Increase In NT-proBNP Research Articles

P1390 Myocardial work indices in the assessment of the systolic function of the left ventricle in amateur half marathon runners

Abstract Background Myocardial work (MW) has been recently introduced as a tool for non-invasive assessment of left ventricular (LV) systolic function. It is based on myocardial strain analysis but incorporates also data regarding loading conditions, which is potential advantage of this technique. Purpose We south to evaluate the impact of a three-month training before the half-marathon on cardiac function using indices of MW. Methods The study included 28 young amateur runners (11 women, mean age 32 years). None of the participants had a prior history of cardiovascular disease. The group was assessed at the beginning of training period, after three month (within 48 hours before half-marathon), and within 72 hours after the run. We collected clinical, laboratory and echocardiographic data. All participants underwent echocardiography to assess myocardial mechanics and MW indices using speckle-tracking technique. Results 23 participants completed the training and all of them finished the race. After the training period we observed significant increase in LV end-diastolic diameter only (49,9 ± 0,94 mm vs 51,6 ± 0,9 mm, p= 0,007) with no significant change after the run. There were no changes in global longitudinal strain (GLS), global work index (GWI) global wasted work (GWW) neither after the training period nor after the run. We observed significant changes suggesting myocardial injury after the race, including slight increase of NT-proBNP and troponin levels, increase in left atrial volume index, and reduction of tissue Doppler lateral e` wave. Global constructive work (GCW) decreased significantly after the training period, with no change after the run (2122,0 ± 299,4 vs 1929,0 ± 227 vs 1986,5 ± 295,7 mmHg%; start of the training vs before the run assessment vs after the run assessment, respectively; p = 0,005). GCW was correlated significantly with systolic blood pressure, which decreased also significantly after the training period. Conclusion Three-months training before the participation in half-marathon run was not associated with significant changes in myocardial work indices except the global constructive work, which could be related to decrease of loading conditions. Despite the signs of myocardial injury there was no deterioration in myocardial mechanics parameters, which may indicate the beneficial effects of training before the half-marathon run.

Efficacy and Safety of Tafamidis Doses in the Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR-ACT)

Introduction Tafamidis was shown to be an effective treatment for transthyretin amyloid cardiomyopathy (ATTR-CM) in the Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR-ACT). Hypothesis While ATTR-ACT was not designed for a definitive assessment by dose, further analysis may assist determination of the optimal dose. Methods In ATTR-ACT, adult patients with ATTR-CM (variant or wild-type) were randomized (2:1:2) to tafamidis 80 mg, tafamidis 20 mg, or placebo for 30 months, with pooled tafamidis (80mg and 20mg) compared with placebo. In this analysis, tafamidis 80 mg and 20 mg are presented separately. Efficacy outcomes included the hierarchical combination of all-cause mortality and frequency of cardiovascular-related hospitalisations, all-cause mortality, and change in NT-proBNP. Results The combination of all-cause mortality and cardiovascular-related hospitalizations over 30 months vs placebo was significantly reduced with both tafamidis 80 mg (P=0.003) and 20 mg (P=0.005). All-cause mortality was significantly reduced with tafamidis 80 mg (Cox-proportional hazard model [95% CI], 0.690 [0.487, 0.979], P=0.0378), and there was a trend towards reduction with tafamidis 20 mg (0.715 [0.450-1.137], P=0.1564), compared with placebo. The increase in NT-proBNP was reduced with tafamidis 80 mg, compared with both 20 mg (P=0.0468) and placebo (P Conclusions Tafamidis 80 mg and tafamidis 20 mg effectively reduced the combination of mortality and cardiovascular-related hospitalizations. Given the lack of dose-related safety concerns, and the NT-proBNP and survival data, tafamidis 80 mg is the preferred dose.

ATRIAL FIBRILLATION COMBINED WITH ARTERIAL HYPERTENSION AND OBESITY PARADOX

Purpose. To study the peculiarities of the clinical course of atrial fibrillation in patients with arterial hypertension and obesity.Materials and methods. 127 patients were observed within the observational cohort studies. Of these, 64 patients with atrial fibrillation, arterial hypertension and obesity in the control group, while the experimental group consisted of 63 patients with atrial fibrillation, arterial hypertension and normal BMI (24.1±2.2) kg/m2. During our work we assessed clinical, anthropometric and laboratory indicators, as well as the results of instrumental examination: ElectroCG; Daily monitoring of ECG, EchoCG. Comparison of binary and categorical indicators was carried out upon an accurate bilateral F test. Statistical hypothesis testing was carried out at critical significance value p=0.05, i.e. the difference was considered statistically significant if p<0.05.Results. Body mass index (BMI) in patients with atrial fibrillation, hypertension and obesity amounted to 35.2±4.6 kg/m2. The average age in all clinical groups was 60.5±9.2 years old, and patients with obesity were significantly younger (p<0.05) - 53.3±6.1 years old than patients with normal BMI - who were 59.8±7.4 years old. Patients with hypertension, atrial fibrillation and obesity often had a persistent form of AF 71%. General assessment of the lipid profile indicated that only patients with obesity and hypothyroidism showed a significantly high level of triglycerides. (p<0.001). There was an increase in NT-proBNP (p=0.001) and galectin-3 (p=0.005). There was a consistent increase of the end-diastolic dimension of the left ventricle in the left atrium; thickening of the left ventricular posterior and the interventricular septum in compared groups proved equivocal, while the LVMMI (p<0.05) was significantly lower in patients with obesity than in the experimental group.Conclusion. The presence of obesity in patients with atrial fibrillation and arterial hypertension adversely affects certain biochemical and ultrasound parameters, however, many of the criteria characterizing cardiovascular risk and prognosis did not reveal significant differences, which requires further in-depth study of this problem and identification of a possible “obesity paradox” in the group of patients with atrial fibrillation, arterial hypertension and obesity.

Abstract P033: NT-proBNP as a Biomarker to Detect Salt Sensitivity

Finding a biomarker to identify salt sensitive individuals would be an important step in the personalized management of hypertension. The natriuretic peptide, amino terminal pro-type B natriuretic peptide NT-proBNP, secreted by the heart in response to volume overload, is positively associated with incident hypertension. We hypothesized that when exposed to low salt diets, individuals with elevated NT-proBNP (≥ 100 pg/mL) will have a greater decrease in systolic blood pressure than those with NT-proBNP within the physiological range (40 - 90 pg/mL). Methods: Individuals with systolic/diastolic blood pressures greater than 120/85 mmHg and NT-proBNP values ≥ 40 pg/mL were included if they were not on blood pressure lowering medications and were free of cardiovascular or renal disease, diabetes, chronic obstructive pulmonary disease, pulmonary hypertension or any condition that would be associated with secondary causes of hypertension. Low salt diets consisted of meals containing total sodium 50 mmol/day. Meals were prepared at the Fairview University Hospital kitchen and provided to each participant for 10 days. Subjects were instructed to eat only the meals provided by the study. Sitting blood pressure, NT-proBNP, plasma glucose, sodium, creatinine and urinary sodium and creatinine were measured before and after 10 days on the low salt diet. Urinary creatinine and sodium was determined in 24-hour urine on day 10. Statistical analysis. Change (blood pressure after - blood pressure before low salt diet) in systolic blood pressure values were linearly regressed on log transformed NT-proBNP values. Results: 9 individuals (5 females) mean (SD) age 58.3 (8.1) years were classified into physiological 51.2 (7.8) pg/mL (n = 4) and an elevated 165.7 (84.5) pg/mL (n = 5) category of NT-proBNP. Systolic blood pressures was 127.9 (13.9) and 139.5 (9.6) mmHg for the physiological and elevated category of NT-proBNP, respectively, p = 0.18. Body mass index and plasma glucose, sodium and creatinine at baseline were also similar between the two groups. Following 10 days of low salt diet, systolic blood pressure decreased by a mean (SE) 16.9 (6.8) mmHg in those with elevated levels of NT-proBNP and by 10.9 (3.3) mmHg in those with physiological levels of NT-proBNP, p = 0.4. Baseline log NT-proBNP was inversely associated with change in systolic blood pressure r = - 0.60, p = 0.09. For log NT-proBNP values between 3.697 and 5.745 pg/mL, every log unit increase in NT-proBNP at baseline was associated with a mean (range) systolic blood pressure decrease of 10.4 (5 - 37.7) mmHg, p = 0.09. Conclusions: Results from a large-scale study are required to confirm the findings from this small pilot study that elevated values of NT-proBNP can predict who will have a decrease in systolic blood pressure in response to a low sodium diet.

Graded Cardiac Response Correlates with Relapse and Survival in AL Amyloidosis

Seventy percent of all patients with light chain amyloidosis (AL) have cardiac involvement, and most of those patients ultimately die from complications related to their heart disease. While consensus guidelines outline criteria for grading hematologic response to chemotherapy for AL, there are no currently validated criteria for grading cardiac response to therapy. Recently, Muchtar et al. created a system for grading organ response, but excluded previously treated patients and those requiring multiple lines of therapy to achieve a response. Because the majority of AL patients receive multiple lines of therapy during their treatment course, we sought to validate cardiac grading criteria and demonstrate that they can be applied to a heterogeneous group of patients, including those who have been treated previously. Here we show how depth of best cardiac response at any point during a treatment course predicts both overall survival and risk of subsequent cardiac relapse defined as progression after an initial cardiac response.This is a retrospective cohort study of patients followed at the Stanford Amyloid Center with underling plasma cell dyscrasias causing biopsy-proven systemic AL involving the heart. Grading cardiac response involves categorizing the best response (the lowest NT-proBNP value) after initiation of treatment as either no response (NR), partial response (PR), very good partial response (VGPR), or complete response (CR). PR and VGPR are defined as a >30% and >60% reduction in NT-proBNP respectively; CR is defined as NT-proBNP<450 pg/mL. Per consensus guidelines, cardiac progression is defined as a >30% and >300 ng/L increase in NT-proBNP, whereas NR does not meet response criteria requiring a >30% and >300 ng/L reduction in NT-proBNP. Survival times were calculated from the time of first treatment to patient death or end of study (January 2018).Out of 252 patients with cardiac AL treated between June 2007 and January 2018, 114 had sufficient data for evaluation. Of those, 74 patients (65%) had cardiac responses to treatment, and 40 (35%) did not demonstrate a cardiac response. Of the responders, 60% had received more than one line of therapy by the time they achieved their best cardiac response. Kaplan Meyer survival analyses of patients grouped by cardiac response to therapy reveal that best depth of cardiac response to therapy at any point during the treatment course is predictive of overall survival by the log-rank test using a pre-treatment NT-proBNP assessment (p<0.0001). Patients who achieve CR have a 5-year overall survival of 96% compared to 74% for VGPR, 43% for PR, and 13% for NR. Results of a landmark analysis using NT-proBNP values after 6 months of treatment yielded the same statistically significant result (p<0.0001). A subset analysis of patients who required multiple lines of therapy to achieve their best cardiac response was also significant (p=0.0014). Patients who achieve deeper cardiac responses are also less likely to experience subsequent cardiac relapse (p=0.012), and patients who relapse have less robust percent reductions in NT-proBNP than those who do not (p=0.0017). For example, 5% of responders in our cohort achieved a CR and subsequently experienced a cardiac relapse, as compared to 11% of VGPR patients and 19% of PR patients. Additionally, deeper cardiac responses take longer to achieve that shallower responses (p=0.027). Median time to response for CR patients is 595 days, as compared to 405 days for VGPR patients and 96 days for PR patients. Depth of hematologic response is significantly associated with cardiac response (p<0.0001), but not with cardiac relapse (p=0.69), while in contrast, hematologic relapse is strongly associated with cardiac relapse (p=0.0002).Our findings validate cardiac response grading as a useful tool for prognostication. Moreover, we demonstrate that cardiac response grading can be applied to patients who received several lines of therapy. This both increases the applicability of the tool and, in the context of CRs taking longer to achieve, demonstrates the clinical imperative to continue aggressive therapy in patients with suboptimal cardiac responses. Indeed, a CR or even VGPR achieved later in an illness trajectory has a demonstrated overall survival and cardiac progression free survival benefit. [Display omitted] DisclosuresSchrier:Forty Seven Inc.: Consultancy. Liedtke:Amgen/Onyx: Consultancy, Honoraria, Research Funding; BlueBirdBio: Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; celgene: Research Funding; Caelum: Membership on an entity's Board of Directors or advisory committees; Prothena: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Genentech/Roche: Research Funding; Gilead: Membership on an entity's Board of Directors or advisory committees, Research Funding.

Pomalidomide and Dexamethasone Grant Rapid Hematologic Responses in Patients with Relapsed and Refractory AL Amyloidois: A European Retrospective Series of 150 Patients

Background: The immunomodulatory agent pomalidomide is active in patients with relapsed/refractory multiple myeloma, including those who failed prior lenalidomide and bortezomib. Phase II clinical trials showed that pomalidomide is also effective in previously treated AL amyloidosis. The combination of pomalidomide and dexamethasone (PDex) showed a good hematologic response rate (more than partial response from 48 to 68%). Aim of this study is to report the efficacy of PDex in a retrospective real-world series of patients with AL amyloidosis from three European referral centers.Methods: The databases of the Pavia Amyloid Research and Treatment Center (Italy), the Heidelberg Amyloidosis Center (Germany) and the National Amyloidosis Center of London (United Kingdom) were searched for patients with a diagnosis of AL amyloidosis treated with pomalidomide and dexamethasone (PDex). The patients received 28-day cycles of pomalidomide (from day 1 to 21) and dexamethasone (once weekly). All patients gave written informed consent for their clinical data to be used for research purposes. Hematologic and organ responses were assessed according to the International Society of Amyloidosis criteria.Results: One hundred and fifty patients were included, 91 treated in Pavia, 30 in Heidelberg and 29 in London. Median age at the time of PDex initiation was 65 years (range: 34-85 years) and 92 (61%) patients were males. The heart was involved in 92 (61%) patients, the kidney in 87 (58%) and 91 (60%) of patients had two or more organs involved. The median NT-proBNP concentration at the time of PDex initiation was 1.670 ng/L (interquartile range, IQR: 527-4.963 ng/L) and 23 (15%) had NT-proBNP >8.500 ng/L. The estimated glomerular filtration rate was <30 mL/min per 1.73 m2 in 13 (9%) of patients and 16 (11%) were on dialysis at the time of PDex initiation. Median bone marrow plasma cells infiltrate at diagnosis was 18% (IQR: 10-30%) and this was ≥10% in 114 (76%) subjects. The median difference between involved and uninvolved concentration of free light chains (dFLC) was 150 mg/L (IQR: 76-397 mg/L). Median time from AL amyloidosis diagnosis to PDex treatment initiation was 11 months (IQR: 5-24 months). The median number of previous lines of therapy was 3 (range: 2-7) with 98 (65%) patients refractory to previous lines. One hundred and thirty-eight (92%) patients had previously received bortezomib, 120 (80%) lenalidomide and 114 (76%) melphalan and 39 (26%) underwent autologous stem cell transplant. The median number of PDex cycles performed was 3 (range: 1-30). Pomalidomide dosage was 4 mg in 56% of patients, 2 mg in 27%, 3 mg in 14% and 1 mg in 3% of subjects. Adverse events observed in 42 (28%) of subjects. With the limit of the retrospective setting, the more frequently reported were infections in 13 (31%), cardiac heart failure in 11 (26%), creatinine increase in 7 (16%) and cytopenia 4 (9%). The hematologic response rate at the end of cycle 3 was 36%, with 14 (16%) very good partial responses (VGPR) and 20 (20%) partial responses (PR). After cycle 6, the overall hematologic response rate was 56%, with 15 (26%) VGPR and 17 (30%) PR. A hematologic response to therapy was noted in 16 out of 39 subjects who were previously refractory to bortezomib, lenalidomide and melphalan. Median follow-up of living patients was 12 months (IQR: 7-27 months) and 64 (42%) patients died. Obtaining at least partial response at the end of cycle 3 was associated with a significant survival advantage (median survival not reached vs. 25 months, P=0.007, Figure). Cardiac responses were observed in 7 of 74 patients with measurable NT-proBNP (10%), but this can be underestimated due to the pomalidomide-related increase of NT-proBNP, and renal response in 13 of the 56 evaluable patients (23%).Conclusions: The combination of pomalidomide and dexamethasone is active, with a 56% of response rate at cycle 6, in heavily pretreated patients with AL amyloidosis. The hematologic response rate of this real word retrospective study compares with those reported in phase 2 clinical trials, improved over time and patients who obtained a quick reduction of the burden of free light chains, had a significant survival benefit. Pomalidomide is an effective rescue agent for relapsed refractory AL amyloidosis. [Display omitted] DisclosuresMerlini:Akcea: Consultancy; Janssen: Consultancy; Ionis: Consultancy; Millenium: Consultancy; Prothena: Consultancy; Pfizer: Consultancy. Wechalekar:Janssen: Honoraria. Palladini:Janssen: Membership on an entity's Board of Directors or advisory committees; Celgene: Other: Travel support; Prothena: Honoraria.

Evaluation of the impact of treatment with hematopoietic stem cells transplantation (HSCT) on biochemical markers of heart function and novel electrocardiographic markers of repolarization in patients with hematological malignancies

High-dose chemotherapy (HDC) followed by stem cell transplantation (HSCT) is a well-established method in patients with hematological malignancies, and for last few years, many efforts have been made to estimate short- and long-term efficacy of this method, as well as early and late complications. The present study concentrates on cardiotoxic effects, mainly early changes using biochemical markers such as N-terminal natriuretic peptide type B (NT-proBNP) and cardiac troponins (cTn). Simultaneously, the analysis of 12-lead ECG was done before and after the procedure in which the novel repolarization markers: Tp–e and Tp–e/QT ratio were measured, together with standard markers: QT, QTc. It was found that NT-pro BNP was significantly increased after HSCT in comparison to results before it, and no significant changes were present in Troponin levels. Simultaneously, Tp–e interval and Tp–e/QT ratio were significantly higher after HSCT. The use of cyclophosphamide, advanced age, and higher level of blood cholesterol concentration were risk factors for the increase in NT-proBNP and treatment with cyclophosphamide as well as fludarabine and higher creatinine levels were risk factors for the increase in Tp–e/QT ratio. In conclusion, in the early term evaluation after HSCT in patients with no previously diagnosed heart disease, the mild changes in markers of heart overload and repolarization were noted. The observations suggest that in all patients undergoing HSCT, even the ones without pre-existing cardiovascular disease, the evaluation, and monitoring of heart function should be considered.

Plasma marinobufagenin immunoreactivity in patients with chronic kidney disease: a case control study.

Experimental data have shown increased plasma levels of marinobufagenin in kidney failure. In this case-controlled retrospective analysis, we evaluated plasma marinobufagenin immunoreactivity in hemodialysis patients compared with subjects with normal kidney function. Sixty-eight adult hemodialysis patients with chronic kidney disease (34 females and 34 males) as well as 68 age-, gender-, and blood pressure-matched subjects without chronic kidney disease were enrolled. Patients on stable hemodialysis regimen for at least 3 mo before the study were included. Exclusion criteria were: age <18 yr, severe liver or heart insufficiency, and overhydration. Subjects without chronic kidney disease must have had an estimated glomerular filtration rate ≥60 ml·min-1·1.72 m-2 according to the Modification of Diet in Renal Disease formula. Plasma marinobufagenin immunoreactivity was significantly ( P < 0.001) higher in hemodialysis patients (1.66 ± 1.13 nmol/l) compared with subjects with normal kidney function (0.46 ± 0.23). In hemodialysis patients, plasma marinobufagenin immunoreactivity was higher in men compared with women. A significant positive correlation has been found between plasma marinobufagenin immunoreactivity and serum NT-proBNP, NT-proANP, or aldosterone concentrations in all analyzed subjects. In hemodialyzed patients with plasma marinobufagenin immunoreactivity above median value 5-yr, all-cause mortality was higher compared with those with plasma marinobufagenin concentration below median. We have shown that plasma marinobufagenin immunoreactivity is increased in patients with end-stage kidney failure treated with hemodialysis parallel to the increase in serum NT-proBNP, NT-proANP, and aldosterone concentrations. Higher marinobufagenin immunoreactivity has been associated with worse survival in hemodialyzed patients.

Cardiac impact of R-wave triggered irreversible electroporation therapy

Irreversible electroporation (IRE) is a novel tumor ablative therapy technique, using electric fields to induce apoptosis in target tissues. Whether these electric pulses of high field strength can cause cardiac damage and/or ablation-induced arrhythmias is unclear. The purpose of this study was to systematically evaluate the safety of electrocardiogram (ECG)-gated IRE with regard to cardiac side effects. In all patients, 12-lead ECG and signal-averaged ECG (SAECG) recordings were performed before and after IRE and 24-hour Holter recording on the day of the IRE procedure. Venous blood samples (N-terminal pro-brain-type natriuretic peptide [NT-proBNP], high-sensitive troponin I [hsTnI]) were obtained before and 4 and 16 hours after the procedure. Patients with abnormal findings were reevaluated after 3 months. In total, 26 patients with an oncologic indication for IRE (11 females, mean age 62.9 years) were prospectively enrolled. Nine patients (34.6%) showed an increase in hsTnI and 21 patients (80.8%) an increase in NT-proBNP after ablation. Fifteen patients (57%) developed arrhythmias related to the procedure. One patient, in whom hsTnI and NT-proBNP had increased, developed multiple, nonsustained ventricular tachycardia events. In another patient, atrial fibrillation was triggered twice in 2 separate procedures. Twelve patients had clinically benign arrhythmias. SAECG was negative in all patients. Subclinical myocardial injury and nonfatal cardiac arrhythmias can occur in the context of IRE treatment. Although no sustained cardiac injuries could be found at 3-month follow-up, we propose implementation of a cardiac safety algorithm consisting of cardiac biomarkers and ECG monitoring when IRE is conducted.

Clinical use of submaximal treadmill exercise testing and assessments of cardiac biomarkers NT-proBNP and cTnI in dogs with presymptomatic mitral regurgitation.

Exercise intolerance is the first symptom of heart disease. Yet an objective and standardised method in canine cardiology to assess exercise capacity in a clinical setting is lacking. In contrast, exercise testing is a powerful diagnostic tool in humans, providing valuable information on prognosis and impact of therapeutic intervention. To investigate whether an exercise test reveals differences between dogs with early stage mitral regurgitation (MR) and dogs without cardiac disease, 12 healthy beagles (healthy group, HG) and 12 dogs with presymptomatic MR (CHIEF B1 / B2, patient group, PG) underwent a six-stage submaximal exercise test (ET) on a motorised treadmill. They trotted in their individual comfort speed for three minutes per stage, first without incline, afterwards increasing it by 4% for every subsequent stage. Blood samples were taken at rest and during two 3-minute breaks in the course of the test. Further samples were taken after the completion of the exercise test and again after a 3-hour recovery period. Measured parameters included heart rate, lactate and the cardiac biomarkers N-terminal pro-B-Type natriuretic peptide and cardiac Troponin I. The test was performed again under the same conditions in the same dogs three weeks after the first trial to evaluate individual repeatability. Cardiac biomarkers increased significantly in both HG and PG in the course of the test. The increase was more pronounced in CHIEF B1 / B2 dogs than in the HG. N-terminal pro-B-Type natriuretic peptide increased from 435 ± 195 to 523 ± 239 pmol/L (HG) and from 690 to 815 pmol/L (PG). cTnI increased from 0.020 to 0.024 ng/mL (HG) and from 0.06 to 0.08 ng/ml (PG). The present study provides a method to assess exercise-induced changes in cardiac biomarkers under clinical conditions. The increase of NT-proBNP and cTnI is more pronounced in dogs with early-stage MR than in healthy dogs. Results indicate that measuring the parameters before and after exercise is adequate and taking blood samples between the different stages of the ET does not provide additional information. Also, stress echocardiography was inconclusive. It can be concluded that exercise testing, especially in combination with measuring cardiac biomarkers, could be a helpful diagnostic tool in canine cardiology.

Kardiomiopatia przerostowa u bezobjawowej 24-letniej kobiety w ciąży — postępowanie według wytycznych ESC

We present the case of a 24-years old asymptomatic pregnant woman in 18hbd with hypertrophic cardiomyopathy (HCM). An echocardiogram revealed the hypertrophy of all walls of left ventricle (LV), except for the posterolateral wall, from 21mm to 31mm and septal hypertrophy up to 36mm. During the first 48-h-ECG monitoring 5 episodes of slowVT consisted of 3 ExV up to 108/min were recorded. The 5-year HCM SCD (sudden cardiac death) risk score revealed the low risk of 2,25% - implantable cardioverter-defibrylator (ICD) not indicated. After a C-section delivery in 37hbd the control echocardiography revealed the enlargement of LV wall hypertrophy up to 38mm. In 48h-ECG monitoring 2 episodes of asymptomatic nsVT consisted of 4 and 7 ExV up to 162/min were registered. The 5-year HCM SCD risk came up to intermediate level: 5,91% (ICD may be considered, class IIb B of recommendations). Based on the clinical and echocardiographic findings with dynamic progress in the LV hypertrophy, exacerbation of ventricular arrhythmias and increase of NT-proBNP, the ICD was implanted. As presented by Maron & Maron at ESC Congress in London 2015, an MRI scanning with the late gadolinium enhancement (LGE) estimation may be helpful in making the decision on the ICD implantation, especially within the group of the intermediate 5-year risk of SCD (4-6%) with massive LV hypertrophy. Authors suggest the extensive LGE (≥15%) as a primary SCD risk factor and also as a potential risk factor when conventional evaluation of the ICD implantation indications is ambiguous.

Biomarkers of cardiovascular stress and fibrosis in preclinical hypertrophic cardiomyopathy

ObjectiveSarcomeric gene mutation carriers without overt left ventricular hypertrophy (G+/LVH−) can harbour subclinical changes in cardiovascular structure and function that precede the development of hypertrophic cardiomyopathy (HCM). We sought to...

11 Cpex testing detects subclinical cardiac limitation to exercise in early stage ckd

Introduction Effort tolerance is impaired in end stage kidney disease. Peak oxygen uptake (VO2peak) has been shown to be a powerful predictor of survival in haemodialysis patients. A low VO2peak and percent predicted VO2 at the anaerobic threshold (VO2 AT) have also been associated with excess mortality in patients undergoing kidney transplantation. Data on effort tolerance and cardiovascular disease in early chronic kidney disease (CKD) are very sparse though it is well recognised that cardiovascular mortality begins to increase at a glomerular filtration rate (eGFR) of about 75ml/min/m2. Methods This study examined effort tolerance, cardiac structure and function in 60 patients with CKD (stages 2 to 5) without known cardiovascular disease or diabetes. All patients underwent a cardiopulmonary exercise bicycle test using an individualised ramp protocol. Myocardial ischaemia was excluded by exercise stress echocardiography or 99m technetium tetrofosmin single photon electron computed tomography. Lung disease was excluded by formal lung function testing. Cardiac magnetic resonance imaging without gadolinium contrast was used to assess cardiac function and structure. The Kruskall Wallis test was used to compare the difference in mean values across stages of CKD. Correlation coefficients were measured to look for trends between continuous variables. Results Table 1 shows the baseline characteristics per CKD stage. Percent predicted peak VO2 was negatively associated with eGFR (r=−0.358, p=0.007) even after correction for age and haemoglobin (p=0.005). NT pro-BNP was negatively associated with eGFR (r=−0.586, p=0.001), even after similar correction (p Discussion and implications Effort tolerance falls from the earliest stages of CKD in association with a progressive increase in LV mass and NT pro-BNP. This is the first study to examine exercise capacity in patients with early stage CKD in whom coronary artery disease has been excluded, and further study is needed to confirm whether the reduction in exercise capacity is a reflection of diastolic impairment and myocardial fibrosis that characterise end-stage kidney disease.

Anemia considerations when assessing natriuretic peptide levels in ED patients

IntroductionThe incidence of heart failure (HF) has reached epidemic levels in western populations, and the majority of these patients are admitted to hospitals through the emergency department (ED). We aimed to aid clinicians assessing natriuretic peptide (NP) levels in cases with suspected HF. In this study, we investigated the effect of anemia on amino-terminal pro-BNP (NT-proBNP) and on B-type natriuretic peptide (BNP) levels. MethodsThis retrospective study examined patients who were admitted to the ED with suspected HF. After admission, the treating physician requested complete blood count and creatinine tests with NT-proBNP (n=2.637) or BNP (n=11.159). The exclusion criteria were used to minimize the factors that could affect the NT-proBNP and BNP results. We examined the data using the Mann-Whitney U test, Chi-square test, Spearman correlation test, and multivariate linear regression analyses. ResultsThe NT-proBNP and BNP levels were statistically higher in the groups with anemia (p=0.016 and p=0.009, respectively). There was a statistically significant negative correlation between hemoglobin and NP levels (r=−0.272, p<0.001 for NT-proBNP and r=−0.179, p<0.001 for BNP). The results indicated that advanced age and low hemoglobin levels were significantly associated with the increase in NT-proBNP (p=0.024 and p=0.004, respectively). Advanced age, low hemoglobin and low GFR-MDRD levels were significantly associated with the increase in BNP (p<0.001, p=0.002 and p=0.013, respectively). DiscussionThe data suggest that clinicians examining patients admitted to the ED with suspected HF should consider that anemia could lead to increases in NT-proBNP and BNP levels.

Urinary sodium excretion after gastric bypass surgery

BackgroundGut–kidney signaling is implicated in sodium homeostasis and thus blood pressure regulation. Roux-en-Y gastric bypass (RYGB) surgery for morbid obesity confers a pronounced and long-lasting blood pressure lowering effect in addition to significant weight loss. ObjectivesWe set out to establish whether RYGB is associated with an intrinsic change in urinary sodium excretion that may contribute to the reported blood pressure lowering effects of the procedure. SettingUniversity hospital MethodsFive female patients (age range: 28–50 yr) without metabolic or hypertensive co-morbidities were included in a study involving four 24-hour residential visits: once before surgery and 10 days, 3 months, and 20 months after surgery. Creatinine and sodium were measured in fasting plasma samples and 24-hour urine samples and creatinine clearance, estimated glomerular filtration rate, and indices of urinary sodium excretion were calculated. Fasting and 60-minute postprandial blood samples from each study day were assayed for pro-B-type natriuretic peptide (NT-proBNP). ResultsIncreases in weight-normalized urinary sodium excretion of up to 2.3-fold in magnitude occurred at 20 months after surgery. Median fractional excretion of sodium at 20 months was double that seen before surgery. Fasting NT-proBNP levels were stable or increased (1.5- to 5-fold). Moreover, a small postprandial increase in NT-proBNP was observed after surgery. ConclusionsRenal fractional excretion of sodium is increased after RYGB. A shift toward increased postoperative basal and meal associated levels of NT-proBNP coincides with increased urinary sodium excretion. The data support a working hypothesis that an enhanced natriuretic gut–kidney signal after RYGB may be of mechanistic importance in the blood pressure lowering effects of this procedure.

Prognostic power of NT-proBNP in left ventricular non-compaction cardiomyopathy

BackgroundThe risk of adverse events in patients with left ventricular non-compaction cardiomyopathy (LVNC) is substantial. This study was designed to determine the prognostic value of NT-proBNP, left ventricular ejection fraction (LVEF), NYHA class, and exercise capacity in LVNC patients. MethodsCox regression analyses were performed for evaluating the prognostic value of NT-proBNP, LVEF, NYHA class, and exercise capacity on the occurrence of death or heart transplantation. 153 patients were included. ResultsDuring 1013 person-years (longest follow-up 18.5years) 23 patients (15%) died or underwent heart transplantation. We observed a significant relationship of NT-proBNP (adjusted HR 2.44, 95% CI 1.45–4.09, for every NT-proBNP doubling, p=0.0007) and LVEF (adjusted HR for age 60years: 2.68, 95% CI 1.62–4.41, p=0.0001) with the risk of death or heart transplantation. Combined covariate analysis indicated a strong influence of NT-proBNP (adjusted 2.89, 95% CI 1.33–6.26, p=0.007), whereas LVEF was no longer significant (adjusted HR 0.82, 95% CI 0.42–1.67, p=0.66) demonstrating a favorable prognostic power of NT-proBNP over LVEF. An increase in NYHA class was associated with a worse outcome, and exercise capacity revealed a trend in the same direction. For all the abovementioned analyses, similar results were obtained when assessing the values at first presentation. ConclusionThis study provides evidence that an increase in NT-proBNP is a strong predictor of outcome in patients with LVNC. The prognostic power of NT-proBNP is at least as good as that of LVEF, indicating that routine NT-proBNP measurement may improve risk assessment in LVNC.

Increased Atrial β-Adrenergic Receptors and GRK-2 Gene Expression Can Play a Fundamental Role in Heart Failure After Repair of Congenital Heart Disease with Cardiopulmonary Bypass.

Surgeries to correct congenital heart diseases are increasing in Brazil and worldwide. However, even with the advances in surgical techniques and perfusion, some cases, especially the more complex ones, can develop heart failure and death. A retrospective study of patients who underwent surgery for correction of congenital heart diseases with cardiopulmonary bypass (CPB) in a university tertiary-care hospital that died, showed infarction in different stages of evolution and scattered microcalcifications in the myocardium, even without coronary obstruction. CPB is a process routinely used during cardiac surgery for congenital heart disease. However, CPB has been related to increased endogenous catecholamines that can lead to major injuries in cardiomyocytes. The mechanisms involved are not completely understood. The aim of this study was to evaluate the alterations induced in the β-adrenergic receptors and GRK-2 present in atrial cardiomyocytes of infants with congenital heart disease undergoing surgical repair with CPB and correlate the alterations with functional and biochemical markers of ischemia/myocardial injury. The study consisted of right atrial biopsies of infants undergoing surgical correction in HC-FMRPUSP. Thirty-three cases were selected. Atrial biopsies were obtained at the beginning of CPB (group G1) and at the end of CPB (group G2). Real-time PCR, Western blotting, and immunofluorescence analysis were conducted to evaluate the expression of β1, β2-adrenergic receptors, and GRK-2 in atrial myocardium. Cardiac function was evaluated by echocardiography and biochemical analysis (N-terminal pro-brain natriuretic peptide (NT-ProBNP), lactate, and cardiac troponin I). We observed an increase in serum lactate, NT-proBNP, and troponin I at the end of CPB indicating tissue hypoxia/ischemia. Even without major clinical consequences in cardiac function, these alterations were followed by a significant increase in gene expression of β1 and β2 receptors and GRK-2, suggesting that this is one of the mechanisms responsible for the exacerbated response of cardiomyocytes to circulating catecholamines. These alterations could explain the irreversible myocardial damage and lipid peroxidation of membranes classically attributed to catecholamine excess, observed in some infants who develop heart failure and postoperative death. Although other factors may be involved, this study confirms that CPB acts as a potent inducer of increased gene expression of β- adrenergic receptors and GRK-2, making the myocardium of these infants more susceptible to the effects of circulating endogenous catecholamines, which may contribute to the development of irreversible myocardial damage and death.

No relationship exists between urinary NT-proBNP and GPS technology in professional rugby union.

We investigated the level of cardiovascular stress associated with professional rugby union and whether these changes could be explained through external workload systems like GPS and video analysis. Urine samples (14 in game one and 13 in game two) were collected from professional rugby players before, immediately post- and 36h post-play in two consecutive games. Urine was analysed for NT-proBNP by ELISA. Comparison with GPS (player-load and distance covered at specific speed bands) and video analysis (total impacts) were conducted. There was a significant increase in urinary NT-proBNP during game one (31.6±5.4 to 53.5±10.8pg/mL) and game two (35.4±3.9 to 49.8±11.7pg/mL) that did not correlate with the number of impacts, total distance covered, distance covered at pre-determined speed bands or player-load. Concentrations returned to pre-game concentrations 36h post-game whilst a large inter-individual variation in NT-proBNP was observed among players (p<0.001). Professional rugby union causes a transient increase in cardiovascular stress that seems to be independent of the external workload characteristics of a player.

Significant Iatrogenic High Flow AV-Communication after MitraClip Treated with Endovascular Covered Stent

The percutaneous mitral valve repair therapy (MitraClip) constitutes an alternative for high peri- operative risk patients with severe symptomatic mitral regurgitation. Various complications, especially access -related have been described post mitraclip procedure as iatrogenic femoral arteriovenous fistulas with an incidence approximately of 0.1-1.5% following cardiac catheterization. We report a case of a 84-year-old male with a high flow AVcommunication at the puncture site after mitral clip procedure accompanied with decompensated heart failure symptoms and NTproBNP increase treated with endovascular covered stent.

Practice Patterns of Re-Initiation of Therapy at Time of Relapse or Progression Post- Autologous Stem Cell Transplant (ASCT) Among Patients with AL Amyloidosis

Background: Among patients with immunoglobulin light chain (AL) amyloidosis, there is little consensus on when reinstitution of chemotherapy should occur (Milani and Dispenzieri, International Society of Amyloidosis 2016). AL amyloidosis patients who are treated with high dose chemotherapy followed by autologous stem cell transplant (ASCT) are a relatively low-risk and homogenous population, making them an ideal group to study practice patterns.Methods: We conducted a retrospective study to evaluate the patterns of relapse or progression and the timing of re-initiation of therapy among 146 patients who were initially treated with ASCT at Mayo Clinic between 1996 and 2009 and who received second-line therapy between 7/9/1997 and 4/12/2012.Results: The median time from ASCT to second-line therapy was 23.6 months and the median follow up post ASCT was 57.5 months. The indications for second-line treatment were: 1) both hematologic and organ progression 24.7% (36 patients); 2) organ progression only 41.1% (60); 3) hematologic relapse only 34.2% (50). The median dFLC at the time of starting second-line therapy was 10.5 mg/dL (1.6 - 59.5 mg/dL), which was 44.9% (13.8-167.2%) of dFLC level at diagnosis. Increase in proteinuria by > 50% from nadir (that was also at least 1g/24 hours, i.e. renal progression) was present in 35.8%. Increase in NT proBNP by >30% from nadir and minimum of 300 pg/mL was present in 48.9% of patients. The respective 4 years overall survival rates from the time of ASCT were 87.8%, 63.9%, and 56.7% (p=0.0016) for patients who had hematologic relapse, organ progression only and both organ and hematologic progression. Comparisons of laboratory markers at diagnosis, nadir of post ASCT and initiation of second-line therapy are listed in the table.Conclusions: Our study investigated the patterns of relapse / progression following upfront ASCT. This provides some insights on practice patterns of when physicians re-initiate therapy. [Display omitted] DisclosuresGertz:NCI Frederick: Honoraria; Celgene: Honoraria; Med Learning Group: Honoraria, Speakers Bureau; Research to Practice: Honoraria, Speakers Bureau; Novartis: Research Funding; Prothena Therapeutics: Research Funding; GSK: Honoraria; Sandoz Inc: Honoraria; Ionis: Research Funding; Alnylam Pharmaceuticals: Research Funding; Annexon Biosciences: Research Funding. Kumar:Millennium: Consultancy, Research Funding; Array BioPharma: Consultancy, Research Funding; Sanofi: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Noxxon Pharma: Consultancy, Research Funding; AbbVie: Research Funding; Glycomimetics: Consultancy; Janssen: Consultancy, Research Funding; BMS: Consultancy; Skyline: Honoraria, Membership on an entity's Board of Directors or advisory committees; Onyx: Consultancy, Research Funding; Kesios: Consultancy. Kapoor:Celgene: Research Funding; Amgen: Research Funding; Takeda: Research Funding. Dispenzieri:Prothena: Membership on an entity's Board of Directors or advisory committees; Alnylam: Research Funding; Celgene: Research Funding; Jannsen: Research Funding; pfizer: Research Funding; GSK: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding.