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Left ventricular (LV) diastolic dysfunction, atrial fibrillation (AF), and heart failure with preserved ejection fraction (HFpEF) share common risk factors and are closely related to one another and to adverse cardiovascular events. Exertional dyspnoea in patients with AF should trigger a comprehensive LV diastolic function evaluation since AF frequently precedes incident HFpEF. An echocardiographic assessment of LV diastolic function in patients with AF is challenging, mainly because of variability in cycle length, the absence of atrial contraction, and the frequent occurrence of left atrial enlargement regardless of LV filling pressures (LVFPs). The algorithm of the 2016 recommendations for the evaluation of LV diastolic function cannot be directly applied in this setting. This review discusses the modalities available for diastolic function assessment and HFpEF diagnosis in patients with AF. Based on currently available data, a reasonable clinical target of diastolic function evaluation in AF would be to reach a binary conclusion: LVFP elevated or not. Recently, a two-step algorithm that combined several echocardiographic parameters plus the inclusion of body mass index has been proposed to differentiate normal from elevated LVFP in patients with AF. The echocardiographic evaluation must be complemented by a thorough clinical evaluation along with natriuretic peptides and cardiac catheterization in selected cases. If a diagnosis of HFpEF cannot be ascertained, a close follow-up for timely identification of diastolic dysfunction markers, along with monitoring and correction of modifiable risk factors, is recommended., Competing Interests: Conflict of interest: B.A.P. has received research support and speaker honoraria from GE Healthcare. C.C.B. has received speaker honoraria from GE Healthcare. A.C.P. and F.G.C. report no conflicts., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Heart failure with preserved ejection fraction (HFpEF) is a major healthcare problem that is raising in prevalence. There has been a shift in HpEF management towards early diagnosis and phenotype-specific targeted treatment. However, the diagnosis of HFpEF remains a challenge due to the lack of universal criteria and patient heterogeneity. This review aims to provide a comprehensive assessment of the diagnostic workup of HFpEF, highlighting the role of echocardiography in HFpEF phenotyping., Competing Interests: Conflict of interest: GE Healthcare has provided research facilities to Rennes University Hospital through a contract with Erwan Donal and CHU-Rennes., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

This article reviews and discusses non-myocardial disorders that represent diagnostic challenges when evaluating patients for suspected heart failure with preserved left ventricular ejection fraction. This includes pre-capillary pulmonary hypertension, which is important to differentiate from post-capillary hypertension caused by left-sided heart disease. The impact of electrical disorders on LV diastolic function is also reviewed, and includes a discussion of left bundle branch, which has both a direct effect on LV diastolic function, as well as a long-term effect due to remodelling. Furthermore, evaluation of diastolic function in patients with atrial fibrillation is discussed. Pericardial diseases are reviewed as well as effects of a normal pericardium on diastolic function in failing hearts. Finally, the article reviews how valvular diseases impact LV diastolic function., Competing Interests: Conflict of interest: O.A.S. is co-inventor of ‘Method for myocardial segment work analysis’, is patent inventor of ‘Estimation of blood pressure in the heart’, and has received one speaker honorarium from GE Healthcare., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Competing Interests: Conflict of interest: O.A.S. is a co-inventor of ‘Method for myocardial segment work analysis’, has a patent on ‘Estimation of blood pressure in the heart’, and has received one speaker honorarium from GE Healthcare.

Introduction: Pulmonary arterial hypertension and left ventricular diastolic dysfunction are associated with significant morbidity and mortality in systemic sclerosis. N-terminal pro-brain natriuretic peptide has been proposed as part of composite screening algorithms for pulmonary arterial hypertension. Our aim was to assess the prevalence of pulmonary hypertension and diastolic dysfunction, and evaluate their association with serum N-terminal pro-brain natriuretic peptide in systemic sclerosis patients., Methods: Patients with systemic sclerosis were prospectively enrolled to undergo N-terminal pro-brain natriuretic peptide testing and transthoracic echocardiography at a tertiary Australian centre from January to October 2022. We collected demographic and transthoracic echocardiography variables including pulmonary hypertension estimated by tricuspid regurgitant velocity and diastolic dysfunction assessed by the ASE/EACVI 2016 guidelines. Pearson's correlation coefficient was used to evaluate association between N-terminal pro-brain natriuretic peptide and echocardiographic parameters., Results: Sixty-one patients were enrolled (median age = 62 years (interquartile range = 55-69 years); 84% female). Two-thirds of patients had limited systemic sclerosis (40/61). Five patients (8%) had high likelihood of pulmonary hypertension by transthoracic echocardiography. Seven patients (11%) had diastolic dysfunction; however, seven patients (11%) had indeterminate diastology. Six patients underwent right heart catheterisation, with five patients diagnosed with pulmonary hypertension. N-terminal pro-brain natriuretic peptide in patients with pulmonary hypertension or diastolic dysfunction was significantly higher (median = 207 and 226 pg/mL, respectively) compared to patients without either condition (median = 69 pg/mL, p = 0.01). N-terminal pro-brain natriuretic peptide showed a statistically significant although limited correlation with estimated pulmonary pressures measured by tricuspid regurgitant velocity (r = 0.44, p = 0.002) and left ventricular filling pressures (r = 0.27, p = 0.04)., Conclusion: Pulmonary hypertension and diastolic dysfunction are both observed in systemic sclerosis. N-terminal pro-brain natriuretic peptide is associated with both conditions; however, it cannot distinguish between the two disease processes. Right heart catheterisation may be required to make this distinction., Competing Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship and/or publication of this article: M.N. holds an NHMRC Investigator Grant (GNT1176538) and has received research support and/or honoraria from Janssen and Boehringer Ingelheim. The other authors have disclosed no conflicts of interest., (© The Author(s) 2024.)

Background: Prematurely born adults have increased risk for cardiovascular disease. There are limited cardiac data on US-born preterm individuals. We aimed to determine whether adolescents and adults born prematurely have altered left ventricular (LV) structure and function, and to interrogate diastolic function using isometric handgrip exercise., Methods and Results: Adolescents and adults born moderately to extremely preterm (≤32 weeks gestation or <1500 g birth weight) were recruited from the Parkland Health Neonatal Intensive Care Unit Registry. Full-term participants were recruited from the local area. Study procedures included anthropometrics and vitals, handgrip testing, and echocardiography performed at rest and during isometric handgrip exercise. Data were reported as mean±SD. The study enrolled 107 preterm and 48 term participants. Preterm participants (gestational age: 29.5±2.5 weeks) were shorter with higher body mass index ( P <0.001) compared with term participants. Preterm participants exhibited smaller LV end-diastolic volume index (50.8±10.1 versus 56.9±10.0 mL/m 2 , P <0.001), LV stroke volume index (29.6±6.0 versus 34.1±6.5 mL/m 2 , P <0.001), and LV mass index (67.2±13.1 versus 73.3±14.2 g/m 2 , P =0.002) compared with term individuals. Preterm participants also had subclinical reductions in LV peak systolic tissue velocity and peak early diastolic tissue velocity lateral at rest. Isometric handgrip exercise promoted a reduction in diastolic function and an increase in hemodynamic measures, but changes during isometric handgrip exercise were similar between groups., Conclusions: Adolescents and adults born preterm exhibit overall normal cardiac function despite smaller cardiac volumes and mass compared with individuals born full term. Effects are most pronounced at the lowest gestational ages.

Heart failure with preserved ejection fraction (HFpEF) and atrial fibrillation (AF) are comorbid conditions that are increasingly prevalent and have a high socioeconomic burden. This article discusses their shared pathophysiology, focusing on the triad of hypertension, obesity, and aging. We highlight the misperception that pharmacological heart rate lowering is beneficial, which has resulted in an overprescription of β-blockers in HFpEF and AF. In contrast, heart rate modulation through accelerated pacing provides hemodynamic and structural advantages, which have yielded significant improvements in quality of life, physical activity, and AF burden in the personalized pacing for diastolic dysfunction and heart failure with preserved ejection fraction (myPACE) trial of patients with preclinical or overt HFpEF., Competing Interests: Disclosures Drs Habel, Meyer, and Lustgarten have received research funding from Medtronic. Dr Meyer has received research funding from the Engdahl Family Foundation. Dr Meyer and the University of Vermont have licensed patents for the use of pacemakers for the prevention and treatment of atrial fibrillation and heart failure with preserved ejection fraction. Dr Infeld reports no conflicts of interest., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Despite a rigorous screening process, including cardiac catheterization, a subset of patients with a single right ventricle (SRV) demonstrates suboptimal short-term outcomes after the Fontan operation. The goal of this study was to perform a comprehensive assessment of diastolic function in pre-Fontan patients with an SRV using invasive reference-standard measures and determine their associations with post-Fontan outcomes., Methods and Results: Children aged 2 to 6 years with SRV physiology undergoing pre-Fontan heart catheterization were recruited prospectively. Patients were divided into those who had an optimal or suboptimal outcome. A suboptimal outcome was defined as length of stay ≥14 days or heart transplant/cardiac death in first year after Fontan. Patients underwent pressure-volume loop analysis using reference-standard methods. The measure of ventricular stiffness, β, was obtained via preload reduction. Cardiac magnetic resonance imaging for extracellular volume and serum draws for matrix metalloproteinase activity were performed. Of 19 patients with an SRV, 9 (47%) had a suboptimal outcome. Mean age was 4.2±0.7 years. Patients with suboptimal outcomes had lower ventricular stiffness (0.021 [0.009-0.049] versus 0.090 [0.031-0.118] mL -1 ; P =0.02), lower extracellular volume (25% [28%-32%] versus 31% [28%-33%]; P =0.02), and lower matrix metalloproteinase-2 (90 [79-104] versus 108 [79-128] ng/mL; P =0.01) compared with patients with optimal outcomes. The only invasive measure that had an association with suboptimal outcome was β ( P =0.038)., Conclusions: Patients with an SRV with suboptimal outcome after the Fontan operation had lower ventricular stiffness and evidence of maladaptive extracellular matrix metabolism compared with patients with optimal outcome. This appears to be a novel phenotype that may have important clinical implications and requires further study.

Abstract Background This cardiovascular magnetic resonance (CMR) study investigates the impact of trabeculae and papillary muscles (TPM) on diastolic function parameters by differentiation of the time-volume curve. Differentiation causes additional problems, which is overcome by standardization. Methods Cine steady-state free-precession imaging at 1.5 T was performed in 40 healthy volunteers stratified for age (age range 7–78y). LV time-volume curves were assessed by software-assisted delineation of endocardial contours from short axis slices applying two different methods: (1) inclusion of TPM into the myocardium and (2) inclusion of TPM into the LV cavity blood volume. Diastolic function was assessed from the differentiated time-volume curves defining the early and atrial peaks, their filling rates, filling volumes, and further dedicated diastolic measures, respectively. Results Only inclusion of TPM into the myocardium allowed precise assessment of early and atrial peak filling rates (EPFR, APFR) with clear distinction of EPFR and APFR expressed by the minimum between the early and atrial peak (EAmin) (100% vs. 36% for EAmin

Abstract Aims In healthy subjects, adrenergic stimulation augments left ventricular (LV) long‐axis shortening and lengthening, and increases left atrial (LA) to LV intracavitary pressure gradients in early diastole. Lower increments are observed in patients with heart failure with preserved ejection fraction (HFpEF). We hypothesized that exercise in HFpEF would further impair passive LV filling in early‐mid diastole, during conduit flow from pulmonary veins. Methods and results Twenty HFpEF patients (67.8 ± 9.8 years; 11 women), diagnosed using 2007 ESC recommendations, underwent ramped semi‐supine bicycle exercise to submaximal target heart rate (∼100 bpm) or symptoms. Seventeen asymptomatic subjects (64.3 ± 8.9 years; 7 women) were controls. Simultaneous LA and LV volumes were measured from pyramidal 3D‐echocardiographic full‐volume datasets acquired from an apical window at baseline and during stress, together with brachial arterial pressure. LA conduit flow was computed from the increase in LV volume from its minimum at end‐systole to the last frame before atrial contraction (onset of the P wave), minus the reduction in LA volume during the same time interval; the difference was integrated and expressed as average flow rate, according to a published formula. The slope of single‐beat preload recruitable stroke work (PRSW) quantified LV inotropic state. 3D LV torsion (rotation of the apex minus rotation of the base divided by LV length) was also measurable, both at rest and during stress, in 10 HFpEF patients and 4 controls. There were divergent responses in conduit flow rate, which increased by 40% during exercise in controls (+17.8 ± 37.3 mL/s) but decreased by 18% in patients with HFpEF (−9.6 ± 42.3 mL/s) (P = 0.046), along with congruent changes (+1.77 ± 1.13°/cm vs. −1.94 ± 2.73°/cm) in apical torsion (P = 0.032). Increments of conduit flow rate and apical torsion during stress correlated with changes in PRSW slope (P = 0.003 and P = 0.006, respectively). Conclusions In HFpEF, conduit flow rate decreases when diastolic dysfunction develops during exercise, in parallel with changes in LV inotropic state and torsion, contributing to impaired stroke volume reserve. Conduit flow is measurable using 3D‐echocardiographic full‐volume atrio‐ventricular datasets, and as a marker of LV relaxation can contribute to the diagnosis of HFpEF.

Introduction. Increased arterial stiffness is one of the key links in the formation of cardiovascular pathology in older age groups. At the same time, the effect of vascular stiffness on myocardial function in cardiac patients with frailty remains insufficiently studied.Aim of study. Тo analyze the data of arterial stiffness and diastolic function of left ventricle (LV) in patients older than 65 years with arterial hypertension and frailty.Materials and methods. The study included 90 outpatient and inpatient patients older than 65 years with the presence of arterial hypertension. All patients were divided into two groups: with the presence and absence of frailty. To identify frailty, we used the questionnaire “Age is not a hindrance”, a short battery of physical activity tests. Methods of volumetric sphygmometry, echocardiography, including tissue Doppler were used. The obtained data were analyzed using a package of statistical programs.Results. The results of a comparative simultaneous non-randomized descriptive study of two groups of patients are presented. The study found that the systolic function, diastolic dysfunction of the left ventricle by the type of slowing down of LV relaxation in both groups did not significantly differ in their indicators. In the group of patients with frailty, LV diastolic dysfunction was significantly more often detected by the type of pseudonormalization – with an increase in filling pressure. When analyzing data of arterial stiffness, differences were obtained in both groups in the left cardio-ankle vascular index (LCAVI), systolic blood pressure (LB SAD), pulse pressure (LB PD) in the left shoulder area, and the delta of average blood pressure in the left ankle area (LA% IDA), which were significantly higher in patients with frailty.Conclusion. In the group of patients with hypertension older than 65 years with frailty, a violation of the LV diastolic function by the type of pseudonormalization with an increase in filling pressure prevails. An increase in filling pressure in the group of patients older than 65 years with hypertension and the presence of frailty is associated with an increase in the complex of indicators characterizing arterial stiffness – the cardio-ankle vascular index, systolic blood pressure, pulse pressure in the left shoulder area, the delta of average blood pressure in the left ankle area.

Abstract Background Identification of the effective subtypes of treatment for heart failure (HF) is an essential topic for optimizing treatment of the disorder. We hypothesized that the beneficial effect of SGLT2 inhibitors (SGLT2i) on the levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) might depend on baseline diastolic function. To elucidate the effects of SGLT2i in type 2 diabetes mellitus (T2DM) and chronic HF we investigated, as a post-hoc sub-study of the CANDLE trial, the effects of canagliflozin on NT-proBNP levels from baseline to 24 weeks, with the data stratified by left ventricular (LV) diastolic function at baseline. Methods Patients (n = 233) in the CANDLE trial were assigned randomly to either an add-on canagliflozin (n = 113) or glimepiride treatment groups (n = 120). The primary endpoint was a comparison between the two groups of the changes from baseline to 24 weeks in NT-pro BNP levels, stratified according to baseline ventricular diastolic function. Results The change in the geometric mean of NT-proBNP level from baseline to 24 weeks was 0.98 (95% CI 0.89–1.08) in the canagliflozin group and 1.07 (95% CI 0.97–1.18) in the glimepiride group. The ratio of change with canagliflozin/glimepiride was 0.93 (95% CI 0.82–1.05). Responder analyses were used to investigate the response of an improvement in NT-proBNP levels. Although the subgroup analyses for septal annular velocity (SEP-e′) showed no marked heterogeneity in treatment effect, the subgroup with an SEP-e′

Depressive disorders are a leading cause of disability and are globally pervasive. It is estimated that 80% of depression occurs in low-income and middle-income countries. Depression is associated with worse outcomes in patients with cardiac disease including heart failure (HF); however, mechanistic understanding to explain heightened risk in HF remains poorly characterized. We examined the association between depressive symptoms and cardiac structure and function by transthoracic echocardiography. We selected a random sample of adult participants in Puno and Pampas de San Juan de Miraflores, Peru, from the CRONICAS cohort study. Depression symptoms were self-reported and measured with the Center for Epidemiological Studies Depression Scale in 2010. Participants underwent transthoracic echocardiography in 2014. Multivariable linear regression was used to examine the relationship between depressive symptoms and echocardiographic measures of cardiac structure and function and was adjusted for relevant covariates. Three hundred and seventy-three participants (mean age 56.7 years, 57% female) were included in this analysis of which 91 participants (24%) had clinically significant depressive symptoms. After adjustment, clinically significant depressive symptoms were associated with a reduced diastolic relaxation velocity compared to non-depressed subjects (–0.72 cm/s, 95% CI –1.21 to –0.24, p = 0.004). Other differences between depressed and non- depressed participants were less obvious. In conclusion, clinically significant depressive symptoms were associated with a lower septal e’ velocity in the Peruvian population. Depressive symptoms were not obviously associated with other abnormalities in cardiac structure or function.

Heart transplant (HTx) still represents the most effective therapy for end-stage heart failure, with a median survival time of 10 years. The transplanted heart shows peculiar physiology due to the profound alterations induced by the operation, which inevitably influences several echocardiographic parameters assessed during these patients’ follow-ups. With these premises, the diastolic function is one of the main aspects to take into consideration. The left atrium (LA) plays a key role in this matter, and that same chamber is significantly impaired with the transplant, with different degrees of altered function based on the surgical technique. Therefore, the traditional echocardiographic evaluation of diastolic function applied to the general population might not properly reflect the physiology of the graft. This review attempts to provide current evidence on diastolic function in HTx starting from defining its different physiology and how the standard echocardiographic parameters might be affected to its prognostic role. Furthermore, based on the experience of our center and the available evidence, we proposed an algorithm that might help clinicians distinguish from actual diastolic dysfunction from a normal diastolic pattern in HTx population.

BackgroundThe association between arterial stiffness and left ventricular (LV) diastolic function has been demonstrated in several studies, but the samples size in those studies was small. This study aims to verify this issue in a large number of study subjects.MethodsA total of 7,013 consecutive participants (mean age 60.6 years and 43.3% female) who underwent both baPWV and transthoracic echocardiography were retrospectively analyzed. Subjects with significant cardiac structural abnormalities were excluded.ResultsThere were significant correlations of baPWV with septal e′ velocity (r = – 0.408; P < 0.001), septal E/e′ (r = 0.349; P < 0.001), left atrial volume index (LAVI) (r = 0.122; P < 0.001) and maximal velocity of tricuspid valve regurgitation (TR Vmax) (r = 0.322; P < 0.001). The baPWV values increased proportionally with an increase in the number of LV diastolic indices meeting LV diastolic dysfunction criteria (P-for-trend < 0.001). In multivariable analyses with adjustment for confounding effects of various clinical covariates, higher baPWV was independently associated with septal e′ < 7 (odds ratio [OR], 1.30; 95% confidence interval [CI] 1.20–1.60; P < 0.001), septal E/e′ ≥ 15 (OR, 1.46; 95% CI, 1.21–1.78; P < 0.001), and TR Vmax > 2.8 m/s (OR, 1.60; 95% CI, 1.23–2.09; P < 0.001) but not with LAVI ≥ 34 mL/m2 (OR, 0.89; 95% CI, 0.76–1.03; P = 0.123).ConclusionsIncreased arterial stiffness, as measured by baPWV, was associated with abnormal diastolic function parameters in a large number of study participants, providing strong evidence to the existing data about ventricular-vascular coupling.

Background Whether coronary artery disease (CAD) is a significant risk factor for heart failure (HF) with preserved ejection fraction (HFpEF) is unclear. Methods and Results Among 9902 participants in the ARIC (Atherosclerosis Risk in Communities) study, we assessed the association of incident CAD with subsequent incident HFpEF (left ventricular ejection fraction [≥50%]) and HF with reduced ejection fraction (HFrEF; left ventricular ejection fraction 1 year post‐CAD event, adjusted incidence of HFrEF and HFpEF were similar (7.2 [95% CI, 5.2–10.0] and 6.7 [4.8–9.2] per 1000 person‐years, respectively) and CAD remained predictive of both (HFrEF: hazard ratio, 2.76 [95% CI, 1.99–3.84]; HFpEF: 1.85 [1.35–2.54]) after adjusting for demographics and common comorbidities. Among 4779 HF‐free participants at Visit 5 (2011–2013), the 490 with prevalent CAD had lower left ventricular ejection fraction and higher left ventricular mass index, E/e’, and left atrial volume index (all P

The assessment of diastolic function has received great interest in order to comprehend its crucial role in the pathophysiology of heart failure and for the early identification of cardiac events. Silent changes in the intraventricular flow (IVF) dynamics occur before the deterioration of the cardiac wall, although they cannot be detected using conventional echocardiography. Collective information on left ventricular (LV) pressures throughout the cardiac cycle has great value when dealing with patients with altered hemodynamics. Accurate pressure measurement inside the ventricle can be obtained by invasive methods to determine the LV diastolic pressures, which reflect the myocardial relaxation and compliance. However, catheterization is only feasible in the laboratory setting and is not suitable for clinical use due to its disadvantages. In contrast, echocardiography is simple, safe, and accessible. Color M-mode echocardiography (CMME) is an advanced cardiac evaluation technique that can measure the intraventricular pressure differences (IVPDs) and intraventricular pressure gradients (IVPGs) based on the Doppler shift of the IVF. Recently, the assessment of IVPD and IVPG has gained growing interest in the cardiovascular literature in both animal and human studies as a non-invasive method for the early diagnosis of cardiac dysfunctions, especially diastolic ones. The usability of IVPD and IVPG has been reported in various surgically induced heart failure or pharmacologically altered cardiac functions in rats, dogs, cats, and goats. This report aims to give an overview of the current studies of CMME-derived IVPD and IVPG in animal studies and its feasibility for clinical application in veterinary practice and to provide the prospects of the technique’s ability to improve our understanding.

Aims: We investigated the effects of CD34+ cell therapy in patients with heart failure with preserved ejection fraction (HFpEF).Methods and Results: In a prospective pilot study, we enrolled 30 patients with HFpEF. In Phase 1, patients were treated with medical therapy for 6 months. Thereafter, all patients underwent CD34+ cell transplantation. Using electroanatomical mapping, we measured local mechanical diastolic delay and myocardial viability to guide the targeting of cell injections. Patients were followed for 6 months after cell transplantation (Phase 2), and the primary endpoint was the difference in change in E/e' between Phase 1 and Phase 2. In Phase 1, the decrease in E/e' was significantly less pronounced than in Phase 2 (-0.33 ± 1.72 vs. -3.77 ± 2.66, p = 0.001). During Phase 1, there was no significant change in global systolic strain (GLS; from -12.5 ± 2.4% to -12.8 ± 2.6%, p = 0.77), N-terminal pro-B-type natriuretic peptide (NT-proBNP; from 1463 ± 1247 pg/ml to 1298 ± 931 pg/ml, p = 0.31), or 6-min walk test (6MWT; from 391 ± 75 m to 402 ± 93 m, p = 0.42). In Phase 2, an improvement was noted in NT-proBNP (from 1298 ± 931 pg/ml to 887 ± 809 pg/ml, p = 0.02) and 6MWT (from 402 ± 93 m to 438 ± 72 m, p = 0.02). Although GLS did not change significantly in Phase 2 (from -12.8 ± 2.6% to -13.8 ± 2.7%, p = 0.36), we found improved local systolic strain at cell injection sites (-3.4 ± 6.8%, p = 0.005).Conclusions: In this non-randomized trial, transendocardial CD34+ cell therapy in HFpEF was associated with an improvement in E/e', NT-proBNP, exercise capacity, and local myocardial strain at the cell injection sites.Clinical Trial Registration: ClinicalTrials.gov NCT02923609. [ABSTRACT FROM AUTHOR]

Hypertension is an important risk factor in the pathogenesis of diastolic dysfunction. Growing evidence indicates that glucose metabolism plays an essential role in diastolic dysfunction. TP53‐induced glycolysis and apoptosis regulator (TIGAR) has been shown to regulate glucose metabolism and heart failure (HF). In the present study, we investigated the role of TIGAR in diastolic function and cardiac fibrosis during pressure overload (PO)‐induced HF. WT mice subjected to transverse aortic constriction (TAC), a commonly used method to induce diastolic dysfunction, exhibited diastolic dysfunction as evidenced by increased E/A ratio and E/E′ ratio when compared to its sham controls. This was accompanied by increased cardiac interstitial fibrosis. In contrast, the knockout of TIGAR attenuated PO‐induced diastolic dysfunction and interstitial fibrosis. Mechanistically, the levels of glucose transporter Glut‐1, Glut‐4, and key glycolytic enzyme phosphofructokinase 1 (PFK‐1) were significantly elevated in TIGAR KO subjected to TAC as compared to that of WT mice. Knockout of TIGAR significantly increased fructose 2,6‐bisphosphate levels and phosphofructokinase activity in mouse hearts. In addition, PO resulted in a significant increase in perivascular fibrosis and endothelial activation in the WT mice, but not in the TIGAR KO mice. Our present study suggests a necessary role of TIGAR‐mediated glucose metabolism in PO‐induced cardiac fibrosis and diastolic dysfunction. [ABSTRACT FROM AUTHOR]

Some patients with pacemakers present with first-degree atrioventricular (AV) block. To avoid right ventricular (RV) pacing, preserving intrinsic AV conduction as much as possible is recommended. However, there is no clear cutoff AV interval to determine whether intrinsic AV conduction should be preserved or RV pacing should be delivered. This study aimed to compare a pacing mode-preserving, intrinsic AV conduction with the DDD mode delivering RV pacing in terms of echocardiographic parameters in patients with first-degree AV block and to investigate whether RV pacing induces heart failure (HF). Stroke volume (SV) was measured to determine the optimal AV delay with the intrinsic AV conduction rhythm and the DDD pacing delivering RV pacing. Echocardiographic evaluation was performed for 6-month follow-up period. Seventeen patients were studied. At baseline, mean intrinsic PQ interval was 250 ± 40 ms. SV was greater with RV pacing with optimal AV delay of 160 ms than with intrinsic AV conduction rhythm in all patients. Therefore, pacemakers were set to the DDD to deliver RV pacing. During follow-up, seven patients developed HF. Mean baseline E/E′ ratio in patients who developed HF (HF group) during RV pacing was higher than in patients without HF (non = HF group; 17.9 ± 8 versus 11.5 ± 2, P = 0.018) Even within HF group patients without a high baseline E/E′ ratio, it increased with RV pacing (22.2 ± 6 versus 11.6 ± 2; P < 0.001). In patients with pacemaker and first-degree AV block, RV pacing with the optimal AV delay of 160 ms increased SV. However, the risk of HF may be increased with RV pacing if the E/Eʹ ratio is > 15 during intrinsic AV conduction or RV pacing. RV pacing should be avoided in patients with high E/Eʹ ratio under intrinsic AV conduction or RV pacing. [ABSTRACT FROM AUTHOR]

Aim: We present the baseline characteristics of the PREFERS Stockholm epidemiological study on the natural history and course of new onset heart failure (HF) aiming to improve phenotyping focusing on HF with preserved left ventricular ejection fraction (HFpEF) pathophysiology. Methods and results: New onset HF patients diagnosed in hospital or at outpatient HF clinics were included at five Stockholm hospitals 2015–2018 and characterized by N‐terminal pro brain natriuretic peptide (NT‐proBNP), biomarkers, echocardiography, and cardiac magnetic resonance imaging (subset). HFpEF [left ventricular ejection fraction (LVEF) ≥ 50%] was compared with HF with mildly reduced LVEF (HFmrEF; LVEF 41–49%) and with HF with reduced LVEF (HFrEF; LVEF ≤ 40%). We included 547 patients whereof HFpEF (n = 137; 25%), HFmrEF (n = 61; 11%), and HFrEF (n = 349; 64%). HFpEF patients were older (76; 70–81 years; median; interquartile range) than HFrEF (67; 58–74; P < 0.001), more often women (49% vs. 30%; P < 0.001), and had significantly higher comorbidity burden. They more often had atrial fibrillation, hypertension, and renal dysfunction. NT‐proBNP was lower in HFpEF (896; 462–1645 ng/L) than in HFrEF (1160; 563–2370; P = 0.005). In HFpEF, left ventricular (LV) diameters and volumes were smaller (P < 0.001) and septal and posterior wall thickness and relative wall thickness higher (P < 0.001). E/é ≥ 14 was present in 26% of HFpEF vs. 32% of HFrEF (P = 0.017) and left atrial volume index > 34 mL/m2 in 57% vs. 61% (P = 0.040). HFmrEF patients were intermediary between HFpEF and HFrEF for LV mass, LV volumes, and RV volumes but had the highest proportion of left ventricular hypertrophy and the lowest proportion of elevated E/é. Conclusions: Phenotype data in new onset HF patients recruited in a broad clinical setting showed that 25% had HFpEF, were older, more often women, and had greater comorbidity burden. PREFERS is well suited to further explore biomarker and imaging components of HFpEF pathophysiology and may contribute to the emerging knowledge of HF epidemiology. Clinical trial registration: Clinicaltrials.gov identifier: NCT03671122. [ABSTRACT FROM AUTHOR]

Objective. Right ventricular (RV) dysfunction after coronary artery bypass grafting (CABG) is associated with increased mortality and morbidity. In previous studies, the parameters of RV systolic function were mainly assessed, while the dynamics of RV diastolic function after surgery was practically not studied. The aim of this study was to study the dynamics of indicators of systolic and diastolic RV function after CABG as well as to identify factors associated with their presence. Methods. The study included 160 patients who underwent CABG and 36 volunteers with no history of coronary artery disease (CAD) as a control group. Echocardiographic examination of patients was performed to assess systolic and diastolic RV dysfunction before surgery and 18 months after CABG. A level of s't < 10 cm/sec or TAPSE < 16 mm was considered as a sign of existing RV systolic dysfunction. RV diastolic dysfunction was defined as an Et/At ratio < 0.8 or >2.1 and/or an Et/et' ratio > 6. Results. In CAD patients 18 months after CABG, there was an increase in the frequency of the right ventricular systolic (from 7.5% to 30%, p < 0.001) and diastolic (from 41.8% to 57.5%, p < 0.001) dysfunction. An increase in TAPSE (p = 0.007), a decrease in e't (p = 0.005), and the presence of RV systolic dysfunction before surgery (p = 0.023) was associated with a significant increase in the likelihood of detecting RV systolic dysfunction 18 months after CABG (χ2(3) = 17.4, p = 0.001). High values of At before surgery (p = 0.021) and old myocardial infarction (p = 0.023) were significantly associated with an increased likelihood of detection of RV diastolic dysfunction 18 months after CABG (χ2(2) = 10.78, p = 0.005). Conclusions. This study demonstrated that in CAD patients 18 months after CABG, there was an increase in the frequency of right ventricular systolic and diastolic dysfunction. We also established the initial clinical, echocardiographic parameters, and perioperative complications associated with the presence of these changes in the postoperative period. The clinical and prognostic significance of the presence of systolic and/or diastolic RV dysfunction in patients 18 months after CABG remains to be explored. [ABSTRACT FROM AUTHOR]

New antidiabetic therapy that includes sodium-glucose co-transporter 2 (SGLT2) inhibitors, glucagon-like peptide-1 receptor (GLP-1R) agonists, and dipeptidyl peptidase 4 (DPP-4) inhibitors showed significant benefit on cardiovascular outcomes in patients with and without type 2 diabetes mellitus, and this was particularly confirmed for SGLT2 inhibitors in subjects with heart failure (HF) with reduced ejection fraction (HFrEF). Their role on patients with HF with preserved ejection fraction (HFpEF) is still not elucidated, but encouraging results coming from the clinical studies indicate their beneficial role. The role of GLP-1R agonists and particularly DPP-4 inhibitors is less clear and debatable. Findings from the meta-analyses are sending positive message about the use of GLP-1R agonists in HFrEF therapy and revealed the improvement of left ventricular (LV) diastolic function in HFpEF. Nevertheless, the relevant medical societies still consider their effect as neutral or insufficiently investigated in HF patients. The impact of DPP-4 inhibitors in HF is the most controversial due to conflicting data that range from negative impact and increased risk of hospitalization due to HF, throughout neutral effect, to beneficial influence on LV diastolic dysfunction. However, this is a very heterogeneous group of medications and some professional societies made clear discrepancy between saxagliptin that might increase risk of HF hospitalization and those DPP-4 inhibitors that have no effect on hospitalization. The aim of this review is to summarize current clinical evidence about the effect of new antidiabetic medications on LV diastolic function and their potential benefits in HFpEF patients. [ABSTRACT FROM AUTHOR]

The use of untwisting rate as a novel index of LV diastolic function in clinical practice has been limited due to its tedious and time-consuming analysis. Therefore, we simplify the untwist measurement by only measuring the LV apex's recoil rate and validating and applying peak apical recoil rate (PARR) as an index of diastolic dysfunction (DD) in pediatric subjects during increased and decreased lusitropic states. We recruited 153 healthy subjects (mean age 13.8 ± 2.9 years), of whom 48 performed straight leg raising exercise and an additional 46 patients (mean 8.4 ± 5.6 years) with documented pulmonary capillary wedge pressures (PCWP) (validation cohort). In addition, we studied 16 dilated cardiomyopathy patients (mean age 9.5 ± 6.3 years) (application cohort). PARR and isovolumic relaxation time (IVRT) were compared to PCWP. Both PARR and PARR normalized by heart rate (nPARR) were excellent in detecting patients with PCWP ≥ 12 mmHg and greatly superior to IVRT in this respect (AUC: 0.98, 95% CI [0.96, 1.0] vs. AUC: 0.7 95%CI [0.54,0.86]). In DCM patients, PARR and nPARR were greatly decreased compared to controls (− 38.6 ± 18.6º/s vs − 63.1 ± 16.3º /s, p < 0.001) and (− 0.43 ± 0.20 º/ s/min vs − 0.83 ± 0.28º/s/min, p < 0.0001) but increased with straight leg raising exercise (− 59.4 ± 19.4º/s vs − 97.8 ± 39.0 º/s, p < 0.01) and − 0.85 ± 0.36 vs − 1.4 ± 0.62 º/s/min (p < 0.0001) respectively. PARR and nPARR successfully detected increased and decreased lusitropic states and superior to IVRT in correlation with PCWP. This highly reproducible parameter offers incremental value over traditional indices of DD and may potentially serve as a useful index of elevated PCWP in children. [ABSTRACT FROM AUTHOR]

Hemodialysis (HD) decreases preload and its acute effect on the diastolic function is still controversial even with the introduction of new non-volume-dependent tissue Doppler echocardiographic indices. This study is designed to evaluate these acute changes following HD sessions. We enrolled 39 patients receiving standard thrice weekly HD for more than 6 months and performed two dimensional speckle tracking echocardiography (2DSTE) and tissue Doppler studies with a standard cardiac ultrasound device shortly before and after HD. We observed significant changes in most of the transmitral flow and tissue Doppler echocardiographic parameters after HD. The left atrial volume index, left ventricular mass index, mitral E, mitral E/A, and lateral annular E/é levels decreased after HD (p: < 0.001, p: 0.026, p: < 0.001, p: 0.011, p: < 0.001, respectively). Medial á, medial myocardial performance index (MPI), medial ś, lateral ś, and lateral MPI values increased significantly after HD (p: 0.049, p: 0.007, p: 0.001, p: < 0.001, p: 0.01, respectively). Diastolic parameters like diastolic strain ratio early diastole (DSRE), diastolic strain ratio late diastole (DSRA), E/DSRE, and E/DSRA did not change significantly after HD (p: 0.716, p: 0.117, p: 0.114, and p: 0.211, respectively). The global longitudinal strain value obtained with 2DSTE worsened after HD (− 18.4 ± 4.0 before vs − 15.9 ± 5.4 after HD, p: 0.011). Transmitral flow and tissue Doppler parameters changed significantly after HD while the change in 2DSTE findings was not significant. The diastolic measurements made with 2DSTE may be less volume and cardiac preload dependent compared to conventional echocardiography and this may explain the difference. [ABSTRACT FROM AUTHOR]

Objective: This study evaluates whether food intake affects systolic and diastolic echocardiographic measurements in healthy seniors. Methods: Thirty healthy subjects 65–70 years of age were investigated with echocardiography, at fasting and then 30, 90, and 180 min after a meal. Results: After 30 min the biggest changes were seen in left ventricular wall stress and myocardial performance index with a decrease of 45% and 33%, respectively, compared to fasting values. Significant (p <.05) increases also were seen in left ventricular stroke volume, left ventricular cardiac output, left ventricular cardiac index, left ventricular outflow velocity‐time integral, peak of early diastolic (E) and late diastolic (A) mitral flow velocities, the E/A ratio, pulsed tissue Doppler peak systolic (s') and early (e') and late (a') diastolic velocities, pulmonary vein peak velocities in systole (S) and diastole (D), mitral annular plane systolic excursion (MAPSE), tricuspid annular plane systolic excursion (TAPSE), and global longitudinal strain (GLS) (increases ranging 6%–19%). After 90 min there remained a decrease in wall stress and myocardial performance index of 31% and 17%, respectively, and smaller, but still significant, changes could be seen in left ventricular stroke volume, left ventricular outflow velocity‐time integral, MAPSE (lateral), TAPSE, GLS, and a few pulsed tissue Doppler peak systolic velocities and late diastolic velocities. An increase also could be seen in deceleration time of E‐wave (DT). After 180 min, all variables except DT were back at baseline or below. No significant changes were seen in S/D ratio, lateral early diastolic velocity (e' lateral) and E/e'ratio. Conclusions: This study shows that food intake affects commonly used echocardiographic parameters, both systolic and diastolic, in healthy seniors. With a few exceptions, the changes seen in the older population were less pronounced than previous studies in younger subjects. [ABSTRACT FROM AUTHOR]

We sought to evaluate ginger's cardiovascular and metabolic effects (Zingiberofficinale) add-on therapy in type 2 diabetes patients over six weeks. We performed a single-arm clinical trial. In well-to-moderately controlled Type 2 diabetic patients with unchanged treatment for at least three months, the intervention consisted of 6-week add-on oral supplementation of powdered ginger extracts in capsules at a dose of 399 mg three times per day. Transthoracic Doppler echocardiography, ambulatory blood pressure monitoring (ABPM), glycatedhaemoglobin (HbA1c), lipid profile, kidney and liver function analysis were performed at initial and final visits, with a follow-up visit on day 21. Adherence to treatment, palatability and safety were also assessed. Overall, 21 participants (16 females) were included in the analysis. We found a non-significant decrease of E' wave from 0.05[0.04-0.09] to 0.06[0.05-0.7]cm/s, A-wave from 0.8[0.6-0.8] to 0.7[0.6-0.8] cm/s, and E-wave from 0.6[0.5-0.7] to 0.5[0.425-0.6]cm/s. There was a significant reduction of HbA1c from 49.7[47.0-57.4] to 44.3[38.8-53.0] mmol/mol and triglycerides from 1.6[1.4-1.9] to 1.2[0.9-1.8] mmol/l. A 5% decrease or more was observed for diurnal DBP, diurnal MAP and 24-hour DBP. Zingiberofficinale used as add-on therapy tend to improve diastolic function, blood pressure and lipid profile of type 2 diabetes patients. Further studies are needed to define the dosage and duration of this supplementary treatment accurately. Trial Registration number:NCT04222738. [ABSTRACT FROM AUTHOR]

Background: Echocardiographic parameters of diastolic function depend on cardiac loading conditions, which are altered by positive pressure ventilation. The direct effects of positive end-expiratory pressure (PEEP) on cardiac diastolic function are unknown. Methods: Twenty-five patients without apparent diastolic dysfunction undergoing coronary angiography were ventilated noninvasively at PEEPs of 0, 5, and 10 cmH2O (in randomized order). Echocardiographic diastolic assessment and pressure–volume-loop analysis from conductance catheters were compared. The time constant for pressure decay (τ) was modeled with exponential decay. End-diastolic and end-systolic pressure volume relationships (EDPVRs and ESPVRs, respectively) from temporary caval occlusion were analyzed with generalized linear mixed-effects and linear mixed models. Transmural pressures were calculated using esophageal balloons. Results: τ values for intracavitary cardiac pressure increased with the PEEP (n = 25; no PEEP, 44 ± 5 ms; 5 cmH2O PEEP, 46 ± 6 ms; 10 cmH2O PEEP, 45 ± 6 ms; p < 0.001). This increase disappeared when corrected for transmural pressure and diastole length. The transmural EDPVR was unaffected by PEEP. The ESPVR increased slightly with PEEP. Echocardiographic mitral inflow parameters and tissue Doppler values decreased with PEEP [peak E wave (n = 25): no PEEP, 0.76 ± 0.13 m/s; 5 cmH2O PEEP, 0.74 ± 0.14 m/s; 10 cmH2O PEEP, 0.68 ± 0.13 m/s; p = 0.016; peak A wave (n = 24): no PEEP, 0.74 ± 0.12 m/s; 5 cmH2O PEEP, 0.7 ± 0.11 m/s; 10 cmH2O PEEP, 0.67 ± 0.15 m/s; p = 0.014; E' septal (n = 24): no PEEP, 0.085 ± 0.016 m/s; 5 cmH2O PEEP, 0.08 ± 0.013 m/s; 10 cmH2O PEEP, 0.075 ± 0.012 m/s; p = 0.002]. Conclusions: PEEP does not affect active diastolic relaxation or passive ventricular filling properties. Dynamic echocardiographic filling parameters may reflect changing loading conditions rather than intrinsic diastolic function. PEEP may have slight positive inotropic effects. Clinical trial registration: https://clinicaltrials.gov/ct2/show/NCT02267291, registered 17. October 2014. [ABSTRACT FROM AUTHOR]

Hon-Chun Hsu,1,2 Gavin R Norton,1 Ferande Peters,1 Chanel Robinson,1 Noluntu Dlongolo,3 Ahmed Solomon,4 Gloria Teckie,5 Angela J Woodiwiss,1 Patrick H Dessein1,6,7 1Cardiovascular Pathophysiology and Genomics Research Unit, School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa; 2Nephrology Unit, Milpark Hospital, Johannesburg, South Africa; 3Rheumatology Unit, Rosebank Hospital, Johannesburg, South Africa; 4Division of Rheumatology, Charlotte Maxeke Johannesburg Academic Hospital and Faculty of Health Sciences, University of Witwatersrand, Johannesburg, South Africa; 5Division of Nephrology, Department of Medicine, Chris Hani Baragwanath Hospital and Faculty of Health Sciences, University of Witwatersrand, Johannesburg, South Africa; 6Internal Medicine Department, University of the Witwatersrand, Johannesburg, South Africa; 7Internal Medicine Department, Free University and University Hospital, Brussels, BelgiumCorrespondence: Patrick H DesseinCardiovascular Pathophysiology and Genomics Research Unit, School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, 80 Scholtz Road, Norwood, 2117, Johannesburg, South AfricaTel +27662491468Email patrick.dessein22@gmail.comIntroduction: We hypothesized that post transplantation anaemia and persistent secondary hyperparathyroidism are potential determinants of diastolic function in stable kidney transplant recipients.Methods: We assessed traditional and non-traditional cardiovascular risk factors and determined carotid artery intima-media thickness and plaque by ultrasound, arterial function by applanation tonometry using SphygmoCor software and diastolic function by echocardiography in 43 kidney transplant recipients with a transplant duration of ≥ 6 months, no acute rejection and a glomerular filtration rate of ≥ 15 mL/min/1.73m2.Results: Mean (SD; range) transplant duration was 12.3 (8.0; 0.5– 33.8) years. Post transplantation anaemia and persistent secondary hyperparathyroidism were identified in 27.9% and 30.8% of the patients, respectively; 67.5% of the participants were overweight or obese. In established confounder adjusted analysis, haemoglobin (partial R=− 0.394, p=0.01) and parathyroid hormone concentrations (partial R=0.382, p=0.02) were associated with E/e’. In multivariable analysis, haemoglobin (partial R=− 0.278, p=0.01) and parathyroid levels (partial R=0.324, p=0.04) were independently associated with E/e’. Waist–height ratio (partial R=− 0.526, p=0.001 and partial R=− 0.355, p=0.03), waist circumference (partial R=− 0.433, p=0.008 and partial R=− 0.393, p=0.02) and body mass index (partial R=− 0.332, p=0.04 and partial R=− 0.489, p=0.002) were associated with both e’ and E/A, respectively, in established confounder adjusted analysis. The haemoglobin-E/e’ (partial R=− 0.422, p=0.02), parathyroid hormone-E/e’ (partial R=0.434, p=0.03), waist–height ratio-e’ (partial R=− 0.497, p=0.007) and body mass index-E/A (partial R=− 0.386, p=0.04) relationships remained consistent after additional adjustment for left ventricular mass index and cardiac preload and afterload measures.Conclusion: Haemoglobin and parathyroid hormone concentrations as well as adiposity measures are independently associated with diastolic function in kidney transplant recipients. Whether adequate management of post transplantation anaemia, persistent secondary hyperparathyroidism and excess adiposity can prevent the development of heart failure with preserved ejection fraction in kidney transplant recipients merits further investigation.Keywords: haemoglobin, parathyroid hormone, obesity, diastolic function, kidney transplantation

Abstract Aims To compare left ventricular structure (LV) and diastolic function in young adults with youth- onset diabetes by type, determine the prevalence of abnormal diastolic function by diabetes type using published values from age similar healthy controls, and examine the risk factors associated with diastolic function. Methods In a cross sectional analysis we compared LV structure and diastolic function from two dimensional echocardiogram in participants with type 1 (T1D) and type 2 diabetes (T2D) who participated in the SEARCH for Diabetes in Youth Study. Linear models were used to examine the risk factors associated with worse diastolic function. Results Of 479 participants studied, 258 had T1D (mean age 21.2 ± 5.2 years, 60.5% non-Hispanic white, 53.9% female) and 221 had T2D (mean age 24.8 ± 4.3 years, 24.4% non-Hispanic white, 73.8% female). Median diabetes duration was 11.6 years. Participants with T2D had greater LV mass index and worse diastolic function that persisted after adjustment for differences in risk factors compared with participants with T1D (all p

Abstract Aims Myocardial injury is frequently observed in patients hospitalized with coronavirus disease 2019 (COVID‐19) pneumonia. Different cardiac abnormalities have been reported during the acute COVID‐19 phase, ranging from infra‐clinic elevations of myocardial necrosis biomarkers to acute cardiac dysfunction and myocarditis. There is limited information on late cardiac sequelae in patients who have recovered from acute COVID‐19 illness. We aimed to document the presence and quantify the extent of myocardial functional alterations in patients hospitalized 6 months earlier for COVID‐19 infection. Methods and results We conducted a prospective echocardiographic evaluation of 48 patients (mean age 58 ± 13 years, 69% male) hospitalized 6 ± 1 month earlier for a laboratory‐confirmed and symptomatic COVID‐19. Thirty‐two (66.6%) had pre‐existing cardiovascular risks factors (systemic hypertension, diabetes, or dyslipidaemia), and three patients (6.2%) had a known prior myocardial infarction. Sixteen patients (33.3%) experienced myocardial injury during the index COVID‐19 hospitalization as identified by a rise in cardiac troponin levels. Six months later, 60.4% of patients still reported clinical symptoms including exercise dyspnoea for 56%. Echocardiographic measurements under resting conditions were not different between patients with versus without myocardial injury during the acute COVID‐19 phase. In contrast, low‐level exercise (25W for 3 min) induced a significant increase in the average E/e′ ratio (10.1 ± 4.3 vs. 7.3 ± 11.5, P = 0.01) and the systolic pulmonary artery pressure (33.4 ± 7.8 vs. 25.6 ± 5.3 mmHg, P = 0.02) in patients with myocardial injury during the acute COVID‐19 phase. Sensitivity analyses showed that these alterations of left ventricular diastolic markers were observed regardless of whether of cardiovascular risk factors or established cardiac diseases indicating SARS‐CoV‐2 infection as a primary cause. Conclusions Six months after the acute COVID‐19 phase, significant cardiac diastolic abnormalities are observed in patients who experienced myocardial injury but not in patients without cardiac involvement.

Abstract Aims Echocardiographic predictors of outcomes in heart failure with preserved ejection fraction (HFpEF) have not been systematically or independently validated. We aimed at identifying echocardiographic predictors of cardiovascular events in a large cohort of patients with HFpEF and to validate these in an independent large cohort. Methods and results We assessed the association between echocardiographic parameters and cardiovascular outcomes in 515 patients with heart failure with preserved left ventricular (LV) ejection fraction (>50%) in the MEtabolic Road to DIAstolic Heart Failure (MEDIA) multicentre study. We validated out findings in 286 patients from the Karolinska‐Rennes Prospective Study of HFpEF (KaRen). After multiple adjustments including N‐terminal pro‐brain natriuretic peptide (NT‐proBNP), the significant predictors of death or cardiovascular hospitalization were pulmonary arterial systolic pressure > 40 mmHg, respiratory variation in inferior vena cava diameter > 0.5, E/e' > 9, and lateral mitral annular s' 35% 1 year risk. Adding these four echocardiographic variables on top of clinical variables and NT‐proBNP yielded significant net reclassification improvement (33.8%, P

Twin pregnancy - with a prevalence nearly doubled in the last decades due to the use of assisted reproductive technology and the increasing age of conception - is associated with physiological cardiovascular adaptations to meet the hemodynamic demands of pregnancy. Compared to singleton pregnancies, increased and earlier in pregnancy risk of developing perinatal complications and maternal cardiac disease is demonstrated due to additional stress on the maternal cardiovascular system due to higher circulation volume. Knowledge on maternal adaptation in twin pregnancies are still lacking and often data derive from research studies on singleton pregnancy and including twins without differentiations. Only a few trials considered the impact of twin pregnancies on the maternal cardiovascular system and included echocardiographic evaluations showing how the changes in left ventricular geometry, systolic and diastolic function were comparable to those observed later in uncomplicated singleton pregnancies or in presence of hypertensive disorders. The present work aimed to review the current state of research on maternal cardiovascular function in twin pregnancies as the basis for a new study focused to find premature echocardiographic parameters able to contribute to the design of effective preventive strategies of complications - such as hypertensive disorders - in pregnancies, particularly on twin pregnancy. [ABSTRACT FROM AUTHOR]

Left ventricular diastolic dysfunction is a major cause of heart failure and carries a poor prognosis. Assessment of left ventricular diastolic function however remains challenging for both echocardiography and conventional phase contrast cardiac magnetic resonance. Amongst other limitations, both are restricted to measuring velocity in a single direction or plane, thereby compromising their ability to capture complex diastolic hemodynamics in health and disease. Time-resolved three-dimensional phase contrast cardiac magnetic resonance imaging with three-directional velocity encoding known as ‘4D flow CMR’ is an emerging technology which allows retrospective measurement of velocity and by extension flow at any point in the acquired 3D data volume. With 4D flow CMR, complex aspects of blood flow and ventricular function can be studied throughout the cardiac cycle. 4D flow CMR can facilitate the visualization of functional blood flow components and flow vortices as well as the quantification of novel hemodynamic and functional parameters such as kinetic energy, relative pressure, energy loss and vorticity. In this review, we examine key concepts and novel markers of diastolic function obtained by flow pattern analysis using 4D flow CMR. We consolidate the existing evidence base to highlight the strengths and limitations of 4D flow CMR techniques in the surveillance and diagnosis of left ventricular diastolic dysfunction.

Metabolic syndrome in humans is commonly associated with cardiovascular dysfunction, including atrial fibrillation and left ventricular diastolic dysfunction. Although many differences exist between human and equine metabolic syndrome, both of these conditions share some degree of insulin resistance. The aims of this pilot study were to investigate the relationship between insulin sensitivity and cardiac function. Seven horses (five mares, two geldings, aged 17.2 ± 4.2 years, weight 524 ± 73 kg) underwent insulin-modified frequently sampled intravenous glucose tolerance testing to determine insulin sensitivity (mean 2.21 ± 0.03 × 10−4 L/min/mU). Standard echocardiograms were performed on each horse, including two-dimensional, M-mode, and pulse-wave tissue Doppler imaging. Pearson and Spearman correlation analyses were used to determine the association of insulin sensitivity with echocardiographic measures of cardiac function in 5 horses. Insulin sensitivity was found to be significantly correlated with peak myocardial velocity during late diastole (r = 0.89, P = 0.0419), ratio between peak myocardial velocity in early and late diastole (r = −0.92, P = 0.0263), isovolumetric relaxation time (r = −0.97, P = 0.0072), and isovolumetric contraction time (ρ = −0.90, P = 0.0374). These preliminary data suggest that decreased insulin sensitivity is correlated with alterations in both systolic and diastolic function, as measured with tissue Doppler imaging (TDI). Due to the small sample size of this study, the relationship between insulin sensitivity and myocardial function in horses requires further investigation.

Heart failure (HF) is a major cause of morbidity and mortality worldwide. Current classifications of HF categorize patients with a left ventricular ejection fraction of 50% or greater as HF with preserved ejection fraction or HFpEF. Echocardiography is the first line imaging modality in assessing diastolic function given its practicality, low cost and the utilization of Doppler imaging. However, the last decade has seen cardiac magnetic resonance (CMR) emerge as a valuable test for the sometimes challenging diagnosis of HFpEF. The unique ability of CMR for myocardial tissue characterization coupled with high resolution imaging provides additional information to echocardiography that may help in phenotyping HFpEF and provide prognostication for patients with HF. The precision and accuracy of CMR underlies its use in clinical trials for the assessment of novel and repurposed drugs in HFpEF. Importantly, CMR has powerful diagnostic utility in differentiating acquired and inherited heart muscle diseases presenting as HFpEF such as Fabry disease and amyloidosis with specific treatment options to reverse or halt disease progression. This state of the art review will outline established CMR techniques such as transmitral velocities and strain imaging of the left ventricle and left atrium in assessing diastolic function and their clinical application to HFpEF. Furthermore, it will include a discussion on novel methods and future developments such as stress CMR and MR spectroscopy to assess myocardial energetics, which show promise in unraveling the mechanisms behind HFpEF that may provide targets for much needed therapeutic interventions.

Abstract Background We examined the relationship between epicardial fat thickness (EFT) measured by echocardiography and left ventricular diastolic function parameters in a Beijing community population. Methods We included 1004 participants in this study. Echocardiographic parameters including E and A peak velocity, the early diastolic velocities (e′) of the septal and lateral mitral annulus using tissue doppler imaging, E/e′, and EFT were measured. EFT1 was measured perpendicularly on the right ventricular free wall at end diastole in the extension line of the aortic root. EFT2 was the maximum thickness measured perpendicularly on the right ventricular free wall at end diastole. Multivariable linear regression was used to analyze the relationship between EFT and the mean e′ and E/e′. Results The mean age of the participants was 63.91 ± 9.02 years, and 51.4% were men. EFT1 and EFT2 were negatively correlated with lateral e′, septal e′, and mean e′ (p

Background: Psoriasis is a chronic inflammatory disease affecting many organs. Recent studies have demonstrated that psoriasis is associated with cardiovascular disorders. We investigated the echocardiographic and conduction system changes in psoriasis patients. Methods: In this case-control study, 36 psoriatic patients and 36 healthy controls were enrolled. Demographic and clinical data, echocardiographic and P wave dispersion (PWD) in 12-lead electrocardiogram were evaluated in both groups. We recruited patients with confirmed diagnosis via biopsy and have not been under recent systemic treatment. Patients with underlying cardiovascular disease were excluded from the study. Results: Mean age was 41.56±16.20 and 39.67±13.85 year in case and control groups, respectively. There was no significant difference in the baseline characteristics of the two groups. PWD was significantly higher in the case group (p

Hepatic T1-time derived from cardiac magnetic resonance imaging (cMRI) reflects venous congestion and may provide a simple alternative to invasive end-diastolic elastance (Eed) for assessment of right ventricular (RV) diastolic function. We investigated the association of native hepatic T1-time with single-beat Eed and the value of hepatic T1-time for longitudinal monitoring in pulmonary hypertension (PH). We retrospectively enrolled 85 patients with suspected PH (59% female; 78 with PH diagnosed; 7 with PH excluded) who underwent standard right heart catheterization and cMRI within 24 h between 2015 and 2020. Hepatic T1-time showed moderate to strong correlations (rho >0.3, P ≤ 0.002) with pulmonary vascular resistance, native myocardial T1-time, Eed, RV size and function, brain natriuretic peptide (BNP) level, and 6-min walk distance, and a significant association with functional class (Kruskal-Wallis P < 0.001). Eed, myocardial T1-time, and BNP were independently linked to hepatic T1-time in multivariable regression. Hepatic T1-time > 598 ms predicted elevated Eed with 72.9% sensitivity and 82.1% specificity. Hepatic T1-time was superior to Eed in predicting clinical worsening. In 16 patients with follow-up assessments, those with decreasing hepatic T1-time (7 patients) showed significant hemodynamic improvements, whereas those with increasing hepatic T1-time (9 patients) did not. In a second retrospective cohort of 27 patients with chronic thromboembolic PH undergoing balloon pulmonary angioplasty, hepatic T1-time decreased significantly and hemodynamics improved after the procedure. Hepatic T1-time predicts RV diastolic dysfunction and prognosis, and may be useful for monitoring disease progression and treatment response in PH. [Display omitted] • Hepatic T1-time predicts diastolic RV dysfunction • Non-invasive monitoring of PH progression • Hepatic T1-time reflects treatment response • Validated by longitudinal patient data [ABSTRACT FROM AUTHOR]

Atrial function provides insight into ventricular diastolic function. Invasive assessment of left ventricular (LV) diastolic function correlates with development of sustained ventricular tachyarrhythmias in patients with repaired tetralogy of Fallot (rTOF). Non-invasive assessment of atrial function may prove key towards assessment of diastolic function. We longitudinally evaluated the progression of biatrial function in patients with rTOF, regardless of pulmonary valve replacement (PVR). Patients with rTOF who had multiple CMR were identified. CMR examinations were retrospectively reviewed. Left (LA) and right (RA) atrial size and function were measured in the two and four-chamber views and assessed over time and after PVR. Left and right atrial reservoir, conduit, pump strain and strain rates were determined using tissue tracking. Thirty-six patients with rTOF were identified (64% male), ten (28%) had PVR during the study. Median age of PVR was 16.5 years. No improvement in RA or LA function was observed after PVR. A decline in RA reservoir strain rate (p < 0.05) and RA pump strain (p < 0.05) were observed despite improvements in right ventricular systolic function (p < 0.05). In patients who had multiple CMR without PVR, RA reservoir strain rate (p < 0.05) and pump strain rate (p < 0.05) worsened over time. LA pump strain decreased over time in all patients. There is progressive decline of several RA functional parameters over time. No significant improvement in LA or RA function after PVR was observed. Additional studies are needed to understand how these changes may relate to poor outcomes and potentially better guide timing of PVR. [ABSTRACT FROM AUTHOR]

Diastolic left ventricular (LV) dysfunction is a powerful contributor to the symptoms and prognosis of patients with heart failure. In patients with depressed LV systolic function, the E/A ratio, the ratio between the peak early (E) and the peak late (A) transmitral flow velocity, is the first step to defining the grade of diastolic dysfunction. Doppler echocardiography (echo) is the preferred imaging technique for diastolic function assessment, while cardiovascular magnetic resonance (CMR) is less established as a method. Previous four-dimensional (4D) Flow-based studies have looked at the E/A ratio proximal to the mitral valve, requiring manual interaction. In this study, we compare an automated, deep learning-based and two semi-automated approaches for 4D Flow CMR-based E/A ratio assessment to conventional, gold-standard echo-based methods. Ninety-seven subjects with chronic ischemic heart disease underwent a cardiac echo followed by CMR investigation. 4D Flow-based E/A ratio values were computed using three different approaches; two semi-automated, assessing the E/A ratio by measuring the inflow velocity (MVvel) and the inflow volume (MVflow) at the mitral valve plane, and one fully automated, creating a full LV segmentation using a deep learning-based method with which the E/A ratio could be assessed without constraint to the mitral plane (LVvel). MVvel, MVflow, and LVvel E/A ratios were strongly associated with echocardiographically derived E/A ratio (R2 = 0.60, 0.58, 0.72). LVvel peak E and A showed moderate association to Echo peak E and A, while MVvel values were weakly associated. MVvel and MVflow EA ratios were very strongly associated with LVvel (R2 = 0.84, 0.86). MVvel peak E was moderately associated with LVvel, while peak A showed a strong association (R2 = 0.26, 0.57). Peak E, peak A, and E/A ratio are integral to the assessment of diastolic dysfunction and may expand the utility of CMR studies in patients with cardiovascular disease. While underestimation of absolute peak E and A velocities was noted, the E/A ratio measured with all three 4D Flow methods was strongly associated with the gold standard Doppler echocardiography. The automatic, deep learning-based method performed best, with the most favorable runtime of ∼40 seconds. As both semi-automatic methods associated very strongly to LVvel, they could be employed as an alternative for estimation of E/A ratio. [Display omitted] [ABSTRACT FROM AUTHOR]

Background and Objectives: Cardiac function in patients with Parkinson’s Disease (PD) is not well understood. We conducted a review of the literature to summarize all available data on the cardiac cycle in patients with PD and followed up the review with a case series to describe the cardiac cycle timing intervals in this patient population. Methods: Using the search terms (“Cardiac cycle” OR “echocardiography” OR “LVET” OR “IVCT” OR “IVRT” OR “LVEF” OR “Systolic Dysfunction” OR “Diastolic Dysfunction”) AND (“Parkinson’s Disease”), 514 studies were found with 19 included in the review. Results: Studies focused on the impact of medication, the presence of autonomic dysfunction, and resting-state, descriptive observational studies which considered the cardiac cycle. While inconsistent, the evidence suggests that patients with PD have some systolic dysfunction, with recent research implying the presence of subclinical systolic dysfunction. From the case series, 13 participants with PD were included and collected cardiac data daily for 6 weeks. Heart rate was consistent on a weekly basis at 67–71 bpm. Mean week-by-week cardiac parameters were also consistent with the systolic time interval at 332–348 ms, isovolumic relaxation time at 92–96 ms, and isovolumic contraction time at 34–36 ms. Conclusion: These timing intervals add valuable normative values for this patient population and the review of the literature suggests that more research is required to better understand cardiac cycle timing intervals in patients with Parkinson’s Disease.

Background: Doppler transthoracic echocardiography is routinely performed to measure peak mitral inflow velocities in the assessment of left ventricular diastolic function. The limitations of echocardiography are well documented, but its accuracy in the measurement of transmitral peak velocity in the presence of aortic valve regurgitation has not yet been compared with four-dimensional flow cardiac magnetic resonance imaging. Four-dimensional flow cardiac magnetic resonance imaging offers time-resolved cross-sectional velocity information that can be used to investigate mitral inflow peak velocity. We present a case report demonstrating the potential superior capabilities of four-dimensional flow cardiac magnetic resonance imaging in accurately detecting mitral inflow velocities over Doppler echocardiography in patients with aortic regurgitation.Case Presentation: A 67-year-old Caucasian female presented to our outpatient cardiology clinic with exertional dyspnea. Doppler transthoracic echocardiography identified moderate to severe aortic regurgitation. Mapping of mitral inflow peak velocities proved challenging with Doppler echocardiography. Additionally, four-dimensional flow cardiac magnetic resonance imaging with automated three-dimensional flow streamlines was performed, which allowed for more accurate detection of mitral inflow peak velocities.Conclusions: Doppler echocardiography has a limited role in mitral inflow assessment where aortic regurgitation is present. In such cases, four-dimensional flow cardiac magnetic resonance imaging is an alternative imaging technique that may circumvent this issue and allow mitral inflow assessment. [ABSTRACT FROM AUTHOR]

Objectives: Recent studies have confirmed that heart failure is one of the most important causes of death in patients with idiopathic inflammatory myopathy (IIM). Left ventricle diastolic dysfunction (LVDD) is closely associated with heart failure. Our aim is to determine if the prevalence of LVDD is increased in IIM patients. Methods: We performed a time- and language-restricted literature search to identify studies conducted to compare the echocardiographic parameters in IIM patients and controls. Mean differences were used to calculate the effect sizes of the echocardiographic parameters. Results: A total of 13 studies met the inclusion criteria and comprised a total of 227 juvenile dermatomyositis (JDM) patients, 391 adult IIM patients, and 550 controls. The adult IIM patients had lower mitral annular early diastolic velocity (e') and peak of early diastolic flow velocity/peak of late diastolic flow velocity (E/A) ratio compared to controls. The mean left atrial dimension and E/e' ratio was higher in adult IIM patients as compared to controls. Similarly, in JDM patients, the decreased e' was also observed. Conclusion: Patients with IIM were more likely to have echocardiographic parameters indicative of diastolic dysfunction. The early heart assessments should be performed in IIM patients. [ABSTRACT FROM AUTHOR]

The 2016 American Society of Echocardiography (ASE) and European Association of Cardiovascular Imaging (EACVI) guidelines for the evaluation of left ventricular diastolic function reported a new algorithm to assess diastolic function and to estimate left ventricular filling pressure (LVFP). At least five to six different parameters were necessary to conclude, each of them with their own inter-observer variability. This article examines the reproducibility of each parameter of the algorithm and its influence on the final decision of the clinician. Echocardiographic exams of 12 non-selected patients without any known cardiac disease or follow-up but addressed to the hospital for symptoms were analyzed by two readers (one junior and one senior) in five French cardiologic tertiary centers. Inter-observer reproducibility at each step of the algorithm and final decision were analyzed. There was mild agreement on the final decision. The main reasons of discrepancy were disagreement on the significance of mitral annular calcifications and measured values that are just around the cut-off (despite good reproducibility, a slight variation could lead to misclassification of a dichotomous choice between a normal measure and a pathologic measure). Without considering performance, this multicentric French study puts forward limits to the actual algorithm recommended for LVFP pattern assessment. Agreement is excellent in caricatural (easy) cases (left ventricular pressure clearly normal or clearly elevated) but a great discordance exists in the gray zone. Improvement in the algorithm and in the method for LVFP determination is proposed. [ABSTRACT FROM AUTHOR]

Echocardiographic evaluation of left ventricular diastolic function relies on a multi-pronged algorithm, which incorporates Doppler-based and volumetric parameters. Integration of clinical data in diastolic assessment is recommended, though not clearly outlined. We sought to develop an automated tool for diastolic function, compare its performance to human-generated diagnoses and identify the common sources of error. Our software tool is based on the 2016 diastolic guidelines algorithm, which uses 8 parameters as input, with 10 conditions as the logic and 5 possible outputs as final diagnoses. Initially, we prospectively studied 563 patients whose diastolic function was independently evaluated by an expert echocardiographer and by the automated tool. Incongruent cases were further analyzed, after which features of myocardial disease were integrated into a refined version of the software that was tested in an independent cohort of 1106 patients. In the initial analysis, 202/563 grades (36%) were incongruent between the automated and human reads, with the highest rate of discordance for mild and indeterminate categories. In 17% of cases, human diagnoses differed from that dictated by the algorithm due to integration of clinical factors. Follow-up analysis using the refined automated tool did not improve the discordance rate (440/1106; 40%). There was more discordance in cases of: age > 40 years, impaired mitral inflow patterns (E/A < 0.8) and reduced mitral e' values. Further analysis revealed differences in how readers interpreted the interaction between these factors and diastolic function, which could not be incorporated into the automated tool. In conclusion, although assessment of diastolic function relies on an algorithm that can be automated, this algorithm does not include clear guidance on how to incorporate age, or age-related changes in Doppler-based parameters, often resulting in discordant diagnoses. Standardized interpretation of these factors is needed to improve the reproducibility of diastolic function grading by human readers and the accuracy of the automated classification. [ABSTRACT FROM AUTHOR]