Histomolecular fibrotic profile and an extent of the atrial and ventricular electroanatomical substrate in patients with atrial fibrillation and heart failure

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
V Orshanskaya ◽  
V.S Orshanskaya ◽  
A.V Kamenev ◽  
L.B Mitrofanova ◽  
L.A Belyakova ◽  
...  
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
Plasma Level ◽  
Serum Level ◽  
Interstitial Fibrosis ◽  
Myocardial Interstitial Fibrosis ◽  
Relative Extent ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

Abstract Background and purpose The aim of this pilot study was to investigate the association between an extent of the atrial and ventricular electroanatomical substrate, serum fibrotic biomarkers and histological and immune-histochemical myocardial characteristics in ipatients with atrial fibrillation and heart failure. Methods We prospectively analyzed electroanatomical ultra-high density bipolar maps (HDBM) in 72 patients with AF and CHF, who underwent circular pulmonary veins (PVs) isolation. LA areas outside PVs ostia with bipolar signals ≤0.75mV, associated with local conduction velocity delay were considered as EAS and measured. Relative area of low voltage zones in right (RV) and left ventricles (RV) with bipolar signals in range of 0,5–1,5 mV were also consistently measured. Endomyocardial biopsy samples were taken from low, mediate and high septal areas of RV; histological and immune-histochemical staining was performed and an extent of myocardial interstitial fibrosis (MIF) was calculated. Before the operation we measured plasma MMP2, MMP9, TIMP, MMPs/TIMPs, galectin 3 (Gal3), TGF, soluble ST2 and the cross-linked collagen I/III synthesis and degradation product levels. The patients were divided into groups according to their ejection fraction Simpson (EF) (groups 1: EF≥50%, groups 2: EF 40–49%, and groups 3: EF<40%). Results The data of electroanatomical mapping, serum biomarkers and myocardial expression are presented in the table. According to results of correlation analysis, an extent of LA EAS were correlated with Gal3 and PIIICP plasma level and Gal3 myocardial expression and MIF extent (Rs=0,40, 0,45 and 0,42 respectively). The relative extent of LV EAS was correlated with MMP9 serum level (Rs=0,38); LV volume (LVV) was correlated with sST2 serum level and RVV was correlated with CD 133 myocardial expression (Rs=0,42) (picture 1). The patients with lower EF had larger extent of the LA EAS, (group 3: 28±12.4% vs. 1: 17.7±11.6%, p=0.03), an extent of LV EAS and LVV (group 3: 8,4±4,5% vs. 1: 5,1±3,8% p=0.02; group 3 vs group 1 p=0,05 relatively),higher Gal3 plasma level (group 1: 7,1±2 vs. group 2: 8,9±1,5, p=0.05) and higher MIF extent (group 2: 134±56 vs. 3: 151±30 p=0.04) (picture 2). Conclusion Our data suggest that relative extent of LA EAS in patients with atrial fibrillation is associated with Gal3 plasma level and Gal3 myocardial expression; severity of myocardial remodeling is connected to CD 3/133 myocardial expression and myocardial interstitial fibrosis extent, especially in patients with HF with restricted LV ejection fraction. Funding Acknowledgement Type of funding source: None

scholarly journals How is juvenile rheumatic heart disease different: baseline results from a prospective north Indian registry

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
K Mahajan ◽  
D.R Prakash Chand Negi
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
Pulmonary Hypertension ◽  
Heart Disease ◽  
Funding Source ◽  
Thromboembolic Events ◽  
Group 3 ◽  
Group 2 ◽  
Rheumatic Heart ◽  
Group 1

Abstract Introduction Juvenile rheumatic heart disease (RHD) refers to RHD in patients <20 years of age. There are no contemporary data highlighting the differences between juvenile and older RHD patients. Purpose We aim to report the age related differences in the pattern, and consequencies of valvular dysfunction in patients of RHD. Methods The 2475 consecutive patients of RHD diagnosed using clinical and echocardiographic criteria were registered prospectively from 2011 till December 2019. Patients were divided into 3 groups according to their age: Group 1 (Juvenile RHD), Group 2 (21–50 years), and Group 2 (>51 years).The data concerning the socio-demographic and clinical profile were recorded systematically, and the nature and severity of valvular dysfunction was assessed by echocardiography. The data were analyzed using the Epi-InfoTM Software. Results Out of 2475 RHD patients, Juvenile RHD comprised of 211 (8.5%) patients. Group 2 and 3 comprised of 1691 (68.3%) and 573 (23.2%) patients respectively. Overall, 1767 (71.4%) patients were females, however this female predilection was less pronounced in juvenile RHD (55.5% females vs 44.5% males) as compared to older groups. Past history of acute rheumatic fever was more commonly recorded in Juvenile RHD group (37.9% vs 18.8% in group 2 and 10% in group 3, p=0.0001). At the time of registration, the presence of advanced heart failure symptoms (dyspnea class III and IV) (11.4% group 1 vs 13.9% group 2 vs 20.6% group 3, p<0.0001), right heart failure symptoms (0.9% group 1 vs 2.5% group 2 vs 7.3% group 3, p<0.01), thromboembolic events (0% group 1 vs 4.1% group 2 vs 3.3% group 3, p<0.01), atrial fibrillation (2.8% group 1 vs 24.5% group 2 vs 45.9% group 3, p<0.0001), and pulmonary hypertension (27.1% group 1 vs 40.3% group 2 vs 51.9% group 3, p<0.01), were all more commonly recorded in non-juvenile older RHD groups. Multivalvular involvement was also less common in juvenile RHD (34.6% vs 42.4% and 44.5%, p=0.04). Mitral regurgitation was the most common lesion in Juvenile RHD followed by aortic regurgitation (68.7% and 40.2% respectively). Stenotic lesions (both mitral and aortic) were present more commonly in older age groups. Conclusion RHD is predominantly a disease of females, however the predilection is less common in juvenile patients. Juvenile RHD predominantly affects the mitral valve and mainly leads to regurgitant lesions. As the age advances, the complications of RHD, mainly heart failure symptoms, thromboembolic events, pulmonary hypertension, and atrial fibrillation, become more common. Funding Acknowledgement Type of funding source: Public hospital(s). Main funding source(s): Self sponsored registry

scholarly journals Comorbidities Associated with One-Year Mortality in Patients with Atrial Fibrillation and Heart Failure

Healthcare ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 830
Author(s):  
Ruxandra Nicoleta Horodinschi ◽  
Camelia Cristina Diaconu
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
Ejection Fraction ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction ◽  
Group 3 ◽  
Group 2 ◽  
One Year ◽  
Group 1

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.

scholarly journals Factors That Determine the Prothrombin Time in Patients With Atrial Fibrillation Receiving Rivaroxaban

2018 ◽  
Vol 24 (9_suppl) ◽  
pp. 188S-193S
Author(s):  
Jen-Hung Huang ◽  
Yung-Kuo Lin ◽  
Cheng-Chih Chung ◽  
Ming-Hsiung Hsieh ◽  
Wan-Chun Chiu ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Prothrombin Time ◽  
Factor Xa ◽  
International Normalized Ratio ◽  
Biochemical Properties ◽  
Study Patient ◽  
Group 3 ◽  
Multiple Variables ◽  
Group 2 ◽  
Group 1

Rivaroxaban, a direct factor Xa inhibitor, is widely used to reduce the chance of stroke in patients with atrial fibrillation (AF). It is not clear why the prothrombin time (PT) of the international normalized ratio (INR) fails to correlate with treatment using rivaroxaban in patients with AF. In this study, patient characteristics, the rivaroxaban dosage, AF type, drug history, biochemical properties, and hematological profiles were assessed in patients treated with rivaroxaban. In 69 patients with AF receiving rivaroxaban, 27 (39.1%) patients had a normal INR (≤1.1, group 1), 27 (39.1%) patients had a slightly prolonged INR (1.1∼1.5, group 2), and 15 (21.7%) patients had a significantly prolonged INR (>1.5, group 3). Group 1 patients had a higher incidence of a stroke history than did patients in group 2 ( P = .026) and group 3 ( P = .032). We scored patients with a persistent AF pattern (1 point), paroxysmal AF pattern (0 point), renal function (ie, the creatinine clearance rate in mL/min/1.73 m2 of >60 as 0 points, of 30∼60 as 1 point, and of <30 as 2 points), and no history of stroke (1 point), and we found that group 3 had a higher score than groups 2 or 1 (2.9 ± 0.8, 2.4 ± 0.7, and 2 ± 0.7, respectively; P < .05). There were similar incidences of bleeding, stroke, and unexpected hospitalizations among the 3 groups. The PT of the INR is determined by multiple variables in patients with AF receiving rivaroxaban. Rivaroxaban-treated patients with AF having different INR values may have similar clinical outcomes.

scholarly journals Anti-CD28 Monoclonal Antibody Therapy Prevents Chronic Rejection of Renal Allografts in Rats

2002 ◽  
Vol 13 (2) ◽  
pp. 519-527
Author(s):  
Igor A. Laskowski ◽  
Johann Pratschke ◽  
Markus J. Wilhelm ◽  
Victor M. Dong ◽  
Francisca Beato ◽  
...  
Keyword(s):  
Single Dose ◽  
T Cell ◽  
Chronic Rejection ◽  
Interstitial Fibrosis ◽  
Inflammatory Factors ◽  
Renal Allografts ◽  
Short Course ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

ABSTRACT. The effects of a signaling anti-CD28 mAb (JJ319), which interferes with the CD28-B7 T cell costimulation pathway thought to be involved in the development of chronic rejection of organ transplants, was investigated. Functional, morphologic, and molecular changes in rat renal allografts were examined up to 24 wk after placement. Control Lewis rats, recipients of F344 kidneys, received a single dose of a nonspecific mouse mAb intravenously on the day of transplantation (group 1). Group 2 animals were given anti-CD28 mAb in similar fashion. Group 3 animals were treated with a short course of cyclosporin A (CsA), and group 4 received both anti-CD 28 mAb and CsA. The majority (>95%) of animals in groups 2, 3, and 4 survived throughout the follow-up, compared with 28% in group 1 (P < 0.001). Group 2 and 4 recipients produced negligible proteinuria, whereas group 1 controls developed progressively increasing proteinuria after 4 wk and group 3 animals developed proteinuria by 24 wk. Allografts in groups 2 and 4 were morphologically unremarkable at 24 wk. Kidneys of group 1 animals rapidly developed changes of acute rejection, and those that survived long-term showed extensive glomerulosclerosis and interstitial fibrosis. Changes of early chronic rejection were noted in group 3 grafts. By reverse transcriptase–PCR, expression of representative inflammatory factors interferon-γ and interleukin-10 were significantly elevated at 24 wk only in the surviving group 1 animals. A single dose of a signaling anti-CD28 mAb administered at transplantation or in combination with a short course of CsA significantly prolonged recipient survival, normalized function, and preserved the morphology of renal allografts in an established model of chronic rejection. These data support an important role for T cell costimulation in the evolution of the chronic process.

Abstract 13073: ECG, Clinical, and Imaging Characteristics of Arrhythmogenic Right Ventricular Cardiomyopathy With Fat and Fibrotic Invasion Into the Left Ventricular Myocardium Revealed by Four-dimensional (4D) Cardiac CT

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Nobusada FUNABASHI ◽  
Yoshio Kobayashi
Keyword(s):  
Heart Failure ◽  
Right Ventricular ◽  
Cardiac Ct ◽  
4D Ct ◽  
Imaging Characteristics ◽  
Group 3 ◽  
Clinical Heart Failure ◽  
Group 2 ◽  
Group 1 ◽  
T Waves

Introduction: 4D cardiac CT can reveal characteristics of arrhythmogenic right ventricular (RV) cardiomyopathy (ARVC) such as fat and fibrotic invasion into the RV and LV myocardium (RVM, LVM), an enlarged RV, reduced RV motion and bulging. Hypothesis: We could differentiate ARVC patients with fat and fibrotic invasion into the LVM from those without, using ECG, clinical, and other imaging characteristics. Methods: Retrospective analysis of 17 patients (11 males, 57±17 years) with suspected ARVC who underwent 4D cardiac CT. Results: 9 patients met the 2010 ARVC task force criteria. 4 had fat and fibrotic invasion into the LVM (group 1) but 5 did not (group 2). The remaining 8 did not fulfill the ARVC criteria (group 3). The proportion of males and age did not differ between groups. In groups 1, 2 and 3, respectively, 3 (75%), 4 (80%), and 1 (13%) patients had epsilon waves in V1-3 (group 1>3, P=0.033, group 2>3, P=0.005). 2 (50%), one (20%) and 4 (50%) had complete right bundle branch block (CRBBB) (all P=NS). Three (75%), 3 (60%), and 1 (13%) had inverted T waves in V1-3 or beyond (group 1>3, P=0.033). One (50%), 3 (75%), and 2 (50%) had terminal activation duration of QRS ≥55 ms measured from the nadir of the S wave to the end of the QRS, including R’, in V1, V2, or V3, in the absence of CRBBB (all P=NS). One (25%), 4 (80%) and 1 (13%) had sustained ventricular tachycardia (SVT; group 2>3, P=0.005). Two (50%), 1 (20%), and 3 (38%) had non-SVT (all P=NS). 4 (100%), 2 (40%), and 2 (25%) had clinical heart failure (group 1>2, P=0.019, group 1>3, P<0.001). Finally, 4 (100% and 80%) and 6 (75%) had RV enlargement on TTE (all P=NS). On 4D CT, 4 (100%), 5 (100%), and 5 (63%) of patients in groups 1, 2 and 3, showed RV enlargement (all P=NS); 4 (100%), 2 (40%), and 1 (13%) showed reduced RV motion (group 1>2, P=0.019, group 1>3, P<0.001); 75, 100, and 0%, had RV fat invasion (group 1>3, P=0.002, group 2>3, P<0.001); and 25, 0, and 0% showed bulging (all P=NS). Conclusions: Most patients had RV enlargement on TTE and/or 4D CT. Presence of epsilon waves, reduced RV motion, and RV fat invasion on 4D CT may differentiate groups 1 and 2 from group 3, inverted T waves in V1-3 leads or beyond may differentiate group 1 from group 3, SVT may differentiate group 2 from group 3 but only clinical heart failure may differentiate groups 1 and 2.

Abstract 15948: Impact of Age on Safety of Radiofrequency Ablation in Patients With Atrial Fibrillation

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Janet W Elcano ◽  
Hui Nam Pak
Keyword(s):  
Atrial Fibrillation ◽  
Phrenic Nerve Palsy ◽  
Adjusted Risk ◽  
Ablation Time ◽  
Group 4 ◽  
Major Complications ◽  
Group 3 ◽  
Group 2 ◽  
The Impact ◽  
Group 1

Background: The incidence of atrial fibrillation (AF) is increasing in the elderly population, however, there is paucity of data on the safety outcomes of this patient subgroup thus we sought to investigate on the impact of age on the safety of catheter ablation for AF. Methods and Results: We included 1,293 (male 75%) patients enrolled in Yonsei AF Ablation Cohort database in Seoul, South Korea, from March 2009 to November 2013. We divided the patients into 4 groups according to age (Group 1, aged 17-49, N=295 ; Group 2 50-59, N=421; Group 3 60-69 N=408; and Group 4 ≥ 70, N=169) and evaluated the incidence of procedure related complications. No procedure-related death occurred in this study. There was a trend of increasing incidence of procedure related complications with age noted as follows: Group 1= 3.7%; Group 2= 4.0%; Group 3=6.6%; and Group 4 7.1%, (p= 0.15). There were 28 cases (2.2%) of major complications (Group 1=1.7%, Group 2=1.9%, Group 3=2%, Group 4 4.1%), tamponade being the most common. Major complications in group 4 include: tamponade 4 cases, phrenic nerve palsy 1 case, atrioesophaeal fistula 1 and 3rd degree AV block in 1 patient. Multivariate regression analysis shows ablation time (odds ratio (OR) 1.2 confidence interval (CI)1.0-1.017, p=0.017), procedure time (OR 1.008, CI 1.0-1.15, p=0.04), decreasing eGFR (OR 1.013, CI 1.002-1.026 p=0.018), coronary artery disease (CAD) (OR 1.847, CI 1.003-3.524, p0.04) and age (OR 1.028, CI 1.003-1.055, p=0.03) were associated with increased adjusted risk of total complications. Predictors of major complications include age (OR 1.044, CI 1.003-1.086, p0.02) and ablation time (OR 1.009, CI 0.999-1.000, p=0.033). Conclusion: Our data suggest that incidence of procedural complications in RFA of AF increase with age. Ablation time and age are independent predictors of a major complication.

Abstract 9411: Urine Aquaporin-2 Level is a Novel Marker for the Better Prognosis After Long-Term Tolvaptan Treatment in Patients With Advanced Heart Failure

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Teruhiko Imamura ◽  
Koichiro Kinugawa ◽  
Takeo Fujino ◽  
Toshiro Inaba ◽  
Hisataka Maki ◽  
...  
Keyword(s):  
Heart Failure ◽  
De Novo ◽  
Collecting Duct ◽  
Initial Response ◽  
Aquaporin 2 ◽  
Long Term Treatment ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

Introduction: Preserved function of collecting duct is essential for the response to tolvaptan (TLV), and urinary level of aquaporin 2 (U-AQP2) can be a marker for vasopressin-dependent activity of collecting duct. Hypothesis: Higher levels of U-AQP2 in proportion to plasma levels of vasopressin (P-AVP) may be associated with better initial responses to TLV and eventually result in the improved prognosis after long-term treatment of TLV. Methods: Consecutive 60 in-hospital patients with stage D heart failure (HF) who received TLV on a de novo basis were enrolled during 2011-2013. We also selected 60 HF patients by propensity score matching who were hospitalized during the same period but never treated with TLV. Events were defined as death and/or HF re-hospitalization. Results: TLV (3.75-15 mg/day) was continuously administered except death or ventricular assist device implantation occurred. There were 41 patients (group 1) who had increases in UV over the first 24 h after TLV initiation, and all of them had U-AQP2/P-AVP ≥0.5 х103 with higher U-AQP2 levels (5.42 ± 3.54 ng/mL) before TLV treatment. On the other hand, UV rather decreased even after TLV initiation in 19 patients over the first 24 h (group 2). Those in the group 2 universally had U-AQP2/P-AVP <0.5 х103, extremely low U-AQP2 levels (0.76 ± 0.59 ng/mL, p<0.001 vs. group 1), and similar P-AVP with the group 1 at baseline. The 41 and 19 patients without TLV treatment (group 3 and 4) were respectively matched to the group 1 and 2 by propensity scores. Interestingly, every patient in the group 3 had U-AQP2/P-AVP ≥0.5 х103, and vice versa in the group 4. Among the four groups, congestion-related symptoms were only improved in the group 1 after 1 month of enrollment. The patients in the group 1 had significantly better event-free survival over 2-year by TLV treatment compared with the group 3 (76% vs. 43%, p<0.014). In contrast, the patients in the group 2 and 4 had very poor prognoses regardless of TLV treatment (7% vs. 11%, p=0.823). Conclusions: U-AQP2/P-AVP is a novel predictor for the initial response to TLV in HF patients. Patients with higher U-AQP2/P-AVP may enjoy a better prognosis by long-term TLV treatment probably due to efficient resolution of congestion.

P4766Edoxaban Treatment in routiNe clinical prActice for patients with atrial fibrillation (AF) in Europe (ETNA-AF-Europe): 1-year follow-up according to body mass index

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
T Weiss ◽  
R De Caterina ◽  
P Kelly ◽  
P Monteiro ◽  
J C Deharo ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Body Weight ◽  
Oral Anticoagulants ◽  
Anticoagulation Therapy ◽  
Normal Weight ◽  
Routine Practice ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

Abstract Background Non-vitamin K antagonist (VKA) oral anticoagulants (NOACs) have substantially improved anticoagulation therapy for prevention of stroke and systemic embolism in patients with atrial fibrillation (AF), and available routine care data have so far broadly confirmed the safety of different NOACs in routine practice. However, such data for edoxaban are scarce, especially in extremely low and high body weight (BW). These extreme BWs may affect the bioavailability, distribution, and half-life of NOACs and, consequently, outcomes of treatment. Methods We analysed outcomes in normal-weight (BMI 18.5–25) vs overweight (BMI 25–30) and obese (BMI >30) patients enrolled into the ETNA-AF-Europe observational study (NCT02944019) collecting information on patients treated with edoxaban in 825 sites in 10 European countries. This snapshot analysis set includes data of 7,672 patients (56.3% of all enrolled patients) which have completed their 1-year follow-up visit (mean follow-up: 343.5 days). Results Median patient age was 74 years for all patients, 76 years for patients with a BMI 18.5–25 (group 1), 75 years for patients with BMI 25–30 (group 2), and 72 for patients with a BMI >30 (group 3). CrCl was 64 mL/min for patients with a BMI 18.5–25, 68 mL/min for patients with BMI 25–30, and 72 mL/min for patients with a BMI >30. The CHA2DS2-VASc (mean 3.1±1.38) and HAS-BLED (mean 2.5±1.10) score did not differ significantly between groups. As expected, diabetes and hypertension were significantly less prevalent in leaner patients and - accordingly - inversely correlated to age. There was no correlation between body weight and life-threatening bleeding (group 1: 0.28%; group 2: 0.40%; group 3: 0.14%). Also, stroke rates (group 1: 0.74%; group 2: 0.81%; group 3: 0.76%) did not differ between groups. Conclusion BMI, within the range here assessed, does not affect 1-year outcomes in European AF patients treated with edoxaban. Acknowledgement/Funding Daiichi Sankyo Europe GmbH, Munich, Germany

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
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Right Ventricle ◽  
Preserved Ejection Fraction ◽  
Stratified Medicine ◽  
Cardiac Events ◽  
Group 4 ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

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 &lt; 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 &lt; 0.05, 95 vs. 1% p &lt; 0.05, and median 167 vs. 223 ms p &lt; 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 &lt; 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.

1409Use of phenomapping to determine response of treatment by sacubitril/valsartan in patients with heart failure with reduced ejection fraction

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
M Godet ◽  
O Raitiere ◽  
H Chopra ◽  
P Guignant ◽  
C Fauvel ◽  
...  
Keyword(s):  
Heart Failure ◽  
Pulmonary Hypertension ◽  
Ejection Fraction ◽  
Left Ventricular ◽  
Heat Map ◽  
Reduced Ejection Fraction ◽  
Patients With Heart Failure ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

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.

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