Higher NT-proBNP Levels Research Articles

Pulmonary artery pulsatility index by echocardiography predicts mortality in patients with pulmonary hypertension

Abstract Funding Acknowledgements Type of funding sources: None. Background Pulmonary hypertension (PH) is a progressive pulmonary vascular disorder with an elevated mortality risk due to right ventricular failure. Pulmonary arterial pulsatility index (PAPi) based on invasively acquired parameters has emerged as a potentially valuable hemodynamic risk predictor. Whether non-invasively derived PAPi (PA pulse pressure/ RA pressure) is valuable is unclear. Purpose To assess whether PAPi measured non-invasively by transthoracic echocardiography acts as a prognostic hemodynamic biomarker of patient risk. Methods Consecutive patients undergoing transthoracic echocardiography for known or suspected PH over a one year period were included. PA systolic and diastolic pressure were estimated in standard fashion from peak tricuspid and end-pulmonary regurgitant Doppler profiles. Right atrial pressure was estimated based on 2D & Doppler assessment of the inferior vena cava hepatic vein. In those patients with PH (mean PA pressure > 20 mm Hg), PAPi was divided into 3 groups based on prior publications with invasive data as <1.5, 1.5 to 3 and >3. Mortality was assessed over 5 years. Results Of 1,045 patients enrolled 64% had PH. Patients with the lowest PAPi (table) had higher NT-proBNP levels, larger right ventricles, worse right heart systolic function (cardiac output, TAPSE, systolic annular velocity, free wall systolic strain) and greater degrees of tricuspid regurgitation (Table). In patients with PH, PAPi was inversely associated with death (figure, p < 0.0001) with each group of PAPi correlating with incrementally worse survival. Patients with a PAPi of <1.5 had worst right heart size and dysfunction on echo (table) and worst survival (figure). Conclusions In patients with PH, low PAPi derived non-invasively by transthoracic echocardiography is associated with markers of right heart failure, right ventricular dysfunction and worse survival. PAPi could be incorporated into the conventional echo parameters reported in patients with known or suspected PH and maybe a useful predictor of outcome. Abstract Table Abstract Figure

Short-Period Temporal Dispersion Repolarization Markers in Elderly Patients with Decompensated Heart Failure.

Aging and chronic heart failure (CHF) are responsible for the temporal inhomogeneity of electrocardiogram (ECG) repolarization phase. In the past, short period repolarization-dispersion parameters were used as makers of mortality risk in different heart diseases, yet. Aim of this work was to evaluate risk of mortality or worsening condition in CHF elderly subjects by mean of these repo-larization variables. An observational, prospective cohort study was performed, collecting 5 minutes ECG recordings to assess the mean and standard deviation (SD) of the following variables: QT end (QTe), QT peak (QTp) and T peak to T end (Te) in 117 decompensated CHF (age range: from 49 to 103 years). 30-day mortality and high levels of NT-pro BNP (<75 percentile) were considered markers of decompensated CHF. A total of 27 patients (23%) died during the 30-day follow-up (overall mortality rate 23%). Te mean (odd ratio (OR): 1.04, 95% confidence limit (Cl 7u): 1.02-1.09, p<0.01), NT-pro BNP (OR: 1.00, 95% cl: 1.00-1.00, p<0.01) and LVMI (OR : 0.98, 95% cl: 0.96-0.10, p<0.05) were associated to risk of mortality at the multivariable logistic analysis. On the contrary, the same statistical analysis selected TeSD (OR: 1.36, 95% cl: 1.16-1.59, p<0.001) and LVEF (OR: 0.91, 95% cl: 0.87-0.95, p<0.001) as marker of decompensated CHF. In decompensated CHF elderly subjects, Te mean seem be associated to mortality and TeSD could be considered a risk factor for CHF worsening and complications. These evidences could provide useful tools for telemonitoring CHF elderly patients, amelio-rating treatments and outcomes.

Prevalence, Related Factors and Association of Left Bundle Branch Block With Prognosis in Patients With Acute Heart Failure: a Simultaneous Analysis in 3 Independent Cohorts

To determine the prevalence, characteristics and association with prognosis of left bundle branch block (LBBB) in 3 different cohorts of patients with acute heart failure (AHF). We retrospectively analyzed 12,950 patients with AHF who were included in the EAHFE (Epidemiology Acute Heart Failure Emergency), RICA (National Heart Failure Registry of the Spanish Internal Medicine Society), and BASEL-V (Basics in Acute Shortness of Breath Evaluation of Switzerland) registries. We independently analyzed the relationship between baseline and clinical characteristics and the presence of LBBB and the potential association of LBBB with 1-year all-cause mortality and a 90-day postdischarge combined endpoint (Emergency Department reconsultation, hospitalization or death). The prevalence of LBBB was 13.5% (95% confidence interval: 12.9%-14.0%). In all registries, patients with LBBB more commonly had coronary artery disease and previous episodes of AHF, were taking chronic spironolactone treatment, had lower left ventricular ejection fraction and systolic blood pressure values and higher NT-proBNP levels. There were no differences in risk for patients with LBBB in any cohort, with adjusted hazard ratios (95% confidence interval) for 1-year mortality in EAHFE/RICA/BASEL-V cohorts of 1.02 (0.89-1.17), 1.15 (0.95-1.38) and 1.32 (0.94-1.86), respectively, and for 90-day postdischarge combined endpoint of 1.00 (0.88-1.14), 1.14 (0.92-1.40) and 1.26 (0.84-1.89). These results were consistent in sensitivity analyses. Less than 20% of patients with AHF present LBBB, which is consistently associated with cardiovascular comorbidities, reduced left ventricular ejection fraction and more severe decompensations. Nonetheless, after taking these factors into account, LBBB in patients with AHF is not associated with worse outcomes.

Purpura fulminans, presenting feature of multisystem inflammatory syndrome in children (MIS-C)

Introduction. Coronavirus disease 2019 (COVID-19) has been a worldwide health issue since early 2020, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Even though children do not usually present with se­vere COVID-19 unless the patient has an underlying di­sease, post­in­fectious complications, such as the multisystem in­flam­ma­to­ry syndrome in children (MIS-C), have been a sig­ni­fi­cant cause of child morbidity and mortality during the pan­de­mic. Even more challenging is that MIS-C has a very broad differential diagnosis due to its clinical heterogeneity. Case report. We report the case of a 6-month-old infant with­out another medical history who was brought to the ge­ne­ral practitioner’s office for persistent fever and cough. The symp­toms did not ameliorate under antipyretic and mucolytic treat­ment, so the patient later presented in the emergency room with associated dyspnea, diarrhea, vomiting and rapidly ge­ne­ra­li­zing purpuric skin lesions suggestive of purpura ful­mi­nans. He was admitted into our hospital and received em­pi­ri­cal antibiotic treatment. He also developed neck stif­fness. Meningococcemia was thus suspected; however, all cultures came out negative. Laboratory studies showed an important inflammatory syndrome, thrombocytopenia, se­vere anemia, coagulopathy, low protein C, protein S and an­ti­throm­bin levels, low fibrinogen, high D-dimer levels and hypo­al­bu­mi­ne­mia. Cerebral magnetic resonance imaging (MRI) showed no evidence of brain lesions. SARS-CoV-2 IgG-type antibodies were positive, therefore MIS-C was sus­pec­ted. The laboratory studies were extended and revealed high NT-proBNP, IL-6 and IL-2 soluble antigen levels. Other pos­si­ble diagnoses were excluded, which permitted our team to establish the diagnosis of MIS-C. The specific treatment was initiated with intravenous immunoglobulins (IVIG) and high-dose methylprednisolone associated with enoxaparin, broad-spectrum antibiotics and with symptomatic treatment. The patient rapidly evolved well, with the remission of fe­ver, inflammatory syndrome, coagulopathy and all other clinical and laboratory alterations. The skin lesions ame­lio­ra­ted as well, however, at a slower pace. Conclusions. MIS-C is a potentially life-threatening complication of COVID-19 in children. Therefore, clinicians must maintain a high degree of suspicion in the setting of the ongoing SARS-CoV-2 pandemic. However, the diagnostic criteria should be strictly followed due to the clinical similarities this pathology might have with other known diseases.

Частота и структура поражения сердца при системной красной волчанке

Study Objective: To identify the structure and prevalence of cardiac involvement in patients with systemic lupus erythematosus (SLE); evaluation of the relationship with the activity, disease duration and antirheumatic therapy. Study Design: Prospective cross-sectional study. Material and Methods. The study included 87 patients with SLE (90.8% women), with the median age of 32 [28; 41] years old and disease duration of 6 [1; 10] years; Systemic Lupus Erythematosus Disease Activity Index, modification 2К, was 9 [4; 16] points, Systemic Lupus International Collaborating Clinics Damage Index was 0 [0; 1] points. All patients were examined by a cardiologist, and traditional risk factors (TRF) of cardiovascular diseases were identified. Patients underwent transthoracic echocardiography (ECHO); if indicated, 24-hour ECG and blood pressure monitoring was performed. Serum NT-proBNP concentration was measured with electrochemiluminescence. Study Results. The most common cardiac complication was valvular insufficiency with various degree of regurgitation, which was diagnosed in 92% patients; endocarditis was recorded in 30%; mitral or tricuspid valve prolapse was observed in 33.3%. Pericardium pathologies were diagnosed in 44.8% patients, and adhesive pericarditis prevailed (61.5%). Myocarditis was observed in 4.6%, ischemic heart disease (IHD) — in 5.7%, cardiac failure (CF) — in 11.5%, rhythm and cardiac conduction disturbances — in 18.4% and 2.3%, respectively, myocardial infarction (MI) — in 2.3%. Dislipidemy and arterial hypertension (AH) were recorded in 50.6% and 46% patients. 31% demonstrated high NT-proBNP levels (&gt; 125.0 pg/mL); median NT-proBNP concentration was 91.8 [27.1–331.2] pg/mL. Patients were divided into two groups: group 1 did not take any glucocorticoids (GC), immunosuppressants and genetically engineered biologic drugs; group 2 had various combinations of these products. Patients in both groups were of similar age and sex; they did not have any differences in the prevalence of valvular insufficiency (86.7% and 97.6%), endocarditis (26.2% and 33.3%), pericarditis (42.9% and 46.7%), rhythm disturbance (19% and 17,8%), and impaired cardiac conduction (2.4% and 2.2%), IHD (2.4% and 8.9%), CF (7% and 15.5%). MI and myocarditis were diagnosed only in group 1 (4.4% and 9.5%, respectively); however, these differences were not statistically significant. AH was observed more frequently in group 2 than in group 1 (62.2% and 28.6%, р &lt; 0.01); other TRFs did not demonstrate any differences; however, total cholesterol concentration and body mass index in group 2 were higher than in group 1: 5.7 and 4.5 mmol/L (р &lt; 0.05); 22.66 and 22.10 kg/m2 (р &lt; 0.01). NT-proBNP concentration in untreated patients was higher than in group 2 (150.7 and 32.6 pg/mL, respectively, р &lt; 0.01), exceeding the normal values. Conclusion. Despite the juvenile age of patients, the therapy (mostly GC) and longer disease duration are associated with higher incidence of TRF (AH, hypercholesterolemia, overweight), while myocarditis and high NT-proBNP concentration are typical of untreated patients with highly active SLE. SLE patients should be followed up by a cardiologist; symptom-free CF markers should be identified as this condition is life-threatening, especially in patients with extremely active disease; TRFs should be monitored; and minimal GC doses should be used during remission/low-activity disease. Keywords: systemic lupus erythematosus; cardiac involvement; pericarditis; myocarditis; endocarditis; NT-proBNP; ECHO.

Prevalence and outcomes of concomitant cardiac amyloidosis and aortic stenosis: A systematic review and meta-analysis

ObjectiveCardiac amyloidosis (CA) is an increasingly recognised condition in patients with aortic stenosis (AS). However, there is a large variation in the reported prevalence figures, due to differences in populations and diagnostic methods. We aimed to investigate the prevalence, risk factors and outcomes of concomitant CA and AS. MethodsWe performed a systematic review and meta-analysis of the literature searched on MEDLINE, Embase, Scopus and CENTRAL. We analysed the prevalence of CA in patients with AS grouped according to the diagnostic techniques, and the risk factors and outcomes of concomitant CA and AS were analysed in AS patients referred for surgical or transcatheter aortic valve replacement (AVR). ResultsA total of 21 studies were included, involving 4,243 patients. The pooled prevalence of CA in patients with AS was 14.4%, with substantial heterogeneity. The pooled prevalence of AS in patients CA was 8.7%, with substantial heterogeneity. Patients with both AS and CA had higher all-cause mortality than those with AS or CA alone. In AS patients requiring AVR, CA was associated with increasing age, male sex, higher NT-proBNP levels, increased interventricular septal end diastole (IVSd) thickness and lower left ventricular ejection fraction. Concomitant AS and CA was associated with increased all-cause mortality and pacemaker implantation post-procedure. Study limitations included heterogeneity of the results and the fair to good quality of the studies published. ConclusionOverall, a substantial proportion of patients with AS may have CA, and they have poorer prognosis. A high degree of clinical suspicion is needed to identify the “red flags” and perform appropriate diagnostic imaging.

Abstract 10162: NT-proBNP is Associated with Stroke, Heart Failure Hospitalizations, and Death in Patients with Atrial Fibrillation Without Oral Anticoagulation Regardless of Heart Rhythm

Background: NT-proBNP is elevated in patients with a diagnosis of atrial fibrillation (AF) and associated with risk of stroke and other outcomes. The associations have mainly been studied in patients on oral anticoagulation and not considering if samples were obtained during AF or sinus rhythm. We investigated the association of NT-proBNP with heart rhythm and cardiovascular (CV) events in patients with AF without oral anticoagulation. Methods: Plasma samples were obtained at baseline in 3184 patients with diagnosis of AF (2142 in AF rhythm at blood sampling) receiving aspirin in two multicenter randomized clinical trials with median follow-up 1.2 years (AVERROES) and 3.8 years (ACTIVE A), respectively. NT-proBNP was analyzed using Elecsys electrochemiluminescence immunoassay. Association of NT-proBNP with clinical variables was assessed with multivariable linear regression models. Association with outcomes were estimated with Cox-regression models adjusting for clinical variables. Results: Median age was 71 years, 57.8% were men, and median NT-proBNP 713 ng/L (25 th -75 th percentiles, 282-1388 ng/L). Variables contributing to NT-proBNP level were, in reducing order: AF rhythm (ratio of geometric means 2.9), age, creatinine, and prior heart failure. Levels of NT-proBNP were significantly associated with ischemic stroke (HR 3 rd vs 1 st quartile 2.1, 95%CI 1.5-3.0), heart failure hospitalizations (HR 2.2, 95%CI 1.6-2.9), and CV death (HR 2.4, 95% CI 1.8-3.3), all p&lt;0.001, without significant interaction with AF rhythm. Figure depicts NT-proBNP distribution by rhythm and association with ischemic stroke. Conclusion: In patients with a diagnosis AF, plasma levels of NT-proBNP are three times higher during AF rhythm compared with sinus rhythm. Higher levels of NT-proBNP are independently associated with ischemic stroke, heart failure hospitalizations, and CV death in AF patients without oral anticoagulation treatment, irrespective of heart rhythm.

Abstract 11882: The Relationship Between Day-to-Day Variability in Home Blood Pressure and Multiple Organ Function

Introduction: Blood pressure variability (BPV) is associated with the prognosis of cardiovascular disease. Continuous home BP measurements can be used to assess day-to-day BPV. Day-to-day BPV is associated with poor cognitive function, and the onset and progression of dementia. However, it is not clear how BPV is related to various organs. Hypothesis: Day-to-day BPV is related to various organ functions. Methods: Three hundred sixty-six participants (136 male, mean age: 71±9 years) who were participated in the community-based health checkup survey in Tarumizu city. All participants measured home blood pressure using HEM-9700T (OMRON Healthcare, Kyoto, Japan). Day-to-day variability of systolic blood pressure were evaluated by coefficient of variation (CV) of home systolic blood pressure in morning during one month. CV was categorized into quartiles. NT-pro BNP and high-sensitivity (hs-)troponin T as cardiac biomarkers were measured. Liver stiffness and renal function were evaluated by Fibrous-4 (Fib4) index and estimated glomerular filtration rate (eGFR), respectively. NT-pro BNP and hs-troponin T were divided by median value. Fib4 index greater than 2.67 and eGFR less than 60 mL/min/1.73 m2 were defined as high Fib4 index and high eGFR. Results: Mean CV was 6.0±1.7%. In logistic analysis adjusted age, gender and receiving antihypertensive medication, the odds ratios for high eGFR and high Fib4 index were higher in the higher quartiles, and only the fourth quartile was an independently associated factor. Moreover, for high NT-pro BNP levels, it was an independent factor in all three quartiles of CV. In contrast, for high troponin T levels, no associations were found for all quartiles of CV (Figure). Conclusion: Day-to-day BPV is independently associated with NT-pro BNP, eGFR and Fib4 index, but not with hs-troponin T.

Prognostic Value of Myocardial Enzymes and Therapeutic Potential of Cardioprotective Agents in Chronic Lymphocytic Leukemia Patients with Cardiovascular Comorbidities

Introduction: Chronic lymphocytic leukemia (CLL) is the most common leukemia among adults in the western world. Cardiovascular disease (CVD), with a high incidence among comorbidities, is associated with significant morbidity and inferior quality of life in cancer patients. In CLL, comorbidities are associated with increased mortality from infections, second cancers and CVD. However, previous studies have not uncovered the relationships between cardiac biomarkers and the prognosis of CLL patients. In addition, whether cardioprotective drugs affect the effect of therapy in CLL patients remains undefined.Methods: Five hundred and ten CLL patients diagnosed in Shandong Provincial Hospital affiliated to Shandong University from October 2010 to July 2020 were enrolled in our study. The Kaplan-Meier curves were used to estimate survival rates, while the log-rank tests were used for comparison. Univariate and multivariate logistic regression analysis was used to verify prognostic independence. The available expression data and survival information of CLL samples and normal samples were extracted from 2 databases. The expression level of genes involved in the KEGG lipid and atherosclerosis pathway was analyzed to evaluate the prognosis of CLL patients. GSEA enrichment analysis was performed to explore the potential function of TNFRSF1A. Cell proliferation assay with the Cell Counting Kit-8 (CCK-8) was performed to detect the therapeutic potential of the common cardioprotective drugs atorvastatin, metoprolol and losartan in CLL.Results: Among the cohort, 30% CLL patients were complicated with CVD. Compared with those without CVD, CLL patients with CVD were of significantly advanced age (p<0.001), larger proportion with diabetes (p=0.003), as well as higher levels of N-terminal brain natriuretic peptide precursor (NTpro-BNP; p=0.016) and myohemoglobin (MYO; p=0.005). The Kaplan-Meier curves revealed that Binet stage (χ2=3.863, p=0.049), creatine kinase isoenzyme (CK-MB; χ2=4.335, p=0.037) and MYO (χ2=4.010, p=045) were related to the OS time of CLL patients with CVD (shown in Figure 1). The univariate logistic analysis showed that sex (p=0.031), Rai stage (p=0.036), Binet stage (p=0.017), β2-MG (p=0.004), creatine kinase (CK; p=0.017), α-hydroxybutyrate dehydrogenase (α-HBDH; p=0.017), MYO (p=0.025) and C-reactive protein (p=0.007) were associated with the outcomes of CLL patients with CVD. The multivariate logistic analysis confirmed that α-HBDH (p=0.046) and MYO (p=0.013) were independent prognostic biomarkers for the outcomes of CLL patients with CVD.To further evaluate the prognosis of CLL patients and CVD, the expression of genes involved in the KEGG lipid and atherosclerosis pathway were assessed. Most of them were dysregulated (shown in Figure 2A-B). The genes which were differential expression were performed with Kaplan-Meier analysis and univariate and multivariate Cox analysis subsequently. TNFRSF1A was upregulated among CLL cells and was independent prognostic biomarkers of both OS (shown in Figure 2C) and time to first treatment (TTFT) in CLL patients (shown in Figure 2D). GSEA enrichment illuminated that TNFRSF1A was related to the lipid catabolic and metabolic process, as well as other metabolic processes (shown in Figure 2E-F).To investigate the effect of cardioprotective drugs on chronic lymphocytic leukemia patients, cell proliferation assays were performed. Atorvastatin, metoprolol and losartan decreased the proliferation of CLL cell lines with IC50 values of 94.19 uM, 123.60 uM and 411.80 uM in EHEB cells, and 79.20 uM, 138.60 uM and 318.5 uM in MEC-1 cells, respectively (shown in Figure 3).Conclusions: In conclusion, we demonstrated CLL patients with CVD were of older age, larger proportion of patients with diabetes, higher levels of NTpro-BNP and MYO compared those without CVD for the first time. α-HBDH and MYO were independent prognostic biomarkers for survival in CLL patients with CVD. TNFRSF1A was an independent prognostic biomarker of OS and TTFT in CLL patients. Furthermore, atorvastatin, metoprolol and losartan exhibited inhibitory effects in CLL cell lines. The evaluation of cardiac biomarkers is beneficial to predict the clinical outcomes of CLL patients. CLL patients may benefit from the application of cardioprotective agents. Strengthening the evaluation of CVD risk and preventing CVD may improve the prognosis of CLL patients. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Efficacy and Safety of Daratumumab Monotherapy in Newly Diagnosed Patients with Stage 3B Light Chain Amyloidosis: A Phase 2 Study By the European Myeloma Network

Efficacy and Safety of Daratumumab Monotherapy in Newly Diagnosed Patients with Stage 3B Light Chain Amyloidosis: A Phase 2 Study By the European Myeloma Network

The risks and benefits of spironolactone use in heart failure with a reduced left ventricular ejection fraction and chronic kidney disease

Abstract Purpose Mineralocorticoid receptor antagonists (MRAs) remain underused in cases of heart failure with a reduced left ventricular ejection fraction (HFrEF) and chronic kidney disease (CKD), largely due to the fear of inducing worsening of renal function (RF) and hyperkalemia (HK), particularly in combination with renin angiotensin inhibitors. The aim was to investigate the safety use of spironolactone (SP) in patients with HFrEF (ejection fraction &amp;lt;40%) and CKD and determine predictors of worsening of RF and developing HK. Methods 208 patients with HFrEF (on top of standard therapy including ACE-I or an ARB) and CKD (baseline eGFR between 30 and 60 ml/min) were included in the study. The potassium (K) and creatinine (C) levels, plasma aldosterone (AS) and NT-proBNP were estimated at baseline and at week 12. After biochemical evaluation, 101 patients started on SP treatment with a median dose of 23 mg daily (titrated). K and RF were checked at weeks 1, 2, 4, 6, 8, 12. Results K and C levels increased significantly after start of SP: mean K levels increased from 4.47±0.59 to 5.23±0.57 mEq/l, (P&amp;lt;0.01) and was dose dependent. After 12 weeks of treatment the incidence of severe HK (K+ ≥6.0 mmol/L) was &amp;lt;5%, K 5.5–5.9 mmol/L occurred in 13 patients (13%) and it was predicted by baseline eGFR≤35 ml/min/1.73 m2. and K ≥5.0 mmol/L/. Subsequently, these patients required a prescription of K binders. Mean eGFR on SP decreased from 48.34±2.23 to 42.19±2.65 ml/min/1.73 m2 (P&amp;lt;0.01) and a significant decrease in GFR was observed only during the first month (P &amp;lt;0.01) with not significant increasing to 6 and 12 weeks after the start of SP. Five patients (5%) on SP experienced significant decline of RF result in withdrew SP. Age, NT-proBNP concentration &amp;gt;1550 ng/L and eGFR ≤35 ml/min/1.73 m2 at baseline had modest discriminative powers for predicting decline of RF (0.456, P&amp;lt;0.01; 0.542, P&amp;lt;0.001; 0.712, P&amp;lt;0.001; respectively). At baseline in patients with HFrEF was an inverse correlation between GFR and NT-proBNP level (r=−0.298, p&amp;lt;0.001). The SP treatment resulted in significantly reduced NT-proBNP and AS (P&amp;lt;0.01; P&amp;lt;0.05 respectively). By linear regression analysis in SP group the eGFR was associated with NT-proBNP change (0.362, P&amp;lt;0.05). Conclusion In patient with HFrEF and CKD the risk-benefit ratio of spironolactone with respect to renal failure appears favourable due to improvement of the neurohumoral profile. Although the renal disfunction and hyperkalemia on spironolactone are common: approximately 18% patients required the prescription of K binders and 5% required the withdrew SP duo to decline RF, the occurrence of hyperkalemia was predicted by baseline potassium level and eGFR. Age, higher level of NT-proBNP and eGFR were identified as potential predictors of worsening of RF. So, caution should be advised when using spironolactone in HFrEF with CKD and potassium of ≥5.0 mmol/L and eGFR ≤35 ml/min/1.73 m2 and NT-proBNP concentration &amp;gt;1550 ng/L for safety reasons. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): National Medical University

RV free wall longitudinal strain as an independent predictor of survival in wtATTR-CA patients

Abstract Background Wild type transthyretin cardiac amyloidosis (wtATTR-CA) is increasingly recognized as a cause of heart failure with preserved ejection fraction (HFpEF) but prognosis is often limited due to late or misdiagnosis.Longitudinal left ventricular strain and biomarkers are established as markers of disease severity, but the role of RV free wall strain, reflecting RV contractility, is less well understood. Purpose We sought to determine whether RV free wall strain might add incremental prognostic value in wtATTR-CA. Methods Consecutive patients diagnosed with wtATTR-CA with tissue confirmation at Mayo clinic between 2013 and 2015 were included. Patients with TTR gene mutations were excluded. Baseline characteristics and transthoracic echocardiography measurements were obtained from the medical records. Speckle tracking RV free wall longitudinal 2D strain and peak LA longitudinal 2D strain were measured using Tom Tec Imaging System. Survival was determined using Kaplan Meier estimates and using the cox proportional hazard ratio, univariate and multivariable analysis were performed to identify predictors of mortality in patients with wtATTR. Results The study group comprised 139 patients (mean age 74.9±8.6, 92.8% male), of which 102 had adequate image quality for RV strain, and 99 for LA strain. Amongst these, 102 (73.3%) had AF and 118 patients (84.8%) had HF. During 3.23±2.0 years of follow up, 66 patients died. Both mean RV and LA strain were impaired at baseline: RV free wall strain was −14.7±4.9, and peak atrial longitudinal strain (PALS) was 13.2±8.8%. Using ROC analysis, RV strain of −16.8% was an independent predictor of all-cause mortality. In univariate modeling, higher levels of NT-proBNP (HR: 1.1 per 1000 pg.ml; 95%, CI 1.05–1.15, p&amp;lt;0.001) and Troponin T (HR: 2.0 per 0.1ng/ml; 95% CI 1.49–2.61, p&amp;lt;0.001) were associated with increased all-cause mortality. In addition, LV GLS (HR: 1.13 per 1%; 95% CI1.04–1.24, p=0.003), RV free wall LS (HR: 2.16 per 5%; 95%, CI 1.57–3.03, p&amp;lt;0.0001), and PALS (HR: 0.91 per1%; 95% CI 0.85–0.96, p&amp;lt;0.0001) were univariate predictors of all-cause mortality. In multivariate analysis using a stepwise regression model, RV free wall longitudinal strain (HR: 1.81; 95% CI 1.29–2.62, p&amp;lt;0.001) and Troponin T (HR: 1.7; 95% CI 1.25–2.26, p=0.001) remained independent predictors. Kaplan-Meier survival analysis demonstrated a higher mortality rate above −16.8 RV strain cut-off (Wilcoxon &amp;lt;0.0001). All stages were divided into two groups by −16.8% RV strain, and survival in individual stages analyzed. Stage 1 and 2 with &amp;lt;−16.8 RV free wall strain value had higher mortality than ≤-16.8% RV strain (Stage 1: Wilcoxon = 0.0041 and Stage 2: Wilcoxon = 0.023). However, there was not a survival difference between two RV strain groups in stage3 (Wilcoxon = 0.34) Conclusion RV free wall strain is an independent predictor of survival in wtATTR patients and may add incremental prognostic value to NT-proBNP and Troponin. Funding Acknowledgement Type of funding sources: None. Kaplan-Meier curve of all patientsKaplan-Meier curve of stages

Impact of cardiac rehabilitation on inflammation in patients with ischaemic cardiomyopathy

Abstract Introduction The benefits of cardiac rehabilitation (CR) in patients with ischaemic cardiomyopathy are well-known. However, inflammatory states have been associated to an increased risk of cardiovascular events. Purpose Evaluate the impact of CR in the serum levels of inflammatory biomarkers and identify potential predictors of that effect. Methods We retrospectively studied consecutive patients with ischaemic cardiomyopathy who completed a CR programme between 2011 and 2017. Patients underwent a supervised exercise training protocol, twice a week during a period of 8 to 12 weeks. Functional capacity was evaluated by metabolic equivalents assessed prior the beginning and 3 months after the programme with a symptom limited exercise treadmill test. Patients without levels of serum C-reactive protein at beginning and at the end of CR programme were excluded. Median variation of serum C-reactive protein was assessed and two groups were defined: one with levels above that and one with levels below. Results Of 250 patients (60.3±11.1 years, 84% male), 67% were admitted after an acute myocardial infarction. Left ventricular ejection fraction ≤40% before CR was present in 32% of individuals. Median levels of serum C-reactive protein before CR were 8.8 (3.1–21.7) mg/L and median variation after CRP was a decrease of 5.1 (0.9–17.7) mg/L (p&amp;lt;0.001). Before CR, higher levels of serum C-reactive protein were seen in obese (15.7 [8–52.7] versus 8.8 [3.2–27.8], p=0.04) and those with higher NT-proBNP (p&amp;lt;0.001). Patients with decrease of &amp;gt;5.1mg/L of serum C-reactive protein had lower prevalence of hypertension (18% versus 30%, p=0.02), higher prevalence of obesity (16% versus 7%, p=0.03), lower levels of HDL cholesterol (38.3 [11.1] versus 43.2 [12.6], p&amp;lt;0.001) and higher levels of NT-proBNP (1079 [610.3–1988] versus 488 [215–777], p&amp;lt;0.001) at baseline. An increase of at least of 10% of functional capacity after CR was reached in 65% of patients, similar between groups. Patients with decrease of serum C-reactive protein &amp;gt;5.1mg/L had also higher reduction of NT-proBNP after CR comparing to baseline (491.1 [142.7–948.5] versus 162.0 [30.9–295.2], p&amp;lt;0.001). Conclusions Serum levels of inflammatory biomarkers decreased after CR in patients with ischaemic cardiomyopathy. Normotension, obesity, lower HDL and higher levels of natriuretic peptides are associated to a better response. Funding Acknowledgement Type of funding sources: None.

Comparison of 2-years follow-up of optimal medical therapy versus balloon pulmonary angioplasty for inoperable chronic thromboembolic pulmonary hypertension

Abstract Introduction Balloon pulmonary angioplasty (BPA) has emerged as a therapeutic option for chronic thromboembolic pulmonary hypertension (CTEPH) considered ineligible for pulmonary endarterectomy (PEA). The initial publications showed very good short-term outcomes for the technique, but there are limited data regarding medium-term outcomes and its comparison with optimal medical treatment (OMT). Objectives To evaluate and compare the medium-term outcomes of OMT versus (vs) BPA in inoperable CTEPH. Methods Retrospective study of consecutive patients (pts) with CTEPH followed in a referral centre for Pulmonary Hypertension. Selected those pts considered ineligible for PEA and with at least 2 years of follow-up. Comparison between two treatment strategies: OMT alone [maximum tolerated doses of pulmonary vasodilator drugs (PVD), as indicated] vs BPA (pts who completed the program with or without OMT). Endpoint was a composite of all-cause death and unplanned right heart failure admission at 2-year. Results From 62 pts, 19 pts were included (11 pts were excluded due to recent diagnosis; 32 were submitted to EAP): mean age 65.0±15.3 years, 89.5% female. At diagnosis, all pts had functional capacity limitation and elevated serum NTproBNP levels (median value 1255.0 pg/mL). Mean pulmonary arterial pressure (mPAP) was 46.2±9.3 mmHg and pulmonary vascular resistance (PVR) 15.3±8.3 Wood units (WU). Concerning treatment, 12 pts (63.2%) underwent OMT alone. These pts had higher NTproBNP levels (2670.0 vs 538.0 pg/mL, p&amp;lt;0.01) and PVR values (19.7±7.6 vs 9.7±5.4 WU, p=0.01) and lower CI (1.6±0.3 vs 2.4±0.5 L/min/m2, p&amp;lt;0.01), at baseline; the remaining basal features didn't differ among groups (Fig.A). At 2-year follow-up, pts submitted to BPA were under PVD in 71.4% of cases with a mean of 1±0.8 drugs per patient and no difference compared to OMT group (83.3%, 1.7±0.9 drugs per patient), although oxygen therapy was higher in medical group (50% vs 0%, p=0.04). A significant overall improvement was observed in BPA group (Table – A): all pts were in functional class I (p&amp;lt;0.01), no one had right ventricular dysfunction (p&amp;lt;0.01) and mPAP decreased to 25.1±6.7 mmHg (p=0.01) and RVP to 2.9±0.8 WU (p=0.01). Inversely, no change was observed in pts under OMT alone (p&amp;gt;0.05 in all, Table – A). Endpoint rate was 31.6% with all adverse events occurring in the OMT group (50% vs 0%, p=0.04). After adjustment by Cox regression, no difference in baseline or follow-up features besides treatment influenced the outcome. Kaplan-Meier analysis (Graphic – B) confirmed significant benefit of BPA in 2-year outcome occurrence (long rank 4.6, p=0.03). Conclusions BPA strategy seems to improve medium-term functional capacity, right ventricular function and haemodynamics and decrease oxygen therapy dependence in inoperable CTEPH. Pts under OMT alone have a poor prognosis. These data encourage the development and implementation of the technique for inoperable CTEPH. Funding Acknowledgement Type of funding sources: None.

Left ventricular noncompaction: the importance of identifying high-risk patients within the scope of left ventricular hypertrabeculation

Abstract Introduction Prominent left ventricular (LV) trabeculation is frequently encountered, however LV noncompaction (LVNC) criteria are not always fulfilled. The clinical and prognostic significance of these findings remains unclear. Objectives To characterize the patients (P) with echocardiographic suspicion of LVNC and to assess clinical outcomes. Methods Retrospective single-centre study that included all echocardiograms between January 2018 and June 2020 perceiving LV hypertrabeculation. The cohort underwent diagnostic assessment for LVNC by Chin and Jenni criteria. Baseline characteristics were evaluated. Composite endpoint of cardiovascular death, heart failure (HF) hospitalization, ventricular arrythmias (VA) and nonfatal stroke was considered. Results 51P, 75% male, mean age 50±18 years. 35P (69%) had associated heart conditions, of which 57% had other known cardiomyopathy (mainly dilated cardiomyopathy), 14% congenital, 26% ischemic and 3% valvular heart disease. 2P were in postpartum period and 1P was an athlete. Family history of cardiomyopathy was present in 8P (16%). 12P underwent genetic testing, with TTN and MYH7 mutations being the most frequently detected. Prior clinical HF was reported in 53%, previous stroke in 14%, and non-sustained and sustained VA in 24% and 4%, respectively. Mean NYHA classification was 1.8±0.7, with 31% being asymptomatic. The prevalence of LVNC by Chin criteria was 31% and by Jenni criteria was 55%. 32P (63%) met at least one LVNC criteria. This group was younger (45±18 vs 59±15, p=0.004), had higher NT-proBNP levels (3644±2819 vs 389±640, p=0.048) and QRS fragmentation (59% vs 21%, p=0.027). Significantly higher LV end-diastolic volume (84 (41) vs 64 (28)ml/m2, p=0.008) and end-systolic volume (51 (37) vs 35 (20)ml/m2, p=0.004), along with lower LV ejection fraction (39±12 vs 49±13%, p=0.009) and global longitudinal strain (−11±5 vs −17±4%, p=0.003) were noticed. P who met LVNC criteria also had higher number of affected LV segments (6.4±1.8 vs 4.2±1.6, p&amp;lt;0.001). Over a mean follow-up of 18±9 months, the incidence of composite endpoint was 35%. Univariate Cox analysis showed a significant association between the presence of LVNC criteria and adverse outcomes (HR: 5.108, 95% CI: 1.682–11.236, p=0.030) (Fig. 1). Conclusion LV hypertrabeculation can be encountered in a variety of clinical scenarios and often overlaps with other heart diseases. P satisfying criteria for LVNC had more impairment in LV performance and worse clinical outcomes. Funding Acknowledgement Type of funding sources: None. Figure 1

Morphological and secretory dysfunction of left atrium in Marfan syndrome

Abstract Introduction Marfan syndrome (MFS) is characterized by a mutation in the FBN1-gene which leads to a structural deficiency of the extracellular matrix component fibrillin-1 and a dysregulation of TGFβ. In recent years, cardiac remodeling with systolic and/or diastolic left ventricular dysfunction was shown in some MFS patients (Marfan Cardiomyopathy). Interestingly, in animal studies it has been shown that fibrillin-1 is abundantly present in atria and that TGFβ overexpression leads to atrial but not ventricular fibrosis (1, 2). However, the role of MFS for atrial remodeling and secretion (NT-proBNP) is unclear. Purpose To assess morphological and secretory function of the left atrium (LA) in patients with MFS and its relationship to left ventricular function. Methods We retrospectively analyzed echocardiographic and laboratory data in 307 Patients with MFS and in 147 healthy controls who had presented at our Marfan clinic between 23 February 2016 and 15 June 2020. At every visit, echocardiography had been carried out and NT-proBNP levels had been taken. A two-level mixed effects model was now performed to compare left atrial size between patients with MFS and controls. Results Left atrial size was significantly increased in patients with Marfan syndrome with and without aortic operation in medical history compared with controls (adjusted means: 18.4cm2 and 17.6cm2 vs. 15.5cm2 p&amp;lt;0.05). Body surface area (6.12, 95% CI: 4.26, 7.98 p&amp;lt;0.001), age (0.06, 95% CI: 0.02, 0.1 p&amp;lt;0.01), E/e' (0.3, 95% CI: 0.14, 0.46 p&amp;lt;0.001) and EF (−0.05, 95% CI: −0.10, −0.01 p=0.011) were significantly correlated with LA size. NT-proBNP was also increased, after logarithmic transformation, mean difference between unoperated patients with MFS and controls was 0.34 (95% CI: 0.11,0.57 p=0.004). Interestingly, NT-proBNP and LA size both were increased also in patients with normal left ventricular filling pressures, assessed by E/e' (see Figure 1). For increased LV filling pressures (E/e'&amp;gt;8), regression analyses revealed a more extensive dilatation of LA size in patients with MFS for further increase of E/e' compared to controls, although not significant for the latter. Haploinsufficiency mutations were associated with significant higher levels of NT-proBNP than dominant-negative (p=0.043) (see Figure 2), although this could not be shown for LA size. Atrial fibrillation (AF) tended to be more common in Marfan group (17/307 to 4/147, χ2 (1) = 1.79, p=0.181) but most patients with AF also had prior aortic operation. Conclusions Our data show that Marfan syndrome is associated with left atrial dilatation, accompanied by increased levels of NT-proBNP which seem to be independent of elevated left ventricular filling pressure. This supports the idea of a primary impairment of cardiac function. If this leads to an impaired clinical outcome, e.g. characterized by increased prevalence of AF and stroke, needs be investigated by further research. Funding Acknowledgement Type of funding sources: None.

Predictors of Acute Heart Failure Decompensation at 30 days After Discharge. Results from a Multidisciplinary Heart Failure unit

Abstract Background Unexpected readmissions are frequent among heart failure (HF) patients (pts). These are associated with high economic cost and have great clinical relevance. HF Units are cornerstones to build early intervention to prevent readmissions. Due to their natural history HF implies multiple readmissions, with high costs and clinical relevance. HF Units are cornerstones to avoid early readmission. Purpose We aimed to identify predictors of early HF decompensation (at 30 days) that could recognize high risk patients during the systematic follow-up in our Multidisciplinary Heart Failure Program (MHFP) that was launched in February 2019. Methods We carried out an analytical and observational study including all patients admitted to our University Hospital, which covers 220,000 individuals. We built a predictive multivariate model with Logistic Regression using relevant predictors (clinical and statistical) that were identified. Results A total of 235 acute HF decompensations were referred to our MHFP. The 69.8% of them were men with median age of 75 years (interquartile range, IR 71–81). Mean left ventricular ejection fraction was 41% (IR 29–54%. A total of 55% with reduced and 30% with preserved ejection fraction). The 26% of the patients had right ventricle dilatation and 35% disfunction. Left bundle branch block was present in 27% of them. Median glomerular filter was 54ml/min (IR 37–73ml/min) and median pulmonary artery systolic pressure 50mmhg (IR 42–66mmg). Mean time to readmission was 19.6 months. Among decompensations that we detected in MHFP during 30 days after discharge, just 39% (5 pts) could be detected and managed in day hospital and 61% (8 pts) as an admission. In Table 01 we show the predictors that were included in the multivariate model. We finally found that it was just the NTproBNP level in a blood test within 7–10 days after discharge (R2N 0.59) which remains significative. Risk increased 1.20 times (1.0001851000) for each 1000 units rise in blood test (Table 1. Graph 1). Conclusion According to our results, detecting high NTproBNP levels in blood test within 7–10 days after discharge might predict a higher HF decompensation risk. The final multivariate model would explain 59% of those events at one month after discharge. Funding Acknowledgement Type of funding sources: None. Graph 1

Measuring lung water adds prognostic value in heart failure patients undergoing cardiac magnetic resonance

To assess whether a simplified cardiac magnetic resonance (CMR)–derived lung water density (LWD) quantification predicted major events in Heart Failure (HF). Single-centre retrospective study of consecutive HF patients with left ventricular ejection fraction (LVEF) < 50% who underwent CMR. All measurements were performed on HASTE sequences in a parasagittal plane at the right midclavicular line. LWD was determined by the lung-to-liver signal ratio multiplied by 0.7. A cohort of 102 controls was used to derive the LWD upper limit of normal (21.2%). The primary endpoint was a composite of time to all-cause death or HF hospitalization. Overall, 290 patients (mean age 64 ± 12 years) were included. LWD measurements took on average 35 ± 4 s, with good inter-observer reproducibility. LWD was increased in 65 (22.4%) patients, who were more symptomatic (NYHA ≥ III 29.2 vs. 1.8%; p = 0.017) and had higher NT-proBNP levels [1973 (IQR: 809–3766) vs. 802 (IQR: 355–2157 pg/mL); p < 0.001]. During a median follow-up of 21 months, 20 patients died and 40 had ≥ 1 HF hospitalization. In multivariate analysis, NYHA (III–IV vs. I–II; HR: 2.40; 95%-CI: 1.30–4.43; p = 0.005), LVEF (HR per 1%: 0.97; 95%-CI: 0.94–0.99; p = 0.031), serum creatinine (HR per 1 mg/dL: 2.51; 95%-CI: 1.36–4.61; p = 0.003) and LWD (HR per 1%: 1.07; 95%-CI: 1.02–1.12; p = 0.007) were independent predictors of the primary endpoint. These findings were mainly driven by an association between LWD and HF hospitalization (p = 0.026). A CMR-derived LWD quantification was independently associated with an increased HF hospitalization risk in HF patients with LVEF < 50%. LWD is a simple, reproducible and straightforward measurement, with prognostic value in HF.

CARDIOVASCULAR OUTCOMES OF ACUTE CORONARY SYNDROMES IN INDIGENOUS COMPARED WITH NON-INDIGENOUS PATIENTS IN NORTHERN SASKATCHEWAN

<h3>BACKGROUND</h3> Indigenous compared with non-Indigenous patients have historically been known to have higher cardiovascular risk. With improved care delivery of acute myocardial infarction, we sought to compare contemporary profiles between indigenous versus non-Indigenous patients presenting with acute coronary syndromes (ACS) to a single PCI cardiac center in Saskatchewan. <h3>METHODS AND RESULTS</h3> We prospectively evaluated consecutive ACS admissions (no exclusion criteria applied) from March 15, 2019 to March 30, 2021 at the Royal University Hospital, Saskatoon. Categorized by self-reported Indigenous and non-Indigenous status, we describe presenting demographics, treatment patterns, unadjusted all-cause mortality and all-cause rehospitalization. Continuous variables are presented as medians (25th, 75th percentiles), categorical values as frequencies (%). Of the 1950 ACS admissions, 260 (13.3%) were Indigenous. Indigenous compared with non-Indigenous patients were younger, more likely female, have a history of heart failure and a significant burden of both traditional and non-traditional cardiovascular risk factors. Both groups were revascularized comparably with PCI. Indigenous compared with non-Indigenous patients were however more likely to present with higher levels of NTproBNP and higher incident rates of cardiogenic shock and/or cardiac arrest, with a greater severity of left ventricular systolic dysfunction (Table 1). While in-hospital mortality is comparable between the two groups, Indigenous compared with non-Indigenous have significantly higher unadjusted 1-year mortality (11.9% vs. 8.0%, p=0.039). <h3>CONCLUSION</h3> Indigenous compared with non-Indigenous patients hospitalized with an acute coronary syndrome have a significantly greater burden of premorbid cardiovascular risk and present with greater clinical acuity. While the in-hospital outcomes are comparable, likely due to established pre-hospital/in-hospital ACS processes of care, the higher one-year mortality suggest that the higher residual risk in Indigenous patients is likely driven by the greater burden of modifiable traditional and non-traditional risk factors in this patient population.

Soluble vascular endothelial growth factor receptor 2 and prognosis in patients with chronic heart failure.

AimsEndothelial cell vascular endothelial growth factor receptor 2 (VEGFR‐2) plays a pivotal role in angiogenesis, which induces physiological cardiomyocyte hypertrophy via paracrine signalling between endothelial cells and cardiomyocytes. We investigated whether a decrease in circulating soluble VEGFR‐2 (sVEGFR‐2) levels is associated with poor prognosis in patients with chronic heart failure (HF).Methods and resultsWe performed a multicentre prospective cohort study of 1024 consecutive patients with HF, who were admitted to hospitals due to acute decompensated HF and were stabilized after initial management. Serum levels of sVEGFR‐2 were measured at discharge. Patients were followed up over 2 years. The outcomes were cardiovascular death, all‐cause death, major adverse cardiovascular events (MACE) defined as a composite of cardiovascular death and HF hospitalization, and HF hospitalization. The mean age of the patients was 75.5 (standard deviation, 12.6) years, and 57% were male. Patients with lower sVEGFR‐2 levels were older and more likely to be female, and had greater proportions of atrial fibrillation and anaemia, and lower proportions of diabetes, dyslipidaemia, and HF with reduced ejection fraction (<40%). During the follow‐up, 113 cardiovascular deaths, 211 all‐cause deaths, 350 MACE, and 309 HF hospitalizations occurred. After adjustment for potential clinical confounders and established biomarkers [N‐terminal B‐type natriuretic peptide (NT‐proBNP), high‐sensitivity cardiac troponin I, and high‐sensitivity C‐reactive protein], a low sVEGFR‐2 level below the 25th percentile was significantly associated with cardiovascular death [hazard ratio (HR), 1.79; 95% confidence interval (CI), 1.16–2.74] and all‐cause death (HR, 1.43; 95% CI, 1.04–1.94), but not with MACE (HR, 1.11; 95% CI, 0.86–1.43) or HF hospitalization (HR, 1.03; 95% CI, 0.78–1.35). The stratified analyses revealed that a low sVEGFR‐2 level below the 25th percentile was significantly associated with cardiovascular death (HR, 1.76; 95% CI, 1.07–2.85) and all‐cause death (HR, 1.49; 95% CI, 1.03–2.15) in the high‐NT‐proBNP group (above the median), but not in the low‐NT‐proBNP group. Notably, the patients with high‐NT‐proBNP and low‐sVEGFR‐2 (below the 25th percentile) had a 2.96‐fold higher risk (95% CI, 1.56–5.85) for cardiovascular death and a 2.40‐fold higher risk (95% CI, 1.52–3.83) for all‐cause death compared with those with low‐NT‐proBNP and high‐sVEGFR‐2.ConclusionsA low sVEGFR‐2 value was independently associated with cardiovascular death and all‐cause death in patients with chronic HF. These associations were pronounced in those with high NT‐proBNP levels.