Global constructive work and left atrial reservoir function is reduced in patients with heart failure with preserved ejection fraction compared with patients with preclinical diastolic dysfunction

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
L.G Tunyan ◽  
A.L Chilingaryan ◽  
K.G Adamyan ◽  
P.H Zelveyan ◽  
L.R Tumasyan ◽  
...  

Abstract   Heart failure with preserved ejection fraction (HFpEF) remains an unresolved issue with morbidity and mortality comparable with that of reduced EF HF. Diastolic dysfunction (DD) is the hallmark of HFpEF but it is unclear why some patients do not develop symptoms and remain in preclinical DD (PDD) stage with the same degree of DD as patients with HFpEF. We assumed that patients with HFpEF might have more deteriorated global myocardial work (GW) and left atrial reservoir longitudinal strain (LALS) parameters compared with PDD patients. Methods 210 patients (150 female, mean age 71±5 years) of which 118 with PDD and 92 with HFpEF were enrolled in this study. PDD was diagnosed if patients had normal NT-proBNP values, and at least 3 of the following echocardiographic criteria at rest or after diastolic stress echocardiography: end-systolic left atrial volume index (LAVi) >34 ml/m2, LV E/e' >13, average LV e' >8.5, and systolic pulmonary artery pressure >30 mmHg. GW index (GWI) was obtained from pressure-strain loops composed from speckle tracking analysis indexed to brachial systolic blood pressure, global constructive work (GCW) was measured as the sum of positive work due to myocardial shortening during systole and negative work due to lengthening during isovolumic relaxation, global wasted work (GWW) was calculated as energy loss by myocardial lengthening in systole and shortening in isovolumic relaxation, and GW efficiency (GWE) as the percentage ratio of constructive work to the sum of constructive work and wasted work. LALS was measured by speckle tracking echocardiography as average value of two basal segments in apical 4 chamber view along LAVi and 4D LV mass index (LVMi) offline by experienced echocardiographer who was unaware of the study aims. Results Patients with PDD and HFpEF have comparable values of LAVi, LVMi, GWI, GWW, and GWE (LAVi 38.4±3.9 ml/m2 vs 39.1±4.1 ml/m2, p=NS; LVMi 82.8±11.4 g/m2 vs 83.5±10.2 g/m2, p=NS; PDD GWI 2389±154 mmHg% vs 2368±139 mmHg%, p=NS; GWW 62±5 mmHg% vs 65±4 mmHg%, p=NS; GWE PDD 89±9% vs 87±11%, p=NS). LALS and GCW were significantly reduced in patients with HFpEF compared with PDD patients (LALS 21.3±7% vs 29±5%, p<0.01; GCW 1964±112 mmHg% vs 2259±164 mmHg%, p<0.01). Conclusion Patients with HFpEF have reduced LALS and GCW compared with PDD patients. Both parameters are indicative for LA and LV myocardial fibrotic burden respectively which might be one of the probable explanations of PDD transition to HFpEF. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): Committee of Science at Ministry of Education of Republic of Armenia

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
A Katbeh ◽  
T De Potter ◽  
P Geelen ◽  
G Di Gioia ◽  
M Kodeboina ◽  
...  

Abstract Background Diagnosis of heart failure with preserved ejection fraction (HFpEF) in patients with dyspnea and paroxysmal atrial fibrillation (AF) is challenging. Speckle tracking-derived left atrial strain (LAS) provides an accurate estimate of left ventricular filling pressures and left atrial phasic function. However, data on clinical utility of LAS in patients with dyspnea and AF are scarce. Objective To assess relationship between LAS and probability of HFpEF in patients with dyspnea and paroxysmal AF. Methods The study included 205 consecutive patients (62±10 years, 58% males) with limiting dyspnea (NYHA ≥ II), paroxysmal AF and preserved LVEF (≥50%), who underwent speckle tracking echocardiography and natriuretic peptide (NT-proBNP) assessment during sinus rhythm. Patients with manifest ischemic heart or valve disease, and cardiomyopathy were excluded. Probability of HFpEF was estimated using H2FPEF and HFA-PEFF scores, which combine clinical characteristics, echocardiographic parameters and natriuretic peptides. Results A total of 61 (30%), 115 (56%) and 29 (14%) had respectively high, intermediate and low probability of HFpEF. Patients with high probability of HFpEF were significantly older, had higher body mass index, NT-proBNP, E/e', pulmonary artery pressure and larger LA volume index than patients in low-to-intermediate probability groups (all p<0.05). Two distinct patterns of LA phasic function were observed. Firstly, reservoir LAS showed close inverse association with increasing probability of HFpEF. Secondly, contractile LAS showed initial decrease with subsequent compensatory increase in intermediate probability category with final decrease in patients with high HFpEF probability. In contrast, LV global longitudinal strain was similar between groups (NS). In multivariable regression analysis, reservoir LAS emerged as the strongest independent predictor of HFpEF defined by using both scores. Reservoir LAS with optimal cut off value of 24% showed sensitivity of 86% and specificity of 70% to identify high probability of HFpEF. Combination of LAS with NT-proBNP did not increase the accuracy of each parameter alone. Conclusions Reservoir LAS shows a strong independent association with probability of HFpEF in patients with dyspnea and paroxysmal AF. This advocates for more liberal use of LAS assessment to distinguish cardiac from non-cardiac dyspnea in patients with history of AF. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): International PhD programme in Cardiovascular Pathophysiology and Therapeutics (CardioPaTh).


2018 ◽  
Vol 71 (11) ◽  
pp. A831
Author(s):  
Alex Michael Parker ◽  
Kenneth Bilchick ◽  
Hunter Mwansa ◽  
Anthony Peters ◽  
Khadijah Breathlet ◽  
...  

BMJ Open ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. e044605
Author(s):  
Shiro Hoshida ◽  
Koichi Tachibana ◽  
Yukinori Shinoda ◽  
Tomoko Minamisaka ◽  
Takahisa Yamada ◽  
...  

ObjectivesThe severity of diastolic dysfunction is assessed using a combination of several indices of left atrial (LA) volume overload and LA pressure overload. We aimed to clarify which overload is more associated with the prognosis in patients with heart failure and preserved ejection fraction (HFpEF).SettingA prospective, multicenter observational registry of collaborating hospitals in Osaka, Japan.ParticipantsWe enrolled hospitalised patients with HFpEF showing sinus rhythm (men, 79; women, 113). Blood tests and transthoracic echocardiography were performed before discharge. The ratio of diastolic elastance (Ed) to arterial elastance (Ea) was used as a relative index of LA pressure overload.Primary outcome measuresAll-cause mortality and admission for heart failure were evaluated at >1 year after discharge.ResultsIn the multivariable Cox regression analysis, Ed/Ea, but not LA volume index, was significantly associated with all-cause mortality or admission for heart failure (HR 2.034, 95% CI 1.059 to 3.907, p=0.032), independent of age, sex, and the serum N-terminal pro-brain natriuretic peptide (NT-proBNP) level. In patients with a higher NT-proBNP level, the effect of higher Ed/Ea on prognosis was prominent (p=0.015).ConclusionsEd/Ea, an index of LA pressure overload, was significantly associated with the prognosis in elderly patients with HFpEF showing sinus rhythm.Trial registration numberUMIN000021831.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
E Jasic-Szpak ◽  
T H Marwick ◽  
M Przewlocka-Kosmala ◽  
E A Jankowska ◽  
P Ponikowski ◽  
...  

Abstract Atrial fibrillation (AF) is a frequent comorbidity in heart failure with preserved ejection fraction (HFpEF), worsening the clinical course. Although various contributors to the development of AF have been identified, effective screening strategies to prevent this arrhythmia are ill-defined. Aim To investigate the factors associated with incident AF in a well-characterized HFpEF population, with special focus on left atrial (LA) strain. Methods 170 pts with symptomatic HFpEF (mean age 65±8 yrs), free of baseline AF, underwent clinical evaluation, echocardiography and cardiopulmonary exercise testing. AF was diagnosed by clinical review, standard ECG, and single lead portable ECG monitoring. Results Over a median follow-up of 49 months, incident AF was identified in 39/170 pts (23%). Pts who developed AF were older, had higher clinical risk scores, BNP, creatinine, LA volume index (LAVI), LV mass, lower LA strain, exercise capacity, and more impaired LV diastolic function. The highest areas under ROC curves for AF prediction were for peak-atrial contraction strain (PACS; 0.76), total peak-atrial longitudinal strain (PALS; 0.71) and LAVI (0.72). Nested Cox regression models showed that the predictive value of LA strain was independent from and incremental to clinical data, LAVI and E/e' ratio estimating LV filling pressure (Figure). Addition of total PALS to the model including CHA2DS2VASc score, LAVI and E/e' improved classification by 37% (p=0.04), and subsequent addition of PACS improved classification by 54% (p=0.003). Figure 1 Conclusions LA strain, especially PACS, provides incremental predictive information about incident AF in HFpEF. The inclusion of LA strain to the diagnostic algorithm may help guide screening for AF risk in this population.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
M S Dzeshka ◽  
E Shantsila ◽  
V A Snezhitskiy ◽  
G Y H Lip

Abstract Introduction Atrial fibrillation (AF) and heart failure with preserved ejection fraction (HFpEF) commonly coexist. AF is associated with left atrial (LA) and ventricular (LV) myocardial fibrosis, contributing to diastolic dysfunction in HFpEF. Many profibrotic pathways have been studied in AF and HFpEF, but scarce data are available on the role of circulating microparticles (MPs). Purpose To evaluate association of circulating biomarkers of fibrosis and MPs subsets with Doppler-derived parameters of diastolic function in AF and HFpEF. Methods We studied 274 patients with non-valvular AF and HFpEF (median age 62 years, 37% females). Paroxysmal AF was diagnosed in 150 patients (55%) and non-paroxysmal AF (persistent or permanent) in 124 (45%). Median CHA2DS2-VASc score was 3 in males and 4 in females. Transthoracic echocardiography was performed to assess LV diastolic function, including early mitral inflow velocity (E), E/A velocities ratio (on sinus rhythm), early mitral annular diastolic velocity (E') for LV septal and lateral basal regions, E/E' ratio, LA maximum volume index (LAVi), E-wave velocity deceleration time (DT), flow propagation velocity (Vp). Average values from ten consecutive cardiac cycles were calculated. E/E' ratio was chosen as valid and reproducible index of diastolic function in AF patients for regression analysis. Blood levels of galectin 3, interleukin-1 receptor-like 1 (ST2), transforming growth factor beta 1 (TGF-β1), procollagen type III aminoterminal propeptide (PIIINP), matrix metalloproteinase 9 (MMP-9), tissue inhibitor of matrix metalloproteinase 1 (TIMP-1), angiotensin II and aldosterone level were assayed as surrogate biomarkers of myocardial fibrosis and profibrotic signaling. Using microflow cytometry, numbers of platelet-derived (CD42b+), monocyte-derived (CD14+), endothelial (CD144+), and apoptotic MPs (Annexin V+) were quantified in plasma samples. Linear regression was used to reveal parameters associated with diastolic function assessed as E/E' ratio. Data were normalized with Box-Cox transformation. Results Grade I diastolic dysfunction was found in 149 (54%); 94 (34%), and 31 (11%) patients had grade II and grade III diastolic dysfunction, respectively. On univariate analysis, age (β=0.23, p=0.0001); male gender (β=-0.19, p=0.02); history of hypertension (β=0.15, p=0.02); AF type, i.e. progression from paroxysmal to permanent (β=0.14, p=0.02); AnV+ MPs (β=0.19, p=0.01); angiotensin II (β=0.13, p=0.04); ST2 (β=0.1, p=0.04); and TIMP-1 (β=0.13, p=0.03) were associated with E/E' ratio. Using stepwise multivariate regression, AnV+ MPs (β=0.15, p=0.01) and TIMP-1 (β=0.3, p=0.04) remained significant predictors of E/E' ratio, adjusted for age, gender, hypertension and AF type. Relation of E/E' to TIMP-1 and AnV+ MPs Conclusion Apoptotic (AnV+) MPs and TIMP-1 were independently associated with diastolic dysfunction in AF and HFpEF. These may contribute to the pathophysiology of AF and HFpEF, and complications related to the presence of both. Acknowledgement/Funding ESC Research Grant, EHRA Academic Research Fellowship Programme


2019 ◽  
Vol 10 ◽  
pp. 204201881986159 ◽  
Author(s):  
Gaurav S. Gulsin ◽  
Prathap Kanagala ◽  
Daniel C. S. Chan ◽  
Adrian S. H. Cheng ◽  
Lavanya Athithan ◽  
...  

Background: Attempts to characterize cardiac structure in heart failure with preserved ejection fraction (HFpEF) in people with type 2 diabetes (T2D) have yielded inconsistent findings. We aimed to determine whether patients with HFpEF and T2D have a distinct pattern of cardiac remodelling compared with those without diabetes and whether remodelling was related to circulating markers of inflammation and fibrosis and clinical outcomes. Methods: We recruited 140 patients with HFpEF (75 with T2D and 65 without). Participants underwent comprehensive cardiovascular phenotyping, including echocardiography, cardiac magnetic resonance imaging and plasma biomarker profiling. Results: Patients with T2D were younger (age 70 ± 9 versus 75 ± 9y, p = 0.002), with evidence of more left ventricular (LV) concentric remodelling (LV mass/volume ratio 0.72 ± 0.15 versus 0.62 ± 0.16, p = 0.024) and smaller indexed left atrial (LA) volumes (maximal LA volume index 48 ± 20 versus 59 ± 29 ml/m2, p = 0.004) than those without diabetes. Plasma biomarkers of inflammation and extracellular matrix remodelling were elevated in those with T2D. Overall, there were 45 hospitalizations for HF and 22 deaths over a median follow-up period of 47 months [interquartile range (IQR) 38–54]. There was no difference in the primary composite endpoint of hospitalization for HF and mortality between groups. On multivariable Cox regression analysis, age, prior HF hospitalization, history of pulmonary disease and LV mass/volume were independent predictors of the primary endpoint. Conclusions: Patients with HFpEF and T2D have increased concentric LV remodelling, smaller LA volumes and evidence of increased systemic inflammation compared with those without diabetes. This suggests the underlying pathophysiology for the development of HFpEF is different in patients with and without T2D. ClinicalTrials.gov identifier: NCT03050593.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Ilona Cuijpers ◽  
Paolo Carai ◽  
Pedro Mendes-Ferreira ◽  
Steven J. Simmonds ◽  
Paul Mulder ◽  
...  

Abstract Heart failure with preserved ejection fraction (HFpEF) is currently untreated. Therapeutics development demands effective diagnosis of diastolic dysfunction in animal models mimicking human pathology, which requires appropriate anaesthetics. Here, we investigated which anaesthetic, ketamine/xylazine or isoflurane, could be used to reveal diastolic dysfunction in HFpEF-diseased obese ZSF1 rats by echocardiography. First, diastolic dysfunction was confirmed by pressure-volume loops in obese compared to lean control ZSF1 rats. In echocardiography, ketamine/xylazine, unlike isoflurane, was able to demonstrate impaired relaxation in obese ZSF1 rats, as reflected by impaired early (E) and late (A) filling peak velocities, decreased E/A ratio, and a prolonged deceleration and isovolumic relaxation time. Interestingly, ketamine/xylazine induced a wider separation of both tissue and pulsed wave Doppler-derived echocardiographic waves required for diastolic dysfunction diagnosis, potentially by reducing the heart rate (HR), while isoflurane resulted in merged waves. To assess whether HR-lowering alone explained the differences between the anaesthetics, echocardiography measurements under isoflurane with and without the HR-lowering drug ivabradine were compared. However, diastolic dysfunction could not be diagnosed in ivabradine-treated obese ZSF1 rats. In summary, ketamine/xylazine compared to isoflurane is the anaesthetic of choice to detect diastolic dysfunction by echocardiography in rodent HFpEF, which was only partly mediated by HR-lowering.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
F.H Verbrugge ◽  
Y.N.V Reddy ◽  
S Kapa ◽  
B.A Borlaug

Abstract Background Diastolic reserve decreases with aging. A recently developed artificial intelligence (AI) algorithm can predict age based on 12-lead electrocardiogram (ECG) analysis. Purpose This study aims to use a validated AI algorithm to assess cardiac senescence and investigate the impact of obesity on cardiac aging in heart failure with preserved ejection fraction (HFpEF). Methods This retrospective cohort study includes 403 patients with HFpEF, admitted for treatment with intravenous diuretics. ECG age was assessed by a convolutional neural network as previously validated. Patients were stratified according to the presence of obesity (body mass index >30 kg/m2) and ECG age was compared between groups. The relationship between ECG versus calendar age and structural/functional alterations on echocardiography, as well as the risk of atrial fibrillation (AF) development, was evaluated. Results In 253 (63%) obese patients with HFpEF, calendar age was 8 years younger compared with their non-obese counterparts, but ECG age was only 3 years younger. ECG minus calendar age was higher in obese patients (P-value <0.001; figure) and correlated moderately strong with weight, fat free, and fat mass (r=0.35–0.41; P-value <0.001). Older ECG age was correlated with worse diastolic function, but not with left ventricular afterload (table). Calendar age correlated less strongly with diastolic dysfunction (table). ECG age did predict AF development, independently of calendar age, gender, and presence of obesity [HR (95% CI) = 1.31 (1.06–1.63) per 5-year; P-value=0.015]. Conclusions Obesity accelerates cardiac senescence in HFpEF as reflected by more pronounced diastolic dysfunction and a higher AF risk, which was identified from ECG analysis by a validated AI algorithm. Figure 1 Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Belgian American Educational Foundation (B.A.E.F.); Special Research Fund (BOF) of Hasselt University (Hasselt, Belgium).


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