scholarly journals Different Pathophysiology and Outcomes of Heart Failure With Preserved Ejection Fraction Stratified by K-Means Clustering

2020 ◽  
Vol 7 ◽  
Author(s):  
Daisuke Harada ◽  
Hidetsugu Asanoi ◽  
Takahisa Noto ◽  
Junya Takagawa

Background: Stratified medicine may enable the development of effective treatments for particular groups of patients with heart failure with preserved ejection fraction (HFpEF); however, the heterogeneity of this syndrome makes it difficult to group patients together by common disease features. The aim of the present study was to find new subgroups of HFpEF using machine learning.Methods: K-means clustering was used to stratify patients with HFpEF. We retrospectively enrolled 350 outpatients with HFpEF. Their clinical characteristics, blood sample test results and hemodynamic parameters assessed by echocardiography, electrocardiography and jugular venous pulse, and clinical outcomes were applied to k-means clustering. The optimal k was detected using Hartigan's rule.Results: HFpEF was stratified into four groups. The characteristic feature in group 1 was left ventricular relaxation abnormality. Compared with group 1, patients in groups 2, 3, and 4 had a high mean mitral E/e′ ratio. The estimated glomerular filtration rate was lower in group 2 than in group 3 (median 51 ml/min/1.73 m2 vs. 63 ml/min/1.73 m2p < 0.05). The prevalence of less-distensible right ventricle and atrial fibrillation was higher, and the deceleration time of mitral inflow was shorter in group 3 than in group 2 (93 vs. 22% p < 0.05, 95 vs. 1% p < 0.05, and median 167 vs. 223 ms p < 0.05, respectively). Group 4 was characterized by older age (median 85 years) and had a high systolic pulmonary arterial pressure (median 37 mmHg), less-distensible right ventricle (89%) and renal dysfunction (median 54 ml/min/1.73 m2). Compared with group 1, group 4 exhibited the highest risk of the cardiac events (hazard ratio [HR]: 19; 95% confidence interval [CI] 8.9–41); group 2 and 3 demonstrated similar rates of cardiac events (group 2 HR: 5.1; 95% CI 2.2–12; group 3 HR: 3.7; 95%CI, 1.3–10). The event-free rates were the lowest in group 4 (p for trend < 0.001).Conclusions: K-means clustering divided HFpEF into 4 groups. Older patients with HFpEF may suffer from complication of RV afterload mismatch and renal dysfunction. Our study may be useful for stratified medicine for HFpEF.

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Sergio Barros-Gomes ◽  
Patricia A Pellikka ◽  
Angela Dispenzieri ◽  
Hector R Villarraga

Introduction: Diastolic dysfunction has been characterized in relation to the relaxation and compliance properties of the left ventricle; limited information exists regarding its relationship to systolic function as assessed by deformation imaging. Objectives: To determine if there is left ventricular systolic dysfunction detected by global longitudinal strain (GLS) measured by two dimensional speckle tracking echocardiography in patients with immunoglobulin light chain (AL) amyloidosis with different degrees of diastolic dysfunction and normal ejection fraction (EF). Methods: Consecutive biopsy-proven AL patients with preserved EF (≥ 55%) who had a comprehensive echocardiogram performed and strain analysis were included. Cohort was divided into 5 groups according to the different grades of diastolic dysfunction: Group 0: normal filling pressures; Group 1: abnormal relaxation; Group 2: pseudo-normal pattern; Group 3: reversible restrictive; Group 4: fixed restrictive. Images were acquired and performed on a Vivid 9 from the 3 apical views, and analyzed on vendor-specific software (Echo-PAC, GE). GLS was averaged from the 16 segments, and their means compared by ANOVA and each pair with Student’s t test. Results: A total of 858 patients were included, mean age was 63.7 years ± 10.1, and 61.5% were male. From those, 205 (24%) were in group 0; 299 (35%) in group 1; 255 (30%) in group 2; 65 (7%) in group 3; and 34 in group 4 (4%). GLS means measurements were -18.95 ± 2.4, -16.86 ± 3.4, -15.60 ± 3.9, -12.31 ± 3.0, and -10.48 ± 3.3, respectively (P<0.0001). All individual GLS values were significantly different statistically when compared between each group (P<0.01 for all pairs; figure). Conclusions: Longitudinal systolic mechanical function is progressively impaired in AL amyloid patients as diastolic dysfunction progresses, despite normal EF. This systolic dysfunction provides insights into the intrinsic relationship between the components of the cardiac cycle.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
M Godet ◽  
O Raitiere ◽  
H Chopra ◽  
P Guignant ◽  
C Fauvel ◽  
...  

Abstract Background Treatment by sacubitril/valsartan decreases mortality, improves KCCQ score and ejection fraction in patients with heart failure with reduced ejection fraction (HF REF), but there is currently no data to predict response to treatment. Purpose The purpose of our work was to assess whether unbiased clustering analysis, using dense phenotypic data, could identify phenotypically distinct HF-REF subtypes with good or no response after 6 months of sacubitril/valsartan administration. Methods A total of 78 patients in NYHA functional class 2–3 and treated by ACE inhibitor or AAR2, were prospectively assigned to equimolar sacubitril/valsartan replacement. We collected demographic, clinical, biological and imaging continuous variables. Phenotypic domains were imputed with 5 eigenvectors for missing value, then filtered if the Pearson correlation coefficient was >0.6 and standardized to mean±SD of 0±1. Thereafter, we used agglomerative hierarchical clustering for grouping phenotypic variables and patients, then generate a heat map (figure 1). Subsequently, participants were categorized using Penalized Model-Based Clustering. P<0,05 was considered significant. Results Mean age was 60.4±13.4 yo and 79.0% patients were males. Mean ejection fraction was 29.3±7.0%. Overall, 16 phenotypic domains were isolated (figure 1) and 3 phenogroups were identified (Table 1). Phenogroup 1 was remarkable by isolated left ventricular involvement (LVTDD 64.3±5.9mm vs 73.9±8.7 in group 2 and 63.8±5.7 in group3, p<0.001) with moderate diastolic dysfunction (DD), no mitral regurgitation (MR) and no pulmonary hypertension (PH). Phenogroups 2 and 3 corresponded to patients with severe PH (TRMV: 2.93±0.47m/s in group 2 and 3.15±0.61m/s in groupe 3 vs 2.16±0.32m/s in group 1), related to severe DD (phenogroup 2) or MR (phenogroup 3). In both phenogroups, the left atrium was significantly enlarged and the right ventricle was remodeled, compared with phenogroup 1. Despite more severe remodeling and more compromised hemodynamic in phenogroups 2 and 3, the echocardiographic response to sacubitril/valsartan was comparable in all groups with similar improvement of EF and reduction of cardiac chambers dimensions (response of treatment, defined by improvement of FE +15% and/or decreased of indexed left ventricule diastolic volume −15% = group 2: 22 (76%); group 3: 18 (60%); group 1: 9 (50%); p=0.17; OR group 2 vs 1: OR=3.14; IC95% [0.9–11.03]; p=0.074; OR group 3 vs 1: OR=1.5; IC95% [0.46–4.87]; p=0.5)). The clinical response was even better in phenogroups 2 and 3 (Group 2: 19 (66%); group 3: 21 (78%) vs group 1: 9 (50%); p=0.05). Heat map Conclusion HF-REF patients with severe diastolic dysfunction, significant mitral regurgitation and elevated pulmonary hypertension by echocardiographic had similar reverse remodeling but better clinical improvement than patients with isolated left ventricular systolic dysfunction.


Author(s):  
Camille Ammann ◽  
Christophe Wyss ◽  
Oliver Gämperli ◽  
Peter Martin Wenaweser ◽  
Roberto Corti ◽  
...  

BACKGROUND AND AIMS: The soluble form of suppression of tumourigenicity 2 (sST2), a recently introduced biomarker, is a strong and NTproBNP-independent predictor of outcome in heart failure patients. This study sought to evaluate the added clinical value of sST2 in addition to NTproBNP in a heterogeneous cardiac outpatient population. METHODS: A total of 297 all-comer patients visiting the outpatient clinic of Heart Clinic Zurich, Switzerland, from January to December 2018 were included. Patients were divided into four groups depending on their sST2 and NTproBNP levels: group 1 (n = 91, 30.6% of all patients) with normal levels of both biomarkers, group 2 (n = 41, 13.8%) with isolated elevation of sST2 but normal NTproBNP, group 3 (n = 97, 32.7%) with elevated NTproBNP but normal sST2 levels, and group 4 (n = 68, 22.9%) with elevation of both biomarkers. Differences between groups, Spearman’s correlations and linear and multiple regression analysis for sST2 were calculated. RESULTS: The median age was 74 ± 19 years and 41.8% were women. NTproBNP levels continuously increased across the groups (medians in pg/ml: group 1 123.0, group 2 152.0, group 3 990.0 and group 4 2610.0), whereas sST2 levels did not (medians in ng/ml: 28.7, 58.9, 28.4 and 63.7 for groups 1 to 4, respectively). In patients with normal NTproBNP (groups 1 and 2), elevation of sST2 (group 2) was associated with significantly higher rates of coronary artery disease, peripheral vascular disease and renal dysfunction. In patients with elevated NTproBNP (groups 3 and 4), the additional elevation of sST2 (group 4) was associated with clinical signs of heart failure, higher EuroScore II and worse left ventricular ejection fraction (LVEF group 3 58.0% vs group 4 53.3%, p = 0.022). Correlation of sST2 was overall weak and weaker than of NTproBNP with most clinical variables. Soluble ST2 significantly correlated with EuroScore II (R = 0.280), kidney function (R = −0.259), C-reactive protein (R = 0.248), right ventricular function (R = 0.213) and left atrial volume (R = 0.199), all p ≤0.001. In multiple regression analysis, left atrial volume was the strongest independent predictor of sST2 elevation (p = 0.002). CONCLUSION: In this all-comer cardiology population, the added clinical value of sST2 measurements in addition to NTproBNP was small. In patients with elevated NTproBNP, the simultaneous elevation of sST2 was associated with clinical signs of heart failure. Soluble ST2 measurements could thus be beneficial in patients with uncertain signs of heart failure and confounding factors for NTproBNP elevation. Surprisingly, this study found elevated sST2 levels in a substantial number of a patients with normal NTproBNP levels, pointing to an additional pathway of sST2 elevation independent of heart failure.


Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Pardeep S Jhund ◽  
Alice M 1 ◽  
Marc A Pfeffer ◽  
Faiez ZANNAD ◽  
Martin P Lefkowitz ◽  
...  

Objective: Heart failure with preserved ejection fraction (HFpEF) is typically a hypertensive phenotype and many HFpEF patients have difficult to control hypertension. We examined the effect of neprilysin inhibition on resistant hypertension in HFpEF patients in the PARAGON-HF trial. Patients entered a 1 to 4-week valsartan run-in (target dose 80mg bd), followed by sacubitril/valsartan run-in, before randomization to valsartan or sacubitril/valsartan (target doses 160mg bd or 200mg bd respectively). Design and methods: Patients were examined according to different definitions of resistant hypertension using systolic blood pressure (SBP) at the end of valsartan run-in. Group 1: SBP≥140mmHg (≥135mmHg if diabetes) despite treatment with a calcium channel blocker (CCB), diuretic and valsartan, Group 2: SBP≥130mmHg despite treatment with a CCB, diuretic and valsartan, or SBP<130mmHg despite treatment with a CCB, diuretic, mineralocorticoid receptor antagonist (MRA) and valsartan, and Group 3: SBP≥140mmHg (≥135mmHg if diabetes) despite treatment with a CCB, diuretic, MRA and valsartan (≥4 classes of SBP-reducing therapy, including MRA). We examined reduction in SBP from end of valsartan run-in to weeks 4 and 16 after randomization and the proportion of patients with controlled SBP at week 16 on sacubitril/valsartan vs valsartan. Results: Of 4796 patients randomized, criteria for resistant hypertension were fulfilled in 726 (15%) using the Group 1 definition, 1146 (24%) using the Group 2 definition and 132 (3%) in the third group. The combination of neprilysin inhibitor, angiotensin receptor blocker, CCB and diuretic (+/-MRA) reduced SBP and significantly increased the proportion of patients with controlled SBP (Table). Conclusion: Sacubitril/valsartan may be useful in treating resistant hypertension in patients with HFpEF, even in those who continue to have an elevated SBP despite treatment with at least 4 antihypertensive drug classes, including an MRA.


2016 ◽  
Vol 64 (4) ◽  
pp. 922.1-922 ◽  
Author(s):  
I Karagodin ◽  
JL Strande ◽  
B Marong

BackgroundDepolarization and repolarization ECG abnormalities such as fragmented QRS and wide frontal QRS-T angles are associated with heart failure with preserved ejection fraction (HFpEF) and are associated with adverse outcomes. However, no studies have investigated whether these abnormalities are present in asymptomatic diastolic dysfunction and whether these abnormalities are predictive of the development of HFpEF in subjects with diastolic dysfunction. The goal of this study is to determine whether fQRS and widening of the QRS-T angle precedes the development of HFpEF in patients with diastolic dysfunction.MethodsThis retrospective cohort study included 100 subjects with diastolic dysfunction and an ejection fraction >50% as reported on transthoracic echocardiography (TTE) who were free of HF at baseline. We analyzed 12-lead ECGs to determine fQRS and frontal QRS-T angle. Patients with QRS>120 ms, bundle branch block pattern, or incomplete right bundle branch block were excluded. The subjects were divided into two groups: Group 1 (n=53) included subjects who were known to progress to HFpEF and Group 2 (n=47) included patients who remained asymptomatic.ResultsThere was no significant difference in the proportion of patients with fQRS in Group 1 compared to Group 2 (33/41 vs. 35/42, p=0.78). The difference was also not significant when comparing hypertensive patients in Group 1 versus Group 2 (28/35 vs. 24/30, p=1.0), as well as patients without hypertension in both groups (5/6 vs. 11/12, p=1.0). On average, the QRS-T angle was wider in Group 1 (64.6) compared to Group 2 (51.7).ConclusionIn patients with asymptomatic diastolic dysfunction, fragmented QRS is present in both patients who progress to HFpEF as well as patients who remain asymptomatic. This suggests that fragmented QRS is associated with diastolic dysfunction, but does not predict the development of heart failure symptoms. The frontal QRS-T angle may be a useful measurement in predicting which patients go on to develop HFpEF. However, larger prospective studies are needed to further investigate this relationship.


Healthcare ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 830
Author(s):  
Ruxandra Nicoleta Horodinschi ◽  
Camelia Cristina Diaconu

Background: Heart failure (HF) and atrial fibrillation (AF) commonly coexist and patients with both diseases have a worse prognosis than those with HF or AF alone. The objective of our study was to identify the factors associated with one-year mortality in patients with HF and AF, depending on the left ventricular ejection fraction (LVEF). Methods: We included 727 patients with HF and AF consecutively admitted in a clinical emergency hospital between January 2018 and December 2019. The inclusion criteria were age of more than 18 years, diagnosis of chronic HF and AF (paroxysmal, persistent, permanent), and signed informed consent. The exclusion criteria were the absence of echocardiographic data, a suboptimal ultrasound view, and other cardiac rhythms than AF. The patients were divided into 3 groups: group 1 (337 patients with AF and HF with reduced ejection fraction (HFrEF)), group 2 (112 patients with AF and HF with mid-range ejection fraction (HFmrEF)), and group 3 (278 patients with AF and HF with preserved ejection fraction (HFpEF)). Results: The one-year mortality rates were 36.49% in group 1, 27.67% in group 2, and 27.69% in group 3. The factors that increased one-year mortality were chronic kidney disease (OR 2.35, 95% CI 1.45–3.83), coronary artery disease (OR 1.67, 95% CI 1.06–2.62), and diabetes (OR 1.66, 95% CI 1.05–2.67) in patients with HFrEF; and hypertension in patients with HFpEF (OR 2.45, 95% CI 1.36–4.39). Conclusions: One-year mortality in patients with HF and AF is influenced by different factors, depending on the LVEF.


Medicina ◽  
2021 ◽  
Vol 57 (4) ◽  
pp. 375
Author(s):  
Marilena-Brîndușa Zamfirescu ◽  
Liviu-Nicolae Ghilencea ◽  
Mihaela-Roxana Popescu ◽  
Gabriel Cristian Bejan ◽  
Sean Martin Maher ◽  
...  

Background and Objectives: Heart failure with preserved ejection fraction (HFpEF) remains a worldwide management problem. Although there is a general effort for characterizing this population, few studies have assessed the predictive value of the echocardiographic E/e’ ratio in patients with acute HFpEF. The aim of the study was to identify groups with different prognosis in patients hospitalized with a first acute episode of HFpEF. Materials and Methods: The primary endpoint of the study was heart failure readmissions (HFR) at 6 months, while the secondary outcome was six-month mortality. We consecutively enrolled 91 patients hospitalized for the first time with acute HFpEF. We examined the E/e’ ratio as an independent predictor for HFR using univariate regression. Results: We identified and validated the E/e’ ratio as an independent predictor for HFR. An E/e’ ratio threshold value of 13.80 was calculated [(area under the receiver operating characteristic curve (AUROC) = 0.693, sensitivity = 78.60%, specificity = 55%, p < 0.004)] and validated as an inflection point for an increased number of HFR. Thus, we divided the study cohort into two groups: group 1 with an E/e’ ratio < 13.80 (n = 39) and group 2 with an E/e’ ratio > 13.80 (n = 49). Compared to group 1, group 2 had an increased number of HFR (p = 0.003) and a shorter time to first HFR (p = 0.002). However, this parameter did not influence all-cause mortality within six months (p = 0.84). Conclusions: The dimensionless E/e’ ratio is a useful discriminator between patients with acute HFpEF. An E/e’ value over 13.80 represents a simple, yet effective instrument for assessing the HFR risk. However, all-cause mortality at six months is not influenced by the E/e’ ratio.


Kardiologiia ◽  
2020 ◽  
Vol 60 (4) ◽  
pp. 48-53
Author(s):  
A. D. Gasanova ◽  
D. O. Dragunov ◽  
A. V. Sokolova ◽  
G. P. Arutyunov

Aim To evaluate the risk of major cardiovascular complications (CVC) in patients with chronic heart failure (CHF) with intermediate and preserved ejection fraction (EF) depending on the presence of bendopnea symptom.Material and methods The study included 104 patients with stage II CHF and left ventricular EF ≥40 %. Mean age of the patients was 72.8±10.6 years. A test for detection of bendopnea symptom was performed for all patients. Two groups were formed: group 1, 69 patients with the bendopnea symptom and group 2, 35 patients with a negative test. Follow-up duration was 24 months. The composite endpoint (CEP) was death and hospitalization for any CVC.Results Mean time to the bendopnea symptom was 17.3±6.61 s. At two years of follow-up, the CEP was observed in 36 (34.6 %) patients, including 30 (43.5 %) patients in group 1 and 6 (17.1 %) patients in group 2. 12 patients died, and 9 of them had the bendopnea symptom. 21 patients of group 1 were hospitalized for CVC. Risk of CEP was significantly 1.7 times higher for men (relative risk, RR 1.7 [1.1; 2.6]) than for women. The presence of bendopnea symptom increased the risk of CEP 1.4 times (ОР 1.4 [1.1;1.9]) for women and 2.3 times (RR 2.3 [1.4; 3.6]) for men.Conclusion Results of the study demonstrated an unfavorable effect of bendopnea symptom on risk of CEP during the two-year follow-up of CHF patients with preserved and intermediate EF.


VASA ◽  
2020 ◽  
Vol 49 (4) ◽  
pp. 281-284
Author(s):  
Atıf Yolgosteren ◽  
Gencehan Kumtepe ◽  
Melda Payaslioglu ◽  
Cuneyt Ozakin

Summary. Background: Prosthetic vascular graft infection (PVGI) is a complication with high mortality. Cyanoacrylate (CA) is an adhesive which has been used in a number of surgical procedures. In this in-vivo study, we aimed to evaluate the relationship between PVGI and CA. Materials and methods: Thirty-two rats were equally divided into four groups. Pouch was formed on back of rats until deep fascia. In group 1, vascular graft with polyethyleneterephthalate (PET) was placed into pouch. In group 2, MRSA strain with a density of 1 ml 0.5 MacFarland was injected into pouch. In group 3, 1 cm 2 vascular graft with PET piece was placed into pouch and MRSA strain with a density of 1 ml 0.5 MacFarland was injected. In group 4, 1 cm 2 vascular graft with PET piece impregnated with N-butyl cyanoacrylate-based adhesive was placed and MRSA strain with a density of 1 ml 0.5 MacFarland was injected. All rats were scarified in 96th hour, culture samples were taken where intervention was performed and were evaluated microbiologically. Bacteria reproducing in each group were numerically evaluated based on colony-forming unit (CFU/ml) and compared by taking their average. Results: MRSA reproduction of 0 CFU/ml in group 1, of 1410 CFU/ml in group 2, of 180 200 CFU/ml in group 3 and of 625 300 CFU/ml in group 4 was present. A statistically significant difference was present between group 1 and group 4 (p < 0.01), between group 2 and group 4 (p < 0.01), between group 3 and group 4 (p < 0.05). In terms of reproduction, no statistically significant difference was found in group 1, group 2, group 3 in themselves. Conclusions: We observed that the rate of infection increased in the cyanoacyrylate group where cyanoacrylate was used. We think that surgeon should be more careful in using CA in vascular surgery.


2019 ◽  
Vol 17 (4) ◽  
pp. 354-364
Author(s):  
Hassan Al-Thani ◽  
Moamena El-Matbouly ◽  
Maryam Al-Sulaiti ◽  
Noora Al-Thani ◽  
Mohammad Asim ◽  
...  

Background: We hypothesized that perioperative HbA1c influenced the pattern and outcomes of Lower Extremity Amputation (LEA). Methods: A retrospective analysis was conducted for all patients who underwent LEA between 2000 and 2013. Patients were categorized into 5 groups according to their perioperative HbA1c values [Group 1 (<6.5%), Group 2 (6.5-7.4%), Group 3 (7.5-8.4%), Group 4 (8.5-9.4%) and Group 5 (≥9.5%)]. We identified 848 patients with LEA; perioperative HbA1c levels were available in 547 cases (Group 1: 18.8%, Group 2: 17.7%, Group 3: 15.0%, Group 4: 13.5% and Group 5: 34.9%). Major amputation was performed in 35%, 32%, 22%, 10.8% and 13.6%, respectively. Results: The overall mortality was 36.5%; of that one quarter occurred during the index hospitalization. Mortality was higher in Group 1 (57.4%) compared with Groups 2-5 (46.9%, 38.3%, 36.1% and 31.2%, respectively, p=0.001). Cox regression analysis showed that poor glycemic control (Group 4 and 5) had lower risk of mortality post-LEA [hazard ratio 0.57 (95% CI 0.35-0.93) and hazard ratio 0.46 (95% CI 0.31-0.69)]; this mortality risk persisted even after adjustment for age and sex but was statistically insignificant. The rate of LEA was greater among poor glycemic control patients; however, the mortality was higher among patients with tight control. Conclusion: The effects of HbA1c on the immediate and long-term LEA outcomes and its therapeutic implications need further investigation.


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