HFrEF Patients Research Articles

Speckle Tracking-Derived Left Atrial Stiffness Predicts Clinical Outcome in Heart Failure Patients with Reduced to Mid-Range Ejection Fraction.

Background and Aim: Left atrial stiffness (LASt) is an important marker of cardiac function, especially in patients with heart failure (HF); it explains symptoms on the basis of pressure transfer to the pulmonary circulation. The aim of this study was to evaluate the relationship between LASt and cardiac events (CE) in HF patients with reduced to mid-range ejection fraction. Methods: The study included 215 consecutive ambulatory HF patients with ejection fraction (EF) < 50% (162 HF reduced EF and 53 HF mid-range EF) of mean age 66 ± 11 years and 24.4% females. Peak LA strain (PALS) was measured by speckle tracking echocardiography and E/e’ recorded from the apical four-chamber view. Non-invasive LASt was calculated using the equation: LASt = E/e’ ratio/PALS. Documented cardiac events (CE) were HF hospitalization and cardiac death. Results: During a median follow up of 41 ± 34 months, 65 patients (30%) had CE. In multivariate analysis model, only raised LV filling pressure (E/e’) (OR = 0.292, (95% CI 0.099 to 0.859), p = 0.02), peak pulmonary artery pressure (PAP) (OR = 1.050 (1.009 to 1.094), p = 0.01), PALS (OR = 0.932 (0.873 to 0.994), p = 0.02) and LASt (OR = 3.781 (1.144 to 5.122), p = 0.001) independently predicted CE. LASt ≥ 0.76% was the most powerful predictor of CE, with 80% sensitivity and 73% specificity (AUC 0.82, CI = 0.73 to 0.87, p < 0.001) followed by PALS ≤ 16%, with 74% sensitivity and 72% specificity (AUC 0.77, CI = 0.71 to 0.84, p < 0.001). These results were consistent irrespective of EF (p < 0.05). Conclusion: In this cohort of ambulatory HFrEF and HFmrEF patients, LASt proved the most powerful predictor of clinical outcome.

Victoria Trial: Vericiguat Joins the Big League, or Does it?

The VICTORIA trial showed Vericiguat once daily (titrated up to 10 mg) significantly reduced its primary end-point, the composite of death from cardiovascular causes or first hospitalization for heart failure, in 5050 class II-IV HFrEF patients (LVEF&lt;45%). This a land-mark trial, one of the largest we have seen in heart failure, and it had some very important novel features; it only recruited patients with a recent (within 6 months) worsening of their heart failure, a group known to be at increased risk of subsequent events, and it included more severe heart failure than most recent trials with NTproBNP levels nearly twice that of Paradigm-HF or DAPA-HF. VICTORIA had substantially higher mortality rate but an apparently less impressive hazard ratio (HR) 0.90 (0.82 – 0.98) compared to Paradigm’s 0.80 (0.73 – 0.87) and DAPA’s 0.74 (0.65 –0.85). This must be considered against a healthy absolute risk reduction at 4.2% compared to Paradigm’s 2.7% and DAPA’s 4.0%, due to the higher risk patients in VICTORIA. Another very important difference with VICTORIA is that it included the higher risk recently discharged HF patients, and patients eGFR’s down to 15 ml per minute per 1.73 m2 of body-surface area, possibly suggesting a special place for Vericiguat in traetring these at-risk subsets of HFrEF patients, but for the fact that the cohort between 15 and 30mL/min/1.73m2 of eGFR was only around 10.0%, and the point estimate for the HR for this small group was above 1.0 at 1.06 (0.83-1.34). Aslo the sub-grouping by NTproBNP level was highly significantly interacting (p&lt;0.001) with the lower three quartiles all being significantly in favour of Vericiguat and the highest quartile (&gt;5,314 pg/mL) being almost significantly worse on Vericiguat with a HR of 1.16 (0.99-1.35). So the two major areas where Vericiguat may have received special notice appear to be less impressive when we look in detail at the trial results. How do we therefore place Vericiguat in the wake of VICTORIA? It is a proven therapy in a disease which still has residual high rates of clinical mortality and morbidity. It conveyed a benefit on top of other therapies, thus it should be not ignored and may indeed be a very effective therapy in some patients.

The importance of developing hyperkalaemia in heart failure during long-term follow-up

Background Hyperkalaemia is a potentially life-threatening condition. Furthermore, it is one of the main reasons for discontinuation and dose reduction of renin-angiotensin-aldosterone system inhibitors (RAASi) in clinical practice. However, exact data on the prevalence and consequences of occurrence of hyperkalaemia when taking RAASi in a dedicated heart failure care setting are scarce. Methods Consecutive patients diagnosed with heart failure from a single tertiary hospital between August 2000 and May 2017 were retrospectively evaluated. Primary endpoint was the development of hyperkalaemia (≥5.5 mmol/L) at any moment during follow-up. Results About 396 patients were included in the current analysis (mean follow-up 6.9 years). 26% (n = 104) and 12% (n = 46) of patients developed hyperkalaemia (≥5.5 mmol/L and ≥6.0 mmol/L, respectively). Diabetes mellitus (OR = 1.80, 95% CI = 1.03–3.19) and baseline creatinine (mg/dL) (OR = 2.37, 95% CI = 2.37–3.85) were independent risk factors for hyperkalaemia. Development of hyperkalaemia was associated with 6.5 higher odds for recurrence. Only 10% developed hyperkalaemia during up-titration of RAASi, while 90% developed during later follow-up on stable doses of RAASi. hyperkalaemia was not associated with worse outcome after multivariate adjustment for baseline co-morbidities. However, hyperkalaemia was associated with discontinuation and lower doses of MRAs during follow-up (p = 0.007). Discontinuation of MRA due to hyperkalaemia was associated with an increase in all-cause mortality in HFrEF patients (HR = 1.77, 95% CI = 1.05–2.99). Conclusions Approximately, one-fourth of patients developed hyperkalaemia during follow-up which was associated with a lower MRA dose during follow-up. Discontinuation of MRA, but not hyperkalaemia itself, was associated with an increased risk of all-cause mortality and heart failure admission in HFrEF patients.

Comparing inpatient costs of heart failure admissions for patients with reduced and preserved ejection fraction with or without type 2 diabetes.

We created a retrospective cohort of acutely decompensated HF patients, using linked data from cost accounting systems and electronic medical records. We stratified patients by LVEF into reduced ejection fraction (HFrEF, LVEF ≤40%) and preserved ejection fraction (HFpEF, LVEF >40%) groups and by DM status at admission. Our population had 544 people: 285 HFrEF patients (43.5% with DM) and 259 HFpEF patients (43.6% with DM). Patients with HFrEF and DM had the longest hospital stay (5.10 ± 5.21 days). Patients with HFrEF and DM had the highest hospitalization cost ($11 576 ± 15 818). HFrEF and HFpEF patients with DM had the highest cost, and cost per day alive was highest for HFpEF patients with DM [$3153 (95% CI 2332, 4262)]. Overall cost was higher for patients with DM, whether or not they were admitted with acute HF due to HFrEF or HFpEF. Cost per day alive for patients with DM continued to exceed corresponding costs for patients without DM, with HFpEF patients with DM having the highest cost.

Clinical characteristics and long-term prognosis of ischemic and non-ischemic cardiomyopathy

ObjectivesThe different etiology of HF has different prognostic risk factors. Prognosis assessment of ICM and NICM has important clinical value. This study is aimed to explore the predicting factors for ICM and NICM. Methods1082 HFrEF patients were retrospectively enrolled from Jan. 01, 2016 to Dec. 31, 2017. On Jan. 31, 2019, 873 patients were enrolled for analysis excluding incomplete, unfollowed, and unexplained data. The patients were divided into ischemic and non-ischemic group. The differences in clinical characteristics and long-term prognosis between the two groups were analyzed, and multivariate Cox analysis was used to predict the respective all-cause mortality, SCD and rehospitalization of CHF. Results873 patients aged 64(53,73) were divided into two groups: ICM (403, 46.16%) and NICM. At the end, 203 died (111 in ICM, 54.68%), of whom 87 had SCD (53 in ICM, 60.92%) and 269 had rehospitalization for HF(134 in ICM, 49.81%). Independent risk factors affecting all-cause mortality in ICM: DM, previous hospitalization of HF, age, eGFR, LVEF; for SCD: PVB, eGFR, Hb, revascularization; for readmission of HF: low T3 syndrome, PVB, DM, previous hospitalization of HF, eGFR. Otherwise; factors affecting all-cause mortality in NICM: NYHA III-IV, paroxysmal AF/AFL, previous hospitalization of HF, β-blocker; for SCD: low T3 syndrome, PVB, nitrates, sodium, β-blocker; for rehospitalization of HF: paroxysmal AF/AFL, previous admission of HF, LVEF. ConclusionsBoth all-cause mortality and SCD in ICM is higher than that in NICM. Different etiologies of CHF have different risk factors affecting the prognosis.

Cardiac resynchronization therapy modulates peripheral sympathetic activity

Heightened sympathetic nerve activity has been associated with poorer prognosis in patients with reduced left ventricular systolic function (ie, heart failure with reduced ejection fraction [HFrEF]). The purpose of this study was to investigate the effects of cardiac resynchronization therapy (CRT) on sympathetic nerve activity, measured by average skin sympathetic nerve activity (aSKNA). This prospective study enrolled 36 patients with HFrEF who received CRT. Ten patients who received an implantable cardioverter-defibrillator for primary prevention served as controls. Patient clinical data, echocardiographic variables, and aSKNA at baseline and 3-month follow-up were collected. CRT patients who exhibited wider QRS duration had higher aSKNA (1.52 ± 0.65 μV vs 0.97 ± 0.49 μV; P = .027) compared to the control group at baseline. In the CRT group, patients with QRS duration ≥150 ms had higher aSKNA than those with QRS duration <150 ms (1.67 ± 0.63 μV vs 1.19 ± 0.51 μV; P =.039). After CRT, left ventricular ejection fraction (LVEF) improved from 29.6% to 35.4% (P = .001). aSKNA decreased significantly (1.52 ± 0.65 μV vs 1.31 ± 0.63 μV; P = .018). Seventeen of the 36 CRT patients were CRT responders, with LVEF improvement ≥5% at 3-month follow-up. aSKNA significantly decreased from 1.47 to 1.15 μV (P = .003) in CRT responders but was unchanged in nonresponders (1.44 ± 0.69 to 1.37 ± 0.70; P = .61). After CRT, a significant reduction in aSKNA was associated with improvement in LVEF (r = 0.638; P = .001). CRT reduces elevated sympathetic activity in HFrEF patients, accompanied by improvement in systolic function at short-term follow-up. The reduction of sympathetic activity is mainly seen in CRT responders.

Mortality and Morbidity in HFrEF, HFmrEF, and HFpEF Patients with Diabetes in the Middle East.

ObjectivesWe sought to estimate the mortality and morbidity in diabetic acute heart failure (AHF) patients stratified by left ventricular ejection fraction.MethodsWe analyzed the data of patients with AHF from seven Middle Eastern countries (Bahrain, Oman, Yemen, Kuwait, UAE, Qatar, and Saudi Arabia) from February to November 2012, who were enrolled in a multinational registry of patients with heart failure (HF).ResultsA total of 2258 AHF patients had diabetes mellitus. The mean age was 63.0±11.0 years (ranging from 18 to 99 years), and 60.3% (n = 1362) of the patients were males. The mean ejection fraction (EF) was 37.0±13.0%. HF with reduced EF (< 40%) (HFrEF) was observed in 1268 patients (56.2%), whereas 515 patients (22.8%) had mid-range (40–49%) (HFmrEF) and 475 patients (21.0%) had preserved EF (3 50%) (HFpEF). The overall cumulative all-cause mortalities at three- and 12-months follow-up were 11.8% (n = 266) and 20.7% (n = 467), respectively. Those with HFpEF were associated with lower three-months cumulative all-cause mortality compared to those with HFrEF (7.6% vs. 5.9%; adjusted odds ratio (aOR) = 0.54, 95% confidence interval (CI): 0.31–0.95; p = 0.031), but not significantly different when compared to those with HFmrEF (aOR = 0.86, 95% CI: 0.53–1.40; p = 0.554). There were largely no significant differences among the groups with regards to the 12-months all-cause cumulative mortality (11% vs. 11% vs. 10%; p = 0.984). There were also no significant differences in re-hospitalization rates between the three HF groups not only at three months (23% vs. 20% vs. 22%; p = 0.520), but at one-year follow-up (28% vs. 30% vs. 32%; p = 0.335).ConclusionsThree-month cumulative all-cause mortality was high in diabetic HFrEF patients when compared to those with HFpEF. However, there were no significant differences in mortality at one-year follow-up between the HF groups. There were also no significant differences in re-hospitalization rates between the HF groups not only at three months but also at one-year follow-up in the Middle East.

Medical treatment of octogenarians with chronic heart failure: data from CHECK-HF

Elderly heart failure (HF) patients are underrepresented in clinical trials, though are a large proportion of patients in real-world practice. We investigated practice-based, secondary care HF management in a large group of chronic HF patients aged ≥ 80years (octogenarians). We analyzed electronic health records of 3490 octogenarians with chronic HF at 34 Dutch outpatient clinics in the period between 2013 and 2016 , 49% women. Study patients were divided into HFpEF [LVEF ≥ 50%; n = 911 (26.1%)], HFrEF [LVEF < 40%; n = 2009 (57.6%)] and HF with mid-range EF [HFmrEF: LVEF 40-49%; n = 570 (16.3%)]. Most HFrEF patients aged ≥ 80years received a beta blocker and a renin-angiotensin system (RAS) inhibitor (angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker), i.e. 78.3% and 72.8% respectively, and a mineralocorticoid receptor antagonist (MRA) was prescribed in 52.0% of patients. All three of these guideline-recommended medications (triple therapy) were given in only 29.9% of octogenarians with HFrEF, and at least 50% of target doses of triple therapy, beta blockers, RAS inhibitor and MRA, were prescribed in 43.8%, 62.2% and 53.5% of the total group of HFrEF patients. Contraindications or intolerance for beta blockers was present in 3.5%of the patients, for RAS inhibitors and MRAs in, 7.2% and 6.1% CONCLUSIONS: The majority of octogenarians with HFrEF received one or more guideline-recommended HF medications. However, triple therapy or target doses of the medications were prescribed in a minority. Comorbidities and reported contraindications and tolerances did not fully explain underuse of recommended HF therapies.

Long-term outcome of carvedilol therapy in Japanese patients with nonischemic heart failure.

Nonischemic heart failure (HF) is common in Japan. We evaluated the long-term outcome of Japanese patients with nonischemic HF receiving carvedilol based on left ventricular ejection fraction (LVEF) category. We conducted a single-center observation study of 1550 patients with nonischemic HF who were initiated with carvedilol between 2005 and 2015. Of these patients, 38% had an LVEF < 40% (HFrEF, median age 57years, 28% female) and 62% had an LVEF ≥ 40% (HFpEF, 64years, 38% female). The primary outcome was all-cause.death The secondary outcomes were cardiac death and sudden cardiac death (SCD). After a median follow-up of 5.5 [interquartile range, 2.9-8.8] years, the median daily maintenance doses of carvedilol in patients with HFrEF and HFpEF were 7.5 [5-12.5]mg and 7.5 [5-10]mg, respectively. The cumulative survival rates of HFrEF patients at 1, 3 and 5years were 96.1%, 90.2% and 85.5%, respectively, and the cumulative survival rates of HFpEF patients at 1, 3 and 5years were 97.8%, 94.4% and 90.7%, respectively. The cumulative cardiac death-free rates at 5years were 94.4% in HFrEF patients and 97.7% in HFpEF patients, and the cumulative SCD-free rates at 5years were96.7% in HFrEF patients and 97.9% in HFpEF patients. The adjusted survival rate showed that a higher dose (≥ 7.5mg daily) was associated with more favourable outcomes than a lower dose (< 7.5mg daily) in HFrEF patients, but not in HFpEF patients. The adjusted survival rate showed that a lower heart rate (< 75bpm) was associated with favourable outcomes than a higher heart rate (≥ 75bpm) in HFrEF patients, but not in HFpEF patients. Long-term survival was good in Japanese patients with nonischemic HF receiving carvedilol. Higher doses and lower heart rates were associated with favourable survival for HFrEF patients, but not in HFpEF patients.

Prognostic value of sST2 in patients with heart failure with reduced, mid-range and preserved ejection fraction

BackgroundsPrognostic value of soluble suppression of tumorigenecity (sST2), a novel circulating biomarker for myocardial fibrosis, remains elusive in the heart failure patients with preserved ejection fraction (HFpEF). Methods405 consecutive patients with heart failure (HF) were enrolled prospectively, and were grouped into HF with reduced ejection fraction (HFrEF, N = 215), HF with mid-range ejection fraction (HFmrEF, N = 80) and HFpEF (N = 110). The primary endpoint was the composite endpoint of all-cause death and HF rehospitalization. ResultsAfter a median of 12 months, 139 patients reached the primary endpoint, with 57 patients died and 82 patients rehospitalized. Multivariate analysis confirmed that sST2 was an independent risk factor of the primary endpoint for all HF patients [hazard ratio (HR) 2.35, 95% confidence interval (CI) 1.30–4.22, P = 0.004]. Predicting efficacy of sST2 on outcomes was higher for HFpEF (HR 6.48, 95%CI 1.89–22.21, P = 0.003) as compared to HFrEF (HR 3.21, 95% CI 1.67–6.19, P = 0.000). But the association between sST2 and outcomes in HFmrEF is not statistical (HR 3.38, 95%CI 0.82–13.86, P = 0.091). The combined use of sST2 and N terminal pro B type natriuretic peptide (NT-proBNP) could improve the prognostic value compared to using NT-proBNP alone in HFrEF (AUC = 0.794 vs. 0.752, P = 0.034). ConclusionHigher baseline sST2 levels are associated with increased risk of all-cause death and HF rehospitalization in patients with HF independent of ejection fraction. The combined use of sST2 and NT-proBNP could improve the prognostic value than using these two values alone, especially for HFrEF patients.

P1751 Right ventricular dysfunction in heart failure patients with reduced ejection fraction with and without chronic respiratory diseases: A treacherous combination for the ominous outcome?

Abstract Background Right ventricular (RV) dysfunction is common in heart failure patients. In the present study, we determined the impact of echocardiography defined RV dysfunction on outcomes in heart failure patients with reduced ejection fraction (&amp;lt;40%, HFrEF) with and without chronic respiratory diseases (CRDs: asthma, chronic obstructive pulmonary disease, occupational lung diseases, sleep apnea syndrome). Methods A total of 1264 HFrEF patients (Mean age: 68 ± 13 years; male: 76.3%) referred to our department between 2009 and 2017 were included. Baseline demographic and clinical data were obtained by reviewing the medical records. All patients subsequently completed a median clinical follow-up of 26 (12-40) months by medical record review or telephone interview. The primary endpoint was all-cause mortality or heart transplantation (HTx). Right heart morphology and function were assessed by multiple echocardiographic parameters, including right atrial area (RAA), RV mid diameter (RVD), tricuspid annular plane systolic excursion (TAPSE) and systolic pulmonary artery pressure (sPAP). Results The proportion of NYHA functional class III-IV was 42.2%. Mean LVEF was 29.4 ± 7.0%. CRDs was identified in 276 (21.8%) patients, 399 (30.5%, without CRDs n = 290, with CRDs n = 109) patients died (n = 386) or underwent HTx (n = 13). All-cause mortality/HTx was significantly higher in HFrEF patients with CRDs than without CRDs (39.5% vs. 29.4%, P = 0.001). Cox regression analysis showed that age, BMI, and other cardiac risk factors and comorbidities including diabetes, atrial fibrillation, coronary artery disease, kidney dysfunction, and anemia were associated with all-cause mortality/HTx (all P &amp;lt; 0.05) besides CRDs. Multivariable Cox regression models showed that sPAP (HR 1.016, P &amp;lt; 0.001), TAPSE (HR 0.964, P = 0.003), RAA (HR 1.030, P &amp;lt; 0.001), and RVD (HR 1.029, P &amp;lt; 0.001) were independent determinants of all-cause mortality/HTx in HFrEF patients without CRDs, but not in HFrEF patients with CRDs after adjusted for above mentioned confounders. With the cut-off values (sPAP &amp;gt; 40mmHg, TAPSE &amp;lt; 12mm, RAA &amp;gt; 25cm², and RVD &amp;gt; 36mm) derived from the 3rd quartiles, patients without CRDs were further grouped as normal RV function (all 4 parameters normal, n = 427); mild to moderate RV dysfunction (1 or 2 parameters abnormal, n = 467) and severe RV dysfunction (≥3 parameters abnormal, n = 94). Risk of all-cause mortality/HTx was significantly higher in HFrEF patients with severe (51.1%) and mild to moderate RV dysfunction (34.7%) as compared to patients with normal RV function (18.7%, severe vs. normal: HR 1.616 , 95% CI 1.232-2.119, P = 0.001; mild to moderate vs. normal HR: 2.657, 95% CI 1.845-3.824, P &amp;lt; 0.001). Conclusions RV dysfunction is significantly associated with increased all-cause mortality in HFrEF patients without CRDs. Increased sPAP, RAA, RVD and decreased TAPSE are independent determinants of worse outcomes in HFrEF patients without CRDs, but not in HFrEF patients with CRDs.

P904 Impact of significant functional mitral regurgitation and aortic stenosis on outcome of HFrEF patients

Abstract Background Concomitant aortic stenosis (AS) and functional mitral regurgitation (FMR) are common in patients with left ventricular dysfunction. We evaluated the impact of significant valve diseases on outcome of patients with reduced left ventricular ejection fraction (HFrEF, LVEF &amp;lt; 40%). Methods A total of 1264 consecutive HFrEF patients referred to our department between 2009 and 2017 were screened. Transthoracic echocardiography was performed at baseline visit in all patients. Patients with primary MR or received mitral valve operation before or after baseline visit (n = 64) as well as patients underwent aortic valve replacement (AVR) before baseline visit (n = 66) were excluded. Finally, 1134 HFrEF patients were included for final analysis, and all completed a median clinical follow-up of 26 (12-40) months by medical record review or telephone interview. The primary endpoint was all-cause mortality or heart transplantation (HTx). Results Moderate or severe FMR or AS was detected in 902 (79.5%) and in 119 (10.5%) patients by echocardiography, respectively. Of patients with significant AS, 47 patients underwent AVR shortly after baseline visit. In total, 353 (31.2%, including HTx n = 11) HFrEF patients died or underwent HTx during follow-up. Age, body mass index, diabetes, atrial fibrillation, coronary artery disease, chronic respiratory diseases, and renal dysfunction (all P &amp;lt; 0.05) were defined as clinical covariates associated with all-cause mortality/HTx and served as potential confounders in the multivariable Cox regression models. All-cause mortality/HTx was significantly higher in HFrEF patients with significant FMR than patients without significant FMR (33.8% vs. 20.7%, P &amp;lt; 0.001). Multivariable Cox regression analysis showed significant FMR remained as an independent determinant of all-cause mortality/HTx in patients with HFrEF after adjusted for above mentioned confounders (HR 1.39, 95% CI 1.02-1.90, P = 0.035). Patients with significant AS without AVR faced increased risk of all-cause mortality/HTx as compared to patients without significant AS (HR 2.34, P &amp;lt; 0.001), while risk of all-cause mortality/HTx was significantly lower in patients with significant AS and underwent AVR as compared to patients without significant AS after adjustment for confounders (HR 0.36, P = 0.008). In the subgroup of HFrEF patients with significant FMR, significant AS without AVR was independently associated with increased all-cause mortality/HTx as compared to patients without significant AS (HR 2.30, P &amp;lt; 0.001), while outcome is better in AS and FMR patients underwent AVR as compared to patients with significant FMR and without significant AS (survival: 85.4% vs. 67.5%, P &amp;lt; 0.001; HR 0.34, P = 0.010) after adjustment for potential confounding factors. Conclusion Moderate to severe FMR and/or AS is incrementally related to higher all-cause mortality/HTx in HFrEF patients. AVR could significantly improve the survival of HFrEF patients with concomitant significant AS and FMR.

P803 Myocardial work in acutely decompensated heart failure patients differs between HFrEF and HFpEF

Abstract OnBehalf AHF Registry Background &amp; Aim A novel echocardiographic method to non-invasively determine left ventricular (LV) myocardial work (MyW) based on speckle-tracking derived longitudinal strain and blood pressure has recently been validated against invasive reference measurements. MyW is considered less load-dependent than LV ejection fraction (EF) and LV longitudinal strain. We investigated MyW indices in patients with reduced ejection fraction (LVEF &amp;lt;40%; HFrEF) and patients with preserved ejection fraction (LVEF ≥50%, HFpEF) admitted for acutely decompensated heart failure (AHF). Methods The AHF registry is a monocentric prospective follow-up study that comprehensively phenotypes consecutive patients hospitalized for AHF. Echocardiography was performed on the day of admission. MyW assessment was performed off-line using EchoPAC (GE, version 202). Here we present MyW indices and performed two-sided t-tests to analyze differences in numerical baseline covariates. Results We analyzed the echocardiograms of 94 AHF patients (72 ± 10 years; 36% female). 46 patients (49%) had an LVEF &amp;lt;40%, while 48 patients (51%) presented with LVEF ≥50%. HFrEF patients were younger, less often female, and hat lower blood pressure (table). Consistent with lower LVEF, HFrEF patients had less negative global longitudinal strain and lower global constructive work, when compared to HFpEF patients. Since HFrEF patients also had higher global wasted work, this yielded a lower myocardial work efficiency compared to HFpEF patients (table). Conclusions This analysis in patients with AHF exhibited marked differences in MyW indices according to subgroups with HFrEF and HFpEF, thus adding information to the classical measures of LV function. Future research has to determine whether constructive and/or wasted MyW are valuable diagnostic or therapeutic targets in patients with AHF. Abstract P803 Figure.

P960 Response of alveolo-capillar membrane diffusion to mitral regurgitation in heart failure with reduced ejection fraction

Abstract Background In HFrEF patients, high pulmonary vascular resistances (PVR) imply a combined increase of both pre- and post-capillary pressures, associated with worse outcome. Mitral regurgitation (MR) may play a role in this complex physiopathology. We sought to investigate MR impact on lung DLCO and pulmonary vascular hemodynamic in HFrEF patient. Methods 27 HFrEF patients (age 69 ± 9; LV EF 34 ± 6) underwent right heart catheterization, rest and exercise echocardiography, right ventricle 3D assessment and lung alveolo-capillary membrane DLCO. We identified 2 subgroups divided by normal (&amp;lt;3 WU, n= 20) or abnormal (&amp;gt;3 WU, n = 7) PVR. Results Abnormal PVR patients showed increased pulmonary artery pressures and TPG, reduced CO and pulmonary artery compliance. Total DLCO was not significantly different between groups. The membrane component (Dm) and the alveolar volume (Va) were significantly reduced in abnormal PVR group, while the capillary volume (VC) showed a strong trend toward higher values. Abnormal PVR group had a very high percentage of moderate-to-severe MR. The TASPE/SPAP ratio and the circumferential component of RV systolic function were significantly reduced in abnormal PVR group. Conclusion The presence of severe MR is associated with alveolar-capillary membrane remodeling (lower Dm), worse hemodynamic profile (higher PA pressures, lower PA compliance and higher PA resistance) and worse right ventricle to pulmonary circulation coupling (lower TAPSE/SPAP and lower 3D RV circumferential EF) in this cohort of HFrEF patients. These results confirm the adequacy of using therapeutic strategies aimed to solve valvular disease.

Cardiorenal Syndrome in Renal Transplant Recipients: Prevalence, Clinical Presentation, Treatment, and Outcome

Background: Data on the cardiorenal syndrome (CRS) in renal transplant recipients (RTR) are scarce. We investigated the prevalence, clinical presentation, treatment, and outcomes of patients with CRS in our renal transplant cohort. Methods: Charts and medical records of adult RTR were investigated to identify patients with renal allograft dysfunction and heart failure (HF) with reduced (HFrEF) or preserved (HFpEF) ejection fraction. Results: From December 2009 to December 2019, a total of 1,610 patients received a kidney allograft at our institution. CRS was diagnosed in 9 patients (0.56%) a median of 11 years after transplantation (4–20 years). Seven of the patients were male, and 2 were female. The median age when CRS was diagnosed was 71 years (64–80 years). The major presenting symptom was dyspnea. Five patients had HFrEF, and 4 had HFpEF. The patient’s median basal creatinine clearance was 37 mL/min (range 29–77 mL/min). At hospitalization, it was decreased to 24 mL/min (range 13–45 mL/min). The patients were treated with diuretics, but 5 of them required extracorporeal fluid removal. At the 16-month follow-up (median), all patients with HFpEF were alive and had returned to initial levels of creatinine clearance. Two of the 5 HFrEF had died, and 2 needed permanent extracorporeal water removal. Conclusion: CRS after renal transplantation was rare (<1.0%), but CRS in HFreF patients was associated with a poor outcome.

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

There is currently no data to predict response to treatment by sacubitril/valsartan. 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. A total of 78 patients treated by ACE inhibitor or AAR2, were prospectively assigned to equimolar sacubitril/valsartan replacement. We collected many 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 ( Fig. 1 ). Subsequently, participants were categorized using Penalized Model-Based Clustering. P < 0,05 was considered significant. Mean age was 60.4 ± 13.4 year old 79.0% patients were males. 16 phenotypic domains were isolated ( Fig. 1 ) and 3 phenogroups were identified ( Table 1 ). Phenogroup 1 was remarkable by left ventricular involvement with moderate diastolic dysfunction (DD), no mitral regurgitation (MR) and no pulmonary hypertension (PH). Phenogroups 2 and 3 corresponded to patients with severe PH, related to severe DD or MR. In both phenogroups, the left atrium was significantly enlarged and the right ventricle was remodelled. The echocardiographic response to sacubitril/valsartan was comparable in all groups with similar improvement of EF and reduction of cardiac chambers dimensions. The clinical response was even better in phenogroups 2 and 3. HF-REF patients with severe diastolic dysfunction, significant mitral regurgitation and elevated pulmonary hypertension by echocardiographic had similar reverse remodelling but better clinical improvement than patients with isolated left ventricular systolic dysfunction.

P214 Clinical audit of in-patient echocardiography in acute heart failure: real world data from a tertiary hospital

Abstract Background Over the last ten years, an increase in admission rates for acute heart failure (HF) has been noted in England and Wales, with one year mortality rates varying between 30% and 60%. Transthoracic echocardiography (TTE) is recommended within 48 hours of admission for suspected acute heart failure, so to guide treatment accordingly. Our centre has a specialist team who assesses patients with suspected HF on admission, and refers them for urgent in-patient TTE, using two priority in-patient echo slots per day. Patients are initially referred for HF assessment by general medics and geriatricians, across non-specialist medical wards. We audited the referrals and results of those who received TTE in this context. Methods and results We screened the medical notes of 252 patients admitted with suspected HF between January and December 2017, and reviewed the echocardiography results of those who received it during their admission. 50% of these patients were female and 59% were elderly (over 80 years old). 245 of these patients (97.2%) had in-patient echocardiography performed during their hospital stay. The mean wait for echocardiography was 0.58 days, with 92% of the scans being performed within 24 hours. The mean admission duration was 8.6 days (SD 10.9). 17.9% of patients were readmitted with suspected heart failure within six months, 69% of which were elderly. The majority of this cohort presented with heart failure with preserved ejection fraction (HFpEF), 50%), followed by heart failure with reduced ejection fraction (HFrEF, 29%) and heart failure with mid-range ejection fraction (HFmrEF, 16%). 41% of the patients who received an echocardiogram were in atrial fibrillation, 51% of which were diagnosed with HFpEF. All patients had their HF medical treatment optimised post-echocardiography and only 18.4% were readmitted within 6 months of the first admission. The majority of these patients was elderly (68.9%). 38.8% of patients who received echocardiography were referred for specialist clinic follow-up, with HFrEF patients more likely to be seen in this setting (42%). Six-month mortality occurred in 19.8% of patients; cause of death (COD) was undocumented in 25.8% of cases. In those where a post-mortem was conducted, the main COD was HF (16.7%), followed by sepsis (13.6%), cardiac (6.1%) and respiratory arrest (6.1%). 66% of the deceased patients were elderly and 48% presented with HFpEF. Conclusion Our cohort is an accurate representation of the current HF statistics seen nationwide. Appropriate treatment was offered to the large majority of patients who received in-patient echocardiography within the first 24 hours of their admission, with low six-month readmission rates. This approach also allowed for the inclusion of these patients on a systematic review plan, including specialist cardiology follow-up. Our numbers are consistent with the higher awareness about HFpEF currently seen in the medical community.

Flow-Mediated Vasodilation and Reactive Hyperemia Index in Heart Failure with Reduced or Preserved Ejection Fraction.

Vascular endothelial dysfunction is part of the underlying pathophysiology of heart failure. However, there are no reports in which vascular endothelial function of both conduit arteries and microvasculature was assessed in patients with heart failure. This study was aimed to assess vascular endothelial function separately in heart failure with reduced (HFrEF) and preserved ejection fraction (HFpEF). We performed simultaneous measurement of both flow-mediated vasodilation for endothelial function of conduit arteries and reactive hyperemia-peripheral arterial tonometry for that of microvasculature in 88 consecutive patients with chronic heart failure. In 55 patients with ischemic heart disease as an underlying cause of heart failure, flow-mediated vasodilation value was comparable between the two groups of HFrEF (left ventricular ejection fraction < 50%, n = 31) and HFpEF (left ventricular ejection fraction ≥ 50%, n = 24). Reactive hyperemia index measured by reactive hyperemia peripheral arterial tonometry, however, was lower in HFrEF patients compared to HFpEF patients (P = 0.014). In contrast, among 33 patients with non-ischemic heart disease, the degree of flow-mediated vasodilation was lower in HFpEF patients (n = 18) compared with HFrEF patients (n = 15) (P = 0.009), while reactive hyperemia index was comparable between the two groups. The clinical and pathophysiological significance of endothelial function in heart failure differs between conduit artery and microvasculature, and these differences may contribute to the underlying pathophysiology of HFpEF and HFrEF, as well as in ischemic heart disease and non-ischemic heart disease.

1028 Early response to a low- dose acubitril/valsartan (ARNI) therapy among stable symptomatic patients with HFrEF

Abstract Funding Acknowledgements no financial support Background Sacubitril/valsartan (S/V) has shown to improve outcomes, that is related to reverse remodeling of the left ventricle (LV) with improved ejection fraction (LVEF) and mitral regurgitation (MR) during long-term therapy. There are limited data on early effects of S/V treatment with respect to the left ventricle function and echocardiographic evaluation of this phenomenon. Aim of the study was to evaluate the early effect of a starting-dose of S/V administered in patients (pts) with stable symptoms of heart failure on clinical symptoms, laboratory tests and echocardiographic parameters using global longitudinal strain (GLS) as a sensitive parameter detecting improvement of LV function. Methods Twenty pts (mean age 60 years, 2 female), with HFrEF (NYHA class II-III) on optimal medical treatment with ICM (75%) or NICM (35%) were included to low-dose S/V treatment (24/26mg) after excluding contraindications. Clinical and echocardiographic evaluation was performed at baseline and after 30 days. The following parameters have been measured: 6-Minutes Walking Test (6MWT) and Minnesota Living with Heart Failure questionnaire, laboratory results and echocardiographic assessment with speckle tracking technique (STE). Results All pts completed 30 days treatment period without complications and no change to medication. During this period the mean values of RR decreased significantly (SBP 129,4mmHg vs 121,25mmHg and DBP 81,6mmHg vs 79,2mmHg respectively). Other clinical parameters did not change. There were no differences NT-pro BNP and TNT levels (respectively 1726 vs 1930 pg/ml and 26 vs 22 ng/ml). After 30days, the mean 6MWT distance increased by 50m (349,5 vs 401,5m p &amp;lt; 0.01), and a positive response was observed in Minnesota Living with Heart Failure Questionnaire (p &amp;lt; 0.001). Echocardiographic parameters revealed positive remodeling of LV and left atrium (LA). There was a significant improvement in LVEDd (67,9mm vs 64,9mm, p &amp;lt; 0.01), LVESd (61,6mm vs 58,8mm, p &amp;lt; 0.01) and stroke volume (40,5 to 45,8ml, p &amp;lt; 0.01). There was no significant increase in LVEF (30% vs 31,5%, p = 0.052). The diastolic parameters of LV function didn’t change during the study. The LA volumes significantly decreased (110 vs 92ml, p &amp;lt; 0.01) during the treatment period as well as the degree of MR (ERO 0.51 vs 0,37 p &amp;lt; 0.01). Out of several LV deformation parameters, only global longitudinal strain has changed significantly (GLS-6,1% vs -7,0%, p = 0,02). The improvement in symptoms and 6MWT correlated only with global systolic radial (RS) and longitudinal (GLS) strain correlated positively after 30 days treatment. Conclusion:Thirty days treatment with low-dose S/V in stable, symptomatic HFrEF patients leads to symptomatic and clinical improvement which correlates with positive remodeling of the left ventricle and reduces the degree of mitral regurgitation. The GLS is a sensitive indicator of LV function improvement after short time S/V treatment and may be used to assess early response.

Exercise oscillatory ventilation and prognosis in heart failure patients with reduced and mid-range ejection fraction.

Exercise oscillatory ventilation (EOV) is a pivotal cardiopulmonary exercise test parameter for the prognostic evaluation of patients with chronic heart failure (HF). It has been described in patients with HF with reduced ejection fraction (<40%, HFrEF) and with HF with preserved ejection fraction (>50%, HFpEF), but no data are available for patients with HF with mid-range ejection fraction (40-49%, HFmrEF). The aim of the study was to evaluate the prognostic role of EOV in HFmrEF patients. We analysed 1239 patients with HFmrEF and 4482 patients with HFrEF, enrolled in the MECKI score database, with a 2-year follow-up. The study endpoint was the composite of cardiovascular death, urgent heart transplant, and ventricular assist device implantation. We identified EOV in 968 cases (16% and 17% of cases in HFmrEF and HFrEF, respectively). HFrEF EOV+ patients were significantly older, and their parameters suggested a more severe HF than HFrEF EOV- patients. A similar behaviour was found in HFmrEF EOV+ vs. EOV- patients. Kaplan-Meier analysis, irrespective of ejection fraction, showed that EOV is associated with a worse survival, and that patients with HFrEF and HFmrEF EOV+ had a significantly worse outcome than the EOV- of the same ejection fraction groups. EOV-associated survival differences in HFmrEF patients started after 18 months of follow-up. Exercise oscillatory ventilation has a similar prevalence and ominous prognostic value in both HFmrEF and HFrEF patients, indicating a group of patients in need of a more intensive follow-up and a more aggressive therapy. In HFmrEF, the survival curves between EOV+ and EOV- patients diverged only after 18 months.