Heart Failure With Preserved Left Ventricular Ejection Fraction Research Articles

Predictive Value of 5-Methoxytryptophan on Long-Term Clinical Outcome after PCI in Patients with Acute Myocardial Infarction-a Prospective Cohort Study.

In recent years, 5-Methoxytryptophan (5-MTP) has been identified as an endothelial factor with vaso-protective and anti-inflammatory properties. In this prospective cohort study, a total of 407 patients with acute myocardial infarction (AMI) who underwent percutaneous coronary intervention (PCI) successfully were enrolled. A 1-year follow-up Kaplan-Meier survival analysis was used for evaluating the correlation between 5-MTP and major adverse cardiovascular event (MACE) while Cox proportional-hazards regression was used to identify predictive values of 5-MTP on MACE after AMI. Increased 5-MTP level led to a significant downtrend in the incidence of MACE (All Log-rank p < 0.05). Thus, a high baseline 5-MTP could reduce the 1-year incidence of MACE (HR = 0.33, 95%Cl 0.17-0.64, p = 0.001) and heart failure (HF) (HR = 0.28, 95% Cl 0.13-0.62, p = 0.002). Subgroup analysis indicated the predictive value of 5-MTP was more significant in patients aged ≤ 65years and those with higher baseline NT-proBNP, T2DM, STEMI, and baseline HF with preserved LVEF (HFpEF) characteristics. Plasma 5-MTP is an independent and protective early biomarker for 1-year MACE and HF events in patients with AMI, especially in younger patients and those with T2DM, STEMI, and baseline HFpEF characteristics.

Clinical significance of echocardiographic signs of right heart dysfunction in patients with chronic heart failure with preserved left ventricular ejection fraction

Aim: To analyze the features of clinical signs, quality of life and psycho-emotional state in patients with heart failure with preserved left ventricular ejection fraction (HFpEF) and non-obstructive atherosclerosis of the coronary arteries, depending on the presence of echocardiographic criteria for dysfunction of the right heart.Material and Methods. Patients underwent an extended protocol of echocardiography with an assessment of the structure and function of the right heart; ultrasound examination of the lungs with the determination of the number of B-lines; a six-minute walk test, a test for the presence of a symptom of bendopnea with the determination of blood oxygen saturation (SpO2) before and during the test. In addition, quality of life was assessed using the Minnesota questionnaire and the SF-36 questionnaire (The Short Form-36); the psycho-emotional state of patients was analyzed according to the HADS (Hospital Anxiety and Depression Scale), the level of adherence to treatment was analyzed according to the Morisky – Green questionnaire. Patients were divided into two groups depending on signs of right heart dysfunction: Tei index more than 0.54, tricuspid annulus systolic excursion (TAPSE) less than 17 mm, tricuspid annulus systolic velocity (RV S’) less than 9,5 cm/sec.Results. Echocardiographic signs of right heart dysfunction in patients with HFpEF was associated with lower quality of life indicators according to the SF-36 questionnaire, in particular, general health status (p = 0.008) and role limitations due to emotional problems (p = 0.03). During the bendopnea test (p = 0.04), the majority of patients with signs of dysfunction of the right heart (66.7%) had a decrease in SpO2, while in the comparison group the proportion of such patients was 36.7% (p = 0.04). The psycho-emotional state according to the HADS scale and adherence to treatment did not differ in both groups (p &gt; 0.05). The frequency of detection of B-lines according to lung ultrasound was also comparable.

Simvastatin Attenuates Cardiac Fibrosis under Pathophysiological Conditions of Heart Failure with Preserved Left Ventricular Ejection Fraction by Inhibiting TGF-β Signaling

Introduction: There is still no effective treatment for heart failure with preserved left ventricular ejection fraction (HFpEF), and therapies to improve prognosis are urgently needed. Clinical studies in patients with HFpEF have shown that statins and HMG-CoA reductase inhibitors may reduce their mortality rate. However, the mechanisms underlying the effects of statins on HFpEF remain unknown. In the present study, we examined whether simvastatin administration inhibits the development of cardiac fibrosis in HFpEF model mice. We further examined the contribution of the Smad and mitogen-activated protein (MAP) kinase pathways to the transforming growth factor-β (TGF-β) signaling pathway in the development of HFpEF. Methods: HFpEF animals were prepared by feeding C57BL/6 N mice a high-fat diet and providing water containing N^[w]-nitro-<sc>l</sc>-arginine methyl ester hydrochloride (<sc>l</sc>-NAME) for 15 weeks. Simvastatin (30 mg/kg/day) or vehicle was administered orally daily during the experimental period. Cardiac function was measured by echocardiography, and cardiac fibrosis was evaluated by Masson’s trichrome staining. Changes in the TGF-β signaling proteins in myocardial tissue were examined by Western blotting. Results: A high-fat diet and <sc>l</sc>-NAME solution load induced cardiac diastolic dysfunction with cardiac fibrosis. Simvastatin treatment markedly attenuated cardiac fibrosis and reduced cardiac diastolic dysfunction. In addition, simvastatin prevented the increase in phosphorylation levels of Smad (Smad2 and Smad3) and MAPK (c-Raf, Erk1/2) pathway proteins downstream of the TGF-β receptor in cardiac tissue. Conclusions: Our present study demonstrated that simvastatin attenuated diastolic dysfunction by reducing cardiac fibrosis in HFpEF hearts. Furthermore, our findings suggest that the mechanisms by which simvastatin attenuates HFpEF development involve, at least in part, inhibition of the TGF-β signaling pathway, which is activated in the HFpEF heart.

Abstract 15927: Polyunsaturated Fatty Acid Levels and Their Relationship With Peak Exercise Measures in HFpEF

Background: Polyunsaturated fatty acids (PUFAs) regulate the inflammatory cascade and have been implicated in potential pathologic and therapeutic roles in heart failure with preserved LVEF (HFpEF). The purpose of this study was to explore the relationship between plasma levels of omega-3 (ω-3) fatty acids and invasive hemodynamic profiles characteristic of early HFpEF. Methods: In a single-center referral cohort undergoing evaluation for exertional dyspnea and suspected HFpEF, we assayed ω-3 concentrations in plasma by liquid chromatography. We derived an ω-3 score by summing Z-scores of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). Linear regression was used to relate plasma ω -3 levels to simultaneously collected physiologic data from cardiopulmonary exercise testing (CPET) with invasive catheterization. Results: 588 patients (52% female, age 62 ± 12 years, BMI 30 ± 6 kg/m 2 , peak oxygen uptake (VO 2 ) 15.5 ± 5.1 mL/min/kg [76 ± 20% predicted], NTproBNP 118 [33 - 405] pg/mL) were studied. Median ω -3 concentrations were 72 [46 - 107] pg/mL for EPA and 315 [225 - 457] pg/mL for DHA. Female sex and increased age were associated with higher levels of ω-3 fatty acids ( Table , p=0.03). After adjustment for age, sex, and BMI, a higher ω-3 score was associated with greater exercise capacity measured by peak VO 2 (p&lt;0.001) and peak workload (p&lt;0.001) along with an increase in peak exercise peripheral O 2 extraction (CavO 2 ; p &lt; 0.001). Notably, increased ω-3 score was associated with lower supine pulmonary capillary wedge pressure (PCWP; p=0.03), PCWP to cardiac output (CO) slope during exercise (p = 0.009), and NTproBNP (p &lt; 0.001). Conclusion: These data demonstrate that circulating ω-3 fatty acid levels are associated with exercise capacity and both central cardiac and peripheral function in HFpEF. Further studies are needed to unravel the relationship between modulation of plasma PUFAs and rest and exercise hemodynamic profiles of HFpEF.

The Sympathetic Nervous System in Hypertensive Heart Failure with Preserved LVEF.

The neurohormonal model of heart failure (HF) pathogenesis states that a reduction in cardiac output caused by cardiac injury results in sympathetic nervous system (SNS) activation, that is adaptive in the short-term and maladaptive in the long-term. This model has proved extremely valid and has been applied in HF with a reduced left ventricular (LV) ejection fraction (LVEF). In contrast, it has been undermined in HF with preserved LVEF (HFpEF), which is due to hypertension (HTN) in the vast majority of the cases. Erroneously, HTN, which is the leading cause of cardiovascular disease and premature death worldwide and is present in more than 90% of HF patients, is tightly linked with SNS overactivity. In this paper we provide a contemporary overview of the contribution of SNS overactivity to the development and progression of hypertensive HF (HHF) as well as the clinical implications resulting from therapeutic interventions modifying SNS activity. Throughout the manuscript the terms HHF with preserved LVEF and HfpEF will be used interchangeably, considering that the findings in most HFpEF studies are driven by HTN.

Right ventricular and right atrial free wall deformation predicitive value in transformation of preclinical diastolic disfunction to heart failure with preserved ejection fraction.

Aim To study echocardiographic parameters of heart chamber strain in patients with left ventricular (LV) preclinical diastolic dysfunction (PDD) for determining predictors of the PDD transition to heart failure with preserved LV ejection fraction (HFpEF).Material and methods The study included 113 patients (including 69 women) with metabolic syndrome and LV PDD (mean age, 65±7 years). The control group consisted of 40 healthy individuals (mean age, 63.0±6.0 years, including 59% women). Metabolic syndrome was diagnosed in consistency with criteria of NCEP-ATP III 2001. PDD was diagnosed based on the absence of heart failure symptoms, normal level of brain natriuretic peptide, and the presence of at least three of the following echocardiographic criteria at rest or after diastolic stress-echocardiography (stress-echoCG): left atrial volume index (LAVI) &gt;34 ml / m2; the ratio of peak early transmitral filling velocity (E) to average lateral and medial mitral annular velocity (e'), Е / е' &gt;14, е' &lt;8.5, and peak tricuspid regurgitation velocity &gt;2.8 m /s. EchoCG that determined LV longitudinal strain (LS), right ventricular (RV) LS, right atrial (RA) LS, and left atrial (LA) LS was performed every year during the 3-year follow-up.Results During the follow-up period, 31 patients developed HFpEF. 19 of them reported symptoms while in the other 12 patients, HFpEF was detected by diastolic stress-echoCG. Patients with HFpEF had significantly lower absolute values of RV LS, LA LS, and RA LS (-27.8±2.9 in the PDD group vs. -23.8±3.2 in the HFpEF group; р&lt;0.03; 38.2±9.1 vs. 28.6±10.2; р&lt;0.03; and 46.2±10.4 vs. 31.6±8.3; р&lt;0.03, respectively). RV LS and RA LS were the strongest independent predictors for PDD transformation into HFpEF (odds ratio, OR, 2.7; 95 % confidence interval, CI, 1.48-2.91; р&lt;0.001 and OR 2.6; 95 % CI: 1.40-2.75; р&lt;0.001, respectively).Conclusion PDD is not a separate clinical nosology but rather an initial stage in the pathogenesis of HFpEF. Approximately ⅓ of PDD patients develop HFpEF. RV LS and RA LS are considered predictors of HFpEF. The duration of PDD is apparently an important factor that provides the development of HFpEF.

Clinical Features of Heart Failure With Normal Ejection Fraction: Insights From the ASIAN-HF Registry

BackgroundHeart failure and left ventricular ejection fraction in the normal range (HFnEF) (left ventricular ejection fraction [LVEF] of ≥55% for men and ≥60% for women) is understudied. ObjectivesThe authors aimed to characterize patients with HFnEF compared with those with preserved (≥50%) yet below the normal LVEF. MethodsIn an Asian HF registry, clinical characteristics, echocardiographic features, and outcomes were compared across: 1) HFnEF; 2) heart failure with preserved left ventricular ejection fraction (HFpEF) (LVEF of ≥50%) and below normal LVEF; and 3) community-based controls without HF. Cluster analysis of echocardiographic parameters was performed and validated in an external cohort. ResultsAmong 1,765 patients with HFpEF (age 68 ± 12 years; 50% women), 1,313 (74.4%) had HFnEF. Compared with patients with HFpEF and below normal LVEF, patients with HFnEF had less coronary artery disease (33.7% vs 27.9%), greater LV wall thickness, and higher stroke volume, but similar 2-year age-adjusted all-cause mortality (HR: 0.8; 95% CI: 0.6-1.2). Five echocardiographic clusters with similar 2-year mortality were identified: 1) normal LV (normal structure despite increased filling pressure; least comorbidities) in 25%; 2) restrictive (smallest stroke volume; predominantly elderly women) in 26%; 3) hypertrophic (most concentric hypertrophy; more men) in 25%; 4) high output (greatest stroke volume; predominantly obese younger men) in 10%; and 5) atrial dominant (most left atrial myopathy; mainly elderly women with multiple comorbidities) in 10%. Similar patterns were found in the validation cohort. ConclusionsThe majority of patients with HFpEF had normal LVEF, which consists of patients with different patterns of cardiac features and clinical characteristics. Results may carry implications for targeted treatment approaches in HFpEF.

Colchicine in patients with heart failure and preserved left ventricular ejection fraction: rationale and design of a prospective, randomised, open-label, crossover clinical trial

IntroductionSystemic low-grade inflammation is a fundamental pathophysiological mechanism of heart failure with preserved left ventricular ejection fraction (HFpEF). The efficacy of anti-inflammatory therapy in HFpEF is largely understudied. The aim...

The role of epicardial obesity in the development of left ventricular diastolic dysfunction

To study the effect of epicardial adipose tissue on risk of left ventricular (LV) diastolic dysfunction (DD) in patients with visceral obesity. Obesity leads to the development of LV DD and is a major cause of heart failure with preserved LV ejection fraction (HFpEF). However, the contribution of epicardial adipose tissue to DD is understudied. This study included 101 men with general obesity (body weight index, 32.9±3.6 kg /m2). Based on severity of epicardial obesity (EO), two groups were formed: group 1, patients with an epicardial adipose tissue thickness (EATt) &gt;7 mm (n=70), and group 2, patients with EATt &lt;7 mm (n=31). Arterial hypertension, diabetes mellitus, coronary atherosclerosis, and disorders of LV diastolic function according to echocardiography (EchoCG) were the exclusion criteria. Diastolic function and LV mechanics were evaluated by speckle-tracking EchoCG for all patients at the start of the study and again at 4.7±0.3 years. At baseline, none of the patients of either group had significant differences in EchoCG characteristics of LV diastolic function (left atrial volume index, LV early diastolic longitudinal lengthening velocity, peak tricuspid regurgitation velocity, and the ratio of diastolic transmitral flow velocity to mean mitral annular velocity (E / e'). However, there were significant increases in the LV untwisting velocity to -122.11 [-142.0; -116.0 degrees /s -1] degrees/s and the time to LV peak untwisting velocity to 472.3 ms. Repeated EchoCG showed an increase in left atrial volume index in group 1 to 35.04 [33.0; 39.7] ml /m2. Repeated evaluation of the LV mechanics revealed increases in the times to LV peak untwisting and twisting and decreases in the LV twisting and untwisting velocities. The logistic regression analysis showed that EATt was a risk factor for LV DD in obesity. Furthermore, the ROC analysis determined the optimal EATt cut-off threshold of ≥9 mm as a predictor for LV DD development. EO facilitates the development of LV DD and, thus, represents a major cause for HFpEF. An EATt value of ≥9 mm can be considered as a risk factor for LV DD development in patients with EO.

P2 A RARE CASE OF MUTANT TRANSTHYRETIN CARDIAC AMYLOIDOSIS

Abstract A 65–year–old man with a history of multiple hospitalizations in the past 12 months for heart failure with preserved left ventricular ejection fraction (HFpEF) attended the emergency department for exertional dyspnea, peripheral edema, abdominal bloating, and weight gain. An ECG showed sinus bradycardia with first degree AV block, RBBB, and inferior pseudo–q. Blood tests showed NT–proBNP 8985 pg/ml, troponin hs–cTnI 106 ng/L. An echocardiogram demonstrated severe left ventricular hypertrophy, EF 50%, GLS –11% with apical sparing, and restrictive transmitral pattern, raising suspicion of infiltrative disease (Figure 1). A cardiac MRI corroborated the suspicion, showing altered gadolinium kinetics, diffuse subendocardial LGE, and increased native T1 and extracellular volume (Figure 2). A search for monoclonal components on serum and urine was negative. A bone tracer scintigraphy showed cardiac uptake (Perugini grade 2). A genetic test showed the presence of p.Ile88Leu (Ile68Leu) mutation in heterozygosity, so a non–biopsy diagnosis of mutant transthyretin cardiac amyloidosis (ATTRv) was posed. A thorough neurological evaluation did not document signs of amyloid neuropathy. The patient was then started on tafamidis therapy. Transthyretin cardiac amyloidosis (ATTR) is still an underdiagnosed but increasingly recognized condition, causing up to 13% of HFpEF cases. ATTR is caused by extracellular accumulation of amyloid substance resulting from transthyretin misfolding. In Italy ATTRv is rare and Ile68Leu is among the most frequent mutations, especially in the Tuscan–Emilian Apennines. Ile68Leu is usually associated with an almost exclusively cardiac phenotype, clinically indistinguishable from ATTR wild type, except for an earlier age of onset. Because effective treatments are available for ATTRv with cardiac and/or neurological involvement, it is important to suspect the diagnosis of ATTR in patients with HFpEF and to proceed with genetic testing to identify individuals with ATTRv.

Spironolactone effect on circulating procollagen type I carboxy-terminal propeptide: Pooled analysis of three randomized trials

BackgroundSpironolactone might improve the prognosis of patients with heart failure with preserved left ventricular ejection fraction (HFpEF), but the mechanisms by which it acts are uncertain. Serum concentrations of procollagen type I carboxy-terminal propeptide (PICP) reflect the synthesis of type I collagen and correlate well with histologically proven cardiac fibrosis. AimsTo investigate the effect of spironolactone on serum PICP concentration in patients with stage B and C HFpEF across three trials (HOMAGE, ALDO-DHF, and TOPCAT) for which measurements of serum PICP were available. MethodsRandom-effects meta-analysis. ResultsA total of 1038 patients with PICP measurements available both at baseline and 9–12 months were included in this analysis: 488 (47.0%) from HOMAGE, 386 (37.2%) from ALDO-DHF, and 164 (15.8%) from TOPCAT. The median (percentile25–75) serum PICP was 98 (76–128) ng/mL. Compared to placebo or usual care, administration of spironolactone for 9 to 12 months reduced serum PICP by −7.4 ng/mL, 95%CI -13.9 to −0.9, P-value =0.02. The effect was moderately heterogeneous (I2 = 64%) with the most pronounced effect seen in TOPCAT where PICP was reduced by −27.0 ng/mL, followed by HOMAGE where PICP was reduced by −8.1 ng/mL, and was least marked in ALDO-DHF where PICP changed by −2.9 ng/mL. The association between spironolactone and serum PICP was not mediated substantially by blood pressure. ConclusionsSpironolactone reduced serum concentrations of PICP in patients with HFpEF with different severity and stages of disease. These findings are consistent with spironolactone having an anti-fibrotic effect.

Рossibility of using European (HFA-PEFF) and American (H2FPEF) algorithms for diagnosing heart failure with preserved ejection fraction in Russian clinical practice

This article focuses on the significance of a unified approach to diagnosing heart failure with preserved left ventricular ejection fraction (HFpEF). The key hemodynamic index of HFpEF is increased left ventricular filling pressure (LVFP) and its noninvasive marker, the E / e' value obtained by tissue Doppler echocardiography (EchoCG). The modern verified algorithms for HFpEF diagnosis, HFA-PEFF and Н2FPEF, mandatorily take into account the E / e' value. However, the routing use of these algorithms in the Russian practice may be complicated since even among "advanced" specialists who are interested in heart failure, 38% of the interviewed do not use or do not know how to use tissue Doppler EchoCG or the algorithm for diagnosing HFpEF with E / e'. In addition to the obvious way of overcoming this problem by equipping respective medical facilities with ultrasonic apparatuses with tissue Doppler EchoCG software and educating physicians, a possibility of using simplified HFA algorithm without the E / e' value is being considered. However, such approach will inevitably lead to erroneous estimation of the probability of HFpEF and, at the best, to underestimation of this probability with ensuing mistakes in diagnosis and treatment. Simplifying the HFA-PEFF and H2FPEF algorithms by omitting one or more parameters is possible but this requires a special investigation to develop a new rating scale and actually a new algorithm, which, in turn, will require a new validation.

Kinematic Parameters That Can Discriminate in Levels of Functionality in the Six-Minute Walk Test in Patients with Heart Failure with a Preserved Ejection Fraction.

It is a challenge to manage and assess heart failure with preserved left ventricular ejection fraction (HFpEF) patients. Six-Minute Walk Test (6MWT) is used in this clinical population as a functional test. The objective of the study was to assess gait and kinematic parameters in HFpEF patients during the 6MWT with an inertial sensor and to discriminate patients according to their performance in the 6MWT: (1) walk more or less than 300 m, (2) finish or stop the test, (3) women or men and (4) fallen or did not fall in the last year. A cross-sectional study was performed in patients with HFpEF older than 70 years. 6MWT was carried out in a closed corridor larger than 30 m. Two Shimmer3 inertial sensors were used in the chest and lumbar region. Pure kinematic parameters analysed were angular velocity and linear acceleration in the three axes. Using these data, an algorithm calculated gait kinematic parameters: total distance, lap time, gait speed and step and stride variables. Two analyses were done according to the performance. Student’s t-test measured differences between groups and receiver operating characteristic assessed discriminant ability. Seventy patients performed the 6MWT. Step time, step symmetry, stride time and stride symmetry in both analyses showed high AUC values (>0.75). More significant differences in velocity and acceleration in the maximum Y axis or vertical movements. Three pure kinematic parameters obtained good discriminant capacity (AUC > 0.75). The new methodology proved differences in gait and pure kinematic parameters that can distinguish two groups according to the performance in the 6MWT and they had discriminant capacity.

Heart failure with preserved left ventricular ejection fraction amidst diabetes mellitus: from general mechanisms to possible therapy tactics

The review discusses the relationship between chronic heart failure and diabetes mellitus type 2, metabolic phenotypes of patients w ith chronic heart failure with preserved left ventricular ejection fraction (HFpEF), features of the pathophysiological interaction between diabetes mellitus and HFpEF. Chronic inflammatory condition, metabolic disorders and comorbidities are the pathophysiological basis of HFpEF. The review discusses the concept of diabetic cardiomyopathy, its molecular mechanism and current possibilities of treating this pathology, considering the impact on the prognosis.

Disease progression of heart failure in type 2 diabetes patients in Germany; a real world data analysis using health insurance claims data

Abstract Individuals with Type 2 Diabetes (T2D) show two- to four-fold increased risk of Heart failure (HF). Given the increasing T2D prevalence in Germany, researching the interaction of T2DM and HF is of high importance. HF still progresses rapidly. Left ventricular ejection fraction (LVEF) plays an important role in understanding disease progression. Commonly, LVEF is being distinguished into three categories: HF with preserved LVEF (HFpEF), HF with moderate reduced LVEF (HFmEF) and HF with reduced LVEF (HFrEF). In Germany there are no recent data on disease progression in HF especially according to LVEF categories. Purpose of this study is to a) measure how many T2DM patients acquire HF over two years; b) understand the progression of HF in these patients in a five-year follow-up; and c) visualize disease progression with Sankey plots. We used insurance claims data from German Statutory Health Insurances (SHI). As LVEF category is not included in these data, a model was used to classify patients into HFrEF or HFpEF (with omitting the HFmEF category due to better statistical performance of a binary model). The model was derived from a set of 34 proxy variables (disease coding, interventions, drug prescriptions). Selection period for T2D patients is 2013. Inclusion period was 2014–2015, follow-up 2016–2020. Baseline characteristics include demographic data, disease stage, comorbidities, and risk factors. Follow-up criteria were MACE (including hospital admission) changes in LVEF category and mortality. 173,195 individuals with T2D were identified in 2013, median age 66 yrs. 6,725 (3.88% of the overall sample) developed HF in 2014 or 2015, median age 74 yrs. As Sankey plot visualizations show, 34.4% of the patients had MACE over the course of five years; 24.5% were still alive and 9.9% died from CV-death. Further 33% died of other causes. Myocardial infarct was the most common MACE, followed by stroke (32%), hospital admission for HF (28%) and CV death (7%). 40% of patients were never admitted to a hospital over the study period. Exploratory analyses identified 5,282 HFpEF patients (78.54%) and 1,443 HFrEF patients (21.46%). Survival after 5 years in HFpEF patients was 71%, in HFrEF patients 29%. After five years 3,430 (90%) surviving patients were still in HFpEF and 399 (10%) in HFrEF. This analysis provides disease progression insights in T2D patients who developed HF in Germany. The sample is representative for the country and numbers can be extrapolated to the overall German SHI population. A significant number of patients die within 5 years of initial diagnosis. As echo diagrams are not available in German insurance claims, validity of the predicted LVEF cannot be assessed. Further research featuring real world LVEF score validation would be highly desirable. Beyond therapeutic care, digital solutions for closer monitoring of these patients may improve the outcome of these patients. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Sanofi

Blood pressure target achievement in older adults with hypertension and chronic heart failure with preserved ejection fraction: the impact of adipose tissue function

Objective. To assess the impact of adipose tissue dysfunction for target blood pressure levels achieving in arterial hypertension (AH) and chronic heart failure with preserved left ventricular ejection fraction (HFpEF) in real clinical practice.Materials and methods. We examined 91 elderly patients (&gt; 75 y.o.) with AH and HFpEF during hospital admission. The mass and mass fraction of adipose tissue, serum levels of adipokines (adiponectin, leptin) and proinflammatory cytokines (TNFa and IL6) were assessed. Steady normotension at discharge was used as a marker of the target blood pressure level achievement possibility.Results. By the time of the planned discharge, stable normotension was recorded in 24.2% of patients. In senile patients with failure to achieve normotension, isolated systolic AH was most common - 55.1%. Patients with persistent hypertension at the time of the planned discharge were characterized by a low ability of adipose tissue to secrete adiponectin: 0.05 (0.03; 0.12) vs 0.37 (0.12; 0.5) μg/mL/kg (p = 0.037 ). The minimum values of adiponectin (corrected for adipose tissue mass) were in patients with systolic-diastolic AH (0.04 (0.03; 0.06) μg/ml/kg, Jonkhier-Terpstra test, p = 0.033). A regression model for achieving normotension in senile patients with HFpEF was built with a total percentage of correct classifications of 93.8% before bootstrap and 95.8% after: the maximum values of the Wald statistics were achieved with respect to the predictors "adiponectin", "TNF-a" and "heart rate".Conclusion. The development of adipose tissue dysfunction, accompanied by a decrease in the “rescue hormone” adiponectin synthesis, is associated with the failure to achieve normotension during medication of the inpatient treatment in senile patients with AH and HFpEF.

Resistance Training in Patients With Coronary Artery Disease, Heart Failure, and Valvular Heart Disease: A REVIEW WITH SPECIAL EMPHASIS ON OLD AGE, FRAILTY, AND PHYSICAL LIMITATIONS.

Current guidelines recommend individually adapted resistance training (RT) as a part of the exercise regime in patients with cardiovascular diseases. The aim of this review was to provide insights into current knowledge and understanding of how useful, feasible, safe, and effective RT is in patients with coronary artery disease (CAD), heart failure (HF), and valvular heart disease (VHD), with particular emphasis on the role of RT in elderly and/or frail patients. A review based on an intensive literature search: systematic reviews and meta-analyses published in 2010 or later; recent studies not integrated into meta-analyses or systematic reviews; additional manual searches. The results highlight the evaluation of effects and safety of RT in patients with CAD and HF with reduced ejection fraction (HFrEF) in numerous meta-analyses. In contrast, few studies have focused on RT in patients with HF with preserved ejection fraction (HFpEF) or VHD. Furthermore, few studies have addressed the feasibility and impact of RT in elderly cardiac patients, and data on the efficacy and safety of RT in frail elderly patients are limited. The review results underscore the high prevalence of age-related sarcopenia, disease-related skeletal muscle deconditioning, physical limitations, and frailty in older patients with cardiovascular diseases (CVD). They underline the need for individually tailored exercise concepts, including RT, aimed at improving functional status, mobility, physical performance and muscle strength in older patients. Furthermore, the importance of the use of assessment tools to diagnose frailty, mobility/functional capacity, and physical performance in the elderly admitted to cardiac rehabilitation is emphasized.

Contractile Reserve in Heart Failure with Preserved Ejection Fraction.

Background: Diastolic stress echocardiography (SE) is useful for confirming the diagnosis of heart failure with preserved left ventricular ejection fraction (HFpEF) when it is uncertain. The aim of this study was to assess the value of new echocardiographic parameters during diastolic SE in patients with dyspnea and suspected HFpEF. Methods: Sixty-two patients with exertional dyspnea and inconclusive rest echocardiography for a diagnosis of HFpEF were enrolled. Exercise SE was performed in all patients. Contractile reserve (LVCR) was assessed by measuring: 1. changes in the left ventricular ejection fraction (LVEF) between rest and peak stress; 2. stress-to-rest ratio of force (force was defined as the ratio between systolic arterial pressure and left ventricular end-systolic volume); and 3. mechanical reserve, defined as the change in systolic strain (GLS) between rest and peak stress. Results: Diagnosis of HFpEF was performed by SE in 26 patients. Comparing patients with a diagnosis of HFpEF (group A) to patients with other causes of dyspnea (group B), we found a significant increase in the E/e’ ratio in group A at peak stress. LV GLS was significantly reduced in group A compared to group B at rest and stress (p value 0.01 at rest; p value 0.04 at stress). At peak stress, GLS did not significantly increase in group A, while it increased in group B (p value 0.04). LVEF increased significantly in both groups. Conclusion: Patients with HFpEF have impaired LVCR when assessed using GLS. Thus, the assessment of mechanical reserve could give additional diagnostic information during stress tests in patients with HFpEF.

Treatment of patients with heart failure and preserved ejection fraction: reliance on clinical phenotypes

The article discusses the problem of improving the effectiveness of treatment of heart failure with preserved left ventricular ejection fraction (HFpEF). The relative "failure" of early studies with renin-angiotensin-aldosterone system inhibitors was largely due to the lack of understanding that patients with HFpEF represent a heterogeneous group with various etiological factors and pathogenetic mechanisms of the disease. Therefore, the so-called personalized approach should be used in the treatment of these patients. This approach is based on the identification of clearly defined disease phenotypes, each characterized by a set of demographic, pathogenetic, and clinical characteristics. Based on the literature and own experience, the authors consider four main phenotypes of HFpEF: 1) phenotype with brain natriuretic peptide "deficiency" syndrome associated with moderate/severe left ventricular hypertrophy; 2) cardiometabolic phenotype; 3) phenotype with mixed pulmonary hypertension and right ventricular failure; and 4) cardiac amyloidosis phenotype. In the treatment of patients with phenotype 1, it seems preferable to use the valsartan + sacubitril (possibly in combination with spironolactone) combination treatment; with phenotype 2, the empagliflozin treatment is the best; with phenotype 3, the phosphodiesterase type 5 inhibitor sildenafil; and with phenotype 4, transthyretin stabilizers. Certain features of different phenotypes overlap and may change as the disease progresses. Nevertheless, the isolation of these phenotypes is advisable to prioritize the choice of drug therapy. Thus, the diuretic treatment (preferably torasemide) should be considered in the presence of congestion, regardless of the HFpEF phenotype; the valsartan + sacubitril and spironolactone treatment is appropriate not only in the shortage of brain natriuretic peptide but also in the presence of concentric left ventricular hypertrophy (except for the amyloidosis phenotype); and the treatment with empagliflozin and statins may be considered in all situations where pro-inflammatory mechanisms are involved.

Left ventricular dysfunction with preserved ejection fraction: the most common left ventricular disorder in chronic kidney disease patients.

Chronic kidney disease (CKD) is a risk factor for premature cardiovascular disease. As kidney function declines, the presence of left ventricular abnormalities increases such that by the time kidney replacement therapy is required with dialysis or kidney transplantation, more than two-thirds of patients have left ventricular hypertrophy. Historically, much research in nephrology has focussed on the structural and functional aspects of cardiac disease in CKD, particularly using echocardiography to describe these abnormalities. There is a need to translate knowledge around these imaging findings to clinical outcomes such as unplanned hospital admission with heart failure and premature cardiovascular death. Left ventricular hypertrophy and cardiac fibrosis, which are common in CKD, predispose to the clinical syndrome of heart failure with preserved left ventricular ejection fraction (HFpEF). There is a bidirectional relationship between CKD and HFpEF, whereby CKD is a risk factor for HFpEF and CKD impacts outcomes for patients with HFpEF. There have been major improvements in outcomes for patients with heart failure and reduced left ventricular ejection fraction as a result of several large randomized controlled trials. Finding therapy for HFpEF has been more elusive, although recent data suggest that sodium-glucose cotransporter 2 inhibition offers a novel evidence-based class of therapy that improves outcomes in HFpEF. These observations have emerged as this class of drugs has also become the standard of care for many patients with proteinuric CKD, suggesting that there is now hope for addressing the combination of HFpEF and CKD in parallel. In this review we summarize the epidemiology, pathophysiology, diagnostic strategies and treatment of HFpEF with a focus on patients with CKD.