Indeterminate Diastolic Function Research Articles

New onset of left ventricular dysfunction and diastolic dysfunction are uncommon in patients with her2+ breast cancer after completion of cancer therapy

Abstract Background Cardiotoxicity from anthracyclines and trastuzumab is common among patients with breast cancer during therapy. However, there are limited data on new onset of cardiotoxicity (systolic or diastolic dysfunction) after completion of therapy. This knowledge has implications to guide long-term follow-up. Purpose The aim of this study was to evaluate the incidence of cancer therapy related cardiac systolic dysfunction (CTRCD) and diastolic dysfunction (DD) in women with HER2+ breast cancer after completion of cancer therapy and compare to incidence during cancer therapy. Methods We conducted a prospective cohort study of women with HER2+ breast cancer who were treated with sequential anthracycline and trastuzumab therapy, with or without radiation therapy (The EMBRACE-MRI trial, NCT02306538). Comprehensive surveillance echocardiograms were performed at baseline and every 3 months during treatment, early post-trastuzumab, then at years 1, 2, and 3 post trastuzumab completion. CTRCD was defined as a reduction in 3D-left ventricular ejection fraction (LVEF) by ≥ 10% from baseline to < 55%. Diastolic dysfunction was defined as per the American Society of Echocardiography guidelines. Results A total of 136 female patients, with a mean age of 51.1 ± 9.2 years were recruited. Among them, 15.4% had hypertension, 3.7% had diabetes mellitus, and 10.3% had dyslipidemia. The mean cumulative doxorubicin equivalent dose was 203.9 ± 12.5 mg/m2, 120 patients received radiation therapy with the mean heart dose of 170.8 ± 75.9 cGy. During cancer treatment, 27 out of 136 patients (19.9%) developed CTRCD. In long-term follow-up, due to death or interruption due to the COVID-19 pandemic, follow-up was available in 128 patients at 1 year, 117 at 2 years and 111 at 3 years. 5 of the 27 patients still had persistent LV dysfunction (3 at 1 year, 1 at 2 year and 1 at 3 year), however, there were no new diagnosis of CTRCD post completion of therapy. Of 129 patients with baseline normal or indeterminate diastolic function, new DD was identified in 25/129 patients (19.4%) during cancer treatment (17 grade I, 2 grade II, 6 unable to grade). After completion of cancer therapy, 5 patients had persistent DD. In patients with no DD during therapy and completed 3 year follow-up, 5 patients developed new DD after therapy (2 grade I, 3 unable to grade). Figure 1 illustrates the percentage of patients with new CTRCD or new diastolic dysfunction at each timepoint. None of the patients developed clinical heart failure. Conclusion Although both CTRCD and diastolic dysfunction are common during sequential therapy with anthracyclines and trastuzumab in women with HER2+ breast cancer, new onset after treatment completion is rare during a careful follow-up. These findings have implications for long-term surveillance.

Application of the 2016 ase-eacvi criteria for the assessment of diastolic function in arterial hypertension

Abstract Background No data are available on diagnostic algorithms recommended by guidelines for the assessment of diastolic dysfunction (DD) in patients with arterial hypertension. Purpose To fill this gap, we evaluated left ventricular (LV) diastolic function in hypertensive patients matched with healthy subjects. Methods Healthy subjects, hypertensive patients without and with LV hypertrophy (LVH) were matched 1:1:1 based on age, sex, and body mass index from two prospective registries. All participants had normal LV ejection fraction (EF). Diastolic function was assessed basing on 2016 ASE-EACVI guidelines, by applying algorithm A, recommended in normal LVEF, and algorithm B recommended in reduced LVEF or normal LVEF and myocardial disease. Results A total of 717 participants were enrolled. By applying algorithm A, an indeterminate pattern was found in 0.4% of healthy subjects, in 6.3% of hypertensive patients without LVH (p=0.015 vs. healthy subjects), and in 21% of hypertensive patients with LVH (p=0.001 vs. healthy subjects). DD was absent in healthy individuals, whereas it was found in 2% and 8% of hypertensives without (p=0.06) and with LVH (p=0.001 vs. healthy subjects), respectively. By applying algorithm B, no cases of indeterminate diastolic function were found. DD was observed in 2.9% of healthy subjects, 7% and 10.5% of hypertensives without (p=0.001 vs. healthy subjects) and with LVH (p=0.002 vs. healthy subjects). Conclusion When diastolic function is assessed by echocardiography, the use of algorithm A should be limited only to truly normal subjects, whereas algorithm B should be applied to all patients with hypertension irrespective of LVH

Left Ventricular Diastolic Dysfunction with Elevated Filling Pressures Is Associated with Embolic Stroke of Undetermined Source and Atrial Fibrillation.

Background/Objectives: Left ventricular diastolic dysfunction (LVDD) and elevated left ventricular filling pressure (LVFP) are strong predictors of clinical outcomes across various populations. However, their diagnostic utility in embolic stroke of undetermined source (ESUS) remains unclear. We hypothesized that LVDD with elevated LVFP (based on echocardiography) was more likely to be prevalent in ESUS compared to non-cardioembolic stroke (NCE) and to be associated with atrial fibrillation (AF) on follow-up monitoring. Methods: This is a single-center retrospective study that included adult patients with a diagnosis of acute ischemic stroke between January 2016 and June 2017. LV function was assessed by inpatient transthoracic echocardiogram (TTE), and stroke etiology was adjudicated by the neurologist per the consensus criteria. Patients with cardioembolic stroke and those with indeterminate diastolic function on TTE were excluded. Baseline patient characteristics and clinical variables were compared among patients with and without LVDD and elevated LVFP. Multivariable regression models were used to assess the associations between diastolic dysfunction, ESUS, and AF detection in ESUS patients. Results: We identified 509 patients with ESUS and NCE stroke who had reported diastolic function. The mean age was 64.19 years, 45.19% were female, and 146 had LVDD with available LVFP data. LVDD was not associated with ESUS (adjusted OR: 1.43, 95% CI: 0.90-2.27, p = 0.130) or atrial fibrillation (AF) detection on cardiac monitoring (adjusted OR: 1.88, 95% CI: 0.75-4.72, p = 0.179). However, LVDD with elevated LVFP was borderline associated with ESUS (adjusted OR: 2.17, 95% CI: 0.99-4.77, p = 0.054) and significantly associated with AF detection (adjusted OR: 3.59, 95% CI: 1.07-12.06, p = 0.038). Conclusions: Our data suggest that LVDD with elevated LVFP is borderline associated with ESUS and significantly associated with AF detection on follow-up cardiac monitoring. Therefore, the presence of LVDD with an increased probability of elevated LVFP may help identify a subset of stroke patients more likely to have ESUS, potentially due to atrial cardiopathy with underlying occult AF. Further studies are needed to confirm our findings and to evaluate the safety and efficacy of anticoagulation in patients with ESUS and LVDD with elevated LVFP.

P095 LEFT VENTRICULAR DIASTOLIC FUNCTION IN HYPERTENSIVE PATIENTS WITH HEART FAILURE WITH PRESERVED EJECTION FRACTION

The aim of this work was to study the prevalence of the left ventricular diastolic dysfunction and indeterminate diastolic function in sinus hypertension individuals with left ventricular hypertrophy and preserved ejection fraction, and its associated factors. Methods. We enrolled 56 patients (aged 62, 95% confidence intervals (CI) 58–65 years, 53.6% men) with uncontrolled in-treated arterial hypertension who underwent transthoracic echocardiography (TTE, Esaote, MyLabEight). Cardiac diastolic dysfunction was defined when more than half of the TTE criteria was met according to the existing algorithm (average E/e‘, septal / lateral e‘, tricuspid regurgitation velocity, left atrium volume) and indeterminate one, when half of the criteria was encountered. A binary logistic regression analysis (Stata 15, USA) was performed to evaluate parameters for indeterminate diastolic function state. Results. TTE detected the left ventricular diastolic dysfunction only in 5.4%, however, 80.0% subjects had indeterminate diastolic function. Associated with the indeterminate diastolic function pattern factors were age and mitral regurgitation (odds ratios (OR) 8.0, 95% CI 2.19-29.25, p=0.002 and OR 1.06, 95% CI 1.01-1.12, p=0.014, respectively), however, not sex, height, weight, body mass index, diabetes, overweight/obese, and E/e‘. After adjustment for age, sex (female vs male) mitral regurgitation was occurred significantly more often in patients with indeterminate diastolic function in multivariate logistic regression model (OR 5.97, 95% CI1.47-24.35, p=0.013). Conclusions. Prevalence of the left ventricular diastolic dysfunction pattern is low (5.4%) and the indeterminate diastolic function is considerable (80.0%) in cohort of hypertensions with preserved ejection fraction with sinus rhythm. Mitral regurgitation identifies as a factor that associated with the indeterminate diastolic function patterns in hypertension patients.

Artificial intelligence-enabled ECG for left ventricular diastolic function and filling pressure

Assessment of left ventricular diastolic function plays a major role in the diagnosis and prognosis of cardiac diseases, including heart failure with preserved ejection fraction. We aimed to develop an artificial intelligence (AI)-enabled electrocardiogram (ECG) model to identify echocardiographically determined diastolic dysfunction and increased filling pressure. We trained, validated, and tested an AI-enabled ECG in 98,736, 21,963, and 98,763 patients, respectively, who had an ECG and echocardiographic diastolic function assessment within 14 days with no exclusion criteria. It was also tested in 55,248 patients with indeterminate diastolic function by echocardiography. The model was evaluated using the area under the curve (AUC) of the receiver operating characteristic curve, and its prognostic performance was compared to echocardiography. The AUC for detecting increased filling pressure was 0.911. The AUCs to identify diastolic dysfunction grades ≥1, ≥2, and 3 were 0.847, 0.911, and 0.943, respectively. During a median follow-up of 5.9 years, 20,223 (20.5%) died. Patients with increased filling pressure predicted by AI-ECG had higher mortality than those with normal filling pressure, after adjusting for age, sex, and comorbidities in the test group (hazard ratio (HR) 1.7, 95% CI 1.645–1.757) similar to echocardiography and in the indeterminate group (HR 1.34, 95% CI 1.298–1.383). An AI-enabled ECG identifies increased filling pressure and diastolic function grades with a good prognostic value similar to echocardiography. AI-ECG is a simple and promising tool to enhance the detection of diseases associated with diastolic dysfunction and increased diastolic filling pressure.

Prognosis of diastolic dysfunction in patients with preserved LVEF. Value of left atrial strain

Abstract Introduction The assessment of diastolic function is of paramount importance in a context of an epidemic of HFpEF. (1) Left atrial reservoir Strain (LARS) <18% identif patients with elevated filling pressures when one of the three standard criteria is not available. (2) However, LARS has better accuracy in patients with reduced than preserved EF. (2,3) The aim of our study was to assess the prognosis of patients with preserved LVEF according to the different grades of diastolic function and to determine whether LARS can improve the prognostic assessment of these patients. Methods Observational, prospective, single-center study. We included 364 patients referred for transthoracic echocardiography at the indication of their responsible physician. Inclusion criteria were: LVEF>50% and sinus rhythm. Diastolic function was assessed according to current ASE/EACVI guidelines. LARS was measured in 4 and 2 chambers, obtaining a mean value. Clinical and echocardiographic parameters were evaluated. The primary endpoint was a combined event of heart failure (HF), atrial fibrillation (AF) or stroke, whichever occurred first. Events were recorded from the electronic medical record. Results 364 patients were included (53% women), age 68 years (±14), LVEF Simpson 64.4% (± 6.9), BMI 28.31 (±5.65). Patients were grouped into 4 groups: normal diastolic function (NDF) 88 patients, grade 1 diastolic dysfunction (DD1) 88 patients, grade 2-3 diastolic dysfunction (DD2-DD3) 114 patients and indeterminate diastolic function or diastolic dysfunction of undetermined grade (IDF-DDI) 76 patients. After a mean follow-up of 2.44 (±1.03) years, 55 events were recorded (15% of the sample). Compared to patients with NDF (1 event/88 patients), those with DD1 had no increased risk, HR 0.73 (0.05- 11.87), p=0.82, while those with FDI-DDI and DD2-DD3 had increased risk of events, HR 9.21 (1.16-73.35), p= 0.04 and HR 16.88 (2.09- 136.31), p=0.008, respectively. Figure 1. On the other hand, compared to patients with LARS >24%, those with a LARS 18-24% and with a LARS ≤18% presented higher risk of events, HR 2.99 (1.37- 6.53), p=0.006 and HR 5.25 (2.14- 12.88), p=0.0003, respectively. Figure 2A. Analyzing only patients with IDF-DDI, again those with LARS ≤18% and LARS 18-24% were at higher risk than those with LARS >24%. Figure 2B. Conclusions In our population of patients with preserved LVEF and sinus rhythm, those with DD2-DD3 and with IDF-DDI are at increased risk of presenting combined HF/ AF/stroke events, not so those with DD1. A LARS value ≤24% identifies patients at increased risk of events, also in those with IDF-DDI. Therefore, from a prognostic point of view, in our study a LARS value ≤24% better identifies patients at increased risk of events than a LARS value ≤18%. This could have implications in AF screening and risk factors management. More studies will be needed to confirm these results.Figure 1.Kaplan-Meier curves of combineFigure 2.Kaplan-Meier curves for the pr

Left atrial stiffness evaluation in beta-thalassemia major patients

Abstract Introduction Diastolic dysfunction is the earliest cardiac abnormality in β-thalassemia major (β-TM) patients and HFpEF is the predominant cardiac phenotype in symptomatic β-TM patients. Left atrial stiffness index (LASI) has been proved to have prognostic value in HFpEF patients. Purpose In our study we aimed to evaluate LASI in β-TM patients and assess its relation with conventional indices of diastolic function. Methods Sixty β-TM patients and twenty-nine controls were included in this cross-sectional study. Left ventricular ejection fraction (LVEF), early mitral inflow velocity to basal septal early diastolic velocity ratio (E/e'), left atrial volume index (LAVI), tricuspid valve regurgitation velocity (TVR) and left atrial deformation at reservoir phase (LASr) were calculated. T2* was used for myocardial iron load estimation. LASI was calculated as the [E/e’]/[LASr] ratio. Patients with LVEF <50% were excluded. LAVI, E/e’ and TVR were used as criteria of diastolic dysfunction. Results LASI was greater in patients compared to controls (0.30 ± 0.22 vs 0.18 ± 0.06, p = 0.003). Patients with diastolic dysfunction (n = 16) had greater LASI than patients without (n = 20) (0.49 ± 0.35 vs 0.21 ± 0.05, p = 0.001) as well as lower LASr (34.0 ± 15.6% vs 42.1 ± 6.7%, p = 0.043). Patients with indeterminate diastolic status (n = 24) had LASI = 0.26 ± 0.08 and LASr = 45.5 ± 13.6%. No correlation was found between LASI and T2* (p = 0.221). Conclusions β-TM patients with echocardiographic evidence of diastolic dysfunction have increased LASI. Myocardial iron load did not correlate with left atrial stiffness. A significant portion of β-TM patients have indeterminate diastolic function based on conventional criteria and novel indices, such as LASI or LASr, could be useful for reclassification of these particular patients.

Noninvasive assessment of left ventricular end-diastolic pressure using machine learning-derived phasic left atrial strain.

While transthoracic echocardiography (TTE) assessment of left ventricular end-diastolic pressure (LVEDP) is critically important, the current paradigm is subject to error and indeterminate classification. Recently, peak left atrial strain (LAS) was found to be associated with LVEDP. We aimed to test the hypothesis that integration of the entire LAS time curve into a single parameter could improve the accuracy of peak LAS in the noninvasive assessment of LVEDP with TTE. We retrospectively identified 294 patients who underwent left heart catheterization and TTE within 24 h. LAS curves were trained using machine learning (100 patients) to detect LVEDP ≥ 15 mmHg, yielding the novel parameter LAS index (LASi). The accuracy of LASi was subsequently validated (194 patients), side by side with peak LAS and ASE/EACVI guidelines, against invasive filling pressures. Within the validation cohort, invasive LVEDP was elevated in 116 (59.8%) patients. The overall accuracy of LASi, peak LAS, and American Society of Echocardiography/European Association for Cardiovascular Imaging (ASE/EACVI) algorithm was 79, 75, and 76%, respectively (excluding 37 patients with indeterminate diastolic function by ASE/EACVI guidelines). When the number of LASi indeterminates (defined by near-zero LASi values) was matched to the ASE/EACVI guidelines (n = 37), the accuracy of LASi improved to 87%. Importantly, among the 37 patients with ASE/EACVI-indeterminate diastolic function, LASi had an accuracy of 81%, compared with 76% for peak LAS. LASi allows the detection of elevated LVEDP using invasive measurements as a reference, at least as accurately as peak LAS and current diastolic function guideline algorithm, with the advantage of no indeterminate classifications in patients with measurable LAS.

Improvement of hypertension control and left-ventricular function after cure of primary hyperparathyroidism.

Cardiovascular mortality is significantly higher in patients with primary hyperparathyroidism (PHPT) compared to the general population. The role of the renin-angiotensin-aldosterone system (RAAS) as a mediator of cardiovascular pathology in PHPT is unclear, as is the question whether successful parathyroidectomy (PTX) mitigates hypertension (HT), and left-ventricular (LV) dysfunction. In 45 consecutive, hypercalcemic PHPT patients (91% female, 20 normotensive, mean age 54.6 ± 14.6), laboratory examinations, and 24h ambulatory blood pressure monitoring (ABPM) were performed before, one and six months after successful PTX, while transthoracic echocardiography (TTE) pre- and six months post-PTX. Both in patients with normotension (NT) and HT, lower calcemia and parathyroid hormone (PTH) as well as higher phosphatemia were observed on follow-up, while B-type natriuretic peptide, aldosterone, plasma renin activity, and aldosterone-to-renin ratios were comparable. Six months post-PTX, only in patients with HT, median 24-hour SBP/DBP decreased by 12/6 mmHg, daytime SBP by 10, and nighttime DBP by 5 mmHg. Improvement in BP was observed in approximately 78% of patients with HT. Six months post-PTX, TTE revealed: 1) decrease in median LV mass index (by 2 g/m2) and end-diastolic dimension (by 3mm) among patients with HT; 2) normalization of global longitudinal strain in 22% of patients (comparable between those with NT and HT); 3) a mean 12.7% reduction in left-atrium volume index among patients with HT, which underlay normalization of indeterminate diastolic function in 3 out of 6 patients with HT, who exhibited it at baseline (dysfunction persisted in 2). PTX was shown to significantly reduce BP, LV hypertrophy and diastolic dysfunction parameters in PHPT patients with HT, and improve systolic function in all PHPT patients.

Left ventricular strain-volume loops and diastolic dysfunction in suspected heart failure with preserved ejection fraction

BackgroundPresence of left ventricular diastolic dysfunction (DD) is key in the pathogenesis of heart failure with preserved ejection fraction (HFpEF). However, non-invasive assessment of diastolic function is complex, cumbersome, and largely based on consensus recommendations. Novel imaging techniques may help detecting DD. Therefore, we compared left ventricular strain-volume loop (SVL) characteristics and diastolic (dys-)function in suspected HFpEF patients. Method and results257 suspected HFpEF patients with sinus rhythm during echocardiography were prospectively included. 211 patients with quality-controlled images and strain and volume analysis were classified according to the 2016 ASE/EACVI recommendations. Patients with indeterminate diastolic function were excluded, resulting in two groups: normal diastolic function (control; n = 65) and DD (n = 91). Patients with DD were older (74.8 ± 6.9 vs. 68.5 ± 9.4 years, p < 0.001), more often female (88% vs 72%, p = 0.021), and more often had a history of atrial fibrillation (42% vs. 23%, p = 0.024) and hypertension (91% vs. 71%, p = 0.001) compared to normal diastolic function. SVL analysis showed a larger uncoupling i.e., a different longitudinal strain contribution to volume change, in DD compared to controls (0.556 ± 1.10% vs. -0.051 ± 1.14%, respectively, P < 0.001). This observation suggests different deformational properties during the cardiac cycle. After adjustment for age, sex, history of atrial fibrillation and hypertension, we found an adjusted odds ratio of 1.68 (95% confidence interval 1.19–2.47) for DD per unit increase in uncoupling (range: −2.95–3.20). ConclusionUncoupling of the SVL is independently associated with DD. This might provide novel insights in cardiac mechanics and new opportunities to assess diastolic function non-invasively.

Abstract WP182: Diastolic Dysfunction With Elevated Left Ventricular Filling Pressures Is Associated With Embolic Stroke Of Undetermined Source And Atrial Fibrillation Detection After Ischemic Stroke

Introduction: Diastolic dysfunction, particularly with elevated left ventricle filling pressure (LVFP) is known to be a strong independent predictor of all-cause mortality and major cardiac events. There is limited data on the role of diastolic function in ischemic stroke. We hypothesize that diastolic dysfunction with elevated LVFP is more likely to be present in patients with Embolic stroke of undetermined source (ESUS) compared to non-cardioembolic stroke and is associated with AF on cardiac monitoring in the ESUS group. Methods: This is a single center retrospective study that included adult patients with a diagnosis of acute ischemic stroke from 2014 to 2016. We excluded patients with confirmed cardioembolic stroke and those with indeterminate diastolic function. ESUS was defined as no ipsilateral stenoses ≥ 50%, cardiac telemetry for at least two weeks without evidence of atrial fibrillation or atrial flutter, and a LVEF ≥ 30%. A transthoracic echocardiogram was performed and interpreted by cardiologists. Baseline patient characteristics and clinical variables were compared among patients with and without diastolic dysfunction. Potential associations between diastolic dysfunction, ESUS and AF detection in ESUS patients were assessed using logistic regression. Results: There were 509 patients, the mean age was 64.19, 54.81% were male, and 146 had LVFP data. Diastolic dysfunction overall was not associated with ESUS (adjusted OR 1.44, 95% CI 0.91-2.28, p = 0.125) or AF detection on cardiac monitoring (adjusted OR 1.87, 95% CI 0.75-4.70, p = 0.183). However, diastolic dysfunction and elevated LVFP was associated with ESUS subtype (adjusted OR 2.26, 95% CI 1.03-4.93, p = 0.041) and AF detection on cardiac monitoring (adjusted OR 3.58, 95% CI 1.07-12.01, p = 0.039). Conclusion: Our study suggests that diastolic dysfunction with elevated LVFP is associated with ESUS stroke subtype and AF detection on cardiac monitoring. Therefore, the presence of diastolic dysfunction with elevated LVFP may identify a population of stroke patients more likely to have ESUS, particularly in the setting of occult AF. Studies are needed to confirm our findings and test the safety and efficacy of anticoagulation in patients with ESUS and diastolic dysfunction with elevated LVFP.

Prognostic Impact of Indeterminate Diastolic Function in Patients With Functionally Insignificant Coronary Stenosis

Cardiac diastolic dysfunction is an independent predictor of mortality, regardless of left ventricular (LV) systolic function. However, the current guidelines that define cardiac diastolic dysfunction may underrate the clinical implications of those with indeterminate diastolic function. We sought to evaluate the prognostic implications of indeterminate diastolic function on echocardiography and its association with coronary microvascular dysfunction (CMD). A total of 330 patients without LV systolic dysfunction and significant epicardial coronary stenosis (fractional flow reserve > 0.80) were analyzed from a prospective registry. Cardiac diastolic dysfunction was defined according to 2 algorithms depending on the presence of myocardial disease. First, the presence of myocardial disease and evidence of elevated LV filling pressure indicated diastolic dysfunction. Second, diastolic function in those without myocardial disease was defined using echocardiographic parameters (E/e', e' velocity, tricuspid regurgitation velocity, and left atrial volume index). Patients who did not meet half of the available criteria were classified as having indeterminate diastolic function. Coronary microvascular dysfunction was defined as coronary flow reserve < 2.0 and index of microcirculatory resistance ≥ 25 U. The primary outcome was cardiovascular death or admission for heart failure at 5years. Coronary flow reserve was lower in patients with indeterminate diastolic function compared with those with no diastolic dysfunction (3.5±1.6 vs 3.2±1.6, P=.002). The prevalence of CMD was also higher in patients with indeterminate diastolic function than in those with no diastolic dysfunction (10.6% vs 4.9%, P<.034). Patients with indeterminate diastolic function showed significantly higher risk of cardiovascular death or admission for heart failure than those without indeterminate diastolic function but not greater than those with definite diastolic dysfunction (cumulative incidence: 12.6%, 27.2%, and 32.7%, respectively, log-rank P<.001). Presence of CMD and elevated LV filling pressure (E/e'>14) were independent predictors for cardiovascular death or admission for heart failure in patients with indeterminate diastolic function. Patients with indeterminate diastolic function on echocardiogram showed higher risk of cardiovascular death or admission for heart failure than those with no diastolic dysfunction. Presence of CMD and elevated LV filling pressure were independent predictors for cardiovascular death or admission for heart failure among patients with indeterminate diastolic function.

Clinical trajectories and outcomes of patients with heart failure with preserved ejection fraction with normal or indeterminate diastolic function.

We recently reported that nearly half of patients with heart failure with preserved ejection fraction (HFpEF) did not show echocardiographic diastolic dysfunction (DD), but had normal diastolic function (ND) or indeterminate diastolic function (ID). However, the clinical course and outcomes of patients with HFpEF with ND or ID (ND/ID) remain unknown. From the PURSUIT-HFpEF registry, we extracted 289 patients with HFpEF with ND/ID at discharge who had echocardiographic data at 1-year follow-up. Patients were classified according to the status of progression from ND/ID to DD at 1year. Primary endpoint was a composite of all-cause death or HF rehospitalization. Median age was 81years, and 138 (47.8%) patients were female. At 1year, 107 (37%) patients had progressed to DD. The composite endpoint occurred in 90 (31.1%) patients. Compared to patients without progression to DD, those with progression had a significantly higher cumulative rate of the composite endpoint (P < 0.001) and HF rehospitalization (P < 0.001) after discharge and at the 1-year landmark (P = 0.030 and P = 0.001, respectively). Progression to DD was independently associated with the composite endpoint (hazard ratio (HR): 2.014, 95%CI 1.239-3.273, P = 0.005) and HF rehospitalization (HR: 2.362, 95%CI 1.402-3.978) after discharge. Age (odds ratio (OR): 1.043, 95%CI 1.004-1.083, P = 0.031), body mass index (BMI) (OR: 1.110, 95%CI 1.031-1.195, P = 0.006), and albumin (OR: 0.452, 95%CI 0.211-0.969, P = 0.041) were independently associated with progression from ND/ID to DD. More than one-third of HFpEF patients with ND/ID progressed to DD at 1year and had poor outcomes. Age, BMI and albumin were independently associated with this progression. UMIN000021831.

The clinical implications of left ventricular diastolic dysfunction in systemic sclerosis.

We sought to quantify the burden of left ventricular diastolic dysfunction (LVDD) and heart failure with preserved ejection fraction (HFpEF) in systemic sclerosis (SSc) and assess the progression of LVDD over time and its prognostic importance. Two-hundred and twenty-five participants enrolled in the Australian Scleroderma Cohort Study were included and LVDD was assessed according to 2016 ASE/EACVI Guidelines. Logistic regression analyses and generalised estimating equations were performed to evaluate the relationship between LVDD and SSc disease characteristics and symptoms and signs of heart failure, respectively. The relationship between LVDD and mortality was assessed using Kaplan-Meier survival estimates. Thirty-four (15%) participants were diagnosed with LVDD. A further 89 (40%) participants had indeterminate diastolic function. Older age (p<0.01), hypertension (p=0.02), impaired systolic function (p=0.03) and interstitial lung disease (p=0.01) were all associated with the presence of LVDD. There was no association between the presence of LVDD and clinical signs of heart failure, however, LVDD was associated with more breathlessness and worse functional class (p=0.03). LVDD was observed to progress over time, with significant worsening of parameters of left ventricular filling pressure. There was no significant relationship between LVDD and mortality (p=0.23). Abnormal diastolic function is a common finding in SSc, progresses over time and is associated with more severe dyspnoea. Whilst patients with LVDD are more breathless, LVDD is not clearly associated with clinical findings of heart failure demonstrating that LVDD may be of importance in explaining symptoms even in the absence of HFpEF in SSc.

Clinical trajectory and outcomes of patients with heart failure with preserved ejection fraction with normal or indeterminate diastolic function

Abstract Background Heart failure (HF) with preserved ejection fraction (HFpEF) is a chronic and progressive disease, but limited therapeutic strategies are currently available. Although left ventricular diastolic dysfunction (DD) is a prominent mechanism of HFpEF, a certain number of patients with HFpEF have a normal diastolic function (ND) or indeterminate diastolic function (ID). With the progressive nature of HFpEF, diastolic function may change over time. However, the change of diastolic function, its predictor and prognosis in patients with clinically established HFpEF remains unknown. Purpose To investigate the clinical trajectory and outcomes of patients with HFpEF with ND or ID and to identify factors associated with progression from ND or ID at discharge to DD at 1-year follow-up. Methods Using data from a prospective multicenter observational study of patients with HFpEF, we extracted 289 patients with HFpEF with ND or ID at discharge who had echocardiographic data at 1-year follow-up for the re-evaluation of diastolic function. Diastolic function was assessed according to the 2016 American Society of Echocardiography recommendations. Patients were classified according to the absence or presence of progression from ND or ID to DD at 1 year. The primary endpoint was a composite of all-cause death and HF rehospitalization. Results Median age was 81 years, and 138 (47.8%) patients were female. At 1 year, 107 (37%) patients progressed to DD. During a median follow-up of 709 days, the composite endpoint occurred in 90 (31.1%) patients. Compared to patients without progression to DD, those with progression to DD had a significantly higher cumulative incidence rate of the composite endpoint (incidence rate: 11.7/100 person-year versus 23.3/100 person-year, P&amp;lt;0.001). Progression to DD (adjusted HR: 2.014, 95% CI: 1.239–3.273, P=0.005) was independently associated with the composite endpoint. Age (adjusted OR: 1.046, 95% CI: 1.008–1.087, P=0.018), body mass index (BMI) (adjusted OR: 1.107, 95% CI: 1.029–1.192, P=0.006), and serum albumin (adjusted OR: 0.459, 95% CI: 0.216–0.974, P=0.042) were independently associated with progression from ND or ID to DD at 1 year. Conclusion More than one-third of patients with HFpEF with ND or ID progressed to DD at 1 year and had poor clinical outcomes. Age, BMI, and serum albumin were independently associated with this progression. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): This work was supported by grants from Japan Society for the Promotion of Science KAKENHI (No. JP 17K09496) and Japan Agency for Medical Research and Development (No. JP16lk1010013).

Left atrial dysfunction is an independent predictor of mortality in patients with cirrhosis treated by transjugular intrahepatic portosystemic shunt.

The present study aimed to investigate (1) the association between left ventricular diastolic dysfunction (LVDD), graded according to the algorithm proposed by the Cirrhotic Cardiomyopathy Consortium, and long‐term survival in patients with cirrhosis undergoing transjugular intrahepatic portosystemic shunt (TIPS) and (2) the additive prognostic value of left atrial (LA) function, as assessed by LA reservoir strain, using two‐dimensional speckle‐tracking echocardiography (2D‐STE). A total of 129 TIPS candidates (mean ± SD, 61 ± 12 years; 61% men) underwent a comprehensive preprocedural echocardiography. LA dysfunction was defined by LA reservoir strain ≤35%, based on a previously suggested cut‐off value. The outcome was all‐cause mortality after TIPS. In the current cohort, 65 (50%) patients had normal diastolic function, 26 (20%) patients had grade 1 LVDD, 21 (16%) patients had grade 2 LVDD, and 17 (13%) patients had indeterminate diastolic function. Additionally, LA dysfunction (based on LA reservoir strain ≤35%) was noted in 67 (52%) patients. After a median follow‐up of 36 months (range, 12–80), 65 (50%) patients died. All‐cause mortality rates increased along worse grades of LVDD (log‐rank p = 0.007) and with LA dysfunction (log‐rank p = 0.001). On multivariable Cox regression analysis, Model for End‐Stage Liver Disease score (hazard ratio [HR],1.06; p = 0.003), hemoglobin (HR, 0.74; p = 0.022), and LA strain, expressed as a continuous variable (HR, 0.96; p = 0.005) were independently associated with all‐cause mortality. Notably, the addition of LA strain to the model provided incremental prognostic value over the established prognostic variables (delta χ 2 = 8.27, p = 0.004). Conclusion: LA dysfunction assessed with 2D‐STE is independently associated with all‐cause mortality in patients with cirrhosis treated by TIPS.

Comparison Between Echocardiography and Cardiac Computed Tomography in the Evaluation of Diastolic Dysfunction and Prediction of Heart Failure

Recent data indicate that left atrial (LA) function assessment by cardiac computed tomography (CT) is closely related to diastolic dysfunction (DD). Therefore, we aimed to perform a direct comparison between CT and echocardiography for diagnosis of advanced DD and prediction of future heart failure or cardiovascular death. We identified 340 patients who had both spiral cardiac CT and a proximate echocardiogram. LA total emptying fraction (LATEF), a measure of global LA function, was automatically calculated from CT data, as a surrogate for diastolic function and was compared with echocardiographic grades of diastolic function. The area under the receiver operating characteristic curve for LATEF to differentiate between advanced DD (grades 2 and 3) and all other grades was 0.84 (0.79 to 0.88). Over a median of 4 years, 69 events (admissions for heart failure and cardiovascular deaths) occurred. By multivariate Cox analysis, LATEF &lt;40% provided incremental prognostic information after adjustments for advanced DD by echocardiography (hazard ratio 2.15, 95% confidence interval 1.13 to 3.94). There was a significant interaction (p=0.03) between LATEF and echocardiography-based diastolic grades. Stratified analyses within the diastolic function groups revealed that LATEF &lt;40% was equivalent to echocardiography in predicting events in the subgroup with advanced DD by echocardiography (p=0.20) but was associated with a significantly higher event rates in patients with normal filling pressures (p=0.0001) or indeterminate diastolic function (p=0.04) by echocardiography. In conclusion, LA function derived from CT can accurately detect advanced DD diagnosed by echocardiography and has additive value to echocardiography-derived DD.

Impact of 2016 American Society of Echocardiography/European Association of Cardiovascular Imaging Recommendations for the Evaluation of Left Ventricular Diastolic Function on Predicting Outcomes in Patients with Diabetes and Hypertension without a History of Cardiovascular Disease

Background: The prognostic value of diastolic dysfunction estimates in clinical settings is not well established. We aimed to evaluate the impact of the 2016 American Society of Echocardiography and the European Association of Cardiovascular Imaging recommendations on estimates of diastolic dysfunction and predicting cardiovascular outcomes in patients with diabetes and hypertension. Methods: In total, 111 patients with diabetes and hypertension without a known history of cardiovascular diseases were enrolled. All patients had preserved left ventricular ejection fraction on echocardiography at screening. Echocardiography was performed at baseline. The 2009 and 2016 algorithms were applied in diastolic function assessment. All patients were followed up for 1 year to assess clinical outcomes. Results: There were 65 (58.6%) female patients. The mean age was 59.86 ± 7.45 years, and the mean duration of diabetes was 10.5 ± 5.41 years. Fifty-five (50.5%) patients had left ventricular hypertrophy on echocardiography. The prevalence of diastolic dysfunction was lower and that of indeterminate diastolic function was higher with 2016 recommendations. Concordance between 2016 and 2009 recommendations was poor with a reclassification rate of 41.4%. No patients diagnosed with indeterminate and normal diastolic function using the 2016 algorithm and diastolic dysfunction using the 2009 algorithm developed major adverse cardiac events at 1 year. Two of 11 patients diagnosed with diastolic dysfunction using both recommendations and two of five patients diagnosed with diastolic dysfunction and indeterminate diastolic function using 2016 and 2009 recommendations, respectively, developed major adverse cardiac events at 1 year. The 2016 algorithm showed better accuracy in predicting major adverse cardiac events at 1 year. Conclusion: The updated 2016 criteria detect more advanced diastolic dysfunction cases and predict 1-year cardiovascular outcomes. Further studies are warranted to investigate the prognostic impact of these criteria. Trial registration number: NMRR-16-436-29619.

Diastolic stress echocardiography and biomarkers in patients with preserved left ventricle ejection fraction and heart failure symptoms.

Diastolic dysfunction (DD) is a diagnostic challenge in clinical practice. Our study aimed to evaluate the value of diastolic stress echocardiography (DSE) and heart failure (HF) biomarkers in patients with preserved left ventricular ejection fraction (LVEF) and HF symptoms. All the consecutive patients with HF symptoms, preserved LVEF, and suspected DD were examined on transthoracic echocardiography (TTE) and DSE using the protocol according to the American Society of Echocardiography recommendations. Moreover, blood samples were taken 30 minutes before and after DSE for the following lab markers: N-terminal pro-B type natriuretic peptide (NT-proBNP), mid regional pro-atrial natriuretic peptide (MR-proANP), and serum soluble ST2 receptor (ST2). The study group included 80 patients (mean [standard deviation, SD] age, 69 (8.1) years; 25% males) with dyspnea (New York Heart Association classification IIa - 53; IIb - 17; III - 10) and risk factors: hypertension (96%), diabetes (41%), obesity (56%), and known coronary artery disease (10%). The rest transthoracic echocardiography (TTE) showed preserved systolic function (mean [SD], LVEF 61.1 [10.5]%) and normal or indeterminate diastolic function. DSE revealed a positive result for diastolic dysfunction in 17 patients (21%). The receiver operating characteristic (ROC) analysis showed that age (the area under the curve [AUC], 0.725; P < 0.01), left atrial volume indexed for body surface area [LAVI] rest (AUC, 0.722; P < 0.01), E/e' rest (AUC, 0.790; P < 0.01), and baseline NT-proBNP (AUC, 0.713; P < 0.01) predicted positive DSE. Other parameters, including body mass index, baseline E/A, DT, or e' were not predictive of DSE results. DSE revealed diastolic dysfunction in 21% of study patients and improved the diagnostic value of echocardiography. Rest NT-proBNP, but not MR-proANP and ST2, provided a diagnostic value for diastolic dysfunction.

Additive prognostic and diagnostic value of diastolic exercise parameters in patients referred for exercise echocardiography.

Exercise echocardiography (ExE) may evaluate left ventricular (LV) systolic and diastolic function. We aimed to assess the value of diastolic parameters at exercise [early LV inflow velocity to early tissue Doppler annulus velocity (E/e')] in patients with normal or abnormal resting diastolic function (DF) referred for a clinically indicated ExE. LV systolic and DF according to ASE/EACVI guidelines and mitral regurgitation (MR) were evaluated at rest in 772 patients (age 67 ± 12 years) with preserved LV ejection fraction (LVEF ≥ 50%). We assessed regional/global LV systolic function at peak exercise, while MR and E/e' where evaluated in the immediate post-exercise period. Abnormal ExE was defined as ischaemia or fixed wall motion abnormalities, and raised E/e' values as >15 at rest and at exercise (e' at the septal level). Patients were grouped as complaining or not of dyspnoea. Events were overall mortality, myocardial infarction, admission for unstable angina or cardiac failure, and coronary revascularization. DF was abnormal at rest in 221 patients (29%) and indeterminate in 77 (10%), with similar percentages in patients with and without dyspnoea. Exercise E/e' >15 was found in 37% of patients with abnormal DF, 21% with indeterminate DF, and 6% with normal DF (P < 0.001). Patients with abnormal ExE had more often abnormal resting DF (39% vs. 25%, P = 0.001) and exercise E/e' >15 (25% vs. 13%, P < 0.001) than those with normal ExE. During a median follow-up of 1.68 years, there were 132 events. Independent predictors included peak exercise LVEF [hazard ratio (HR) = 0.93, 95% confidence interval (CI) = 0.91-0.94, P < 0.001], and exercise E/e' (HR= 1.04, 95% CI = 1.01-1.07, P = 0.01). Neither resting E/e' values nor resting abnormal DF by ASE/EACVI guidelines, were independent predictors. Annualized event-rates were 43.2% in patients with (+) ExE plus (+) exercise E/e', 23.8% in those with (+) ExE and (-) exercise E/e', 7.9% in (-) ExE and (+) exercise E/e', and 3.6% with both variables normal. The results of diastolic dysfunction at rest and at exercise were similar between patients with or without dyspnoea referred for ExE, but they were associated with abnormal ExE. Exercise E/e' reclassified 21% of patients with indeterminate DF and further predicted outcome on top of ExE results.