Peak Brain Natriuretic Peptide Research Articles

An Increase in the Ratio of Brain Natriuretic Peptide to Peak Transvalvular Pressure Gradient Suggests Coexistence of Cardiovascular Complications in Elderly Aortic Stenosis Patients.

The aim of this study was to differentiate between elderly aortic stenosis (AS) patients with and without cardiovascular complications (CCs).In total, 156 consecutive patients with AS aged ≥ 70 years were enrolled. Patients were divided into 2 groups as follows: AS without CCs (group I; n = 110) and AS with CCs (group II; n = 46). Routine electrocardiographic and echocardiographic parameters, peak and mean transvalvular pressure gradients (TPGs), aortic valve area (AVA), brain natriuretic peptide (BNP) levels, and BNP/peak TPG ratio were measured.The mean ages in groups I and II were 80.4 ± 5.5 and 82.5 ± 7.2 years. Left ventricular hypertrophy was greater in group II than in group I. Left ventricular end-diastolic and end-systolic dimensions and left ventricular fractional shortening were normal in both groups. Peak and mean TPGs were greater in group II (67.2 ± 39.3 and 40.2 ± 26.4 mmHg) than in group I (52.0 ± 23.0 and 30.2 ± 13.9, both P < 0.005); however, the AVA showed no significant difference between the 2 groups. The median BNP levels were 65.9 and 433.7 pg/mL in groups I and II (P < 0.0001). A correlation between peak TPG and BNP levels was observed in both groups. The BNP/peak TPG ratio was < 3.0 in all patients of group I and ≥ 3.0 in almost all patients of group II (P< 0.0001). The area under the curve using BNP/peak TPG ratio was 0.9883.BNP and BNP/peak TPG ratio could differentiate between AS with and without CCs in elderly patients.

Abstract 14076: Myocardial Tissue Characterization and Strain by Cardiac Magnetic Resonance and Their Relationship in Pediatric Patients With Acute Myocarditis Within 2 Weeks of Presentation

Introduction: Cardiac magnetic resonance (CMR) provides rich data on myocardial function, including indices such as strain, as well as tissue characterization. There is no published data on these values within 2 weeks of the diagnosis of myocarditis. We sought to describe these findings in children with acute myocarditis who underwent CMR early after presentation and determine relationships between these values. Methods: We retrospectively reviewed the clinical and imaging data of patients &lt;21 years clinically diagnosed with acute myocarditis and underwent CMR within 14 days of presentation. Those who suffered cardiac arrest or with autoimmune disease, known cardiomyopathy or congenital heart disease were excluded. Strain was measured using CMR feature tracking. Spearman’s correlation was utilized. Significance was P &lt;0.05. Results: 85 patients underwent CMR at a median of 2 days following presentation (IQR 2 - 4) with median age 16.3 years (IQR 14.3, 17.5). Tissue characteristics, ventricular function and strain are listed in Table 1. 77 studies (90.6%) met Lake Louise criteria for myocarditis and 66 (77.7%) showed late gadolinium enhancement. Global circumferential (GCS) and longitudinal strain correlated with T2 values, biventricular ejection fractions, and peak brain natriuretic peptide (BNP); GCS also correlated with T1 values (Table 1, Figure 1). Conclusions: We present the first data on early strain and tissue characterization for myocarditis. Both global longitudinal and circumferential strain correlated with tissue characteristics and serum measures of acute injury. Strain imaging may be a sensitive marker of myocardial injury in patients with myocarditis.

Prognostic value of brain natriuretic peptide in COVID-19 with or without acute heart failure

Abstract Background Although Brain Natriuretic Peptide (BNP) provides strong prognostic information of an unfavorable outcome in patients with acute heart failure (AHF), there is little information of its relevance as a biomarker for outcomes in COVID-19 and its complications Purpose To evaluate the association of increased BNP levels with complications and in-hospital mortality in a cohort of hospitalized COVID-19 patients. Methods The study included COVID-19 patients with data on BNP levels included in the ISACS COVID-19 registry. The population was categorized according to the presence of peak BNP levels ≥100 pg/mL during hospitalization. Primary outcomes included in-hospital mortality, AHF or acute respiratory failure (ARF, defined as PiO2/FiO2&amp;lt;300 mmHg or need for mechanical ventilation). Calculations were conducted using age and sex-adjusted multivariable logistic regression analyses. Results were also stratified according to presence or absence of cardiovascular disease (CVD) history. Differences between subgroups were verified for statistical significance using test for interaction. Results Of the 1152 patients included in the study, 615 (53.4%) had elevated BNP levels. These subjects were older (69.9±13.8 vs 59.1±16.8, p-value&amp;lt;0.001), had higher rates of cardiovascular risk factors (82.9% vs 57.7%, p-value&amp;lt;0.001) and presented more frequently with a prior history of CVD (either ischemic heart disease, cerebrovascular disease, venous thromboembolism, atrial fibrillation or a history of revascularization) (50.1% vs 27.5%, p-value&amp;lt;0.001). No sex differences were observed. When considering outcomes, BNP levels ≥100 pg/mL were associated with increased rates of in-hospital mortality (32.9% vs 4.9%, p-value&amp;lt;0.001), even after adjustment for demographic characteristics (OR: 7.35; 95% CI: 4.75–11.40; p-value&amp;lt;0.001). High BNP levels were also strongly associated with an increased risk of AHF (OR 19.9; 95% CI 8.6–45.9; p-value&amp;lt;0.001), a correlation that persisted both in patients with and without a prior CVD history (p for interaction=0.29). Of note, patients with elevated BNP also had a higher likelihood of developing ARF (OR 2.7; 95% CI 2.1–3.6; p-value&amp;lt;0.001), even in absence of AHF (OR 3.00; 95% CI 2.20–4.1; p-value&amp;lt;0.001). Conclusions In COVID-19, blood BNP level not only appears to be predictor of in-hospital mortality and AHF but was also independently associated with an increased risk of ARF. This finding supports the routine use of BNP in all patients admitted to hospital for COVID-19, regardless of a prior history of CVD. Funding Acknowledgement Type of funding sources: None.

The prognosis and therapeutic management of patients hospitalized for heart failure in 2010-2020.

We analyzed the mortality risk and its predictors in patients hospitalized for heart failure (HF). Patients discharged from hospitalization for acute decompensation of HF in 2010-2020 and younger than 86 years were followed (n=4097). We assessed the incidence and trends of all-cause death, its main predictors, and the pharmacotherapy recommended at discharge from the hospital. The 30 days all-cause mortality was in discharged patients 3.2%, while 1-year 20.4% and 5-years 55.4%. We observed a modest trend to decreased 1-year mortality risk over time. Any increase of year of hospitalization by one was associated with about 5% lower risk in the fully adjusted model. Regarding predictors of 1-year mortality risk, a positive association was found for age over 65, history of malignancy, and peak brain natriuretic peptide during hospitalization ≥10times higher than normal concentration. In contrast, as protective factors, we identified LDL ≥1.8 mmol/L, treatment with beta-blockers, renin-angiotensin axis blockers, statins, and implanted cardioverter in the same regression model. The ejection fraction category and primary etiology of HF (coronary artery disease vs. others) did not significantly affect the mortality risk in a fully adjusted model. Despite advances in cardiovascular disease management over the last two decades, the prognosis of patients hospitalized for heart failure remained highly unfavorable.

Clinical characteristics, outcomes and prognosticators in adult patients hospitalized with COVID-19

BackgroundCOVID-19 is a novel disease caused by SARS-CoV-2. MethodsWe conducted a retrospective evaluation of patients admitted with COVID-19 to one site in March 2020. Patients were stratified into 3 groups: survivors who did not receive mechanical ventilation (MV), survivors who received MV, and those who received MV and died during hospitalization. ResultsThere were 140 hospitalizations; 22 deaths (mortality rate 15.7%), 83 (59%) survived and did not receive MV, 35 (25%) received MV and survived; 18 (12.9%) received MV and died. Thee mean age of each group was 57.8, 55.8 and 72.7 years, respectively (P = .0001). Of those who received MV and died, 61% were male (P = .01). More than half the patients (n = 90, 64%) were African American. First measured d-dimer >575.5 ng/mL, procalcitonin > 0.24 ng/mL, lactate dehydrogenase >445.6 units/L, and brain natriuretic peptide (BNP) >104.75 pg/mL had odds ratios of 10.5, 5, 4.5 and 2.9, respectively for MV (P < .05 for all). Peak BNP >167.5 pg/mL had an odds ratio of 6.7 for inpatient mortality when mechanically ventilated (P = .02). ConclusionsAge and gender may impact outcomes in COVID-19. D-dimer, procalcitonin, lactate dehydrogenase and BNP may serve as early indicators of disease trajectory.

Dynamic changes of brain natriuretic peptide concentration and its diagnostic value for heart failure in early phase of acute myocardial infarction

To explore the dynamic changes in brain natriuretic peptide (BNP) concentration and the diagnostic value of BNP for heart failure at different time points in the early phase of acute myocardial infarction (AMI). AMI patients who were admitted in our department between January 1, 2016 and July 31, 2016 and underwent emergency percutaneous coronary intervention (PCI) within 12 h after onset were enrolled in this study. All the patients received bedside examinations of BNP concentration and clinical cardiac function within 1 h after PCI and at 12, 20, 24 and 48 h after the onset of AMI. According to the peak BNP concentration, the patients were divided into high peak BNP group (> 400 pg/mL) and normal peak BNP group (≤400 pg/mL). Seventy patients were enrolled in the study. Within 48 h after AMI onset, BNP concentration variations followed a pattern of an initial increase till reaching the peak concentration at 20 to 24 h, with subsequent gradual decrease. BNP concentrations differed significantly among the indicated time points (χ2=141.7, P < 0.05) except for those between 20 h and 24 h (χ2=0.173, P > 0.05). Compared with those in normal peak BNP group, the patients in high peak BNP group had an older age, a lower BMI, a longer time to perfusion, and a higher likeliness of anterior myocardial infarction and pulmonary infection (P < 0.05). Logistic regression analysis showed that age, BMI and anterior myocardial infarction were independently associated with the increase of peak BNP concentration. ROC curve analysis showed that BNP concentration within 1 h after emergency PCI was unable to diagnose heart failure at that time (P > 0.05), while BNP concentrations at 12, 20, 24 and 48 h after AMI onset had significant diagnostic values for heart failure (P < 0.05) with areas under ROC of 0.860, 0.786, 0.768 and 0.863, and optimal cutoff values of 156.5, 313.7, 240.9 and 285.9 pg/mL, respectively. BNP concentration increases first and then decreases in the early phase of AMI, and the peak concentration occurs at 20-24 h after the onset. The diagnostic values of BNP concentrations at different time points also vary.

Risk factors of in-hospital mortality among patients with upper gastrointestinal bleeding and acute myocardial infarction.

Background/Aims:Patients with simultaneous upper gastrointestinal bleeding (UGIB) and acute myocardial infarction (AMI) have higher mortality than patients with either GIB or AMI. We aimed to assess the incidence and risk factors of in-hospital mortality in patients with UGIB and AMI.Patients and Methods:A total of 243 patients with UGIB and AMI were enrolled during 2012–2017. Clinical and laboratory data were collected and analyzed for clinical characteristics and potential risk factors of in-hospital mortality.Results:Among the 243 patients, 60 in-hospital deaths were observed (in-hospital mortality rate of 24.7%). Patients who died were older than the survivors (78.7 ± 6.6 vs. 72.6 ± 10.5 years, P < 0.001). Compared with survivors, patients who died showed increased peak white blood cell (WBC) count (9.74 ± 4.72 vs. 7.60 ± 2.91 × 109/L, P = 0.002), serum creatinine levels [134 (106, 190) vs. 97 (79, 125) mmol/L, P = 0.014], peak blood urine nitrogen levels (16.31 ± 8.48 mmol/L vs. 9.86 ± 6.33 mmol/L, P < 0.001), and peak brain natriuretic peptide (BNP) amounts [13,250 (6071, 30,000) vs. 3598 (728, 12,842) pg/mL, P < 0.001]. Meanwhile, patients who died also displayed lower minimum hemoglobin levels (78.3 ± 21.1 vs. 86.3 ± 22.3 g/L, P = 0.018) and minimum platelet counts (184.3 ± 79.1 vs. 214.6 ± 80.1 × 109/L, P = 0.013). In multivariable logistic analysis, age [OR (95% CI) =1.118 (1.053–1.186), P < 0.001], peak WBC count [OR (95% CI) =1.252 (1.113–1.407), P < 0.001], minimum platelet count [OR (95% CI) = 0.994 (0.989–1.000), P = 0.032], and peak BNP levels [OR (95% CI) =3.880 (1.761–8.550), P = 0.001] were independent predictors of in-hospital mortality.Conclusions:Patients with UGIB and AMI had a high in-hospital mortality, which was independently associated with age, peak WBC count, minimum platelet count, and peak BNP levels.

Brain Natriuretic Peptide Levels and the Occurrence of Subclinical Pulmonary Edema in Healthy Lowlanders at High Altitude

BackgroundHigh altitude (HA) pulmonary edema (PE) results from complex and misunderstood interactions between adaptation mechanisms. We assessed the occurrence of subclinical PE and brain natriuretic peptide (BNP) levels among nonacclimatized individuals during an expedition on Mount Elbrus (5642 m). MethodsSeven subjects underwent assessment of vital signs, Lake Louise Score, ultrasound lung comets using handheld echography and circulating BNP using capillary testing at different stages of ascension, in addition to baseline echocardiography. Friedman tests were used to compare serial measurements. ResultsHeart rate, Lake Louise Score (P < 0.0001) and blood pressure (P = 0.037) increased during ascension; oxygen saturation decreased (P < 0.0001). BNP increased (40.7 ± 16.8 vs 19.7 ± 3.04 pg/mL; P < 0.01) after the summit, as did ultrasound lung comet count throughout ascension (P < 0.0001), but both parameters were not correlated (r = 0.36; P = 0.42). Post-summit peak BNP correlated with baseline left ventricular mass index (r = −0.79; P = 0.033). ConclusionThis study confirms the high incidence of subclinical PE during subacute exposure to hypobaric hypoxia and enhancement of this phenomenon after exertion. Although not correlated with the degree of PE, BNP levels increased after sustained effort at HA, but not at rest. Further investigation is needed to determine the mechanisms underlying the BNP response at HA and its usefulness as a monitoring tool during expeditions.

Relationship of Troponin T and Age- and Sex-Adjusted BNP Elevation Following Subarachnoid Hemorrhage with 30-Day Mortality.

Troponin and brain natriuretic peptide (BNP) levels are predictors of mortality following subarachnoid hemorrhage (SAH). Prior studies used strict cutoffs for BNP elevation; however, normal levels of BNP are increased in older persons and women. We explored the association of troponin elevation and BNP elevation adjusted for sex and age with 30-day mortality. In this retrospective cohort study of patients with SAH, collected data included peak troponin T and BNP levels. Mortality data were obtained from inpatient mortality data and available records. Troponin T elevation was defined as more than 0.10ng/mL; BNP elevation was defined as greater than the 95th percentile reference limit by age and sex for patients without cardiovascular disease. Associations of elevated troponin T and BNP were estimated from a log-binomial regression model reporting relative risks (RRs), 95% CIs, and P values; missing data were imputed with the sample median or most frequent category. This study included 175 SAH patients. In single-variable analysis, peak troponin T level greater than 0.10ng/mL was associated with increased risk in 30-day mortality (RR 4.38; 95% CI 2.43-7.89; P<.001); there was no association with elevated peak BNP adjusted for age and sex (RR 1.13; 95% CI 0.55-2.35; P=.74). There was no evidence suggesting that the combination of elevated peak BNP and elevated peak troponin increased the risk of 30-day mortality. Elevated troponin was an independent predictor of 30-day mortality following SAH; however, when adjusted for age and sex, elevations in BNP did not have this association.

Analysis of Clinical Parameters and Cardiac Magnetic Resonance Imaging as Predictors of Outcome in Pediatric Myocarditis

Myocarditis causes significant morbidity and mortality in pediatric patients, with potential adverse outcomes including heart failure, transplantation requirement, and/or death. The objective of this study was to determine predictors of early and late poor outcomes, defined as requirement for extracorporeal membrane oxygenation, ventricular assist device, transplantation, or death in pediatric myocarditis patients. A retrospective cohort study was conducted to evaluate pediatric myocarditis presenting over a 5-year period at a pediatric institution. Patients were identified using an institutional heart failure database and International Classification of Diseases, Ninth Revision, discharge diagnosis codes for myocarditis and confirmed by review of medical records. Data extraction included epidemiologic factors, the presenting ejection fraction (EF), initial and peak troponin levels, brain natriuretic peptide (BNP) level, pathogen identification, cardiac magnetic resonance imaging (MRI), and outcomes. Univariate and multivariate regression was performed to identify variables predictive of outcomes. Because published pediatric cardiac MRI data are sparse, whether late enhancement was associated with specific clinical variables or predictive of outcomes was also evaluated. Fifty-eight patients were identified. The mean age was 10.5 years, 64% were male, 62% were Caucasian, 15% were African-American, and 23% were Hispanic or Asian. Eighty-one percent presented at the institution <1 week after symptom onset. Presenting EFs were normal (>50%) or mildly decreased (40% to 50%) in 48%, moderately decreased (30% to 40%) in 9%, and severely decreased (<30%) in 42%. Thirty patients (52%) underwent viral studies; 17 of these (56%) had acute viral origins of myocarditis identified, including 8 with parvovirus (2 with influenza coinfection), 7 with enterovirus, 1 with Epstein-Barr virus, and 1 with cytomegalovirus. Twenty-eight percent had poor outcomes. Univariate analysis identified Hispanic or Asian race (odds ratio [OR] 4.5, p = 0.05), a severely decreased EF (OR 13, p = 0.002), initial BNP >10,000 pg/ml (OR 5.6, p = 0.01), and peak BNP >10,000 pg/ml (OR 13.65, p = 0.001) as risk factors for poor outcomes; initial and peak troponin >1 ng/ml were correlated significantly with good outcomes (OR 0.22, p = 0.04, and OR 0.26, p = 0.05, respectively). Multivariate analysis adjusting for severe EF, troponin, BNP, and cardiac MRI revealed peak BNP >10,000 ng/L (OR 27.71, p = 0.04), a severely decreased EF (OR 12.8, p = 0.03), and late enhancement on cardiac MRI (OR 24.51, p = 0.04) as risk factors for poor outcomes. Thirty-four patients underwent cardiac MRI (50% with abnormal and 50% with normal results). No significant differences were found between these groups with respect to gender, race, symptom duration, the EF, BNP, troponin, inflammation on cardiac biopsy, or pathogen identification. In conclusion, this study provides data from a large cohort of pediatric myocarditis patients. A presenting EF <30%, peak BNP >10,000 ng/L, and cardiac MRI late enhancement were identified as predictors of poor outcomes.

Do Optimal Prognostic Thresholds in Continuous Physiological Variables Really Exist? Analysis of Origin of Apparent Thresholds, with Systematic Review for Peak Oxygen Consumption, Ejection Fraction and BNP

BackgroundClinicians are sometimes advised to make decisions using thresholds in measured variables, derived from prognostic studies.ObjectivesWe studied why there are conflicting apparently-optimal prognostic thresholds, for example in exercise peak oxygen uptake (pVO2), ejection fraction (EF), and Brain Natriuretic Peptide (BNP) in heart failure (HF).Data Sources and Eligibility CriteriaStudies testing pVO2, EF or BNP prognostic thresholds in heart failure, published between 1990 and 2010, listed on Pubmed.MethodsFirst, we examined studies testing pVO2, EF or BNP prognostic thresholds. Second, we created repeated simulations of 1500 patients to identify whether an apparently-optimal prognostic threshold indicates step change in risk.Results33 studies (8946 patients) tested a pVO2 threshold. 18 found it prognostically significant: the actual reported threshold ranged widely (10–18 ml/kg/min) but was overwhelmingly controlled by the individual study population's mean pVO2 (r = 0.86, p<0.00001). In contrast, the 15 negative publications were testing thresholds 199% further from their means (p = 0.0001). Likewise, of 35 EF studies (10220 patients), the thresholds in the 22 positive reports were strongly determined by study means (r = 0.90, p<0.0001). Similarly, in the 19 positives of 20 BNP studies (9725 patients): r = 0.86 (p<0.0001).Second, survival simulations always discovered a “most significant” threshold, even when there was definitely no step change in mortality. With linear increase in risk, the apparently-optimal threshold was always near the sample mean (r = 0.99, p<0.001).LimitationsThis study cannot report the best threshold for any of these variables; instead it explains how common clinical research procedures routinely produce false thresholds.Key FindingsFirst, shifting (and/or disappearance) of an apparently-optimal prognostic threshold is strongly determined by studies' average pVO2, EF or BNP. Second, apparently-optimal thresholds always appear, even with no step in prognosis.ConclusionsEmphatic therapeutic guidance based on thresholds from observational studies may be ill-founded. We should not assume that optimal thresholds, or any thresholds, exist.

Short and Long-Term Outcome of Stress-Induced Cardiomyopathy: What Can We Expect?

BackgroundStress-induced/Takotsubo cardiomyopathy (TC) is an increasingly recognized diagnostic entity.ObjectiveThis study was aimed to assess the prevalence and clinical predictors of short and long-term outcome of patients (pts) diagnosed with TC.MethodsWe included all consecutive pts admitted in our department, from November 2006 to August 2011, who met the Mayo Clinic criteria for TC diagnosis.ResultsWe evaluated 37 pts (35 women) with a mean age of 63 ±13 years. TC was precipitated by a stressful emotional event in the majority (57%) and chest pain was the most common symptom (89%). Twelve pts (32%) had ST-segment elevation and 15 pts (41%) had T-wave inversion on the electrocardiogram at admission. Severe left ventricular (LV) dysfunction was found in 16 pts (43%) and the mean troponin I level was 2.6±1.8 ng/mL. The in-hospital complication rate was 30%, with cardiogenic shock being the most common situation. Physical stress, severe LV systolic dysfunction and peak brain natriuretic peptide (BNP) were predictors of acute complications. On the other hand, we found no association between peak troponin I and electrocardiographic presentation. Thirty-five pts were followed for a mean time of 482 ± 512 days, without clinic recurrence.ConclusionIn our cohort of pts, TC was associated with a high in-hospital complications rate. Physical stress, LV dysfunction and peak BNP could predict acute adverse outcomes.

Plasma brain natriuretic peptide is associated with hepatic veno-occlusive disease and early mortality after allogeneic hematopoietic stem cell transplantation

Fluid retention is characteristic of veno-occlusive disease (VOD). We hypothesized that plasma brain natriuretic peptide (BNP), a neurohormone secreted in response to volume expansion, may be associated with VOD after hematopoietic stem cell transplantation (HSCT). BNP was measured before and weekly after HSCT in 46 recipients. Sixteen patients developed VOD. BNP concentrations were similar before and on day 0 in patients with and without VOD, but were significantly higher on day 7 and later in those with VOD. Patients with VOD had significantly higher peak BNP concentrations before engraftment than those without VOD (median, 634.4 versus 80.9 pg ml⁻¹; P=0.01). Multivariate analysis showed that VOD was independently associated with BNP elevation (odds ratio, 50.1; 95% CI: 5.2-478.4; P<0.01). Landmark analysis at day 7 showed that patients with peak BNP concentration of ≥ 180 pg ml⁻¹ had significantly worse 100-day survival than patients with peak BNP <180 pg ml⁻¹ (54 versus 91%; P<0.01). In multivariate analysis, BNP elevation before day 7 significantly predicted 100-day survival (hazard ratio 5.3; 95% CI: 1.1-24.3; P=0.03). These findings suggest that plasma BNP may serve as a diagnostic and prognostic marker of VOD.

174 Is Left Ventricular Longitudinal Function a Determinant of Plasma Brain Natriuretic Peptide during Exercise in Patients with Organic Mitral Regurgitation?

Plasma brain natriuretic peptide (BNP) may be used for risk stratification in patients with organic mitral regurgitation (OMR). Whether exercise can induce changes in BNP in patients with OMR has never been investigated. Resting and exercise transthoracic echocardiography including Doppler, tissue Doppler imaging (TDI) and 2-D speckle-tracking (2DSt) quantification were performed in 56 consecutive patients (61±15 yrs, 54% of male) with moderate to severe OMR. Peak velocity and time-to-peak velocity (TP) were measured using TDI for Ea-, Aa- and Sa-wave. 2DSt was use to evaluate global LV longitudinal strain (GLS). Blood samples were drawn at rest and 5 min after peak exercise to measure plasma BNP level. BNP increases during exercise (from 27±18 to 35±24pg/ml, p<0.001) and peak exercise BNP was correlated to exercise LV ejection fraction (EF) (r=-0.36, p=0.007) and to exercise Sa velocity (r=-0.41, p<0.001), TP-Sa (r=0.32, p=0.02) and TP-Ea (r=0.39, p=0.004). The best correlation with peak BNP was found with peak GLS (r=-0.58, p<0.0001). In addition, there were significant associations between the changes in BNP and the changes in LVEF (r=-0.35, p=0.009), Sa velocity (r=-0.37, p=0.005), TP-Ea (r=0.35, p=0.01), and GLS (r=-0.44, p=0.0001). On multivariate analysis, after adjustment for age, sex and LVEF, only peak GLS and TP-Ea were independently associated with peak BNP (r 2 =0.34, p<0.0001 and r 2 =0.11, p=0.003, respectively). Furthermore, only changes in Sa velocity (r 2 =0.23, p=0.0004) and in GLS (r 2 =0.17, p=0.03) were independently associated, after adjustment, with the changes in BNP. Exercise and exercise-induced changes in LV longitudinal function are the major determinants of both exercise and changes in BNP during exercise, in patients with OMR. These results suggest that LV longitudinal function should be systematically quantified during stress echocardiography to detect latent subclinical LV dysfunction.

Cardiac toxicity of high-dose cyclophosphamide and melphalan in patients with multiple myeloma treated with tandem autologous hematopoietic stem cell transplantation

Tandem autologous hematopoetic stem cell transplantation (HSCT) is an effective treatment in patients with multiple myeloma (MM). Patients receive high-dose cyclophosphamide (CY) followed by two myeloablative dosages of melphalan (MEL). Cardiotoxicity treatment related data are scanty. In 30 patients with MM chemotherapy was followed by high-dose CY (cycle CY), and two autologous tandem HSCT treatments with MEL (cycles MEL I and MEL II). During each 15-day treatment troponin I (TnI), brain natriuretic peptide (BNP) and endothelin-1 (ET-1) were controlled at six time points. All patients underwent conventional and tissue Doppler echocardiography prior to CY therapy (Eho 0), before cycle MEL I (Eho 1), before cycle MEL II (Eho 2), and 3 months after the completion of therapy (Eho 3). None of the patients developed clinical signs of heart failure. The peak TnI concentrations were noted at days 8, 11, and 15 during all three chemotherapy cycles. During all three cycles there was a significant increase in baseline BNP concentrations and BNP levels measured at day 1 after treatment with CY and MEL (CY: P = 0.0001, MEL I: P = 0.001, MEL II: P = 0.001). The highest BNP concentration occurred during CY treatment (0.517 +/- 0.391 microg/L). During cycles MEL I and MEL II we noted the peak BNP concentrations at day 4 following chemotherapy (MEL I 0.376 +/- 0.418 microg/L; MEL II 0.363 +/- 0.379 microg/L). During all three cycles the highest ET-1 levels occurred at day 1 after chemotherapy (CY 1.146 +/- 1.313 ng/L; MEL I 1.054 +/- 2.242 ng/L; MEL II 0.618 +/- 0.539 ng/L). A significant increase in ET-1 concentrations relative to the basal values occurred only in cycle MEL II (P = 0.003). The duration of wave a in the Doppler pulmonary vein flow increased significantly (Eho 0/Eho 1: P = 0.008, Eho 0/Eho 3: P = 0.026). There was a significant decrease in the A/a ratio in flow velocities during chemotherapy (Eho 0/Eho 1: P = 0.002, Eho 0/Eho 3: P < 0.0001). Early diastolic tissue Doppler velocities (Em) decreased significantly during individual cycles of chemotherapy (P = 0.006). A significant post-treatment increase in the incidence of mitral regurgitation was observed (Eho 0/Eho 3: P = 0.003). Treatment of MM patients with tandem autologous HSCT is cardiotoxic. Our patients did not develop clinically overt heart failure or myocardial necrosis. Increased plasma levels of BNP and ET-1 were compatible with transient neurohormonal activation of heart failure. Doppler echocardiography studies revealed worsening of left ventricular diastolic function and occurrence of functional mitral regurgitation.

Augmented release of brain natriuretic peptide during reperfusion of the human heart after cardioplegic cardiac arrest

The aim of the study was to investigate the release of natriuretic peptides during myocardial ischaemia and reperfusion associated with cardioplegic cardiac arrest. Brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) concentrations were measured in paired arterial, central venous and coronary sinus blood samples in 19 patients undergoing elective coronary artery bypass grafting before aortic crossclamping and 1, 5, 10 and 20 min after aortic declamping. Peak myocardial BNP release after aortic declamping was significantly higher than baseline values before aortic crossclamping. Both peak and cumulative BNP release during reperfusion correlated significantly with the severity of ischaemia, as assessed by myocardial lactate production. In 3 patients with perioperative myocardial ischaemia, cumulative and peak myocardial BNP release after aortic unclamping was markedly higher than in the remaining 16 uneventful patients. Myocardial ANP release during reperfusion was not significantly different from baseline values before aortic crossclamping. In conclusion, our data demonstrate a significantly enhanced myocardial BNP release early during reperfusion of the human heart after flobal ischaemia associated with cardioplegic cardiac arrest.