con NT-proBNP elevado (OR = 3,47; IC 95% = 1,21-9,97; p = 0,017). Al análisis multivariado sólo NT-proBNP ≥300 pg/mL se mantuvo como factor de riesgo independiente. Conclusiones: Niveles de NT-proBNP ≥ 300 pg/mL al ingreso en pacientes con COVID-19 moderada-severa se relacionaron con una mayor mortalidad.(AU)

Introduction: Cardiovascular compromise in coronavirus disease 2019 (COVID-19) does not necessarily present with the classic symptoms described in myocarditis. There is growing evidence demonstrating subclinical cardiovascular compromise in the context of the intense inflammation unleashed, the cytokine storm involved, the baseline prothrombotic state, and the consequent endothelial dysfunction. We set out to analyse whether Troponin-T (TT) and the amino-terminal fraction of pro-brain natriuretic peptide (NT-proBNP) determined at hospital admission, are related to mortality during the hospitalization of these patients. Material and methods: Analytical, observational, retrospective cohort and cross-sectional study. It included subjects with COVID-19 hospitalized for moderate-severe illness, from 20/03/20 to 15/11/20. The TT and NT-proBNP obtained in the first 24 hours from admission were analysed. Altered TT was considered if ≥.014 ng/dl and altered NT-proBNP if ≥300 pg/ml. Results: One hundred and eight subjects were included, 63.2% men, age 51.5 years (59-43), 28% were admitted to the Critical Unit and 25% died. The group with elevated TT presented higher mortality (OR = 3.1; 95%CI = 1.10-8.85; p = .02). The group with elevated NT-proBNP also show higher mortality (OR = 3.47; 95%CI = 1.21-9.97; p = .01). On multivariate analysis, only NT-proBNP ≥300 pg/ml remained an independent risk factor. Conclusions: NT-proBNP levels ≥300 pg/ml at admission in patients with moderate-severe COVID-19 were associated with higher mortality.(AU)

Serum Cat S, TSP-1, IL-11, BNP and sST2 Diagnostic and Prognostic Value in Chronic Heart Failure.

Context: Objectives • This study aimed to assess the diagnostic value of serum brain natriuretic peptide (BNP), cathepsin S (Cat S), serum soluble ST2 receptor (sST2), platelet reactive protein-1 (TSP-1) and interleukin-11 (IL-11) in patients with chronic heart failure (CHF). Context: Materials and Methods • A total of 112 patients admitted to in our hospital with HF were enrolled as the HF group and 120 healthy people undergoing physical examination were assigned to the control group. The serum levels of Cat S, TSP-1, IL-11, sST2 and BNP were measured and compared in the subgroups categorized according to New York Heart Association (NYHA) Functional Classification. Pearson correlation was applied to analyze the correlation between serum Cat S, TSP-1, IL-11, sST2 and BNP and NYHA functional class. Moreover, multivariate logistic regression was used to analyze the HF influencing factors. Context: Results • No correlation was found between the 2 groups in terms of general information, such as age, gender, body mass index (BMI), systolic blood pressure, diastolic blood pressure, smoking and heart rate (P > .05). The left ventricular ejection fraction (LVEF) in the HF group was lower than in the control group, while the level of LV end diastolic dimension (LVEDD) and left ventricular end diastolic volume (LVEDV) was significantly higher (P < .05). The levels of Cat S, TSP-1, sST2, IL-11 and BNP in the HF group were higher than in the control group (P < .05). The levels of Cat S, TSP-1, sST2, IL-11 and BNP in the grade IV group were higher than those in the grade II and III groups (P < .05). Serum Cat S, TSP-1, IL-11, sST2 and BNP levels were positively correlated with NYHA functional class (R = 0.568, 0.409, 0.472, 0.547, 0.632, respectively) (P < .001). Multivariate logistic regression analysis demonstrated that LVEF, LVEDD, LVEDV, Cat S, TSP-1, IL-11, sST2 and BNP were independent markers of CHF. Context: Conclusion • Abnormal Cat S, TSP-1, IL-11, sST2 and BNP levels were found in patients with CHF, and were highly associated with the cardiac function grades of CHF. Therefore, serum Cat S, TSP-1, IL-11, sST2 and BNP levels can serve as independent markers for CHF.

N-terminal pro-B-type natriuretic peptide testing patterns in patients with heart failure with reduced ejection fraction.

AIMS: The N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a commonly used biomarker in heart failure for diagnosis and prognostication. We aimed to determine the prevalence of NT-proBNP testing, distribution of NT-proBNP concentrations, and factors associated with receiving an NT-proBNP test in patients with heart failure with reduced ejection fraction (HFrEF), including the subset with a worsening heart failure event (WHFE). METHODS AND RESULTS: This was a retrospective cohort study using two US databases: (i) the de-identified Humana Research Database between January 2015 and December 2018 and (ii) the Veradigm PINNACLE Registry® between July 2013 and September 2017. We included adult patients with a confirmed diagnosis of HFrEF. In each data source, a subgroup of patients with a WHFE was identified, where a WHFE was defined as a heart failure-related hospitalization or receipt of intravenous diuretics. Bivariate and multivariate analyses were conducted to assess factors associated with receiving NT-proBNP testing. In Cohort 1 (n = 249 238), 9.2% of patients with HFrEF and 10.8% of patients with a WHFE received NT-proBNP testing. When restricted to patients with at least one laboratory claim, 11.3% of patients with HFrEF and 13.2% of those with a WHFE received NT-proBNP testing. In Cohort 2 (n = 91 444), 2.3% of patients with HFrEF were tested. Median (inter-quartile range) NT-proBNP concentrations among patients with HFrEF were 1399 (423-4087) pg/mL in Cohort 1 and 394 (142-688) pg/mL in Cohort 2. Median (inter-quartile range) NT-proBNP concentrations in the subset of patients with a WHFE in each cohort were 2209 (740-5894) and 464 (174-783) pg/mL, respectively. In Cohort 1, 13.4% of all HFrEF patients receiving NT-proBNP testing and 18.9% of patients with a WHFE had NT-proBNP values >8000 pg/mL; in Cohort 2, these percentages were 1.0% and 2.5%, respectively. CONCLUSIONS: In US clinical practice, NT-proBNP testing was not frequently performed in patients with HFrEF. NT-proBNP concentrations varied across data sources and subpopulations within HFrEF.

Physiological behavior during stress anticipation across different chronic stress exposure adaptive models.

Anticipation of stress induces physiological, behavioral and cognitive adjustments that are required for an appropriate response to the upcoming situation. Additional research examining the response of cardiopulmonary parameters and stress hormones during anticipation of stress in different chronic stress adaptive models is needed. As an addition to our previous research, a total of 57 subjects (16 elite male wrestlers, 21 water polo player and 20 sedentary subjects matched for age) were analyzed. Cardiopulmonary exercise testing (CPET) on a treadmill was used as the laboratory stress model; peak oxygen consumption (VO2) was obtained during CPET. Plasma levels of adrenocorticotropic hormone (ACTH), cortisol, alpha-melanocyte stimulating hormone (alpha-MSH) and N-terminal-pro-B type natriuretic peptide (NT-pro-BNP) were measured by radioimmunometric, radioimmunoassay and immunoassay sandwich technique, respectively, together with cardiopulmonary measurements, 10 minutes pre-CPET and at the initiation of CPET. The response of diastolic blood pressure and heart rate was different between groups during stress anticipation (p = 0.019, 0.049, respectively), while systolic blood pressure, peak VO2 and carbon-dioxide production responses were similar. ACTH and cortisol increased during the experimental condition, NT-pro-BNP decreased and alpha-MSH remained unchanged. All groups had similar hormonal responses during stress anticipation with the exception of the ACTH/cortisol ratio. In all three groups, ΔNT-pro-BNP during stress anticipation was the best independent predictor of peak VO2 (B = 36.01, r = 0.37, p = 0.001). In conclusion, the type of chronic stress exposure influences the hemodynamic response during anticipation of physical stress and the path of hormonal stress axis activation. Stress hormones released during stress anticipation may hold predictive value for overall cardiopulmonary performance during the stress condition.

LAY SUMMARYThe study revealed differences in hormonal and hemodynamic responses during anticipation of stress between athletes and sedentary participants. Stress hormones released during stress anticipation may hold predictive value for overall cardiopulmonary performance during the stress condition.

The use of cardiac troponins and B-type natriuretic peptide in COVID-19.

Coronavirus disease 2019 (COVID-19) is still challenging health care systems worldwide. Over time, it has become clear that respiratory disease is not the only important entity as critically ill patients are also more prone to develop complications, such as acute cardiac injury. Despite extensive research, the mainstay of treatment still relies on supportive care and targeted therapy of these complications. The development of a prognostic model which helps clinicians to diverge patients to an appropriate level of care is thus crucial. As a result, several prognostic markers have been studied in the past few months. Among them are the cardiac biomarkers, especially cardiac troponins T/I and brain natriuretic peptide, which seem to have important prognostic values as several reports have confirmed their strong association with adverse clinical outcomes and death. The use of these biomarkers as part of a prognostic tool could potentially result in more precise risk stratification of COVID-19 patients and divergence to an adequate level of care. However, several caveats persist causing international guidelines to still recommend in favour of a more conservative approach to cardiac biomarker testing for prognostic purposes.

The impact of cardiomotor rehabilitation on endothelial function in elderly patients with chronic heart failure.

BACKGROUND: To explore the effects of cardiac exercise rehabilitation on peripheral blood endothelial progenitor cells (EPC) in elderly patients with chronic heart failure. METHODS: 80 elderly patients with chronic heart failure were selected from March 2017 to March 2019 and randomly divided into two groups (N = 40). The control group was treated routinely and walked freely for 30-60 min every day. The patients in the exercise rehabilitation group developed a cardiac exercise rehabilitation plan. Then, cardiac function and peripheral blood B-natriuretic peptide (BNP) levels in the two groups were compared. The cell viability, proliferation, apoptosis, and invasion ability of EPCs were detected. The levels of the PI3K/AKT pathway and eNOS and VEGF were compared. RESULTS: There were no significant differences in all indexes between the two groups before treatment (P > 0.05), and both improved significantly after treatment (P < 0.05). After treatment, LVEF and LVFS in the exercise rehabilitation group were significantly higher than those in the control group (P < 0.05), and LVEDD and LVESD were significantly lower than those in the control group (P < 0.05). The BNP level in the exercise rehabilitation group was significantly lower than that in the control group (P < 0.05). The cell viability, proliferation, invasion ability of EPC, and the levels of PI3K, AKT, eNOS, and VEGF mRNA and protein in the exercise rehabilitation group were significantly higher than those in the control group. Apoptosis rate was significantly lower than those in the control group (P < 0.05). CONCLUSIONS: Visceral exercise rehabilitation can improve cardiac ejection and myocardial function in elderly patients with chronic heart failure, and can promote the vitality, proliferation, and invasion of peripheral blood EPC, and promote the expression of eNOS and VEGF by upregulating the PI3K/AKT pathway to promote angiogenesis and endothelial function.

Multimodal assessment of acute cardiac toxicity induced by thoracic radiotherapy in cancer patients. Study protocol.

BACKGROUND: Today, cancer ranks as one of the leading causes of death. Despite the large number of novel available therapies, radiotherapy (RT) remains as the most effective non-surgical method to cure cancer patients. In fact, approximately 50% of all cancer patients receive some type of RT and among these 60% receive RT-treatment with a curative intent. However, as occurs with any other oncological therapy, RT treated patients may experience toxicity side effects that range from moderate to severe. Among these, cardiotoxicity represents a significant threat for premature death. Current methods evaluate cardiotoxic damage based on volumetric changes in the Left Ventricle Ejected Fraction (LVEF). Indeed, a 10% drop in LVEF is commonly used as indicator of cardiotoxicity. More recently, a number of novel techniques have been developed that significantly improve specificity and sensitivity of heart's volumetric changes and early detection of cardiotoxicity even in asymptomatic patients. Among these, the Strain by Speckle Tracking (SST) is a technique based on echocardiographic analysis that accurately evaluates myocardial deformation during the cardiac cycle (ventricular and atrial function). Studies also suggest that Magnetic Resonance Imaging (MRI) is a high-resolution technique that enables a better visualization of acute cardiac damage. METHODOLOGY: This protocol will evaluate changes in SST and MRI in cancer patients that received thoracic RT. Concomitantly, we will assess changes in serum biomarkers of cardiac damage in these patients, including: high-sensitivity cardiac Troponin-T (hscTnT), N-Terminal pro-Brain Natriuretic Peptide (NTproBNP) and Circulating Endothelial Cells (CECs), a marker of endothelial dysfunction and vascular damage. DISCUSSION: The presented protocol is to our knowledge the first to prospectively and with a multimodal approach, study serological and image biomarkers off early cardiac damage due to radiotherapy. With a practical clinical approach we will seek early changes that could potentially be in the future be linked to clinical mayor events with consequences for cancer survivors.

Dexamethasone is associated with early deaths in light chain amyloidosis patients with severe cardiac involvement.

BACKGROUND: Cardiac light chain amyloidosis (AL-CA) patients often die within three months of starting chemotherapy. Chemotherapy for non-immunoglobulin M gammopathy with AL-CA frequently includes bortezomib (Bor), cyclophosphamide (Cy), and dexamethasone (D). We previously reported that NT-ProBNP levels can double within 24h of dexamethasone administration, suggesting a deleterious impact on cardiac function. In this study, we evaluate the role of dexamethasone in early cardiovascular mortality during treatment. METHODS AND FINDINGS: We retrospectively assessed 100 de novo cardiac AL patients (62% male, mean age 68 years) treated at our institute between 2009 and 2018 following three chemotherapy regimens: CyBorDComb (all initiated on day 1; 34 patients), DCyBorSeq (D, day 1; Cy, day 8; Bor, day 15; 17 patients), and CyBorDSeq (Cy, day 1; Bor, day 8; D, day 15; 49 patients). The primary endpoint was cardiovascular mortality and cardiac transplantation at days 22 and 455. At day 22, mortality was 20.6% with CyBorDComb, 23.5% with DCyBorSeq, and 0% with CyBorDSeq (p = 0.003). At day 455, mortality was not significantly different between regimens (p = 0.195). Acute toxicity of dexamethasone was evaluated on myocardial function using a rat model of isolated perfused heart. Administration of dexamethasone induced a decrease in left ventricular myocardium contractility and relaxation (p<0.05), supporting a potential negative inotropic effect of dexamethasone in AL-CA patients with severe cardiac involvement. CONCLUSION: Delaying dexamethasone during the first chemotherapy cycle reduces the number of early deaths without extending survival. It is clear that dexamethasone is beneficial in the long-term treatment of patients with AL-CA. However, the initial introduction of dexamethasone during treatment is critical, but may be associated with early cardiac deaths in severe CA. Thus, it is important to consider the dosage and timing of dexamethasone introduction on a patient-severity basis. The impact of dexamethasone in the treatment of AL-CA needs further investigation.

Telmisartan ameliorates cardiac fibrosis and diastolic function in cardiorenal heart failure with preserved ejection fraction.

Chronic kidney disease (CKD) is a major contributor to the development of heart failure with preserved ejection fraction (HFpEF), whereas the underlying mechanism of cardiorenal HFpEF is still elusive. The aim of this study was to investigate the role of cardiac fibrosis in a rat model of cardiorenal HFpEF and explore whether treatment with Telmisartan, an inhibitor of renin-angiotensin-aldosterone system (RAAS), can ameliorate cardiac fibrosis and preserve diastolic function in cardiorenal HFpEF. Male rats were subjected to 5/6 subtotal nephrectomy (SNX) or sham operation (Sham), and rats were allowed four weeks to recover and form a stable condition of CKD. Telmisartan or vehicle was then administered p.o. (8 mg/kg/d) for 12 weeks. Blood pressure, brain natriuretic peptide (BNP), echocardiography, and cardiac magnetic resonance imaging were acquired to evaluate cardiac structural and functional alterations. Histopathological staining, real-time polymerase chain reaction (PCR) and western blot were performed to evaluate cardiac remodeling. SNX rats showed an HFpEF phenotype with increased BNP, decreased early to late diastolic transmitral flow velocity (E/A) ratio, increased left ventricular (LV) hypertrophy and preserved ejection fraction (EF). Pathology revealed increased cardiac fibrosis in cardiorenal HFpEF rats compared with the Sham group, while chronic treatment with Telmisartan significantly decreased cardiac fibrosis, accompanied by reduced markers of fibrosis (collagen I and collagen III) and profibrotic cytokines (α-smooth muscle actin, transforming growth factor-ß1, and connective tissue growth factor). In addition, myocardial inflammation was decreased after Telmisartan treatment, which was in a linear correlation with cardiac fibrosis. Telmisartan also reversed LV hypertrophy and E/A ratio, indicating that Telmisartan can improve LV remodeling and diastolic function in cardiorenal HFpEF. In conclusion, cardiac fibrosis is central to the pathology of cardiorenal HFpEF, and RAAS modulation with Telmisartan is capable of alleviating cardiac fibrosis and preserving diastolic dysfunction in this rat model.

No difference in biomarkers of ischemic heart injury and heart failure in patients with COVID-19 who received treatment with chloroquine phosphate and those who did not.

BACKGROUND: Chloroquine was promoted as a COVID-19 therapeutic early in the pandemic. Most countries have since discontinued the use of chloroquine due to lack of evidence of any benefit and the risk of severe adverse events. The primary aim of this study was to examine if administering chloroquine during COVID-19 imposed an increased risk of ischemic heart injury or heart failure. METHODS: Medical records, laboratory findings, and electrocardiograms of patients with COVID-19 who were treated with 500 mg chloroquine phosphate daily and controls not treated with chloroquine were reviewed retrospectively. Controls were matched in age and severity of disease. RESULTS: We included 20 patients receiving chloroquine (500 mg twice daily) for an average of five days, and 40 controls. The groups were comparable regarding demographics and biochemical analyses including C-reactive protein, thrombocytes, and creatinine. There were no statistically significant differences in cardiac biomarkers or in electrocardiograms. Median troponin T was 10,8 ng/L in the study group and 17.9 ng/L in the control group, whereas median NT-proBNP was 399 ng/L in patients receiving chloroquine and 349 ng/L in the controls. CONCLUSIONS: We found no increased risk of ischemic heart injury or heart failure as a result of administering chloroquine. However, the use of chloroquine to treat COVID-19 outside of clinical trials is not recommended, considering the lack of evidence of its effectiveness, as well as the elevated risk of fatal arrythmias.