P320Heart failure with mid-range (HFmrEF) or recovered (HFrecEF) ejection fraction: differential determinants of transition

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
R De Maria ◽  
F Macera ◽  
M Gorini ◽  
I Battistoni ◽  
M Iacoviello ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Ejection Fraction ◽  
Clinical Characteristics ◽  
Nyha Class ◽  
Multivariable Logistic Regression Analysis ◽  
Class Iii ◽  
Mild Disease ◽  
Lower Likelihood ◽  
History Of

Abstract Background Heart failure with mid-range ejection fraction (HFmrEF) has been identified as a multi-faceted phenotype that may encompass both patients with mild disease or those who from previous HFrEF recover EF (HFrecEF) Purpose To describe clinical characteristics and factors associated with phenotype transition at follow-up. Methods From 2009 to 2016, 1194 patients with baseline EF<50% and a second echocardiographic determination during clinically stability at a median of 6 months were enrolled in the IN-CHF Registry. Based on EF at enrollment, 335 (28%) had HFmrEF and 859 (72%) had HFrEF. We compared baseline clinical characteristics and predictors associated with follow-up reclassification to HFmrEF or full EF recovery Results When compared to HFrEF patients, those with HFmrEF had less often an ischemic etiology, advanced symptoms and a HF admission in the previous year. No other differences were found in clinical characteristics and drug therapy (Table). At a median follow-up of 6 months, 30% of HFrEF patients improved EF by 14 (9) units: 21% showed partial EF recovery (transition to HFmrEF) and 9% had full EF recovery. Conversely among HFmrEF patients 22% improved EF, by 9 (5) units, to full recovery, and 18% deteriorated by 1.5 (5.5) units sloping to HFrEF. By multivariable logistic regression analysis, variables associated with EF recovery at 6-month follow-up differed between baseline phenotypes. Within HFrEF, ischemic etiology (OR 0.46, 95% CI 0.33–0.64) and NYHA class III-IV symptoms (OR 0.57, 95% CI 0.38–0.68) were associated with a lower likelihood of EF recovery, while a history of HF<6 month correlated with a higher likelihood of EF recovery (OR 2.44, 95% CI 1.76–3.39). Within HFmrEF, while ischemic etiology (OR 0.66, 95% CI 0.19–0.68) was also associated with a lower likelihood of EF recovery, a history of atrial fibrillation at enrollment correlated with higher likelihood of EF recovery (OR 2.66, 95% CI 1.37–5.17) by 6 month-follow-up. At a median follow-up of 36+28 months mortality was 4.6% vs 6.9% in HFrecEF vs non-recovered patients (log rank p=0.08). Baseline characteristics HFrEF vs HFmrEF Conclusions HFmrEF patients showed a less severe clinical picture than HFrEF patients, but had EF recovery less often. EF improvement is negatively associated with ischemic etiology in both phenotypes, and positively associated with atrial fibrillation in HFmrEF and a short history of HF in HFrEF.

scholarly journals 410 Early cardiac reverse remodeling in a large cohort of patients with HFrEF treated with Sacubitril/Valsartan

2020 ◽  
Vol 21 (Supplement_1) ◽  
Author(s):  
V A Sassi ◽  
M Mapelli ◽  
E Salvioni ◽  
I Mattavelli ◽  
V Mantegazza ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Ejection Fraction ◽  
Clinical Characteristics ◽  
Ventricular Remodeling ◽  
Nyha Class ◽  
Large Cohort ◽  
Reverse Remodeling ◽  
High Dose ◽  
Class Iii

Abstract Background Despite the widespread use of Sacubitril/valsartan (Sac/Val) in patients with reduced ejection fraction (HFrEF), definite data on cardiac remodeling under treatment are still lacking. Methods We conducted a retrospective analysis on a large cohort of 201 consecutive HFrEF ambulatory patients who started Sac/Val in our HF unit between Sept. 2016 and Dec. 2018 on top of optimal medical treatment. Patients with both basal and follow up (at least 3 months) echocardiographic assessment (TTE) were included. Results A follow up TTE was performed in 100 patients (male 76%; mean age 67.4 ± 11.1 years; medium follow-up 309 ± 182 days). Baseline characteristics are shown in Tab.1. 34% of the patients reached the maximal dose (97/103 b.i.d.) while 18 interrupted the treatment. We observed an overall significant improvement in ejection fraction (EF), end-diastolic and end-systolic ventricular volumes (EDV/ESV), while just a trend in pulmonary pressures (PAPs) and mitral regurgitation (MR) reduction was noted (p = 0.06 and 0.09 respectively). Non ischemic etiology and high dose of Sac/Val were predictors of better remodeling (Fig.1). Conclusion In our study Sac/Val led to an early favorable ventricular remodeling assessed by echocardiography. The observed benefit was greater in patients on higher dose of the drug and non ischemic etiology. Table 1 n = 100 Clinical characteristics Systolic blood pressure (mmHg) 116 ± 11 Diastolic blood pressure (mmHg) 70 ± 9 Hemoglobin (g/dL) 13 ± 2.0 MDRD (ml/min/1.73 m2) 63 ± 21.4 Potassium (mmol/L) 4.26 ± 0.50 NYHA class II (n;%) 59 (59%) NYHA class III (n;%) 41 (41%) Ischemic etiology (n;%) 58 (58%) ICD (n;%) 41 (41%) CRT (n;%) 32 (32%) Beta-blockers (n;%) 94 (94%) ACEi or ARBs (n;%) 92 (92%) MRA (n;%) 77 (77%) Baseline clinical characteristics Abstract 410 Figure. Fig. 1

NISAR-F SCORE: a simple risk stratification tool for patients implanted with cardiac resynchronization therapy

EP Europace ◽  
2021 ◽  
Vol 23 (Supplement_3) ◽  
Author(s):  
J Correia ◽  
L Goncalves ◽  
I Pires ◽  
J Santos ◽  
V Neto ◽  
...  
Keyword(s):  
Ejection Fraction ◽  
Cardiac Resynchronization Therapy ◽  
Cox Regression ◽  
Nyha Class ◽  
Prognostic Score ◽  
Roc Curves ◽  
Cardiac Resynchronization ◽  
Class Iii ◽  
Resynchronization Therapy

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Individualized estimation of prognosis after cardiac resynchronization therapy (CRT) remains challenging. Outcomes in this group of patients are influenced by multiple factors and a comprehensive and customized approach to estimate prognosis after CRT is lacking Aims To develop and validate a simple prognostic score for patients implanted with CRT (NISAR-F score), based on readily available clinical and echocardiographic variables to predict the combined endpoints of death or hospitalization in 24 months. Methods A single-centre retrospective study was conducted with inclusion of all consecutive patients who underwent CRT implantation between 2012 and 2019. Follow-up started after CRT implantation and ended upon death, hospitalization or 24 months after study entry. Survival analysis was performed using a multivariate Cox regression model, in order to analyze the effect on survival /hospitalization in 24 months of the following factors: age, gender, NYHA Class III-IV, ischemic heart failure, type 2 diabetes, arterial hypertension, dyslipidemia and ejection fraction &lt; 21%. According to the analysis, points were attributed to each factor. Afterwards, the NISAR-F score was calculated for each patient, summing the points of each variable. The authors finally created ROC curves for the NISAR-F score to predict the occurrence of the combined endpoint in 2 groups of patients: CRT responders (ejection fraction increase of at least 10% after CRT implantation) and CRT non-responders. The statistical analysis was performed in SPSS. Results 102 patients were included in the study (75.4% male, mean age 68 ± 10.46 years). 10(9.8%) of the patients were re-hospitalized and 8 (7.8%) died during the 24-month follow-up.  After calculating NISAR-F score for each patient, area under ROC curves were obtained. The analysis of the ROC curves allows us to confirm the good performance of the score created [responders group (AUC 0.812) vs non-responders (AUC 0.721)]. Conclusion The NISAR-F score is a useful tool to predict the combined endpoint (mortality and hospitalization in 24 months) after CRT implantation, in both responders and non-responders, revealing good performance of this new and simple score based only on clinical and echocardiographic variables.

Abstract 13274: Predictors of Mortality in Critically Ill Covid-19 Patients - A Multicenter Prospective Analysis of 159 Patients

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Randy Ip ◽  
Zulfiqar Qutrio Baloch ◽  
manel boumegouas ◽  
Abdullah Al abcha ◽  
Steven Do ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Critically Ill ◽  
Demographic Data ◽  
Prior History ◽  
Multivariable Logistic Regression Analysis ◽  
Elevated Troponin ◽  
Ischemic Disease ◽  
Patient Status ◽  
History Of

Introduction: Certain patient demographics and biomarkers have been shown to predict survival in patients infected with COVID-19. However, predictors of outcome in patients who are critically ill and require advanced respiratory support are unclear. Methods: We performed a multicenter analysis of 159 consecutive patients with confirmed COVID-19 who were admitted to Intensive Care Unit (ICU) between March 01, 2020 and April 30, 2020. Patients were then followed until May 23, 2020. Demographic data (age, sex, race, BMI) and past medical history (hypertension, diabetes, COPD, CKD, history of cardiac ischemic disease, atrial fibrillation and heart failure) were recorded. Laboratory values (troponin, CPK, pro-BNP, ferritin, LDH and d-dimer) were analyzed. Patient status was classified as either alive or deceased at hospital discharge or the end of follow up period. Results: Mean patient age was 66+/-15 and 53% were male. Mean BMI was 31+/- 9. Mean hospital ICU stay was 11+/-8 days. Mortality rate of this ICU cohort at the end of follow-up was 63%. Fifty-five (34%) patients were discharged from the hospital. A multivariable logistic regression analysis identified four factors (age, prior history of diabetes, prior history of atrial fibrillation and elevated troponin) that had significant and independent contributions to the likelihood of survival. Each increase in decade of age above 40 (p = 0.010) was predicted to reduce survival by 30%, the presence of diabetes (p = 0.041) by 57%, a prior history of atrial fibrillation (p= 0.011) by 75%, and each increase of 0.1 ng/mL of troponin above 0.05 ng/ml (p = 0.001) by 55%. Conclusion: Mortality of critically ill COVID-19 patients is high. Early aggressive treatment of high-risk patients identified in this study (advanced age, history of diabetes and atrial fibrillation and elevated troponin) could improve clinical outcome. The highly predictive value of elevated troponin levels on survival may indicate cardiac involvement of COVID-19 infection as a determinant of mortality. Additionally, of available published literature at this time, this is the first study that suggests a relationship between atrial fibrillation and increased mortality from COVID-19. Larger studies are needed to confirm these findings.

scholarly journals Cardiac Myxoma- Surgical treatment and outcome

2015 ◽  
Vol 11 (2) ◽  
pp. 27-30
Author(s):  
D Jaypal Reddy ◽  
Bijay Sah
Keyword(s):  
Malignant Tumors ◽  
Nyha Class ◽  
Cardiac Myxoma ◽  
Malignant Neoplasms ◽  
Class Iii ◽  
Complete Excision ◽  
Fourth Decade ◽  
History Of ◽  
Cardiac Myxomas

Background & Objectives: Cardiac Myxomas include benign and malignant neoplasms, arising within the cardiac chambers or in the myocardium. Because, it is a rare tumor of the heart, there seems a lack of adequate data and its recent optimal treatment for both benign and malignant tumors is limited.Materials & Methods: Literature was searched for review and prospective study of cardiac myxoma surgery done between August 1990 and February 1996 was presented. A total of six patients underwent surgery for cardiac myxoma. All patients (five female; one male) underwent complete excision of the tumor and none of them showed features of remission after six month follow-up.Results: Cardiac Myxoma is a rare disease and it most commonly occurs in the fourth decade of life. Out of six patients operated, five were female and one was male and the age of the patients was between 22 and 50 years (mean age 31). The location of tumors was: LA myxoma in five cases, RA myxoma in one case. Preoperative symptoms were dyspnea (NYHA class III) in four cases, orthopnea in two cases, postural giddiness or syncope in three cases, palpitation in two cases and chest pain in two cases. The mean duration of onset of symptoms to diagnosis was eight months. Echocardiography showed abnormalities in all six cases including mitral stenosis in five cases, and tricuspid stenosis in one case. No recurrence was noted after six months of follow-up after the surgery.Conclusion: Cardiac myxoma is considered an emergency condition which needs urgent procedure, particularly if the patient has a history of embolism or syncope. Atrial Myxoma tends to have more secondary scenarios by embolization.JCMS Nepal. 2015; 11(2):27-30

Abstract 12680: Efficacy and Safety of Edoxaban Compared With Warfarin in Patients With Atrial Fibrillation and Heart Failure: Insights From Engage-AF TIMI 48

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Giulia Magnani ◽  
Robert P Giugliano ◽  
Christian T Ruff ◽  
Sabina A Murphy ◽  
Francesco Nordio ◽  
...  
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
Vitamin K Antagonists ◽  
Nyha Class ◽  
Functional Limitation ◽  
Factor Xa ◽  
Functional Class ◽  
Efficacy And Safety ◽  
Class Iii ◽  
History Of

BACKGROUND: Atrial fibrillation (AF) and heart failure (HF) have emerged as the two epidemics of cardiovascular (CV) disease. The prevalence of AF increases with the severity of HF and contributes to HF disability. Among patients treated with vitamin K antagonists (VKAs), symptomatic HF is an independent risk factor for lower time in therapeutic range (TTR), which reduces the efficacy and safety of VKAs. METHODS: In the ENGAGE AF-TIMI 48 trial, both once-daily regimens of the direct oral factor Xa inhibitor edoxaban [high (HDE) and low dose (LDE)], were non inferior to warfarin (W) for prevention of stroke and systemic embolic events (SEE) in patients with AF and were associated with lower rates of bleeding. We evaluated the safety and the efficacy of edoxaban compared with W in patients with HF presenting with different severity of functional limitation (NYHA class). RESULTS: Among 21,105 patients enrolled 8,981(43%) had no history of HF, 9,489 (45%) had history of HF and a NYHA class I-II, whereas 2,635 (13%) had symptomatic HF with NYHA class III-IV. Patients with more severe HF symptoms had higher rates of stroke SEE, CV death and CV hospitalization (p<0.0005 for all) and among those treated with W we observed a lower mean TTR (62.6% vs. 70.0%, p<0.001). Compared with W, the efficacy of both edoxaban doses in reducing stroke or SEE was similar between patients with and without HF (HDE vs. W, p int=0.96; LDE vs. W, p int=0.63, Fig.) and there were no differences between NYHA classes. CV hospitalization was significantly reduced with HDE relative to W, without heterogeneity by different NYHA classes (p int=0.5, Fig.). Both edoxaban regimens reduced consistently major bleeding and intracranial hemorrhage, regardless of HF severity (Fig.). CONCLUSION: The relative efficacy and safety of both edoxaban regimens, compared to well-managed W in AF patients with HF, was consistent irrespective of the severity of functional class.

Abstract 152: Persistence of Warfarin versus Dabigatran Therapy in Patients with Atrial Fibrillation: Results from the ORBIT AF Registry

2015 ◽  
Vol 8 (suppl_2) ◽  
Author(s):  
Larry R Jackson ◽  
Sunghee Kim ◽  
Peter Shrader ◽  
Rosalia Blanco ◽  
Laine Thomas ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
African American ◽  
Nyha Class ◽  
Risk Scores ◽  
Multivariable Logistic Regression Analysis ◽  
Class Iii ◽  
Clinical Practices ◽  
Persistence Rates ◽  
One Year ◽  
New Onset

Introduction: Warfarin and non-vitamin K antagonist oral anticoagulants (NOACs) such as dabigatran are effective for the prevention of stroke and systemic embolism in patients with atrial fibrillation (AF). However, few analyses have compared persistence rates of warfarin vs. dabigatran-treated patients. Methods: The ORBIT-AF registry enrolled patients with AF from 173 clinical practices across the US. One-year persistence of warfarin vs. dabigatran was defined as treatment at baseline visit and at 1-year follow-up. Multivariable logistic regression analysis was used to identify characteristics associated with warfarin or NOAC persistent use. Results: At baseline, 6.4% (N=459/7,150) were treated with dabigatran and 93.6% (N=6,691/7,150) with warfarin. Patients treated with warfarin at baseline were older (74 vs. 71, p<.0001), had more NYHA class III/IV heart failure (7 vs. 5, p=.0007), lower creatinine clearance (77 vs. 88, p<.0001), higher CHA2DS2-VASc risk scores, and more prior CVA/TIA events (16 vs. 11, p=.003). Patients treated with dabigatran had more severe symptoms (EHRA class III: 20 vs. 14, p<.0001), higher rates of treatment with a rhythm control strategy (42.7 vs. 28.2, p<.0001), more attempts at cardioversion (38.3 vs. 32.1, p<.006), and catheter ablation of AF (9.8 vs. 5.2, p<.0001). At 12 months, adjusted persistence rates for warfarin were higher than dabigatran [82% (80-84) vs. 67% (61-73) p<.0001]. Factors independently associated with one year persistence were: African American race (OR 1.53, 95% C.I. 1.07-2.19, p=0.02), Hispanic race (OR 1.66, 95% C.I. 1.06-2.60), paroxysmal AF (vs. new onset) (OR 1.68, 95% C.I. 1.21-2.33, p=.002), LVH (OR 1.40, 95% C.I. 1.08-1.81, p=.01), persistent AF (vs. new onset) (OR 1.91, 95% C.I. 1.35-2.69, p=.0002), and CHA2DS2-VASc risk scores ≥ 2 (OR 1.94, 95% C.I. 1.18-3.19, p=.009). Conclusion: Persistence rates for warfarin were higher at one year than those on dabigatran. In addition, factors associated with persistence of warfarin include: African American and Hispanic race, type of AF including permanent and persistent, LVH, and CHA2DS2-VASc risk scores ≥ 2.

scholarly journals Clinical characteristics and risk profile of patients with atrial fibrillation with mid-range ejection fraction, insights from the Polish part of EORP-AF Long-Term General Registry

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M Marchel ◽  
A Tyminska ◽  
K Ozieranski ◽  
M Budnik ◽  
A Wancerz ◽  
...  
Keyword(s):  
Risk Factors ◽  
Atrial Fibrillation ◽  
Ejection Fraction ◽  
Clinical Characteristics ◽  
Risk Profile ◽  
Left Ventricular Ejection ◽  
One Year ◽  
Embolic Risk

Abstract Background Atrial fibrillation (AF) comprises a wide range of patients (pts), from those with preserved to those with reduced left ventricular ejection fraction (LVEF). According to 2016 ESC guidelines, pts with LVEF in the range of 40–49% represent a “grey area”, which is defined as heart failure with mid-range ejection fraction (HFmrEF). Not much is known about the clinical characteristics of AF pts with mid-range ejection fraction. Purpose To determine the potential differences in the clinical characteristics, risk profile, and the outcomes of AF with moderate systolic dysfunction, measured by LVEF. Methods The EURObservational Research Programme on AF (EORP-AF) Long-Term General Registry analyzed consecutive AF patients who have presented to cardiologists in 250 centers from 27 European countries, including 25 centers from Poland. We analyzed data collected at baseline and at a 1-year follow-up visit from 568 Polish patients included in 25 Polish centers in the years 2013–2016. Pts were divided into three groups based on LVEF: the preserved LVEF (pEF) group (LVEF ≥50%), the mid-range LVEF (mrEF) group (40–49%), and the reduced LVEF (rEF) group (&lt;40%). Results 117/568 pts with rEF represented 20,6%, 105/568 mrEF 18,5% and 346/568 pEF 60,9% of the whole analyzed group. With regard to the most typical risk factors, the mrEF population appeared between rEF and pEF, presenting a moderate risk profile with the exception of hypertension, which was the most common in the mrEF group. While permanent AF was the most common in the rEF group and paroxysmal in the pEF pts, pts with mrEF had a higher rate of long-lasting persistent AF. Taking into account the risk factors profile, surprisingly, pts with AF and mrEF more often presented with dyspnea/shortnes of breath (mrEF 38,1% vs. rEF 18,8% vs. pEF 22,5%; p=0,001) and fatigue (mrEF 38,1% vs. rEF 23,9% vs. pEF 25,4%; p=0,025). AF pts with mrEF also had the highest thrombo-embolic risk estimated with the CHA2DS2-VASc score (mrEF 4 [2–5], n=105; rEF 3 [2–5], n=117, pEF 3 [2–4], n=346, p=0.005). However, this did not translate into the highest number of thromboembolic events after one year which did not significantly differ (mrEF 10.5%, rEF 15.4%, pEF 11.3%, p=0.30) between the three groups. Conclusions The risk factor profile of AF pts with mrEF was milder than for those with rEF and more severe than for pEF pts. AF pts with mrEF more often presented HF symptoms. Their estimated thrombo-embolic risk was higher but the number of events in the one year follow-up did not significantly differ between groups. Funding Acknowledgement Type of funding source: None

Long-term systolic blood pressure and all-cause mortality in heart failure with preserved ejection fraction: an analysis of the TOPCAT trial

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
P Huang ◽  
C Liu
Keyword(s):  
Heart Failure ◽  
Blood Pressure ◽  
Ejection Fraction ◽  
Funding Source ◽  
Preserved Ejection Fraction ◽  
Risk Of Mortality ◽  
All Cause Mortality ◽  
History Of

Abstract Background Lower systolic blood pressure (SBP) at admission or discharge was associated with poor outcomes in patients with heart failure and preserved ejection fraction (HFpEF). However, the optimal long-term SBP for HFpEF was less clear. Purpose To examine the association of long-term SBP and all-cause mortality among patients with HFpEF. Methods We analyzed participants from the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) study. Participants had at least two SBP measurements of different times during the follow-up were included. Long-term SBP was defined as the average of all SBP measurements during the follow-up. We stratified participants into four groups according to long-term SBP: &lt;120mmHg, ≥120mmHg and &lt;130mmHg, ≥130mmHg and &lt;140mmHg, ≥140mmHg. Multivariable adjusted Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CI) for all-cause mortality associated with SBP level. To assess for nonlinearity, we fitted restricted cubic spline models of long-term SBP. Sensitivity analyses were conducted by confining participants with history of hypertension or those with left ventricular ejection fraction≥50%. Results The 3338 participants had a mean (SD) age of 68.5 (9.6) years; 51.4% were women, and 89.3% were White. The median long-term SBP was 127.3 mmHg (IQR 121–134.2, range 77–180.7). Patients in the SBP of &lt;120mmHg group were older age, less often female, less often current smoker, had higher estimated glomerular filtration rate, less often had history of hypertension, and more often had chronic obstructive pulmonary disease and atrial fibrillation. After multivariable adjustment, long-term SBP of 120–130mmHg and 130–140mmHg was associated with a lower risk of mortality during a mean follow-up of 3.3 years (HR 0.65, 95% CI: 0.49–0.85, P=0.001; HR 0.66, 95% CI 0.50–0.88, P=0.004, respectively); long-term SBP of &lt;120mmHg had similar risk of mortality (HR 1.03, 95% CI: 0.78–1.36, P=0.836), compared with long-term SBP of ≥140mmHg. Findings from restricted cubic spline analysis demonstrate that there was J-shaped association between long-term SBP and all-cause mortality (P=0.02). These association was essentially unchanged in sensitivity analysis. Conclusions Among patients with HFpEF, long-term SBP showed a J-shaped pattern with all-cause mortality and a range of 120–140 mmHg was significantly associated with better outcomes. Future randomized controlled trials need to evaluate optimal long-term SBP goal in patients with HFpEF. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): China Postdoctoral Science Foundation Grant (2019M660229 and 2019TQ0380)

Benefits of tafamidis in patients with advanced transthyretin amyloid cardiomyopathy

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
C Rapezzi ◽  
A.V Kristen ◽  
B Gundapaneni ◽  
M.B Sultan ◽  
M Hanna
Keyword(s):  
Disease Severity ◽  
Nyha Class ◽  
Funding Source ◽  
Class Iii ◽  
Private Company ◽  
Risk Of Death ◽  
6Mwt Distance ◽  
All Cause Mortality ◽  
Amyloid Cardiomyopathy

Abstract Background In the Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR-ACT), tafamidis was shown to be an effective treatment for patients with transthyretin amyloid cardiomyopathy (ATTR-CM). Further assessment of the efficacy of tafamidis in patients with more advanced ATTR-CM would aid treatment decisions. Purpose To characterize the benefits of tafamidis in patients with advanced ATTR-CM. Methods In ATTR-ACT, ATTR-CM patients were randomized to tafamidis (n=264) or placebo (n=177) for 30 months. Efficacy outcomes included all-cause mortality and frequency of cardiovascular (CV)-related hospitalisations. Key secondary endpoints were change from baseline to Month 30 in 6MWT distance and KCCQ-OS score. Efficacy assessments in NYHA Class III patients at baseline (n=141) were a pre-specified analysis. In a post-hoc analysis, mortality and CV-related hospitalizations were assessed in all patients grouped into quartiles of increasing disease severity based on 6MWT distance at baseline. Longer-term all-cause mortality (as of 1 Aug 2019) was assessed in NYHA Class III patients utilizing data from ATTR-ACT patients who enrolled in a long-term, extension study (LTE) and continued treatment with higher dose tafamidis (n=55; median treatment duration 51.6 months); or, if previously treated with placebo, started tafamidis treatment (placebo/tafamidis; n=63 [50.1 months]). Results In advanced ATTR-CM patients (NYHA Class III), tafamidis reduced the risk of death (HR [95% CI] 0.837, [0.541, 1.295], P=0.4253), and the decline in 6MWT distance (LS mean [SE], 31.6 (22.1) m; P=0.1526) and KCCQ-OS score (LS mean [SE], 13.1 (5.0); P=0.0090), vs placebo. Paradoxically, there was a higher frequency of CV-related hospitalizations with tafamidis (RR [95% CI] vs placebo, 1.411 [1.048, 1.900]). In all patients by 6MWT quartile, CV-related hospitalizations/year with tafamidis and placebo increased with disease severity, with the exception that placebo-treated patients in the highest severity quartile had fewer CV-related hospitalisations (0.73) than those in the third quartile (0.92). Mortality with tafamidis and placebo increased, and was greater with placebo, in every quartile (Figure). Survival (NYHA Class III patients in ATTR-ACT and LTE) was improved with high dose tafamidis with longer term follow-up (HR vs placebo/tafamidis [95% CI], 0.6569 [0.4175, 1.0336]; P=0.0692). Conclusions These analyses, including longer-term follow-up, demonstrate that patients with advanced ATTR-CM benefit from tafamidis. The decrease in CV-related hospitalisations in more severe patients treated with placebo suggests that the comparatively greater hospitalisation frequency in NYHA Class III patients treated with tafamidis is a consequence of their lower mortality rate. Figure 1 Funding Acknowledgement Type of funding source: Private company. Main funding source(s): This study was sponsored by Pfizer

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