HF Stage Research Articles

Right ventricular myocardial work predicts heart failure hospitalizations irrespective of ejection fraction

Abstract Hospitalization for heart failure worsening (HFW) associates with increased subsequent rehospitalization rate and mortality irrespective of left ventricular ejection fraction (EF). However there’s little evidence regarding predictors of HFW to timely apply preventive measurements. Since right ventricular (RV) dysfunction often associates with more advanced stages of HF we assumed that RV myocardial work (MW) assessment might be used in prediction of HFW. Methods 158 patients with HF (48% female) 58±7 years on guideline directed medical therapy in sinus rhythm and with at least one hospitalization in the last 6 months were enrolled in the study. Patients with HFrEF, HFmrEF and HFpEF were evenly represented. All patients were appropriately decongested prior to the study. The primary outcome was rehospitalization, HFW or cardiovascular death. RVMW was derived from RV global strain, including interventricular septum, and noninvasively estimated pulmonary arterial pressure (PAP). Systolic PAP (sPAP) was measured as the sum of maximum RV and right atrial (RA) pressure gradient (PGmax) from tricuspid regurgitation (TR) jet peak velocity and mean right atrial pressure (RAP) estimated from diameter and collapsing of inferior vena cava. Mean PAP (mPAP) was measured as the sum of PGmean RV-RA by tracing TR jet and RAP. Diastolic PAP was estimated as dPAP = 1.5 × [mPAP − (sPAP/3)]. Then RV global work index (RVGWI), constructive (RVGCW), and efficient work (RVGWE) were derived by the software dedicated for left ventricular MW. Left ventricular global longitudinal strain, left atrial (LA) reservoir strain (LAS), LA pump strain, LA volume index (LAVi), B lines, inferior vena cava, NT-pro-BNP, TAPSE/sPAP and RVMW were also measured. Patients followed up for 12 months. Results 53 events were registered at 12 months of which 42 rehospitalizations due to HFW and 11 CV deaths. Among all parameters in the multivariate analysis lower RVGCW was associated with HFW (HR 0.978, 95% CI 0.973–0.998, p = 0.014). RVGCW was the most powerful predictor of CV events (AUC 0.91) with cut off value of 148 mmHg% that had 96% sensitivity and 88% specificity. Number of patients who died with RVGCW < 148 mmHg% was 8 of 11 (73%) total deaths (HR 0.421, 95% CI 0.083–0.986, p = 0.028). Conclusion RVGCW was a predictor of HFW and 1 year mortality in patients with HF irrespective of EF.

The Prevalence of Various Stages of Heart Failure in Individuals Over 40 Years Old: The Findings from Yazd Health Study

identification and prevention of HF. Therefore, this study aims to evaluate the prevalence of various stages of HF in individuals over 40 years old within a large population of Iranian adults. Methods: In this descriptive cross-sectional study, a random sub sample of Yazd Health Study (YaHS) participants aged 40-70 years was evaluated. History and clinical examination of the patients was conducted by a cardiologist and then, the participants underwent echocardiography to determine the stages of heart failure. Results: Among 410 Yazd population -the representative sample with mean age 58.0±9.2 years, 183 patients (44.6%) were in stage 0, 121 (29.5%) in stage A, 77(18.8%) in stage B, and 29 (7.1%) in stage C heart failure. No individuals were in stage D. There was a significant difference between the frequency of individuals with different stages of HF in terms of diabetes, hypertension, obesity, and history of ischemic heart disease (p<0.05). In addition, the frequency of HF increased in the age group >60 years and the obesity group (p<0.05). Conclusion: According to these, about half of the patients with HF were in stage A and B. Therefore, appropriate measures are needed to identify these groups of patients, especially individuals with risk factors of diabetes, hypertension, obesity and those over 60 years to prevent the progression of the disease to higher stages which lead to poorer outcome.

Novel Biomarkers of Grade I Left Ventricular Diastolic Dysfunction in Type 2 Diabetes Patients with Metabolic-Dysfunction-Associated Steatotic Liver Disease.

Background/Objectives: Prior research has identified a significant association between heart disease and metabolic-dysfunction-associated steatotic liver disease (MASLD); however, the underlying mechanisms are unclear. This study aimed to identify predictive biomarkers associated with grade I left ventricular diastolic dysfunction (LVDD) in patients with type 2 diabetes mellitus (T2DM). Methods: This single-center, cross-sectional study evaluated 73 T2DM patients for grade 1 LVDD and MASLD using 2D echocardiography, tissue analysis, spectral color Doppler, and Fibromax. Results: This study analyzed 50 patients (mean age 58.0 ± 11.3 years) with a median diabetes duration of 7 years, abdominal obesity (mean body mass index (BMI) 34.4 ± 5.9 kg/m2), and a mean HbA1c of 7.9 ± 1.5%. The prevalence of grade I LVDD, fibrosis, mild steatosis, moderate-to-severe liver steatosis, mild MASLD, and moderate MASLD was 54%, 44%, 14%, 80%, 43%, and 34%, respectively. Regression analysis revealed that grade 1 LVDD was positively associated with age, Fibrotest, α2-macroglobulin, epicardiac adipose tissue (EAT), and negatively associated with lateral s', E wave, E/e', E/A, medium E', and septal e' (p < 0.05 for all). α2-macroglobulin > 1.92 g/L (area under the receiver operating characteristic curve (AUROC) = 0.782, sensitivity 70.4%, specificity 81.2%) and fibrotest score > 0.11 (AUROC 0.766, sensitivity 92.6%, specificity 56.2%) were significant predictors of grade I LVDD. Conclusions: Although the underlying mechanisms remain unclear, innovative non-invasive biomarkers, such as α2-macroglobulin or fibrotest, could concurrently indicate liver stiffness and the likelihood of grade I LVDD, an early, asymptomatic HF stage in T2DM patients.

Detecting heart stress using NT-proBNP in patients with type 2 diabetes mellitus and hypertension or high-normal blood pressure: a cross-sectional multicentric study

BackgroundWe evaluated the prevalence of “heart stress” (HS) based on NT-proBNP cut-points proposed by the 2023 Consensus of the Heart Failure Association (HFA) of the European Society of Cardiology (ESC) in asymptomatic patients with T2DM and hypertension or high-normal blood pressure (BP) eligible for SGLT2 inhibitors (SGLT2i) and/or GLP-1 receptor agonists (GLP1-RA), drugs with proven benefits on reducing the incidence of HF, hospitalizations, cardiovascular events and mortality.MethodsA cross-sectional multicentric study was conducted on 192 consecutive outpatients, aged ≥ 55 years, with hypertension or high-normal BP, referred to three diabetology units. NT-proBNP was collected before starting new anti-diabetic therapy. Patients with known HF were excluded, and participants were classified based on the age-adjusted NT-proBNP cut-points.ResultsMean age: 70.3 ± 7.8 years (67.5% males). Patients with obesity (BMI ≥ 30 Kg/m2): 63.8%. Median NT-proBNP: 96.0 (38.8–213.0) pg/mL. Prevalence of chronic kidney disease (CKD, eGFR < 60 mL/min/1.73m2): 32.1%. Mean arterial BP: 138.5/77.0 ± 15.8/9.9 mmHg. The NT-proBNP values, according to the proposed age-adjusted cut-points, classified 28.6% of patients as “HS likely” (organize elective echocardiography and specialist evaluation), 43.2% as “HS not likely” (a grey area, repeat NT-proBNP at six months) and 28.2% as “very unlikely HS” (repeat NT-proBNP at one year). The presence of CKD and the number of anti-hypertensive drugs, but not glycemic parameters, were independently associated with HS.ConclusionsAccording to NT-proBNP, over a quarter of T2DM patients with hypertension/high-normal BP, among those eligible for SGLT2i and/or GLP1-RA, were already at risk of cardiac damage, even subclinical. Most would receive an indication to echocardiogram and be referred to a specialist, allowing the early implementation of effective strategies to prevent or delay the progression to advanced stages of cardiac disease and overt HF.

QRS narrowing in patients undergoing cardiac resynchronization therapy: LOT-CRT vs. LBBAP

Abstract Background Left bundle branch-optimized cardiac resynchronization therapy (LOT-CRT) is an alternative technique to conventional biventricular pacing (BiVP) and complementary to left bundle branch area pacing (LBBAP). Although it is a more complex technique than LBBAP, it achieves greater QRS narrowing and better resynchronization in most patients. Purpouse The aim of this study was to determine the predictors (echocardiographic, ECG and clinical) of greater QRS narrowing with LOT-CRT vs. LBBAP. Methods 38 consecutive patients with CRT-P indication were included in a period of 1 year. A ventricular lead was implanted in the septum until LBBAP criteria were achieved, evaluated by EGM and electrocardiographic recordings. A lead was subsequently implanted in a subsidiary vein of the coronary sinus (CS). In each patient, the QRS duration was measured during LBBAP and then with the fusion pattern from LBBAP and CS (LOT-CRT). Baseline demographic characteristics, indication for implantation, ECG, echocardiography, and NYHA class were collected in all patients. Results The mean age was 77.2 ± 6.9 years (37% women). The most common cardiomyopathy was idiopathic (55.3%) followed by ischemic cardiomyopathy (21.1%). 76.3% were in NYHA class 2 and 23.7% in NYHA class 3, with a mean LVEF of 34.1 ± 8.2%. 86.8% had a LVEDD ≥ 66mm. In 57.9% of patients the indication for implantation was HF in NYHA class ≥ 2, QRS ≥ 130ms with LBBB QRS morphology and LVEF ≤35%, while in the remaining 42.1% it was an LVEF &amp;lt; 50% and stimulation indication. The initial QRS was 180 ± 22 ms, 152 ± 16 ms with LBBAP and 132 ± 16 ms with LOT-CRT, with an additional QRS narrowing of 20 ± 14 ms with LOT-CRT vs. LBBAP (p &amp;lt; 0.001). Predictors of greater QRS narrowing with LOT-CRT vs. LBBAP were the indication for implantation due to HF in NYHA ≥ 2, QRS ≥ 130ms with LBBB QRS morphology and LVEF ≤35% (p 0.01), LVEDD ≥ 66mm (p 0.04) and advanced NYHA class (3 vs. 2) (p 0.019). Conclusion LOT-CRT significantly reduces QRS duration compared to LBBAP, favoring better resynchronization. Patients with a classic indication for CRT-P, in advanced stages of HF (NYHA class 3 and or/LVEED ≥ 66mm), are those who present greater QRS narrowing with this technique compared to LBBAP.

Association of Reduced Left Atrial Reserve With Exercise Intolerance and Outcome in Hypertension

Hypertensive heart disease (HHD) is a leading contributor to heart failure with preserved ejection fraction (HFpEF). However the mechanisms behind the transition to the symptomatic phase remain unclear. We sought the association of the exercise response of LA mechanical function with functional capacity, symptoms and outcome across the HF spectrum in hypertension. Echocardiography (including LA reservoir [PALS] and contractile strain [PACS], and LA stiffness index) were performed at rest and immediately post-exercise in 139 patients with HHD- 35 with stage A, 48 with stage B and 56 with stage C HFpEF. Patients were followed for HF and atrial fibrillation (AF). Exercise capacity was progressively worse from stage A through stage B to stage C, and accompanied by a gradual impairment of changes in PALS and PACS from rest to exercise, whereas LA stiffness reserve remained unchanged until stage C. PALS and PACS reserves were independently associated with exercise capacity(p=0.017 and 0.008, respectively). LA stiffness reserve and E/e' were the strongest associations of symptomatic HF. Over a median of 25 months, 35 patients developed HF and/or AF. PALS and PACS reserves were associated with the study endpoints after adjusting for age, diabetes, NT-proBNP, LA volume index, resting E/e' and resting PALS/PACS. Impaired exercise reserve of LA strain and stiffness are associated with reduced functional capacity in hypertension, and LA strain reserve is independently associated with outcome. These parameters appear to be determinants of progression to overt HF in HHD, however their contribution may differ depending on HF stage.

Circadian assessment of heart failure using explainable deep learning and novel multi-parameter polar images

Background and objectiveHeart failure (HF) is a multi-faceted and life-threatening syndrome that affects more than 64.3 million people worldwide. Current gold-standard screening technique, echocardiography, neglects cardiovascular information regulated by the circadian rhythm and does not incorporate knowledge from patient profiles. In this study, we propose a novel multi-parameter approach to assess heart failure using heart rate variability (HRV) and patient clinical information. MethodsIn this approach, features from 24-hour HRV and clinical information were combined as a single polar image and fed to a 2D deep learning model to infer the HF condition. The edges of the polar image correspond to the timely variation of different features, each of which carries information on the function of the heart, and internal illustrates color-coded patient clinical information. ResultsUnder a leave-one-subject-out cross-validation scheme and using 7,575 polar images from a multi-center cohort (American and Greek) of 303 coronary artery disease patients (median age: 58 years [50–65], median body mass index (BMI): 27.28 kg/m2 [24.91–29.41]), the model yielded mean values for the area under the receiver operating characteristics curve (AUC), sensitivity, specificity, normalized Matthews correlation coefficient (NMCC), and accuracy of 0.883, 90.68%, 95.19%, 0.93, and 92.62%, respectively. Moreover, interpretation of the model showed proper attention to key hourly intervals and clinical information for each HF stage. ConclusionsThe proposed approach could be a powerful early HF screening tool and a supplemental circadian enhancement to echocardiography which sets the basis for next-generation personalized healthcare.

Prevalence and implications of heart failure stages A-D in patients with chronic kidney disease

Abstract Background Heart failure (HF) is a frequent comorbidity among patients with chronic kidney disease (CKD). Echocardiography allows for simple, non-invasive evaluation of structural and functional heart disease that could potentially classify patients at high risk of HF. Purpose This study aimed to assess the prevalence of HF stages A-D defined by the AHA/ACC/HFSA in CKD patients, and to report the incidence rates of renal outcomes and mortality of these stages. Methods This is a prospective cohort study. Patients aged 30 to 75 years with estimated glomerular filtration rate (eGFR) stages G1 to G5 pre-dialysis were included. All participants were examined using a pre-defined echocardiographic protocol. HF stages B and C/D were defined based on ejection fraction, global longitudinal strain, TAPSE, left ventricular mass, left ventricular diameter, left atrial volume index, and valvular heart disease in accordance with the AHA/ACC/HFSA guidelines. The outcomes examined were (1) a composite of kidney transplantation and dialysis and (2) all-cause mortality. Results A total of 825 patients with CKD were included. Mean age was 58±13 years and 37% were female. The participants were categorized as follows: Stage A HF: 352 (42.7%); stage B HF: 295 (35.8%); and stage C/D HF: 122 (14.8%). In total, 56 participants did not fulfil the criteria of HF stage A, B, C, or D and were classified as HF stage 0. Figure 1 displays the prevalence of HF stages across CKD stages. Poorer eGFR (P for trend 0.001) and urine albumin/creatine ratio (P for trend 0.005) were both significantly associated with increasing HF stages in linear regression models (including age, sex, and systolic blood pressure). During a median follow-up of 4 years, 115 patients (13.9%) developed the composite renal outcome and 74 patients (9.0%) died. Incidence rate per 100 patient-years for the composite renal outcome according to HF-stages was 2.3 (95%CI: [0.95;5.5]) for stage 0, 3.3 (95%CI: [2.5;4.5]) for stage A, 3.8 (95%CI: [2.8;5.1]) for stage B, and 6.3 (95%CI: [4.3;9.3]) for stage C/D. The incidence rate did only significantly differ between stage C/D and stage 0 (p = 0.026), and HF stage C/D was the only stage associated with the composite renal outcome in univariable Cox regression (HR = 2.80 (95%CI: [1.07;7.31], p = 0.036)). Incidence rate of death (per 100 patient-years) by 0, A, B, and C/D HF-stages were 1.3 (95%CI: [0.43;4.2]), 1.0 (95%CI: [0.63;1.7]), 2.5 (95%CI: [1.7.;3.6]), and 7.3 (95%CI: [5.1;10]), respectively. Incidence of death was only significantly higher in stage C/D compared with stage 0 (p&amp;lt;0.001). Also, stage C/D was the only stage that was significantly associated with all-cause mortality in univariable Cox regression (HR = 5.47 (95%CI: [1.67;17.9], p = 0.005)). Conclusion Among patients with CKD, worse HF stages became more prevalent with worsening kidney function, and both incidence rates of the composite renal outcome and of death were higher in HF stage C/D.HF stages distributed on CKD stages

Contribution of reduced skeletal muscle perfusion reserve to exercise intolerance in heart failure with preserved ejection fraction

BackgroundSkeletal muscle (SM)-associated mechanisms of exercise intolerance in HFpEF are insufficiently defined, and inadequate augmentation of SM blood flow during physical effort may be one of the contributors. Therefore, we sought to investigate the association of SM perfusion response to exertion with exercise capacity in this clinical condition. MethodsEchocardiography and SM microvascular perfusion by contrast-enhanced ultrasound were performed at rest and immediately post-exercise test in 77 HFpEF patients in NYHA class II and III, and in 25 subjects with normal exercise tolerance (stage B). Exercise reserve of cardiac function and SM perfusion was calculated by subtracting resting value from exercise value. ResultsIn addition to decreased cardiac functional reserve, HFpEF patients demonstrated significantly reduced SM perfusion reserve as compared to HF stage B, with the degree of impairment being greater in the subgroup with more profound left ventricular (LV) diastolic abnormalities (E/e’ > 15 and TRV > 2.8 m/s).SM perfusion reserve was significantly associated with exercise capacity (beta = 0.33; SE 0.11; p = 0.003), cardiac output reserve (beta = 0.24; SE 0.12; p = 0.039), resting E/e’ (beta = −0.33; SE 0.11; p = 0.006), and patient frailty expressed by the PRISMA 7 score (beta = −0.30; SE 0.11; p = 0.008). In multivariable analysis including clinical, demographic and cardiac functional variables, SM perfusion reserve was in addition to patient frailty, sex and LV longitudinal strain reserve among the independent correlates of exercise capacity. ConclusionsSM perfusion reserve is impaired in HFpEF, and is associated with reduced exercise capacity independent of clinical, demographic and “central” cardiac factors. This supports the need to consider the SM domain in patient management strategies in HFpEF.

Correlations between serum laminin level and severity of heart failure in patients with chronic heart failure.

This study aimed to investigate the correlation between serum laminin (LN) levels and clinical stages of heart failure in patients with chronic heart failure. A total of 277 patients with chronic heart failure were selected from September 2019 to June 2020 in the Department of Cardiology, Second Affiliated Hospital of Nantong University. Based on stages of heart failure, the patients were divided into four groups: stage A, stage B, stage C, and stage D, with 55, 54, 77, and 91 cases, respectively. At the same time, 70 healthy people in this period were selected as the control group. Baseline data were recorded and serum Laminin (LN) levels were measured. The research compared, the differences in baseline data among the four groups of HF and normal controls, and analyzed the correlation between N-terminal pro-brain natriuretic peptide (NT-proBNP) and left ventricular ejection fraction (LVEF). The receiver operating characteristic (ROC) curve was used to evaluate the predictive value of LN in the C-D stage of heart failure. Logistic multivariate ordered analysis was applied to screen the independent related factors of clinical stages of heart failure. Serum LN levels in patients with chronic heart failure were significantly higher than those in healthy people, which were 33.2 (21.38, 101.9) ng/ml and 20.45 (15.53, 23.04) ng/ml, respectively. With the progression of clinical stages of HF, serum LN and NT-proBNP levels increased, while LVEF gradually decreased (P < 0.05). Correlation analysis showed that LN was positively correlated with NT-proBNP (r = 0.744, P = 0.000) and negatively correlated with LVEF (r = -0.568, P = 0.000). The area under the ROC curve of LN for predicting C and D stages of heart failure was 0.913, 95% confidence interval was 0.882-0.945, P = 0.000, specificity 94.97%, and sensitivity 77.38%. Multivariate Logistic analysis showed that LN, Total bilirubin, NT-proBNP and HA were all independent correlates of heart failure staging. Serum LN levels in patients with chronic heart failure are significantly increased and are independently correlated with the clinical stages of heart failure. It could potentially be an early warning index of the progression and severity of heart failure.

Heart failure associations with cerebral structure: combined analysis from the Multi‐Ethnic Study of Atherosclerosis (MESA) and the SECRET‐II trial of heart failure with preserved ejection fraction

AbstractBackgroundHeart failure (HF) with preserved ejection fraction (HFpEF) is the most common form of HF in adults 65 and older, but little is known about its relationship with neurocognitive outcomes. We compared brain magnetic resonance imaging (MRI) markers in older adults across stages of preclinical HF and clinical HFpEF.MethodAll participants completed baseline HF evaluation of risk factors, echocardiography, electrocardiography, and cardiopulmonary exercise by ACC/AHA stages; 3T brain MRI; and cognitive testing using harmonized protocols and teams at Wake Forest School of Medicine (2016‐2021). MESA participants without symptomatic HF were assigned to: Stage 0, no risk factors for HF (n = 30); Stage A, risk factors for HF without cardiac structural abnormalities (n = 111); or Stage B, abnormal cardiac structure or function without HF symptoms (n = 66). Participants with stable clinical HFpEF were recruited from the SECRET‐II trial and assigned to Stage C (n = 43). We compared intracranial volume‐adjusted total gray matter (GM), hippocampal, and white matter hyperintensity lesion (WMH) volumes across HF stages using multivariable linear regression adjusted for age, sex, and race, and report standardized least‐squares (LS) means estimates in SD units with 95% CI and Dunnett‐adjusted p‐values (referent = Stage 0).ResultThe combined sample (N = 250) was aged 72±7 years, 64% female, 47% white, and completed 15±3 years of education. Participants with Stage C HFpEF were younger (69±5 vs. 73±7 years, p&lt;0.001) and more likely to be female (85% vs. 59%, p&lt;0.001) than participants in lower stages. Stage B and Stage C participants had significantly lower GM volume than Stage 0 (0.38 [0.07, 0.69] vs. ‐0.12 [‐0.33, 0.09] in Stage B, p = 0.019; ‐0.36 [‐0.64, ‐0.09] in Stage C HFpEF, p = 0.001; Figure A), and Stages A‐C had non‐significant trends toward lower hippocampal volume (Stage 0 vs. Stage C p = 0.053; Figure B) and greater WMH volume (Stage 0 vs. Stages A‐C combined p = 0.073; Figure C). There were no interactions by sex or race.ConclusionIn this combined analysis from harmonized and diverse cohorts, higher HF stages and clinical HFpEF were associated with significantly lower gray matter volume. Observed trends toward lower hippocampal volume and higher WMH volume in HF Stages A‐C warrant further investigation.

Small Magnitude Events Highlight the Correlation Between Hydraulic Fracturing Injection Parameters, Geological Factors, and Earthquake Occurrence

AbstractHydraulic fracturing (HF) operations are widely associated with induced seismicity in the Western Canadian Sedimentary Basin. This study correlates injection parameters of 12,903 HF stages in the Kiskatinaw area in northeast British Columbia with an enhanced catalog containing 40,046 earthquakes using a supervised machine learning approach. It identifies relevant combinations of geological and operational parameters related to individual HF stages in efforts to decipher fault activation mechanisms. Our results suggest that stages targeting specific geological units (here, the Lower Montney formation) are more likely to induce an earthquake. Additional parameters positively correlated with earthquake likelihood include target formation thickness, injection volume, and completion date. Furthermore, the COVID‐19 lockdown may have reduced the potential cumulative effect of HF operations. Our results demonstrate the value of machine learning approaches for implementation as guidance tools that help facilitate safe development of unconventional energy technologies.

Biomarker prognostication across Universal Definition of Heart Failure stages.

The Universal Definition of Heart Failure (UDHF) provides a framework for staging risk for HF events. It is not clear whether prognostic biomarkers have different meaning across UDHF stages. We sought to evaluate performance of biomarkers to predict HF events among high-risk patients undergoing coronary and/or peripheral angiography categorized into UDHF stages. One thousand two hundred thirty-five individuals underwent coronary and/or peripheral angiography were enrolled. Study participants were categorized into UDHF Stage A (at risk), Stage B (pre-HF), and Stage C or D (HF, including end stage) and grouped into Stage A/B and C/D. Biomarkers and clinical variables were used to develop prognostic models. Other measures examined included total HF hospitalizations. Over a median of 3.67years of follow-up, 155 cardiovascular (CV) deaths occurred, and 299 patients were hospitalized with acute HF. In patients with Stage A/B, galectin-3 (HR=1.52, P=0.03), endothelin-1 (HR=2.16, P=0.001), and N-terminal pro-B-type natriuretic peptide (NT-proBNP; HR=1.43, P<0.001) were associated with incident CV death/HF hospitalization. In Stage C/D, NT-proBNP (HR=1.26, P=0.006), soluble urokinase-type plasminogen activator receptor (suPAR; HR=1.57, P=0.007) and high-sensitivity C-reactive protein (hs-CRP; HR=1.15, P=0.01) were associated with these outcomes. Higher biomarker concentrations were associated with greater total burden of HF events in Stages A/B and C/D. Among higher risk individuals undergoing angiographic procedures, different biomarkers improve risk stratification in different UDHF stages of HF. More precise prognostication may offer a window of opportunity to initiate targeted preventive measures.

Feasibility and Effectiveness of a Multi-Micronutrient Intervention as a Palliative Care Therapy in Patients With Congestive Heart Failure

ObjectivesVeterans with HF are at risk of micronutrient depletion due to combined systemic disease and drug induced altered nutrient disposition. This pilot aimed to test feasibility and effectiveness of a MMI to improve micronutrient status, cardiac function and quality of life in Veterans with HF. MethodsA pre/post repeated measures design was used. Veterans with stable HF stage B-D, left ventricular ejection fraction (LVEF) ≤45%, from ischemic cardiomyopathy with systolic dysfunction were recruited. The 6-month MMI was 3 tabs daily providing thiamin (B1) 100 mg, 50 mg each of riboflavin, niacin, pantothenic acid, pyridoxine (B6), inositol, 25 mg phosphatidyl choline, 400 mcg folic acid, and 50 mcg each of B12 and biotin, and 50 mg elemental zinc (Zn). Ergocalciferol was given as 50,000 IU weekly for 2 months then every 2 weeks for 4 months. Micronutrient status and LVEF (echocardiogram) were determined as least-squares mean (± standard error, SE) estimated from general linear mixed effect models fitted to micronutrient measurements adjusting for age (18–65 Vs. > 65); feasibility of MMI assessed as % consumed. ResultsThis abstract focuses on the nutrient status at baseline, feasibility of the MMI, and change in nutrient status following MMI. Twenty-two male Veterans (86% Caucasian), median 64 years (59–75 interquartile range, IQR) started MMI; 20 completed. At baseline, median (IQR) dietary intake was 1639 (1472–1838) calories, 36 (28–41) % fat, 13 (10–15) % saturated fat, 2981 (2067–3534) mg sodium while following the American Heart Association diet with 2 gm sodium restriction. Micronutrient intake was 1.2 (0.9–1.4) mg B1, 1.2 (1.0–1.8) mg B6, 49 (38–166) IU Vitamin D, and 7 (5–10) mg zinc. Median % compliance with MMI at 3 and 6 months was ≥ 92 and ≥94, respectively. Baseline and changes in blood measures of micronutrients were: B1, 119 (SE 13) and 96 (SE 20, p< 0.0001) nmol/L; B6, 11.4 (SE 6.3) and 57.3 (SE 9.2, p< 0.0001) ng/mL; total 25-OH Vitamin D, 31.2 (SE 2.3) and 6.5 (SE 3.4, p = 0.057) ng/mL; Zn, 81.4 (SE 5.1) and 13.8 (7.6, p = 0.07) mcg/dL. LVEF at baseline and 6 months were 28.9 (SE 1.6) % and 30.0 (SE 1.7) %, respectively (p = 0.64). ConclusionsThe feasibility of adding MMI to complex pharmaceutical regimens in male Veterans with stable HF was high. MMI was effective in improving micronutrient status and preserved LVEF. Funding SourcesDepartment of Veterans Affairs

Mathematical model of linear and non-linear proppant concentration increase during hydraulic fracturing – a solution for sequential injection of a number of proppant types

It is known that much of the technology aimed at intensifying fluid inflow by means of hydraulic fracturing involves the use of proppant. In order to transport and position grains in the fracture, a uniform supply of proppant with a given concentration into the fracturing fluid is ensured. The aim of the operation is to eliminate the occurrence of distortions in the injection program of proppant HF. A mathematically accurate linear increase of concentration under given conditions is possible only if the transient concentration is correctly defined. The proposed approach allows to correctly form a proppant HF work program for both linear and non-linear increase in proppant concentration. The scientific novelty of the work lies in application of a new mathematical model for direct calculation of injection program parameters, previously determined by trial and error method. A mathematical model of linear and non-linear increase of proppant concentration during HF was developed. For the first time, an analytical solution is presented that allows direct calculation of parameters of the main HF stages, including transient concentrations for given masses of the various types of proppant. The application of the mathematical model in formation of a treatment plan allows maintaining correct proppant mass distribution by fractions, which facilitates implementation of information and analytical systems, data transfer directly from a work program into databases. It is suggested to improve spreadsheet forms used in production, which would allow applying mathematical model of work program formation at each HF process without additional labour costs. The obtained mathematical model can be used to improve the software applied in the design, modelling and engineering support of HF processes.

Importance of Vascular Function in Patients with Heart Failure with Preserved Ejection Fraction

There had been no effective cardioprotective medications for heart failure with preserved ejection fraction (HFpEF). Therefore, treatment intervention at the hypertension (HT) stage (stage A), which is a major factor in HFpEF, is necessary. In fact, the SPRINT and STEP trials reported that strict and intensive blood pressure (BP) control was useful, reducing approximately 25% of the primary endpoints, including cardiovascular events. The effectiveness of BP reduction for HFpEF after the onset of HF (stage C or D) has been reported and shown to generally follow the J-curve phenomenon. Both left ventricular systolic/diastolic dysfunction and vascular failure are related with the pathophysiology of HF. In the case of coexisting vascular failure, BP lowering treatment is effective, because it decreases the afterload. However, BP lowering treatment has been reported to increase the incidence of renal dysfunction; therefore, paying attention to the degree of association with vascular failure, and multiple organs when determining the target BP are important to consider. The decision on the target BP and the optimal choice of cardioprotective/antihypertensive medications for HF should be based on the pathologic condition.

Determinants of exercise intolerance symptoms considered non-specific for heart failure in patients with stage A and B: role of the left atrium in the transition phase to overt heart failure

To assess to what extent left atrial (LA) structure and function are associated with non-specific heart failure symptoms, so that patients were classified as HF stage A and B. Mechanisms underlying the transition to overt HF in patients with stage A and B HF are unclear. Consecutive outpatients undergoing echocardiography and clinical evaluation and classified as HF stage A and B with preserved left ventricular ejection fraction (LVEF) were included. The association between LA measures [volume (LAVi), peak longitudinal-(PALS), contraction-(PACS) and conduit-strain] and non-specific HF symptoms was assessed using adjusted logistic regression analyses. The incremental value of atrial myopathy in symptoms prediction on top of clinical or echocardiographic confounders was assessed through ROC curves analyses. The cohort comprehended 185 patients (63 ± 16 years, 47% women) of whom 133 (72%) were asymptomatic, and 52 (28%) reported non-specific HF symptoms. After adjustment for clinical and echocardiographic confounders for HF symptoms, LAVi, PALS and PACS were associated with symptoms (p < 0.05). Among echocardiographic variables, only LA parameters were significantly associated with symptoms on top of clinical confounders (for LAVi OR [95% CI] 1.56 [1.21–2.00], p < 0.0001; for PALS 1.45 (1.10–1.91), p = 0.0009; for PACS 2.10 [1.33–3.30], p = 0.002). After adjustment for age, hypertension and COPD or E/E′, LV mass-i and mitral ERO, atrial myopathy added predictive value for symptoms presence compared to the clinical variables or echocardiographic parameters described (AUC increase 0.80 to 0.88, p = 0.004, and 0.79 to 0.84, p = 0.06, respectively). In patients with HF stages A–B and preserved LVEF, measures of LA structure and function were associated with non-specific HF symptoms. A comprehensive LA remodeling evaluation may help clinicians in the appropriate identification of overt HF.

From Systemic Inflammation to Myocardial Fibrosis: The Heart Failure With Preserved Ejection Fraction Paradigm Revisited.

In accordance with the comorbidity-inflammation paradigm, comorbidities and especially metabolic comorbidities are presumed to drive development and severity of heart failure with preserved ejection fraction through a cascade of events ranging from systemic inflammation to myocardial fibrosis. Recently, novel experimental and clinical evidence emerged, which strengthens the validity of the inflammatory/profibrotic paradigm. This evidence consists among others of (1) myocardial infiltration by immunocompetent cells not only because of an obesity-induced metabolic load but also because of an arterial hypertension-induced hemodynamic load. The latter is sensed by components of the extracellular matrix like basal laminin, which also interact with cardiomyocyte titin; (2) expression in cardiomyocytes of inducible nitric oxide synthase because of circulating proinflammatory cytokines. This results in myocardial accumulation of degraded proteins because of a failing unfolded protein response; (3) definition by machine learning algorithms of phenogroups of patients with heart failure with preserved ejection fraction with a distinct inflammatory/profibrotic signature; (4) direct coupling in mediation analysis between comorbidities, inflammatory biomarkers, and deranged myocardial structure/function with endothelial expression of adhesion molecules already apparent in early preclinical heart failure with preserved ejection fraction (HF stage A, B). This new evidence paves the road for future heart failure with preserved ejection fraction treatments such as biologicals directed against inflammatory cytokines, stimulation of protein ubiquitylation with phosphodiesterase 1 inhibitors, correction of titin stiffness through natriuretic peptide-particulate guanylyl cyclase-PDE9 (phosphodiesterase 9) signaling and molecular/cellular regulatory mechanisms that control myocardial fibrosis.

Comprehensive plasma metabolomic and lipidomic analyses reveal potential biomarkers for heart failure.

Heart failure is a syndrome with symptoms or signs caused by cardiac dysfunction. In clinic, four stages (A, B, C, and D) were used to describe heart failure progression. This study was aimed to explore plasma metabolomic and lipidomic profiles in different HF stages to identify potential biomarkers. Metabolomics and lipidomics were performed using plasma of heart failure patients at stages A (n = 49), B (n = 61), and C+D (n = 26). Analysis of Variance (ANOVA) was used for screening dysregulated molecules. Bioinformatics was used to retrieve perturbed metabolic pathways. Univariate and multivariate receiver operating characteristic curve (ROC) analyses were used for potential biomarker screening. Stage A showed significant difference to other stages, and 142 dysregulated lipids and 134 dysregulated metabolites were found belonging to several metabolic pathways. Several marker panels were proposed for the diagnosis of heart failure stage A versus stage B-D. Several molecules, including lysophosphatidylcholine 18:2, cholesteryl ester 18:1, alanine, choline, and Fructose, were found correlated with B-type natriuretic peptide or left ventricular ejection fractions. In summary, using untargeted metabolomic and lipidomic profiling, several dysregulated small molecules were successfully identified between HF stages A and B-D. These molecules would provide valuable information for further pathological researches and biomarker development.

Cardiac reserve and exercise capacity: insights from combined cardiopulmonary and exercise echocardiography stress testing

Abstract Funding Acknowledgements Type of funding sources: None. Aims. Combined cardiopulmonary exercise test (CPET) and exercise stress echocardiography (ESE) provides a non-invasive tool to study cardiopulmonary pathophysiology. We analyzed how cardiac functional reserve during exercise relates to peak oxygen consumption (VO2). Methods and Results. We performed a symptom-limited graded ramp bicycle CPET-ESE in 30 healthy controls and 357 patients: 113 at risk of developing heart failure (American College of Cardiology/American Heart Association HF Stages A-B) and 244 in HF Stage C with preserved (HFpEF, n = 101) or reduced ejection fraction (HFrEF, n = 143). Peak VO2 significantly decreased from controls to Stage A-B and Stage C (Table 1). A multivariable regression model to predict peak VO2 revealed peak left ventricular systolic annulus tissue velocity (S"), peak TAPSE/PAPs (tricuspid annular plane systolic excursion/systolic pulmonary artery pressure) and low-load left atrial reservoir strain/E/e’ were independent predictors, in addition to peak heart rate, stroke volume and workload (adjusted R²=0.76, p &amp;lt; 0.0001). The model was successfully tested in subjects with atrial fibrillation (n = 49), and with (n = 224) and without (n = 163) beta-blockers (all p &amp;lt; 0.01). Peak S’ showed the highest accuracy in predicting peak VO2 &amp;lt; 10 mL/kg/min (cut-point ≤ 7.5 cm/s; AUC = 0.92, p &amp;lt; 0.0001) and peak VO2 &amp;gt; 20 mL/kg/min (cut-point &amp;gt; 12.5 cm/s; AUC = 0.84, p &amp;lt; 0.0001) in comparison to the other cardiac variables of the model (p &amp;lt; 0.05). Conclusions. A model incorporating different measures of cardiac mechanics is strongly related to peak aerobic capacity and may help in identifying different causes of effort intolerance from HF Stage A to C. Table 1 Variable Overall population (n = 387) Controls (n = 30) Stage A-B (n = 113) Stage C-HFpEF (n = 101) Stage c-HFrEF (n = 143) p-value Age, years 68.9 ± 11.1 67.1 ± 10.6 67.7 ± 10.4 70.5 ± 10.1 68.5 ± 11 0.1 Male, n (%) 247 (64) 18 (60) 70 (62) 57 (56) 102 (71) 0.1 VO2 @peak, mL/min/kg 15.7 (12.1-19.6) 23 (21.7- 29.7) 18 (15.4- 20.7)* 13.6 (11.8- 16.8)*† 14.2 (10.7- 17.5)*† &amp;lt;0.0001 Workload @peak, W 90 (65-120) 130 (115-195) 110 (84-130)* 70 (55-100)*† 80 (60-110)*† &amp;lt;0.0001 Heart rate @peak, bpm 123 ± 22 142 ± 12 130 ± 20* 115 ± 17*† 119 ± 23*† &amp;lt;0.0001 Stroke volume @peak, mL 83 (71-99) 98 (85-114) 86 (76-107) 83 (74-97)* 75 (63-95)*† &amp;lt;0.0001 Average S" @peak, cm/s 11.2 ± 3.8 17.1 ± 3.9 13.3 ± 2.9* 10.6 ± 2.5*† 8.7 ± 2.7*†‡ &amp;lt;0.0001 TAPSE/PAPs @peak, mm/mmHg 0.75 (0.46-0.97) 1.05 (0.93- 1.16) 0.81 (0.52- 0.91)* 0.52 (0.38- 0.83)*† 0.58 (0.41- 0.89)*† &amp;lt;0.0001 Left atrial reservoir strain/E/e" @low-load, % 2.25 (1.17-5.04) 6.23 (4.45-6.77) 4.34 (3.89- 5.58)* 2.23 (1.31- 2.86)*† 1.91 (1.07-2.44)*†‡ &amp;lt;0.0001 * p &amp;lt; 0.01 vs Controls; † p &amp;lt; 0.01 vs Stage A-B; ‡ p &amp;lt; 0.01 vs Stage C-HFpEF. PAPs systolic pulmonary artery pressure; TAPSE: tricuspid annular plane systolic excursion; VO2: oxygen consumption. Abstract Figure 1