Prohormone Brain Natriuretic Peptide Levels Research Articles

Design of the Prospective Comparison of Angiotensin Receptor-Neprilysin Inhibitor Versus Placebo in Patients With Congenital Systemic Right Ventricle Heart Failure (PARACYS-RV) Trial

The presence of a systemic right ventricle (sRV) with biventricular physiology (biV) is associated with increased patient morbidity and mortality. To date, no pharmacologic therapy for heart failure has been proven effective for patients with systolic dysfunction of the sRV-biV. We designed a randomized, double-blind, placebo-controlled crossover trial to compare sacubitril/valsartan treatment to placebo in adults (aged ≥ 18 years) with moderate-to-severe sRV-biV dysfunction and New York Heart Association functional class II to III symptoms. Two primary efficacy endpoints are assessed in the trial: exercise capacity (submaximal exercise duration) and neurohormonal activation (N-terminal prohormone brain natriuretic peptide). Secondary objectives include assessing a change in the Kansas City Cardiomyopathy Questionnaire score and evaluating the safety and tolerance of sacubitril/valsartan. A 6-week open run-in phase identifies the maximum tolerated dose of sacubitril/valsartan, up to 97 mg/103 mg twice daily. After a 2-week washout period, patients are randomized 1:1 to sacubitril/valsartan treatment vs placebo for a 24-week phase, followed by another 2-week washout period and subsequent crossover to the alternative treatment arm for an additional 24-week phase. Data to assess primary and secondary endpoints are collected at baseline and at the end of each phase. A total of 48 patients is required to provide > 80% power to detect a 30% difference in distance walked and in N-terminal prohormone brain natriuretic peptide levels with sacubitril/valsartan treatment vs placebo, each with a 2-sided P-value of 0.025. In summary, the Prospective Comparison of Angiotensin Receptor-Neprilysin Inhibitor vs Placebo in Patients With Congenital Systemic Right Ventricular Heart Failure Trial (PARACYS-RV) should determine the role of sacubitril/valsartan in treating heart failure in patients with sRV-biV and carries the potential to alter management of this patient population.

Correlation between serum laminin levels and prognosis of acute myocardial infarction.

BackgroundAcute myocardial infarction (AMI) is a critical cardiovascular disease (CVD). Laminin (LN) is involved in the process of myocardial fibrosis and ventricular remodeling observed in AMI; however, there are currently no studies on the correlation between LN and AMI prognosis.PurposeTo explore the predictive value of serum LN levels for major adverse cardiovascular events (MACE) in patients, 6 months after an acute myocardial infarction.MethodsA total of 202 AMI patients who were hospitalized in the Department of Cardiology of the Second Affiliated Hospital of Nantong University between December 2019 and December 2020 were included. The observation endpoint was the occurrence of MACE. Univariate and multivariate logistic analyses were used to evaluate the relationships between the variables and endpoint. The predictive value of LN for MACE in AMI patients was assessed using receiver operating characteristic (ROC) analysis.ResultsA total of 47 patients developed MACE. Univariate logistic analysis showed that smoking, emergency percutaneous coronary intervention (EPCI), age, cardiac troponin I (c-TNI) levels, N-terminal prohormone brain natriuretic peptide (NT-proBNP) levels, and LN levels were associated with the occurrence of MACE (p < 0.05). Multivariate logistic analysis showed that LN was an independent predictor of MACE (odds ratio [OR] = 1.021, 95%CI: 1.014–1.032, p < 0.001). According to the ROC curve, LN can be used as an effective predictor of MACE (AUC = 0.856, 95%CI: 0.794–0.918, p < 0.001). According to the cutoff value, LN>58.80 ng/ml (sensitivity = 83.00%, specificity = 76.80%) or LN>74.15 ng/ml (sensitivity = 76.6%, specificity = 83.2%) indicate a poor prognosis for AMI. Different cut-off values are selected according to the need for higher sensitivity or specificity in clinical applications.ConclusionsLN may be a predictor of MACE following AMI in patients and could be utilized as a novel substitute marker for the prevention and treatment of AMI.

Association of amniotic fluid natriuretic peptide levels with ductus venosus Doppler flow in recipient twins with twin-to-twin transfusion syndrome

This study examined the relationships between fetal quantitative Doppler parameters and amniotic fluid N-terminal prohormone brain natriuretic peptide (afNT-proBNP) levels as a biomarker of the increased cardiac load in recipient twins with twin-to-twin transfusion syndrome (TTTS). This single-center, prospective study included all monochorionic diamniotic (MD) twin pregnancies that were diagnosed with TTTS and underwent fetoscopic laser surgery. Doppler flow was used to measure the pulsatility index (PI) of the umbilical artery (UA), ductus venosus (DV), and middle cerebral artery (MCA) of each recipient and donor twins. The afNT-proBNP levels of recipient twins were examined at the time of surgery. The Spearman or Pearson correlation coefficients were used to assess the relationships between afNT-proBNP levels and Doppler parameters. A total of 150 MD twin pregnancies were included. The afNT-proBNP levels of the recipient twins showed a stronger correlation with the DV-PI (r = 0.637; P < 0.001) of recipient twins than with the UA-PI and MCA-PI of recipient twins. The Doppler parameters of donor twins were scarcely correlated with the afNT-proBNP levels of the recipient twins. A positive correlation between the DV-PI and afNT-proBNP levels of recipient twins with TTTS was observed. The recipient twin with an increased DV-PI is expected to be under a high cardiac load; therefore, DV-PI is a useful parameter for assessing increased NT-proBNP levels consecutively and noninvasively. This study was registered with Japanese Clinical Trial Registry "UMIN-CTR" ( http://www.umin.ac.jp/ctr/index-j.htm ; trial ID numbers UMIN000024486 and 000037702).

Tachycardia and Pre-existing Chronic Kidney Disease Are Predictors of the Worse Clinical Outcomes in Patients Recently Hospitalized With Acute Heart Failure.

Background: This study aimed to assess the factors contributing to the outcomes of recently hospitalized patients with heart failure (HF).Methods: A prospective data of 76 adults who were admitted due to acute HF between October 1, 2019 and June 30, 2020 at our center were analyzed. Endpoints included survival and rehospitalization within six months after discharge.Results: The mean age was 64.9 ± 13.8 years, with a male preponderance (68.4%). Approximately 60.5% of patients had the left ventricular ejection fraction (LVEF) <40%, whereas 26.3% of patients had LVEF ≥50%. Coronary artery disease (75%), arterial hypertension (72.4%), chronic kidney disease (46.1%), and diabetes mellitus (46.1%) were the most frequent comorbidities. Poor compliance (40.8%) and non-cardiac infection (21.1%) were the common precipitating factors for hospitalization. The majority of subjects had severe symptoms, indicated by the frequent need of intensive care unit (43%), high N-terminal prohormone brain natriuretic peptide levels [NT-proBNP; median, 4765 (1539.7-11782.2) pg/mL], and presence of either atrial fibrillation, severe mitral regurgitation, or significant pulmonary hypertension in approximately one-third of cases. Even though in-hospital mortality was relatively low (2.6%), the all-cause mortality and rehospitalization rates in the next six months after discharge were still high, reaching 22.54% and 19.72%, respectively. Further survival analysis showed that tachycardia on admission and pre-existing chronic kidney disease (CKD) resulted in low six-month survival rates among these patients.Conclusion: After hospital discharge, patients with HF were still exposed to higher risks of death and readmission albeit with the medication addressed. Tachycardia on admission and pre-existing CKD might predict worse outcomes.

Elevations in High-Sensitive Cardiac Troponin T and N-Terminal Prohormone Brain Natriuretic Peptide Levels in the Serum Can Predict the Development of Anthracycline-Induced Cardiomyopathy.

Anthracyclines remain the cornerstone of the treatment in many cancers including lymphomas, leukemia and sarcomas, and breast cancer. The cardiomyopathy that develops from anthracyclines can lead to heart failure and decreased survival. Multiple mechanisms are involved in the pathophysiology of anthracycline-induced heart failure. We hypothesize that anthracycline-induced cardiac (AIC) pathology can be monitored using a panel of blood biomarkers including high-sensitive cardiac troponin T (hs-cTnT) for myocyte necrosis and N-terminal prohormone brain natriuretic peptide (NT-proBNP) for parietal stress. A prospective, institutionally approved study recruited all patients with cancer scheduled to start anthracycline chemotherapy in the Transylvania University cancer clinics. Transthoracic 2D echocardiography and the measurements of NT-proBNP and hs-cTnT plasma levels were performed at the beginning of the study and 3 months and 6 months after anthracycline treatment initiation. The plasma levels of hs-cTnT at 3 months (rho = 0.439, P = 0.0001) and 6 months (rho = 0.490, P = 0.0001) are correlated with AIC occurrence. For a cutoff value of hs-cTnT at 3 months > 0.008 ng/mL, we obtained 66.7% sensitivity and 67.9% specificity for developing AIC at 6 months, with a 54.5% positive predictive value and a 87.8% negative predictive value. The NT-proBNP serum levels at 3 months (rho = 0.495, P = 0.0001) and 6 months (rho = 0.638, P = 0.0001) are correlated with an AIC diagnosis at 6 months. For a cutoff value of NT-proBNP at 3 months >118.5 pg/mL, we obtained 80% sensitivity and 79.2% specificity for evolution to AIC at 6 months, with 52.2% positive predictive value and 93.3% negative predictive value. In anthracycline-treated cancer patients, the increase in plasma levels of NT-proBNP and of hs-cTnT can predict the development of anthracycline-induced cardiomyopathy. Early identification of at-risk patients will potentially allow for targeted dose reductions and will diminish the number of patients developing cardiac pathology.

Anthracycline-induced cardiotoxicity prevention with angiotensin-converting enzyme inhibitor ramipril in women with low-risk breast cancer: results of a prospective randomized study.

Anthracycline‑induced cardiotoxicity (AIC) remains the main long‑term irreversible side effect in malignancy survivors. Cardiotoxicity prevention is one of the most reasonable approaches. In this prospective randomized open‑label study, we aimed to verify whether ramipril protects from early‑onset AIC in women with breast cancer (BC). We analyzed data from 96 women (median age, 47 years) with BC after breast surgery, without significant cardiovascular diseases, who were eligible for adjuvant anthracyclines. They were randomized to a ramipril or control arm. Cardiotoxicity was estimated with repeat echocardiography and themeasurement of troponin I and N‑terminal fragment of the prohormone brain natriuretic peptide (NT‑proBNP) levels over 1‑year follow‑up. Anthracycline‑induced cardiotoxicity was defined as a decrease in left ventricular ejection fraction (LVEF), elevated biomarker levels, and/or occurrence of heart failure (HF) or cardiac death. A decrease in LVEF above 10‑percent points occurred in 6.3% of ramipril patients and 18.5% ofcontrols (P = 0.15). No cases of HF, cardiac death, or LVEF decline below 50% were reported. The percentage of patients with elevated NT‑proBNP levels increased with time in controls (P = 0.003) and remained unchanged in the ramipril arm. At the end of follow‑up, an increase in NT‑proBNP levels was more common and decline was less common in the control than ramipril arm (P = 0.01). No significant differences in troponin levels were found between the study arms. Ramipril was well tolerated in normotensive women. In relatively young women with BC without serious comorbidities, who received anthracyclines, 1‑year treatment with ramipril exerts potentially protective effects on cardiotoxicity assessed with NT‑proBNP levels.

Effect of Inorganic Nitrite vs Placebo on Exercise Capacity Among Patients With Heart Failure With Preserved Ejection Fraction

There are few effective treatments for heart failure with preserved ejection fraction (HFpEF). Short-term administration of inorganic nitrite or nitrate preparations has been shown to enhance nitric oxide signaling, which may improve aerobic capacity in HFpEF. To determine the effect of 4 weeks' administration of inhaled, nebulized inorganic nitrite on exercise capacity in HFpEF. Multicenter, double-blind, placebo-controlled, 2-treatment, crossover trial of 105 patients with HFpEF. Participants were enrolled from July 22, 2016, to September 12, 2017, at 17 US sites, with final date of follow-up of January 2, 2018. Inorganic nitrite or placebo administered via micronebulizer device. During each 6-week phase of the crossover study, participants received no study drug for 2 weeks (baseline/washout) followed by study drug (nitrite or placebo) at 46 mg 3 times a day for 1 week followed by 80 mg 3 times a day for 3 weeks. The primary end point was peak oxygen consumption (mL/kg/min). Secondary end points included daily activity levels assessed by accelerometry, health status as assessed by the Kansas City Cardiomyopathy Questionnaire (score range, 0-100, with higher scores reflecting better quality of life), functional class, cardiac filling pressures assessed by echocardiography, N-terminal fragment of the prohormone brain natriuretic peptide levels, other exercise indices, adverse events, and tolerability. Outcomes were assessed after treatment for 4 weeks. Among 105 patients who were randomized (median age, 68 years; 56% women), 98 (93%) completed the trial. During the nitrite phase, there was no significant difference in mean peak oxygen consumption as compared with the placebo phase (13.5 vs 13.7 mL/kg/min; difference, -0.20 [95% CI, -0.56 to 0.16]; P = .27). There were no significant between-treatment phase differences in daily activity levels (5497 vs 5503 accelerometry units; difference, -15 [95% CI, -264 to 234]; P = .91), Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (62.6 vs 61.9; difference, 1.1 [95% CI, -1.4 to 3.5]; P = .39), functional class (2.5 vs 2.5; difference, 0.1 [95% CI, -0.1 to 0.2]; P = .43), echocardiographic E/e' ratio (16.4 vs 16.6; difference, 0.1 [95% CI, -1.2 to 1.3]; P = .93), or N-terminal fragment of the prohormone brain natriuretic peptide levels (520 vs 533 pg/mL; difference, 11 [95% CI, -53 to 75]; P = .74). Worsening heart failure occurred in 3 participants (2.9%) during the nitrite phase and 8 (7.6%) during the placebo phase. Among patients with HFpEF, administration of inhaled inorganic nitrite for 4 weeks, compared with placebo, did not result in significant improvement in exercise capacity. ClinicalTrials.gov Identifier: NCT02742129.

Association of left atrial pressure with left atrial volume and N-terminal prohormone brain natriuretic peptide in children with cardiomyopathy.

Enlargement of the left atrium is a non-invasive marker of diastolic dysfunction of the left ventricle, a determinant of prognosis in children with cardiomyopathy. Similarly, N-terminal prohormone brain natriuretic peptide is a useful marker in the management of children with cardiomyopathy and heart failure. The aim of this study is to evaluate the association of left atrial pressures with left atrial volume and N-terminal prohormone brain natriuretic peptide in children with cardiomyopathy. This was a retrospective study reviewing the medical records of patients <18 years of age, who were diagnosed with cardiomyopathy or acute myocarditis with eventual development of cardiomyopathy. Left atrial volume by transthoracic echocardiogram and pulmonary capillary wedge pressure, a surrogate of left atrial pressure, obtained by means of cardiac catheterisation were analysed. In addition, N-terminal prohormone brain natriuretic peptide levels obtained at the time of the cardiac catheterisation were also reviewed. Statistical analysis was performed to evaluate the association of left atrial pressures with left atrial volume and N-terminal prohormone brain natriuretic peptide levels. There was a linear correlation of left atrial pressure estimated in the cardiac catheterisation with indexed left atrial volume (r=0.63; p<0.001) and left atrial volume z-scores (r=0.59; p<0.001). We found no statistically significant association between the left atrial pressure and N-terminal prohormone brain natriuretic peptide levels. Left atrial volume measured non-invasively by echocardiography can be used as a surrogate for left atrial pressure in assessing diastolic dysfunction of the left ventricle in children with cardiomyopathy. The larger the size of the left atrium, worse is the diastolic function of the left ventricle.

Efficacy of Ranolazine in Patients With Symptomatic Hypertrophic Cardiomyopathy: The RESTYLE-HCM Randomized, Double-Blind, Placebo-Controlled Study.

The late sodium current inhibitor ranolazine reverses the main electrophysiological and mechanical abnormalities of human hypertrophic cardiomyopathy (HCM) cardiomyocytes in vitro, suggesting potential clinical benefit. We aimed to assess the effect of ranolazine on functional capacity, symptomatic status, diastolic function, and arrhythmias in HCM. In this multicenter, double-blind, phase 2 study, 80 adult patients with nonobstructive HCM (age 53±14 years, 34 women) were randomly assigned to placebo (n=40) or ranolazine 1000 mg bid (n=40) for 5 months. The primary end point was change in peak VO2 compared with baseline using cardiopulmonary exercise test. Echocardiographic lateral and septal E/E' ratio, prohormone brain natriuretic peptide levels, 24-hour Holter arrhythmic profile, and quality of life were assessed. Ranolazine was safe and well tolerated. Overall, there was no significant difference in VO2 peak change at 5 months in the ranolazine versus placebo group (delta 0.15±3.96 versus -0.02±4.25 mL/kg per minute; P=0.832). Ranolazine treatment was associated with a reduction in 24-hour burden of premature ventricular complexes compared with placebo (>50% reduction versus baseline in 61% versus 31%, respectively; P=0.042). However, changes in prohormone brain natriuretic peptide levels did not differ in the ranolazine compared with the placebo group (geometric mean median [interquartile range], -3 pg/mL [-107, 142 pg/mL] versus 78 pg/mL [-71, 242 pg/mL]; P=0.251). Furthermore, E/E' ratio and quality of life scores showed no significant difference. In patients with nonobstructive HCM, ranolazine showed no overall effect on exercise performance, plasma prohormone brain natriuretic peptide levels, diastolic function, or quality of life. The drug showed an excellent safety profile and was associated with reduced premature ventricular complex burden. Late sodium current inhibition does not seem to improve functional capacity in HCM. URL: https://www.clinicaltrialsregister.eu. Unique identifier: 2011-004507-20.

Elevated serum osteoprotegerin is associated with increased left ventricular mass index and myocardial stiffness

Osteoprotegerin (OPG) is associated with a poor prognosis in patients with heart failure with preserved ejection fraction (HFpEF). OPG has also been associated with fibrosis and collagen cross-linking, which increase arterial and left ventricle (LV) myocardial stiffness. Little is known about the relation of OPG and LV structure and function in African-Americans who are disproportionately affected by HFpEF. Our analysis included 1172 participants with preserved LV ejection fraction (>50%) from the African-American cohort in the Genetic Epidemiology Network of Arteriopathy Study (mean age 63 years, 72% female). We used diastolic wall strain indicator measured by echocardiography to assess LV myocardial stiffness. Diastolic wall strain was calculated as (LV posterior thickness at end-systole - LV posterior thickness at end-diastole)/LV posterior thickness at end-systole. Associations between OPG levels and indices of arterial and LV structure and function were evaluated by using generalized linear mixed models and adjusted for possible confounders. OPG levels were correlated with age, female sex, presence of hypertension and diabetes, and lower estimated glomerular filtration rate (P < 0.05 for all). Multivariable analysis revealed that higher OPG levels were associated with greater LV mass index, increased LV myocardial stiffness, and higher N-terminal prohormone brain natriuretic peptide levels (P < 0.05 for all). In African-Americans, higher OPG levels were associated with characteristics common in patients with HFpEF and were significantly associated with known precursors to HFpEF. These findings indicate a potential role for OPG in the pathophysiology of HFpEF in African-Americans.

Abstract 11417: Elevated Serum Osteoprotegerin is Associated With Increased Left Ventricular Mass Index and Left Ventricular Diastolic Stiffness in African Americans: Insights From the Genetic Epidemiology Network of Arteriopathy (GENOA) Study

Background: Osteoprotegerin (OPG) associates with a poor prognosis in patients that have already developed heart failure with preserved ejection fraction (HFpEF). OPG also associates with fibrosis and collagen cross-linking which increase diastolic stiffness in the left ventricle (LV). Little is known about the relationship of OPG and LV structure and function in African Americans who are disproportionately affected by HFpEF. We hypothesized that OPG may serve as an early indicator of developing LV hypertrophy and stiffening which are prominent precursors to HFpEF. Methods and Results: Our analysis included 1172 participants with preserved LV ejection fraction (EF &gt;50%) from the African American (Jackson) cohort of the Genetic Epidemiology Network of Arteriopathy (GENOA) Study (mean age 62.9 years, 72% female). LV diastolic stiffness was assessed by echocardiography using the recently developed diastolic wall strain (DWS) indicator calculated as (LV posterior wall thickness at end-systole - LV posterior wall thickness at end-diastole) / LV posterior wall thickness at end-systole. Associations between serum OPG levels and indices of LV structure and function were evaluated using a generalized linear mixed models (GLMM) accounting for clustering in siblings, and adjusted for possible confounders including age, gender, past history of hypertension and diabetes, current smoking status and estimated glomerular filtration rate (eGFR). OPG levels correlated with age, female sex, presence of hypertension and diabetes, lower eGFR, and higher N-terminal prohormone brain natriuretic peptide levels (p &lt;0.05 for all). Thus, higher OPG levels were associated with characteristics common in patients with HFpEF. Multivariable linear regression analysis revealed that after adjustment for covariates, higher OPG levels were associated with greater LV mass index and increased LV diastolic stiffness (p &lt;0.05, for all). Conclusions: Higher OPG levels associated with characteristics common in patients with HFpEF in African Americans. The serum OPG levels also significantly associated with known precursors to HFpEF, indicating a potential pathophysiologic role for OPG in the development of HFpEF in African Americans.

Uric Acid, Oxidative Stress and Inflammation in Chronic Heart Failure with Reduced Ejection Fraction

Abstract Background. Oxidative stress (OS) and inflammation are major mechanisms involved in the progression of chronic heart failure (CHF). Serum uric acid (sUA) is related to CHF severity and could represent a marker of xanthine-oxidase activation. The relationship between sUA, oxidative stress (OS) and inflammation markers was assessed in patients with moderate-severe CHF and reduced left ventricular (LV) ejection fraction (EF). Methods. In 57 patients with stable CHF, functional NYHA class III, with EF&lt;40%, the LV function was assessed by N-terminal of the prohormone brain natriuretic peptide (NT-proBNP) levels and echocardiographically through the EF and E/e’ ratio, a marker of LV filling pressures. The relationship between LV function, sUA, malondialdehyde (MDA), myeloperoxidase (MPO), paraoxonase 1 (PON-1) as OS markers and high sensitivity C-reactive protein (hsCRP) and interleukin 6 (IL-6) as markers of systemic inflammation was evaluated. Results. The mean sUA level was 7.9 ± 2.2 mg/dl, and 61% of the CHF patients had hyperuricemia. CHF patients with elevated LV filling pressures (E/e’ ≥ 13) had higher sUA (8.6 ± 2.3 vs. 7.3 ± 1.4, p=0.08) and NT-proBNP levels (643±430 vs. 2531±709, p=0.003) and lower EF (29.8 ± 3.9 % vs. 36.3 ± 4.4 %, p=0.001). There was a significant correlation between sUA and IL-6 (r = 0.56, p&lt;0.001), MDA (r= 0.49, p= 0.001), MPO (r=0.34, p=0.001) and PON-1 levels (r= −0.39, p= 0.003). Conclusion. In CHF, hyperuricemia is associated with disease severity. High sUA levels in CHF with normal renal function may reflect increased xanthine-oxidase activity linked with chronic inflammatory response.

Biological significance of miR-126 expression in atrial fibrillation and heart failure.

We investigated the biological significance of microRNA-126 (miR-126) expression in patients with atrial fibrillation (AF) and/or heart failure (HF) to examine the possible mechanism of miR-126-dependent AF and development of HF. A total of 103 patients were divided into three groups: AF group (18 men and 17 women, mean age: 65.62±12.72 years), HF group (17 men and 15 women, mean age: 63.95±19.71 years), and HF-AF group (20 men and 16 women, mean age: 66.56±14.37 years). Quantitative real-time PCR was used to measure relative miR-126 expression as calculated by the 2−ΔΔCt method. miR-126 was frequently downregulated in the 3 patient groups compared with controls. This reduction was significantly lower in permanent and persistent AF patients than in those with paroxysmal AF (P<0.05, t-test). Moreover, miR-126 expression was markedly lower in the HF-AF group compared with the AF and HF groups. The 3 patient groups had higher N-terminal prohormone brain natriuretic peptide (NT-proBNP) levels, lower left ventricular ejection fraction (LVEF), larger left atrial diameter, and higher cardiothoracic ratio compared with controls. There were significant differences in NT-proBNP levels and LVEF among the AF, HF, and HF-AF groups. Pearson correlation analysis showed that relative miR-126 expression was positively associated with LVEF, logarithm of NT-proBNP, left atrial diameter, cardiothoracic ratio, and age in HF-AF patients. Multiple linear regression analysis showed that miR-126 expression was positively correlated with LVEF, but negatively correlated with the logarithm of NT-pro BNP and the cardiothoracic ratio (all P<0.05). Serum miR-126 levels could serve as a potential candidate biomarker for evaluating the severity of AF and HF. However, to confirm these results, future studies with a larger and diverse patient population are necessary.

Comparison of the long term cardiac effects associated with 9 and 52 weeks of trastuzumab in HER2-positive early breast cancer

Purpose:Trastuzumab induced cardiotoxicity (TIC) was defined as the most serious side effect. Long term cardiac effects of trastuzumab are still not known, thus we aimed to compare the long term cardiac effects of adjuvant trastuzumab therapies of HER2-positive breast cancer according to the treatment duration.Methods:Patients who completed adjuvant trastuzumab treatment at least 6 months before for the adjuvant setting in HER2-positive breast cancer were included in the study. A total of 164 patients were included in this study: 108 and 56 patients were treated with 9 weeks and 52 weeks of trastuzumab, respectively. The main limitation of our study is that due to the cross-sectional evaluation of cardiac biomarkers we cannot predict the status of baseline cardiac biomarkers of this population.Results:The median follow-up of the study was 32 (10–95) months. The accompanying chronic diseases were similar in both groups. Baseline left ventricular ejection fraction (LVEF) was 65.5 ± 3.4% vs 67.1 ± 4.5% in the 9 weeks and 52 weeks trastuzumab treatment groups, respectively (p = 0.13). Symptomatic heart failure was not observed during trastuzumab treatment in either group. Trastuzumab induced cardiotoxicity (TIC) was observed in 2 (1.9%) and 17 (30.3%) patients in the 9 and 52 weeks trastuzumab treatment groups, respectively (p < 0.001). After a median 24 months of follow-up from the last dose of trastuzumab, mean LVEF values were similar between the two treatment arms (p = 0.29). In the subgroup analyses, mean LVEF values were significantly lower in patients who developed TIC compared to those who did not develop TIC (61.9 ± 3.6% vs 64.4 ± 2.6%, p = 0.04). Average mean LVEF loss from baseline was significantly higher in patients who developed TIC compared to those who did not develop TIC (10.0 ± 6.0% vs 1.5 ± 6.2%, p < 0.001). Cardiac biomarkers were similar in both treatment groups. In the subgroup analyses serum High-sensitivity C-reactive protein (hs-CRP) and prohormone brain natriuretic peptide (pro-BNP) levels were significantly higher in patients who developed TIC compared to those who did not develop TIC.Conclusions:TIC was observed to be significantly higher in the 52 weeks trastuzumab group. At the end of 32 months of follow-up mean LVEF values and cardiac biomarkers were similar between the two treatment groups. In the subgroup analyses, significant LVEF loss and higher cardiac biomarkers which show cardiac damage in patients who developed TIC can be permanent in some of the patients and long term cardiac damage may be underestimated.

Dengue myocarditis presenting with mitral valve involvement

We admitted a case of dengue fever who was positive for dengue serotype 2 in the Department of Medicine, King George's Medical University (K.G.M.U.), Lucknow, Uttar Pradesh, India. The patient had developed erythematous rashes with thrombocytopenia and bleeding manifestation in the form of microscopic hematuria. While he was recovering from the illness, he developed a sudden onset of breathlessness. On examination, his chest was full of crepitation bilaterally and his x-ray was suggestive of pulmonary edema. His troponin T (Trop T) and prohormone brain natriuretic peptide (proBNP) levels were elevated. Two-dimensional echo showed global left ventricular (LV) hypokinesia with mitral regurgitation (MR) and tricuspid regurgitation (TR). A diagnosis of myocarditis was made and the patient was managed in an intensive care unit (ICU) setting. The patient recovered from the illness and after a follow-up period of 6 weeks, showed no residual cardiac abnormality.

Elevated Plasma IL-38 Concentrations in Patients with Acute ST-Segment Elevation Myocardial Infarction and Their Dynamics after Reperfusion Treatment

Objective. Recent studies suggest that IL-38 is associated with autoimmune diseases. Furthermore, IL-38 is expressed in human atheromatous plaque. However, the plasma levels of IL-38 in patients with ST-segment elevation myocardial infarction (STEMI) have not yet to be investigated. Methods. On admission, at 24 h, at 48 h, and at 7 days, plasma IL-38, C-reactive protein (CRP), cardiac troponin I (cTNI), and N-terminal of the prohormone brain natriuretic peptide (NT-proBNP) levels were measured and IL-38 gene in peripheral blood mononuclear cells (PBMCs) was detected in STEMI patients. Results. The results showed that plasma IL-38 levels and IL-38 gene expression in PBMCs were significantly increased in STEMI patients compared with control group and were time dependent, peaked at 24 h. In addition, plasma IL-38 levels were dramatically reduced in patients with reperfusion treatment compared with control group. Similar results were also demonstrated with CRP, cTNI, and NT-proBNP levels. Furthermore, IL-38 levels were found to be positively correlated with CRP, cTNI, and NT-proBNP and be weakly negatively correlated with left ventricular ejection fraction (LVEF) in STEMI patients. Conclusions. The results indicate that circulating IL-38 is a potentially novel biomarker for patients with STEMI and IL-38 might be a new target for MI study.

A 6-year follow-up study of adult patients with congenitally corrected transposition.

The aims of this study were to assess the development of heart failure in patients with congenitally corrected transposition of the great arteries in a medium-term follow-up, to identify the impact of tricuspid regurgitation on the development of heart failure, and to determine the most reliable marker for its identification. The prospective 6-year follow-up study included 19 adult patients. All patients were evaluated clinically by the determination of N-terminal pro-hormone brain natriuretic peptide levels, exercise stress testing, echocardiography magnetic resonance, or CT. Among them, two patients died of heart failure. There was a decline in exercise capacity and systolic systemic ventricular function (p=0.011). Systemic ventricular ejection fraction decreased (48.3±13.7 versus 42.7±12.7%, p=0.001). Tissue Doppler imaging showed a decline in peak tricuspid systolic annular velocity (10.3±2.0 versus 8.3±2.5 cm/second, p=0.032) and peak tricuspid early diastolic annular velocity (14.6±4.3 versus 12.0±4.5 cm/second, p=0.048). The tricuspid regurgitation did not increase significantly. N-terminal pro-hormone brain natriuretic peptide levels increased (127.0 ng/L(82.3-305.8) versus 226.0 ng/L(112.5-753.0), p=0.022). Progressive exercise intolerance in congenitally corrected transposition of the great arteries appears to be driven mainly by a progression in systemic right ventricular dysfunction. Tricuspid regurgitation is likely to play a role, especially in patients with structural abnormalities of the tricuspid valve - Ebstein anomaly. The N-terminal pro-hormone brain natriuretic peptide levels and tissue Doppler parameters appear sensitive in detecting changes over time and may guide management.

Quality of Life in Patients With ST-Segment Elevation Myocardial Infarction Undergoing Percutaneous Coronary Intervention—Radial Versus Femoral Access (from the OCEAN RACE Trial)

Numerous studies have compared transradial (TR) versus transfemoral (TF) access for percutaneous coronary intervention (PCI) in patients with acute ST-segment elevation myocardial infarction. These studies have focused on clinical efficacy and safety; yet little is known about the effect of the vessel access on the health-related quality of life (HRQoL). In the present study, patients were randomly assigned to TR (n= 52) or TF (n= 51) access groups. Generic (EQ-5D-3L) and cardiac-specific (Quality of Life Index and MacNew) tools were used to assess HRQoL before PCI and 2hours and 4days after PCI. Baseline HRQoL was comparable in both groups and improved after PCI. The mean ± SD EQ-5D-3L health utility score 2 hours after PCI was 0.46 ± 0.291 and was higher in the TR group (TR: 0.60 ± 0.299 versus TF: 0.32 ± 0.283, p <0.001). Patients in the TR group reported fewer problems with mobility (TR: 71.7% vs TF: 94.4%, p <0.01) and self-care (TR: 62.5% vs TF: 97.2%, p<0.001). At day 4, fewer patients reported problems with anxiety and/or depression in the TR group than in the TF group (TR: 42.9% vs TF: 75.0%, p <0.001); no differences between groups in other measures were observed (Quality of Life Index and MacNew). The N-terminal of the prohormone brain natriuretic peptide levels were inversely correlated with EQ-5D-3L visual analog scale (r=-0.348, p <0.05) and EQ-5D-3L health utility score (r=-0.322, p <0.05). There was a correlation between in-hospital mortality and 2 MacNew domains: physical (r=-0.329, p <0.05) and emotional (r=-0.374, p <0.01). In conclusion, radial access should be the preferred approach in patients with ST-segment elevation myocardial infarction undergoing PCI when considering HRQoL. Radial access is associated with fewer problems with mobility and self-care and better psychological outcome after PCI.

Clinical Implications of Serial Serum N-Terminal Prohormone Brain Natriuretic Peptide Levels in the Prediction of Outcome in Children With Dilated Cardiomyopathy

N-terminal prohormone brain natriuretic peptide (NT-proBNP) is known to be valuable as a prognostic marker for the management of heart failure. This study aimed to assess the serial changes of serum NT-proBNP levels as a prognostic factor for outcomes of pediatric dilated cardiomyopathy (DC). A retrospective study reviewed echocardiographic measurements and serum NT-proBNP levels obtained at the time of diagnosis, 3 and 6 months after diagnosis, and at the last follow-up in 68 children with DC. They were classified into 3 groups according to the last follow-up of the left ventricular (LV) function: group I (n = 37) with LV fractional shortening (FS) ≥25%, group II (n = 15) with 10% ≤ LVFS < 25%, and group III (n = 16) with LVFS <10% or cardiac death. The median age at diagnosis was 30 months and median duration of follow-up was 45 months (range 8 to 108 months). The origin of DC varied. Serial serum NT-proBNP levels showed statistically significant differences among the 3 groups. Although initial levels of serum NT-proBNP at diagnosis were not different from each other, group III maintained a higher NT-proBNP level throughout the duration of the follow-up. On multivariate Cox analysis, only the NT-proBNP level at 3 months was a significant predictor of an adverse outcome (hazard ratio 2.012, p = 0.028). The percent changes of NT-proBNP from diagnosis were not significant. Patients with DC with a serum NT-proBNP level ≥681 pg/ml at 3 months after diagnosis showed an increased risk of severe LV dysfunction or cardiac death (p <0.001, area under the curve = 0.846). In conclusion, the level of NT-proBNP in serum at 3 months after diagnosis could predict an adverse outcome in pediatric DC and could be used as a guide for long-term treatment plans.

Do Predictors of Incomplete Kawasaki Disease Exist for Infants?

Kawasaki disease (KD), an acute febrile vasculitis, is the most common cause of acquired heart disease in infants and young children. However, the diagnosis of infantile KD can be difficult or delayed due to vague clinical manifestations. This current study aimed to assess the clinical characteristics and cardiac complications of infantile KD. The study retrospectively reviewed the data of 242 patients with KD. The clinical, laboratory, and echocardiographic data between infants and older children were analyzed. The patients were divided into two groups: infants 12 months old or younger and children older than 12 months. The rate of incomplete KD was much more frequent in infants. During all phases, prohormone brain natriuretic peptide (Pro-BNP) levels were higher in infants, as was thrombocytosis. The coronary artery z-score was higher in infants at all phases of KD. On tissue Doppler imaging, the E/E' ratio (ratio of transmitral Doppler early filling velocity to tissue Doppler early diastolic mitral annular velocity) was higher at the septal and lateral annulus in infants. Infant patients with KD are at increased risk for the development of coronary abnormalities and diastolic dysfunction. Higher levels of Pro-BNP and thrombocytosis with diastolic echo parameters of a higher E/E' ratio can help to identify incomplete KD in infants.