Elevated BNP Research Articles

BNP and NT-proBNP elevation after running--a systematic review.

A systematic review was carried out to study the pattern of BNP and NT-proBNP release after running. Data were collected by searching the PubMed, ISI Web of Knowledge and Scopus databases. Fifty-three reports were identified as meeting the pre-specified criteria. Twenty-seven reports, representing 1,034 participants, presented data comparing post-running BNP or NT-proBNP levels with a pre-specified cut-off. Values exceeding the upper reference limit were seen in 22.9% and 35.9% of runners, respectively. Studies have shown post-running values exceeding the upper reference limit in up to a third of runners.

Tailoring mineralocorticoid receptor antagonist therapy in heart failure patients: are we moving towards a personalized approach?

The aim of personalized medicine is to offer a tailored approach to each patient in order to provide the most effective therapy, while reducing risks and side effects. The use of mineralocorticoid receptor antagonists (MRAs) has demonstrated major benefits in heart failure with reduced ejection fraction (HFrEF), results with challenging inconsistencies in heart failure with preserved ejection fraction (HFpEF), and 'neutral' preliminary results in acute heart failure. Data derived from landmark trials are generally applied in a 'one size fits all' manner and the development and implementation of more personalized MRA management would offer the potential to improve outcomes and reduce side effects. However, the personalization of pharmacotherapy regimens remains poorly defined in the cardiovascular field (in light of current knowledge) and until further trials targeting specific subpopulations have been conducted, MRAs should be provided to the great majority of HFrEF patients in the absence of contraindication. Spironolactone should be considered for symptomatic HFpEF patients with elevated natriuretic peptides. In the near future, trials should target HFrEF patients using exclusion criteria sourced from landmark trials (e.g. severe renal impairment), select more homogeneous HFpEF populations (e.g. with elevated BNP and structural abnormalities on echocardiography), and determine which patients are likely to benefit from MRAs (e.g. according to prespecified biomarkers).

Abstract 032: Is Bigger Data Better? Predicting Readmissions in Acute Myocardial Infarction on Admission versus Discharge With Electronic Health Record Data

Background: Readmissions after hospitalization for acute myocardial infarction (AMI) are common, but the few available risk prediction models have poor predictive ability. Including more data from hospitalization may improve risk prediction. Objectives: To assess if an AMI-specific electronic health record (EHR) readmission risk prediction model derived and validated from data through the entire hospital course (‘full stay’ model) outperforms a model using data available only from the first day of hospitalization (‘first day’ model). Methods: EHR data from AMI hospitalizations from 6 diverse hospitals in north Texas from 2009-2010 were used to derive a model predicting all-cause non-elective 30-day readmissions which was then validated using five-fold cross-validation. Results: Of 826 consecutive index AMI admissions, 13% were followed by a 30-day readmission. History of diabetes (AOR 2.41, 95% CI 1.37-4.24), SBP <100 mmHg on admission (AOR 2.18, 95% CI 1.68-2.82), elevated Cr (≥2 mg/dL) on admission (AOR 2.56, 95% CI 2.52-6.08), elevated BNP on admission (AOR 6.36, 95% CI 1.65-24.47) and lack of PCI within 24 hours of admission (AOR 1.31, 95% CI 1.02-1.69) were significant predictors of readmission. Our ‘first-day’ AMI readmissions model based on these predictors had good discrimination ( Table ). Adding three other variables from the hospital course - use of IV diuretics (AOR 1.58, 95% CI 1.07-2.31), anemia (hematocrit ≤ 33%) on discharge (AOR 2.04, 95% CI 1.20-3.46), and discharge to post-acute care (AOR 1.50, 95% CI 0.90-2.50) - improved discrimination of the ‘full stay’ AMI model but only modestly improved net reclassification and calibration. Conclusions: A ‘full-stay’ AMI-specific EHR readmission model modestly outperformed a ‘first-day’ EHR model, a multi-condition EHR model, and the CMS AMI model. Surprisingly, incorporating more hospitalization data improved discrimination of the full-stay AMI model but did not meaningfully improve reclassification compared to the first-day model. Readmissions in AMI may be accurately predicted on the first day of hospitalization; waiting until later in hospitalization does not markedly improve risk prediction.

Elevation of Serum Pro-Brain Natriuretic Peptide in G-CSF Stimulated Hematopoietic Progenitor Cell Donors

Introduction:Healthy donors who are treated with GCSF before peripheral blood hematopoietic progenitor cell (HPC) collection may develop side effects and aberrant laboratory values that have been described with the mobilization regimen. Alternatively, unexpected abnormal laboratory results could reflect occult complications or underlying disease. While many serum chemistry test results are affected by G-CSF, there have been no published reports describing an effect on BNP (pro-brain natriuretic peptide), a serum marker of heart failure. We encountered a donor who developed an elevated BNP after GCSF-stimulated HPC collection, and investigated its possible association with GCSF administration in healthy donors.Case Report:A 41-year old woman was evaluated for matched allogeneic peripheral HPC donation. History and physical exam were unremarkable, and standard laboratory values, EKG and chest X-ray revealed no abnormalities. The donor was mobilized with 10mcg/kg GCSF daily for 5 days. Her only complaint was of headache starting on day 4 that was relieved partially with acetaminophen. No other side effects were recorded.Her pre-apheresis peripheral CD34+ count was 87/mcL. At the start of apheresis HPC collection, the donor reported headache 7/10 in intensity and intolerance to light, unrelieved by acetaminophen but partially relieved with oxycodone. She complained of nausea during collection, but the procedure was otherwise successful and uneventful (15L of whole blood processed). Her headache persisted at the time of discharge, and the donor was counseled and prescribed one additional dose of oxycodone.Five hours after discharge the donor reported “the worst headache of her life”, nausea and difficulty breathing. She was evaluated at the ER, where she had stable vital signs and normal oxygen saturation. Her physical exam was unremarkable. Head CT was negative for intracranial hemorrhage or mass effect. A panel of laboratory analyses revealed leukocytosis, decreased platelets, and increased alkaline phosphatase and liver enzymes, which are documented findings associated with GCSF stimulation and large-volume apheresis. Given the donor’s complaint of dyspnea, serum BNP was measured and found increased to 483pg/mL (normal <124pg/mL). The donor had a normal pulmonary examination and no clinical evidence of cardiac insufficiency; a chest X-ray and an echocardiogram were also within normal limits. Her symptoms resolved with IV hydromorphone and she was discharged in stable condition. A follow-up serum BNP 4 weeks after donation was within normal range (105pg/mL).Investigation:A preliminary study evaluated 11 additional HPC donors who were stimulated with 10mcg/kg GSCF for 5 days (Table 1). Nine of twelve (75%) donors were male, and seven were Caucasian. Ten of the total 12 donors demonstrated an increase in BNP levels compared to pre-stimulation results. Follow-up of four total donors 9-17 days after donation demonstrated return of BNP levels to baseline. None of the donors had clinical evidence of heart failure during stimulation, donation, or follow-up. The average increase in BNP was 4.2 fold, and in a total of 3 donors it exceeded the normal range for the laboratory. The presence or degree of BNP elevation did not correlate with age, gender, severity of GCSF side effects, liver panel results, or pre-apheresis peripheral CD34+ count.Conclusion:This case and preliminary study indicate that an increase in BNP levels can be observed in approximately 80% of HPC donors stimulated with 5 days of 10mcg/kg GCSF. The increase in BNP in these donors is not associated with ventricular dysfunction or symptoms of cardiac congestion, and it returns to baseline levels in 2-4 weeks. Two possible molecular mechanisms for this BNP increase include 1) activation of gp130 by increased circulating cytokines associated with GCSF; or 2) direct transcriptional activation of the BNP gene by cardiomyocyte GCSF receptor activation of the JAK-STAT pathway. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Clinical features and three-year outcomes of Takotsubo (stress) cardiomyopathy: Observational data from one center

ObjectiveThe natural history, management, and outcome of Takotsubo (stress) cardiomyopathy (TTC) is not clear. The aim of this study was to investigate clinical features, define prognostic predictors, and assess the clinical course and outcomes of patients with TTC. MethodsWe analyzed 64 patients (52 women) meeting the proposed Mayo Clinic diagnostic criteria for TTC. All patients were treated at Vilnius University Hospital Santariskiu Klinikos from 2001-01-01 to 2014-11-27. Data were collected on the basis of medical records and follow-up data was collected by phone. ResultsThe mean age of analyzed patients was 63.4 ± 14.6 years; the mean follow-up was 2.9 years. More than half of the patients (52%) did not have any clear stressful triggers. During admission, symptoms such as chest pain (64%) and general weakness (45%) were reported more often than other symptoms. Almost all patients (94%) had the classical TTC form; the remaining 6% of patients had “inverted” TTC. The mean left ventricular ejection fraction (LVEF) on admission was 37.7% (± 8.2%). A pseudonormal or restrictive pattern of LV filling, moderate to severe mitral regurgitation (MR), and right ventricular involvement were uncommon in the patients. The in-hospital course showed cardiogenic shock in 23% of the cases, resulting in the death of 5 (8%) patients. We discovered that only peak concentration of troponin I was a significant predictor of in-hospital mortality (HR 1.067, 95%CI 1.022–1.113, p=0.003). At the end of the follow-up period, 45 (87%) women and 8 (67%) men were alive. This makes the overall observed mortality at 3 years approximately 17.2%. Using multivariate analysis, elevation of BNP (HR for increase by 10 ng/l 1.002, 95%CI 1–1.003, p=0.022) and cardiogenic shock on admission (HR 8.696, 95%CI 1.198–63.124, p=0.032) were significant predictors of overall mortality. Other prognostic factors assessed on admission were nonsignificant predictors of overall mortality. ConclusionsOur analysis shows that in-hospital mortality is influenced by the peak concentration of troponin I, and overall mortality is affected by cardiogenic shock and the elevation of BNP during admission. The assessment of troponin I and BNP can help with the prognostication of TTC patients in our daily clinical practice.

A Case of Hypertrophic Obstructive Cardiomyopathy and Vasospastic Angina, in Which Controlling Medical Treatment was in Great Distress

Vasospastic angina (VSA) is accompanied with hypertrophic obstructive cardiomyopathy (HOCM). In such patients, controlling medical treatment may be sometimes difficult, because some drugs for VSA may deteriorate the status of HOCM. We experience such case. A woman in her seventies, was admitted to our institution, because of detail examination of chest symptoms at rest. Coronary angiography showed the presence of coronary spasm. In addition, cardiac catheterization showed that the positive Brochenbrough phenomenon. This patient was diagnosed as having HOCM and VSA. Diltiazem was prescribed and she had been followed by her family doctor. Two years later, she could not walk for a short distance and was admitted to our institution. At admission, she took some medications, such as diltiazem, telmisartan and diuretics. Blood chemical data showed the elevation of BNP (769 pg/mL). Echocardiography (UCG) showed the significant pressure gradient through left ventricle outflow tract (LVOT, 159 mmHg) at rest. We judged the worsening status of HOCM and prescribed cibenzoline with 150 mg, but pressure gradient did not changed. We stopped the diuretics and changed from diltiazem to verapamil. Thereafter, her symptoms improved and the pressure gradient though LVOT reduced and she was discharged. Several cardiovascular medications may affect the status of HOCM and the cardiologists should be careful in selection of such drugs in patients with HOCM.

Does Active Participation in Cardiac Rehabilitation Lead to Sustained BNP Elevation in Post-Acute Myocardial Infarction Patients with High Baseline BNP?

Does Active Participation in Cardiac Rehabilitation Lead to Sustained BNP Elevation in Post-Acute Myocardial Infarction Patients with High Baseline BNP?

Amyloid Cardiomyopathy: All that sparkles is Amyloid

A 73 year old female with no past medical history presented to our emergency department (ED) with gradually worsening shortness of breath for a few weeks. She denied any associated complaints of chest pain, palpitations or dizziness. On physical exam, the patient had bilateral rales at the lung bases. The electrocardiogram showed low voltage complexes with right bundle branch block and left anterior fascicular block (Figure 1). The laboratory work came back significant for an elevated BNP (1452 pg/ml) with a normal complete blood count, serum chemistry and negative cardiac biomarkers. The patient was treated with intravenous diuretics in the ED and admitted to a telemetry floor.

Tlr2 deficiency does not limit the development of left ventricular hypertrophy in a model of transverse aortic constriction induced pressure overload.

BackgroundToll-like receptors (TLRs) are involved in a variety of cardiovascular disorders, including septic cardiomyopathy, ischemia/reperfusion, heart failure, and cardiac hypertrophy. Previous research revealed that TLR4 promotes cardiac hypertrophy in vivo. Therefore, we investigated whether TLR2 is also involved in the development of cardiac hypertrophy.MethodsTlr2 deficient and wild type mice were subjected to transverse aortic constriction (TAC) or sham operation procedure. Left ventricular, heart and lung weights as well as hemodynamic parameters were determined after 3, 14 or 28 days. Real-time RT PCR was used to evaluate left ventricular gene expression. Protein content was determined via ELISA.ResultsTAC increased systolic left ventricular pressure, contraction and relaxations velocities as well as the heart weight in both genotypes. Tlr2 deficiency significantly enhanced cardiac hypertrophy after 14 and 28 days of TAC. Left ventricular end-diastolic pressure and heart rate increased in Tlr2−/− TAC mice only. Fourteen days of TAC led to a significant elevation of ANP, BNP, TGFβ and TLR4 mRNA levels in Tlr2−/− left ventricular tissue.ConclusionThese data suggest that Tlr2 deficiency may promote the development of cardiac hypertrophy and ventricular remodeling after transverse aortic constriction.

A Rare Case of Left Ventricular Non-Compaction Cardiomyopathy

SESSION TITLE: Genetic Disorders SESSION TYPE: Case Report Slide PRESENTED ON: Saturday, April 16, 2016 at 02:15 PM - 03:45 PM INTRODUCTION: Left Ventricular Non-Compaction Cardiomyopathy (LVNCC) is a rare myocardial disorder which results from failure of left ventricle to compact in embryogenesis. It is characterized by a two-layered ventricular wall, an outer compacted epicardial layer and an inner non-compacted layer composed of prominent trabeculations and deep inter-trabecular recesses which communicate with LV cavity. CASE PRESENTATION: A 44 year old male with history of dilated cardiomyopathy s/p AICD presented to our ER with complaints of SOB, dry cough, and leg edema. Patient reportedly stopped taking his Lasix two weeks ago. Exam was significant for elevated JVD, mild crackles and pedal edema. Labs showed elevated troponin (0.41 ng/ml) and BNP (1771 pg/ml). Echocardiogram revealed severely decreased LV systolic function (EF <10%) with severely dilated LV cavity, severe diastolic dysfunction, prominent LV trabeculations, and deep inter-trabecular recesses communicating with the LV cavity, consistent with LVNCC (Fig. 1). Patient was initiated on diuretics and an aldosterone antagonist, added to his regimen of beta blocker and ACE inhibitor, started on IV heparin, and subsequently bridged to Coumadin for anti-coagulation for low EF. He was discharged in stable condition to follow up with advanced heart failure for Cardiac Transplant and LVAD evaluation. DISCUSSION: LVNCC was first reported in 1932 in association with other congenital cardiac abnormalities (1). It is a genetically heterogeneous disorder with familial and sporadic forms and can be linked to mutations in mitochondrial, cytoskeletal, Z-line, and sarcomeric proteins. Reported prevalence of LVNCC varies considerably and is estimated to be between 0.014 and 1.3%, however, the true prevalence is unknown as it is often unrecognized. Patients usually present with heart failure, ventricular arrhythmias or systemic embolic events. Echocardiography is the first line imaging modality and diagnostic criteria include end-systolic ratio of non-compacted layer/compacted layer >2 and evidence of blood flow in intertrabecular recesses from the LV cavity on Color Doppler Imaging, in the absence of other cardiac abnormalities. The Cardiac MRI may be used for confirmation of the diagnosis. Treatment consists of standard heart failure therapy, management of arrhythmias and consideration of oral anti-coagulation in high risk patients to prevent systemic embolic complications. Due to high familial recurrence, genetic testing of affected individuals and screening of first-degree family members is also recommended. CONCLUSIONS: Still considered a novel entity, LVNCC is getting increasingly recognized because of heightened awareness and improved cardiac imaging modalities and physicians should be aware of this rare cardiomyopathy. Reference #1: Bellet S, Gouley BA. Congenital heart disease with multiple cardiac anomalies: report of a case showing aortic atresia, fibrous scar in myocardium and embryonal sinusoidal remains, Am J Med Sci. 1932, 183:458-65. DISCLOSURE: The following authors have nothing to disclose: Jeffrey Le, Shelly Brejt, Sameer Chadha, Nadine Montemarano, Joshua Kerstein, Jacob Shani No Product/Research Disclosure Information

0554 : Right ventricle 2D strain derived from speckle tracking imaging might help to identify patients with pulmonary embolism at low risk

We sought to investigate whether right ventricular deformation parameters as assessed with two-dimensional (2D) speckle tracking imaging (STI) could help in identifying patients at low risk according to the ESC guidelines. From February 2015 to September 2015 all consecutive patients with a PE confirmed by thoracic computed tomography scan or by ventilation/ perfusion scintigraphy were included in the study. 2D Echocardiography was performed at admission. STI Longitudinal strain for the RV free wall and septal wall. We defined as intermediate-to-high risk PE patients with RV systolic dysfunction on echocardiography (defined as RV/LV ratio>0.9) and/or troponin I >0.04 μg/L and/or brain natriuretic peptide >100 pg/mL. When none of these criteria were present, patients were considered at low risk. Fifty-eight patients (mean age 66.1 ± 18.5 years, 55% male) were prospectively included. None of these patients exhibit hemodynamic instability. Twenty-three patients (40%) showed a RV/LV ratio > 0.9, 25 patients (43%) an elevated BNP levels (mean: 454±494 pg/mL) and 17 patients (29%) an elevated troponin levels (mean: 0.36±0.46 μg/L). According to the ESC guidelines, 14 patients (24%) were classified at low risk PE, and 44 (76%) at intermediate-to-high risk. Global 2D RV strain differed significantly between the 2 groups (23.0% vs. 19.3%, p=0.0035), as did RV strain of the free wall (26.9% vs. 21.1%, p=0.0038). However, 2D RV strain of the septal wall did not differ significantly in the 2 groups (20.0% vs. 18.5%, p=0.12). ROC curves were determined to evaluate the ability of RV strain parameters derived from STI to identify low risk patients. The best performance was obtained with global 2D RV strain and a cut off value of 23.0%. Global longitudinal 2D strain is significantly reduced in patients with intermediate-to-high risk PE compared with low risk PE. A cut off value of 23% allowed to identify PE patients at low risk. Figure Comparative receiver operative character The author hereby declares no conflict of interest

Abstract 13456: Screening for Transthyretin Cardiac Amyloidosis Using 99mTc-Pyrophosphate Scintigraphy in Patients Undergoing Transcatheter Aortic Valve Replacement

Background: Transthyretin cardiac amyloidosis (ATTR-CA) is an increasingly recognized cause of heart failure with preserved ejection fraction (EF). Bone scintigraphy has emerged as a non-invasive imaging approach that is highly sensitive and specific for identifying ATTR-CA. We conducted a prospective cohort study using 99m Tc-pyrophosphate scintigraphy ( 99m Tc-PYP) to determine the prevalence of ATTR-CA and other clinical associations with 99m Tc-PYP positivity in older patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR). Methods: A total of 40 patients (53% men) with severe AS underwent 99m Tc-PYP planar cardiac imaging within 30 days of TAVR. Myocardial uptake was assessed with both a semi-quantitative visual score (range 0: no uptake to 3: uptake greater than bone) and by quantitative analysis by drawing a region of interest over the heart, mirroring it to the contralateral chest, and calculating a heart-to-contralateral ratio (HCL). Semi-quantitative score ≥ 2 and HCL ≥ 1.5 were considered positive for ATTR-CA. Demographics and pre-TAVR clinical history, laboratory values, EKG, and echocardiographic data were also analyzed for association with 99m Tc-PYP positivity. Results: Among 40 patients (mean age 85.2 + 5.3 years), 99m Tc-PYP uptake was found in 10% (n=4), all men. Mean semi-quantitative score was 2.8±0.5 and HCL was 1.6±0.1. Elevated BNP (1379±689 vs 438±483 pg/ml, p=0.02), decreased serum albumin (3.2±0.5 vs 3.8±0.5 g/dL, p=0.02), and both larger interventricular septal wall (1.3±0.4 vs 1.0±0.2 cm, p=0.01) and left posterior wall thickness (1.3±0.6 vs 0.9±0.2 cm, p=0.04) at diastole were associated with 99m Tc-PYP positivity. There was no difference in EF, but myocardial contraction fraction, the ratio of stroke volume to myocardial volume, was significantly lower, 24±12% vs 45±18%, in 99m Tc-PYP positive patients (p=0.03). Conclusions: 99m Tc-PYP has potential as a screening tool for ATTR-CA in high-risk populations. Our data suggest that ATTR-CA may be prevalent in patients undergoing TAVR, particularly men, 20% of whom had a positive 99m Tc-PYP scan. Identifying specific etiologies of heart failure in TAVR patients may be important for prognostication and response to therapy.

Abstract 17601: Left Atrial function Assessed by Cardiac Magnetic Resonance Imaging in Patients With Heart Failure With Preserved and Reduced Left Ventricle Ejection Fraction With and Without Symptoms

Introduction: Increased left atrial volume (LAV) is considered a barometer for impaired left ventricular (LV) relaxation. In this study we examined the LAV and LA emptying function in patients with LV systolic (LVSD) and diastolic dysfunction (LVDD) with and without clinical heart failure (HF). Methods: Prospectively enrolled study participants (n=66) underwent cardiac MR (CMR) in a 1.5 T scanner. Patients with atrial fibrillation were excluded. LAV was assessed at end systole (ES) and at end diastole (ED) using area-length methods in cine MR 4-chamber and 2-chamber planes and indexed to body surface area. HF status was based on clinical manifestations, elevated BNP or NT-BNP. Patients also underwent echocardiogram within 2 hours of CMR. LV ejection fraction (LVEF) by CMR &lt; 50% was defined as LVSD. Echocardiographic criteria and/or elevated LVED pressure by catheterization were applied to define LVDD. Results: LAV was significantly increased in HF patients. The greatest increase was seen among those with HFrEF. When compared to normal controls the magnitude of increase in LAV in HF patients was greater at ED than ES. Patients having LVSD and LVDD without clinical HF demonstrated relatively normal LAV at both ES and ED. While LA emptying function was significantly reduced in all HF patients the greatest reduction was found in HFpEF. LA boost function in late diastole was significantly increased only in LVDD (Table). Of the three LA indices, LA emptying function had the strongest correlation with (logarithm transformed) BNP (r = -0.62, p &lt;0.001) and NT-BNP (r = -0.58, p &lt;0.001) supporting its relationship with adverse hemodynamics. Conclusion: Significantly increased LAV and reduced LA emptying function were present in HFrEF and HFpEF. Heightened LA boost function with relatively normal LAV and emptying function was characteristic of LVDD without HF. These LA features demonstrate the importance of atrioventricular interdependence and may be valuable in clinical diagnosis.

A Score for Predicting Paroxysmal Atrial Fibrillation in Acute Stroke Patients: iPAB Score

Detection of paroxysmal atrial fibrillation (PAF) after a stroke is challenging. The purpose of this study was to develop a clinical score to predict PAF in a cohort of acute ischemic stroke patients prospectively and to validate it in an independent cohort. Consecutive acute ischemic stroke patients without permanent atrial fibrillation were enrolled in a derivation sample (n = 294) or a validation sample (n = 155). We developed a score for predicting PAF by independent risk factors derived from a logistic regression analysis of the derivation cohort and validated the score in the external cohort. Multivariate analysis in the derivation cohort identified 3 variables independently associated with PAF. We calculated a score from these variables (history of arrhythmia or antiarrhythmic agent use [yes, 3 points], left atrial dilation [≥40 mm, 1 point], brain natriuretic peptide [BNP, ≥50 pg/mL, 1 point; ≥90 pg/mL, 2 points; ≥150 pg/ml, 3 points], total score, 0-7). The iPAB score (identified by past history of arrhythmia or antiarrhythmic agent use, atrial dilation, and BNP elevation) predicted PAF in the derivation (c statistic, .90) and validation (.94) cohorts at levels statistically superior to other biomarkers and clinical scores. For a total score 2 or more, the sensitivity and specificity were 93% and 71%, respectively. For a total score of 4 or more, the corresponding values were 60% and 95%. Our prospective study suggests that this simple risk score superior to other scores help clinicians predict PAF or identify good candidates for further evaluation to detect PAF.

O9. The functional role of natriuretic peptides in preeclampsia

Background Natriuretic peptide family is believed to have evolved for the common homeostatic purpose of volume, osmosis and pressure regulation of the circulatory system. The activities of natriuretic peptides and endothelins are associated with each other. In the last three decades many members of the natriuretic peptide family was identified. BNP is the member of this family and with the sympathetic nervous system and other hormones they play key roles, like an endogeneous system in the regulation of the body fluid homeostasis and blood pressure. In the last years the potential use of the elevated BNP levels for diagnosis of pre-eclampsia was examined. There is a variable tandem repeat polymorphism in the 5 ′ -flanking region of the natriuretic peptide precursor B gene (NPPB). A previous study showed association of the (TTTC) small tandem repeat (STR) variants of this gene and essential hypertension in females. Methods In our studies blood samples were collected from healthy pregnant normotensive women ( n =235) and patients having severe pre-eclampsia ( n =220). DNA was isolated and fluorescent PCR and DNA fragment analysis was performed for the detection of (TTTC) repeats. The concentration of the BNP was measured by fluorescence immunoassay -Triage BNP test- method. Results The overall distribution of alleles and genotypes was significantly different between the control and pre-eclamptic groups. We detected 12 different (TTTC) repeats on the NPPB gene in the studied population. The pre-eclamptics were a homogeneous population, with only 10 types of alleles and 20 types of genotypes, contrary to control group with 12 types of alleles and 32 types of genotypes. The 11 homozygote patients have a higher frequency among the severe-pre-eclamptics. I found higher levels of BNP in those who had the genotype 11 homozygotes in both groups, significantly higher in pre-eclamptics. The concentration of the BNP is higher pre-eclamptic pregnancies, it shows association with the (TTTC) genotypes. The concentration of BNP was higher in early onset pre-eclamptic patients than in late onset pre-eclamptics. Intrauterine growth restriction shows no connection with BNP levels in severe pre-eclampsia. There was a significant inverse correlation between plasma BNP levels of preeclamptic patients and sodium and total protein concentrations and a significant positive correlation was observed between plasma levels of BNP and 24h proteinuria. The cut-off value Conclusions We introduced a F-PCR and DNA fragment analysis method for the fast and reliable detection of the STR in the 5 ′ -flanking region of the natriuretic peptide precursor B gene. Further investigations may help to understand the details of molecular biology, biochemistry and clinical relevance of natriuretic peptides.

Renin–angiotensin–aldosterone system genotype and serum BNP in a contemporary cohort of adults late after Fontan palliation

BackgroundAdults with single ventricle physiology palliated with a Fontan circulation experience high mortality due to circulatory failure. Renin-angiotensin-aldosterone system (RAAS) genotype contributes to adverse cardiovascular outcomes in acquired heart failure. This study evaluated associations between RAAS genotype, ventricular mass and function in a contemporary cohort of adults with a Fontan circulation. MethodsThis single-center prospective study included adults (n=106) seen after the Fontan operation (mean age 27±9years). Patients were genotyped for 5 pro-hypertrophic RAAS gene polymorphisms. Serum BNP, ventricular mass and function, and clinical events were compared between those with ≥2 homozygous risk genotypes (“high-risk”, n=31) versus those with ≤1 homozygous risk genotypes (“low risk”, n=75). Results“High-risk” genotype was associated with diastolic dysfunction and higher serum BNP levels. There was no association between RAAS genotype and either ventricular mass or systolic function. During a mean follow-up duration of 9.5±7.6years, late Fontan failure occurred in 20% (n=21) of patients, including 7 deaths. Serum BNP emerged as an independent predictor of late Fontan failure (HR 1.11 [CI 1.01–1.23] for each 50unit increase in BNP, p=0.04) and death alone (HR 1.25 [CI 1.07–1.47] for each 50unit increase in BNP, p=0.006). RAAS genotype was not associated with adverse clinical events. ConclusionsFontan failure is common among adults with single ventricle physiology. RAAS genotype is not associated with increased ventricular mass but does appear to influence diastolic function late after the Fontan operation. Elevated BNP is an independent predictor of Fontan failure and mortality in adulthood.

Characterization of Diabetic Cardiomyopathy: A Role for KDAC Activity

The molecular mechanisms leading to myocyte injury, hypertrophy and dysfunction in the diabetic heart are triggered by the characteristic metabolic abnormalities, and by abnormal energetics. Lysine (K) deacetylases (KDACs) inhibition was shown to be protective in models of doxorubicin cardiotoxicity through the reduction of fibrosis, decreased inflammation and the upregulation of antioxidant defenses. KDACs' role in the pathogenesis of diabetic heart disease is unknown.We used a murine model of leptin resistance (db/db mice). These mice were treated for 1 month with angiotensin II to induce severe cardiomyopathy. Echocardiography heart morphology, biochemical markers of injury were measured in the serum and KDAC activity and signaling was measured in cardiac tissues by Western blot and real time qPCR.Hypertensive diabetic mice developed a unique cardiomyopathy characterized by preserved fractional shortening (FS), thickened left ventricle wall and smaller ventricle cavity. Histological staining revealed infiltration of immune cells and extensive fibrosis. Biochemical markers indicated metabolic syndrome. Hypertrophic markers of diabetic hearts exhibited elevated BNP and MMP2 and lower KDAC activity. Elucidating the role of epigenetic mechanisms and KDAC in the development of diabetic cardiomyopathy in order to search for therapeutic strategies based on pharmacological manipulation of histone acetylation, is needed. Funded by Tel Aviv University.

0337: Prognostic value of reflux of contrast into the inferior vena cava or hepatic veins in pulmonary embolism

Computed tomography pulmonary angiography (CTPA) is routinely used to diagnose pulmonary embolism (PE). Reflux of contrast medium into the inferior vena cava or hepatic veins (IVC) on CTPA is a simple sign that could help for PE risk stratification. The purpose of this study was therefore to investigate prognosis significance of contrast reflux into IVC in acute PE. 141 consecutive patients with acute PE confirmed by CTPA were prospectively included between March 2010 and February 2013. Degree of reflux into the IVC and the hepatic veins was graded from 1 (none) to 6 (severe) by 2 independent observers, blinded to each other. The presence of reflux in IVC was compared with clinical parameters used in the ESC guidelines for PE risk stratification: electrocardiographic signs, Troponine I, BNP and right ventricular dilatation (RV/ LV>0,9) or dysfunction (TAPSE < 17 mm, S’<10 cm/s) by echocardiography. Composite endpoint was 30-days mortality or clinical deterioration requiring treatment escalation (catecholamine infusion, thrombolytic treatment or cardiopulmonary resuscitation). The composite end-point was observed in 5% of patients with a 30-day mortality rate of 2.1%. Heart rate >110 bpm (OR 5.6, 1.03-30), atrial fibrillation (OR 6.3, 1.05-37.7), negative anterior T waves (OR 6.1, 1.3-29.1), elevated Troponin Ic (OR 5.4, 1.1-25.8), elevated BNP (OR 11.5, 1.3-98.2), right ventricular dysfunction (OR 5.3, 1.1-25.1) were predictors of death or clinical deterioration. Contrast reflux into IVC from grade 4 to 6 was observed in 17% of patients. Interobserver agreement was excellent (Concordance correlation coefficient 0.91). Grade 4 reflux or greater was a strong predictor of events (OR 15.1, 2.8-83.7) and had a 86% specificity and 71% sensitivity to predict adverse outcomes (AUC 0.88). A grade 4 or higher contrast reflux into the IVC is a simple and frequent CTPA sign, highly predictive of adverse outcomes in PE patients.

Abstract 18297: Clinical and Prognostic Utility of Cardiac Magnetic Resonance Imaging in Multiple Myeloma Patients With Suspected Amyloidosis

Background: Upto 30% of patients with multiple myeloma have AL amyloidosis and cardiac involvement is associated with worse outcomes in these patients. Traditional screening modalities including EKG, echocardiography and biomarkers have limited value. The aim of this study was to evaluate the role of “screening” cardiac MRI in a large multiple myeloma population at a large specialized referral center. Methods &amp; Results: 164 consecutive patients with multiple myeloma who underwent cardiac MRI between 6/2005 and 10/2011 were enrolled in this study. Primary endpoint was all cause death. Clinical, EKG, echocardiographic, biomarker and MRI predictors for death were analyzed. Mean age of population was 63+10 years, 40% females and 16% African Americans. 30% of the population had MRI evidence of cardiac involvement. There were 26 patients who had biopsy proven systemic amyloidosis, of whom 62% showed cardiac involvement on MRI. 81% patients with confirmed cardiac amyloidosis on endomyocardial biopsy had typical MR pattern of cardiac involvement. During a median follow up period of 702 days (mean 1019 (950) days), there were 59 deaths (36%). Amyloid pattern on cardiac MRI (OR 2.19), elevated BNP and increased LV wall thickness on MRI were significant predictors of mortality . (All p&lt;0.05) Conclusions: This is the largest study to date evaluating the role of cardiac MRI in multiple myeloma patients with suspected cardiac amyloidosis. Cardiac MRI is a clinically robust tool for risk stratification of this subset of patients.

Clinical outcomes after neurogenic stress induced cardiomyopathy in aneurysmal sub-arachnoid hemorrhage: A prospective cohort study

IntroductionNeurogenic stress cardiomyopathy (NCM) has been associated with poor outcomes in the setting of aneurysmal subarachnoid hemorrhage (aSAH). Much less is known regarding recovery of cardiac function. The aim of this prospective cohort study was to study the rate of early cardiac recovery after NCM and the potential effect of NCM on short term functional recovery. A secondary aim sought to determine whether certain biomarkers may be associated with the development of NCM. MethodsPatients with confirmed aSAH between November 2012 and October 2013 were prospectively enrolled and received echocardiograms within 48h of admission. Ejection fraction (%) and regional wall motion abnormality score index (RWMI) were noted. All patients with confirmed aSAH had a troponin and BNP level drawn on admission. Patients with confirmed NCM received a follow up echocardiogram 7–21 days after the initial echocardiogram. Clinical follow up at 3 months evaluated mortality, mRS and mBI scores. Results63 patients with confirmed aSAH were enrolled. In this cohort 11 (17%) patients were confirmed to have NCM. The NCM group had higher in-hospital mortality [n=4(36.4%)] compared to the non-NCM group [n=5(9.6%)] (p=.021). At 3 months the development of NCM was associated with an unfavorable mRS (p=0.042) and mBI (p=0.005). Both an elevated BNP (>100pg/mL) and elevated troponin (>0.3mg/dL) were associated with the development of NCM. Follow-up echocardiograms were performed within 21 days of admission on 8 patients with NCM. An abnormal RWMI of 1.5 or higher was present in 5(71%) patients. ConclusionNCM is a frequent complication associated with aSAH. The onset of the disease occurs early in the course of aSAH and an elevated BNP and troponin may be associated with the onset of NCM. Cardiac function often remains impaired during the acute recovery phase potentially impeding resuscitation during this period. The routine use of short term follow-up echocardiography may be recommended.