Previous Heart Failure Hospitalization Research Articles

Renin-angiotensin system inhibitors for patients with mild or moderate chronic kidney disease and heart failure with mildly reduced or preserved ejection fraction

BackgroundRenin-angiotensin system inhibitors (RASI) reduce adverse cardiovascular events in patients with heart failure (HF) with left ventricular ejection fraction (LVEF) ≤40% and mild or moderate chronic kidney disease (CKD). However, RASI administration rate and its association with long-term outcomes in patients with CKD complicated by HF with LVEF >40% remain unclear. MethodsWe analyzed 1923 consecutive patients with LVEF >40% registered within the multicenter database for hospitalized HF. We assessed RASI administration rate and its association with all-cause mortality among patients with mild or moderate CKD (estimated glomerular filtration rate [eGFR]: 30–60 mL/min/1.73 m2). Exploratory subgroups included patients grouped by age (<80, ≥80 years), sex, previous HF hospitalization, B-type natriuretic peptide (higher, lower than median), eGFR (30–44, 45–59 mL/min/1.73 m2), systolic blood pressure (<120, ≥120 mmHg), LVEF (41–49, ≥50%), and mineralocorticoid receptor antagonists (MRA) use. ResultsAmong patients with LVEF >40%, 980 (51.0%) had mild or moderate CKD (age: 81 [74–86] years; male, 52.6%; hypertension, 69.7%; diabetes, 25.9%), and 370 (37.8%) did not receive RASI. RASI use was associated with hypertension, absence of atrial fibrillation, and MRA use. After multivariable adjustments, RASI use was independently associated with lower all-cause mortality over a 2-year median follow-up (hazard ratio: 0.58, 95% confidence interval: 0.43–0.79, P = 0.001), and the mortality rate difference was predominantly due to cardiac death, consistent in all subgroups. ConclusionsApproximately one-third of HF patients with mild or moderate CKD and LVEF >40% were discharged without RASI administration and demonstrated relatively guarded outcomes.

Cost-effectiveness of remote haemodynamic monitoring by an implantable pulmonary artery pressure monitoring sensor (CardioMEMS-HF system) in chronic heart failure in the Netherlands.

Remote haemodynamic monitoring with an implantable pulmonary artery (PA) sensor has been shown to reduce heart failure (HF) hospitalizations and improve quality of life. Cost-effectiveness analyses studying the value of remote haemodynamic monitoring in a European healthcare system with a contemporary standard care group are lacking. A Markov model was developed to estimate the cost-effectiveness of PA-guided therapy compared to the standard of care based upon patient-level data of the MONITOR-HF trial performed in the Netherlands in patients with chronic HF (New York Heart Association class III and at least one previous HF hospitalization). Cost-effectiveness was measured as the incremental cost per quality-adjusted life year (QALY) gained from the Dutch societal perspective with a lifetime horizon which encompasses a wide variety of costs including costs of hospitalizations, monitoring time, telephone contacts, laboratory assessments, and drug changes in both treatment groups. In the base-case analysis, PA-guided therapy increased costs compared to standard of care by €12 121. The QALYs per patient for PA-guided therapy and standard of care was 4.07 and 3.481, respectively, reflecting a gain of 0.58 QALYs. The resulting incremental cost-effectiveness ratio was €20 753 per QALY, which is below the Dutch willingness-to-pay threshold of €50 000 per QALY gained for HF. The current cost-effectiveness study suggests that remote haemodynamic monitoring with PA-guided therapy on top of standard care is likely to be cost-effective for patients with symptomatic moderate-to-severe HF in the Netherlands.

Baroreflex activation therapy in patients with heart failure and a reduced ejection fraction: Long-term outcomes.

Carotid baroreflex activation therapy (BAT) restores baroreflex sensitivity and modulates the imbalance in cardiac autonomic function in patients with heart failure with reduced ejection fraction (HFrEF). We tested the hypothesis that treatment with BAT significantly reduces cardiovascular mortality and heart failure morbidity and provides long-term safety and sustainable symptomatic improvement. BeAT-HF was a prospective, multicentre, randomized, two-arm, parallel-group, open-label, non-implanted control trial. New York Heart Association (NYHA) class III subjects, ejection fraction ≤35%, previous heart failure hospitalization or N-terminal pro-B-type natriuretic peptide (NT-proBNP) >400 pg/ml, no class I indication for cardiac resynchronization therapy and NT-proBNP <1600 pg/ml were randomized to BAT plus optimal medical management (BAT group) or optimal medical management alone (control). The primary endpoint was cardiovascular mortality and HF morbidity; additional pre-specified endpoints included durability of safety, quality of life (QOL), exercise capacity (6-min hall walk distance [6MHWD]), functional status (NYHA class), hierarchical composite win ratio, freedom from all-cause death, left ventricular assists device (LVAD) implantation, heart transplant. Overall, 323 patients had 332 primary events, median follow-up was 3.6 years/patient. Both primary endpoint (rate ratio 0.94, 95% confidence interval [CI] 0.57-1.57; p = 0.82) and components of the primary endpoints were not significantly different between BAT and control. The system- and procedure-related major adverse neurological and cardiovascular event-free rate remained 97% throughout the trial. Symptom improvement (QOL, 6MHWD, NYHA class, all nominal p < 0.001) in the BAT group was durable in time, sustainable in extent. Win ratio (1.26, 95% CI 1.02-1.58) and freedom from all-cause death, LVAD implantation, heart transplant (hazard ratio 0.66, 95% CI 0.43-1.01) favoured the BAT group but did not reach statistical significance. The BeAT-HF primary endpoint was neutral; however, BAT provided safe, effective, and sustainable improvements in HFrEF patient's functional status, 6MHWD and QOL.

Prognostic impact of frailty based on a comprehensive frailty assessment in patients with heart failure.

This study aimed to evaluate the impact of frailty and living function domains based on the Kihon Checklist (KCL), a questionnaire for a comprehensive frailty assessment, on prognosis in patients with acute heart failure (AHF). The Kochi Registry of Subjects with Acute Decompensated Heart Failure (Kochi YOSACOI) study was a prospective multicentre cohort study enrolling 1061 patients hospitalized for AHF from May 2017 to December 2019 in Japan. We divided patients into three groups according to the severity of frailty using the KCL and compared clinical outcomes after discharge. The primary endpoint was all-cause death, and the secondary outcomes were cardiovascular death, heart failure (HF) rehospitalization, and the composite event of cardiovascular death and HF rehospitalization. Of 936 patients (median age, 81years; 48.9% women) who could be assessed for frailty, we identified frailty in 501 patients (53.5%), prefrailty in 290 patients (31.0%), and non-frailty in 145 patients (15.5%). Compared with prefrail and non-frail patients, frail patients were older (83 vs. 79 and 72years, P<0.001), were more likely to be women (53.9% vs. 43.1% and 43.4%, P=0.005), and were more likely to have a history of previous HF hospitalization (35.4% vs. 25.3% and 19.6%, P<0.001) and multimorbidity (90.8% vs. 81.0% and 73.8%, P<0.001). Frail patients had a lower rate of discharge to home (79.7% vs. 94.8% and 96.5%, P<0.001). During the 2year follow-up period, frail patients had a higher incidence rate of all-cause death, cardiovascular death, and HF rehospitalization (log-rank P<0.001, P<0.001, and P=0.003, respectively). After adjusting for other prognostic factors, multivariate analysis showed that frailty was associated with all-cause death [adjusted hazard ratio (HR): 2.917, 95% confidence interval (CI): 1.326-6.417, P=0.008] and cardiovascular death (adjusted HR: 7.026, 95% CI: 1.700-29.030, P=0.007). Among all domains of the KCL, the cognitive function domain was associated with a higher risk of all-cause death (P=0.004) and cardiovascular death (P<0.001). The depression domain remained associated with a higher risk of HF rehospitalization (P=0.045). The risk for all-cause death increased with an increase in total KCL score (adjusted HR: 1.819, 95% CI: 1.300-2.547, P<0.001). The KCL is a useful tool for risk stratification of adverse outcomes in patients with AHF. Functional declines in psycho-emotional domains including cognitive function and depressed mood contribute to adverse outcomes.

Immediate pharmacotherapy intensification after cardiac resynchronization therapy: incidence, characteristics, and impact.

Cardiac resynchronization therapy (CRT) is an established treatment for drug-refractory heart failure (HF) in patients with left bundle branch block (LBBB). Acute haemodynamic improvement after CRT implantation may enable the intensification of HF medication soon thereafter. Immediate pharmacotherapy intensification (IPI) after CRT implantation achieves a synergetic effect, possibly leading to a better prognosis. This study aimed to explore the incidence, characteristics, and impact of IPI on real-world outcomes among CRT recipients with a history of hospitalization for acute HF. This multicentre retrospective study enrolled CRT recipients with LBBB morphology, a QRS width ≥120ms, a left ventricular ejection fraction ≤35%, and New York Heart Association II-IV HF symptoms. All patients had previous HF hospitalizations within the previous year and received guideline-directed medical therapy before CRT implantation. Patient baseline characteristics, including HF medication, were collected. IPI was defined as the intensification of beta-blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and mineralocorticoid receptor antagonists within 30days of CRT implantation. The primary endpoint was all-cause death or first hospitalization for HF; the secondary endpoint was all-cause death. We enrolled 194 patients (75% male; mean age, 65±13years; 78% with non-ischaemic cardiomyopathy). One hundred five (54%) patients received IPI. Patients who received IPI exhibited a significantly shorter QRS duration (159±26 vs. 171±32ms; P=0.004), higher estimated glomerular filtration rate (55.2±20.0 vs. 47.8±24.7mL/min/1.73m2; P=0.022), and more dilated cardiomyopathy. During a median follow-up period of 29months, 70 (36%) patients reached the primary endpoint and 42 (22%) patients died. Patients with IPI showed significantly better outcomes for the primary and secondary endpoints than patients without IPI. The volumetric responder ratio at 6months after implantation was not significantly different between patients with and without IPI; however, patients who received IPI had reduced mortality even at 6months after implantation. In the multivariate analysis, IPI was an independent predictor of the primary endpoint (hazard ratio, 0.51; 95% confidence interval, 0.27-0.97; P=0.043). Immediate intensification of HF medication was achieved in 54% of CRT recipients and was significantly higher in patients without excessive QRS prolongation, preserved renal function, and dilated cardiomyopathy than others. In patients with LBBB morphology and QRS≥120ms, IPI was associated with a significantly better prognosis and fewer HF hospitalizations after CRT implantation than others.

Timing of previous heart failure hospitalization as a prognostic factor for emergency department heart failure patients.

To investigate whether the timing of a previous hospital admission for acute heart failure (AHF) is a prognostic factor for AHF patients revisiting the emergency department (ED) in the subsequent 12-month follow-up. All ED AHF patients enrolled in the previously described EAHFE registry were stratified by the presence or absence of an AHF hospitalization admission in the prior 12months. The primary outcome was 12-month all-cause mortality postED visit. Secondary end points were hospital admission, prolonged hospitalization (> 7days), mortality during hospitalization and a 90-day post-discharge adverse composite event (ACE) rate, defined as ED revisits due to AHF, hospitalizations due to AHF, or all-cause mortality. Outcomes were adjusted for baseline and AHF episode characteristics.Of 5,757 patients included, the median age was 84years (IQR 77-88); 57% were women, and 3,759 (65.3%) had an AHF hospitalization in the previous 12months. The 12-month mortality was 37% (41.7% vs. 28.3% p < 0.001), hospital admission was 76.1% (78.8% vs. 71.1% p < 0.001) ACE was 60.2% (65.1% vs. 50.5% p < 0.001). In the adjusted analysis, patients with AHF hospitalization in the prior 12months had a higher mortality (HR = 1.41; 95% CI 1.27-1.56), 90-day ACE rate (HR = 1.45: 95% CI 1.32-1.59), and more hospital admissions (OR = 1.32; 95% CI 1.16-1.51), with shorter times since the previous hospitalization being related to the outcomes analyzed. One-year mortality, adverse events at 90days, and readmission rates are increased in ED AHF patients previously admitted within the last 12months.

Previous heart failure hospitalization, spironolactone, and outcomes in heart failure with preserved ejection fraction – a secondary analysis of TOPCAT

BackgroundHospitalization for heart failure (HHF) is associated with poor postdischarge outcomes but the role of time since most recent HHF and potential treatment interactions are unknown. We aimed to assess history of and time since previous HHF, associations with composite of cardiovascular (CV) death and total HHF, first HHF and interactions with randomization to spironolactone, in heart failure with preserved ejection fraction. Methods and resultsWe assessed these objectives using uni- and multivariable regressions and spline analyses in TOPCAT-Americas. Among 1,765 patients, 66% had a previous HHF. Over a median of 2.9 years, 1,064 composite events of CV death or total HHFs occurred. Previous HHF was associated with more severe HF, and was independently associated with the composite outcome (HR 1.26, 95%CI 1.05-1.52, P = .014), and all secondary outcomes. A shorter time since most recent HHF appeared to be associated with subsequent first HHF, but not the composite of CV death or total HHF.Spironolactone had a significant interaction with previous HHF (interaction-P .046). Patients without a previous HHF had a larger effect of spironolactone on the composite outcome (HR 0.63, 95%CI 0.46-0.87, P = .005) than patients with a previous HHF (HR 0.91, 95%CI 0.78-1.06, P = .224). ConclusionIn TOPCAT-Americas, previous HHF was associated with CV death and first and total HHF. Duration since most recent HHF seemed to be associated with time to first HHF only. Spironolactone was associated with better outcomes in patients without a previous HHF. This interaction is hypothesis-generating and requires validation in future trials.

COVID-19–Related Thrombotic and Bleeding Events in Adults With Congenital Heart Disease

BackgroundAltered coagulation is a striking feature of COVID-19. Adult patients with congenital heart disease (ACHD) are prone to thromboembolic (TE) and bleeding complications. ObjectivesThe purpose of this study was to investigate the prevalence and risk factors for COVID-19 TE/bleeding complications in ACHD patients. MethodsCOVID-19-positive ACHD patients were included between May 2020 and November 2021. TE events included ischemic cerebrovascular accident, systemic and pulmonary embolism, deep venous thrombosis, myocardial infarction, and intracardiac thrombosis. Major bleeding included cases with hemoglobin drop >2 g/dl, involvement of critical sites, or fatal bleeding. Severe infection was defined as need for intensive care unit, endotracheal intubation, renal replacement therapy, extracorporeal membrane oxygenation, or death. Patients with TE/bleeding were compared to those without events. Factors associated with TE/bleeding were determined using logistic regression. ResultsOf 1,988 patients (age 32 [IQR: 25-42] years, 47% male, 59 ACHD centers), 30 (1.5%) had significant TE/bleeding: 12 TE events, 12 major bleeds, and 6 with both TE and bleeding. Patients with TE/bleeding had higher in-hospital mortality compared to the remainder cohort (33% vs 1.7%; P < 0.0001) and were in more advanced physiological stage (P = 0.032) and NYHA functional class (P = 0.01), had lower baseline oxygen saturation (P = 0.0001), and more frequently had a history of atrial arrhythmia (P < 0.0001), previous hospitalization for heart failure (P < 0.0007), and were more likely hospitalized for COVID-19 (P < 0.0001). By multivariable logistic regression, prior anticoagulation (OR: 4.92; 95% CI: 2-11.76; P = 0.0003), cardiac injury (OR: 5.34; 95% CI: 1.98-14.76; P = 0.0009), and severe COVID-19 (OR: 17.39; 95% CI: 6.67-45.32; P < 0.0001) were independently associated with increased risk of TE/bleeding complications. ConclusionsACHD patients with TE/bleeding during COVID-19 infection have a higher in-hospital mortality from the illness. Risk of coagulation disorders is related to severe COVID-19, cardiac injury during infection, and use of anticoagulants.

Epidemiology and prognostic relevance of morphofunctional classification of secondary mitral regurgitation

Abstract Background Mitral regurgitation has traditionally been divided into organic and functional (FMR) due to its different etiology and prognosis. However, FMR is not a homogeneous entity, and may be secondary to annular dilation, ventricular dilation and dysfunction, or posterior leaflet restriction. Purpose Our aim is to assess the epidemiology of these FMR subtypes and their prognostic impact. Methods Patients with FMR from our center who underwent three-dimensional transesophageal echocardiography (3D-TEE) between 2016 and 2020 were retrospectively evaluated. Patients with at least moderate FMR, effective regurgitant orifice (ERO) by 3D-TEE &amp;gt;0.2 cm2 were selected. They were classified according to the predominant mechanism: type 1 or ventricular dysfunction, type 2 or posterior leaflet restriction, and type 3 or annular dilation. 3D-TEE and the closest transthoracic study variables, as well as baseline demographic and clinical characteristics and evolution events, were obtained and statistical analysis was performed according to FMR types. Results 112 patients were included (66.1% male, mean age 72.3 years). 54.5% had previous hospitalization for heart failure and 53.6% had a history of ischemic heart disease. The most frequently identified FMR mechanism was type 1 (61.6%), followed by type 3 (23.2%) and type 2 (15.2%). There were significant differences in epidemiological factors and echocardiographic parameters (Table) between groups. During follow-up, 43.8% died, received a heart transplant or LVAD and 44.6% had any hospitalization for heart failure. There were no significant differences between FMR types in relation to total mortality (p=0.28), mortality due to heart failure (p=0.13), total hospitalizations (p=0.73), or hospitalization for heart failure (p=0.12). Valvular intervention was performed in 54 patients (48.2%), 33 of them percutaneously with a clip, with no differences in FMR subtypes. Conclusions FMR is a heterogeneous entity and different morphotypes with different epidemiology and etiology can be identified. Despite the different mechanism, all subgroups presented a similar unfavorable prognosis and similar intervention rates.

Associations between baseline heart rate and blood pressure and time to events in HFrEF patients: data from the QUALIFY international registry

Abstract Aims Low systolic blood pressure (SBP) and high resting heart rate (RHR) are both risk indicators for heart failure (HF) outcomes. The purpose of this analysis is to evaluate the associations between RHR and SBP at baseline and time to events in HF patients with reduced ejection fraction (HFrEF) in the QUALIFY international registry. Methods and results The QUALIFY registry enrolled 7317 patients with left ventricular ejection fraction (LVEF) ≤40% and previous HF hospitalization within 1–15 months. Complete Follow-up data were available from 5138 patients. The relationship between RHR and SPB on outcomes were analyzed according to baseline values as high RHR (H-RHR) ≥ 75 vs. low RHR (L-RHR) &amp;lt; 75 bpm) and high SBP (H-SBP): ≥ 110 vs. low SBP (L-SBP): &amp;lt;110 mmHg and analyzed according to each of the following 4 phenotypes: (H-RHR/L-SBP, L-RHR/L-SBP, H-RHR/H-SBP and L-RHR/H-SBP (reference group)). Compared to patients with reference group, patients with L-RHR/L-SBP had the highest all-cause mortality (hazard ratio (HR) 2,57, 95% CI 1.85–3.56 vs. HR 0.80, 95% CI 0.72–0.89, P&amp;lt;0.001). After adjustment for age, Sex, NYHA, AF and eGFR rate, all-cause mortality remains the highest between the all groups (HR 2.62, 95% CI 1.88–3.66 P = &amp;lt;0.001), followed by L-RHR/L-SBP (HR 1.74, 95% CI 1.24–2.45 P = 0.001 and H-RHR/H-SBP (HR 1.44, 95% CI 1.08–1.92 P = 0.01). H-RHR/L-SBP and after adjustment was associated with the worst outcomes for other endpoints: CV death and HF hospitalization HR 1.83, CI 1.66-2.42, p = &amp;lt;0.001), CV mortality (HR 2.7, CI 1.69-4.33, p = &amp;lt;0.001) and HF hospitalization (HR 1.71, CI 1.30-2.25, p = &amp;lt;0.001) Conclusion HFrEF patients, who have previously been hospitalized for HF presented with L-SBP and H-RHR, were at greater risk for all case mortality and CV death and HF hospitalization

Predictors of major adverse cardiovascular events in patients with severe aortic stenosis awaiting aortic valve replacement

Abstract Background Severe aortic stenosis (AS) is a progressive disease associated with an increased risk of heart failure (HF) and mortality if left untreated. Aortic valve replacement (AVR) is the treatment of choice. However, it is not always immediately available, and some patients have experienced major cardiovascular events (MACE) while waiting for AVR. The identification of reliable predictors of MACE can help clinicians risk-stratify severe AS patients and tailor their management to prevent adverse outcomes. Purpose We aimed to evaluate predictors of MACE in real-world patients with severe AS who are waiting for AVR. Methods We conducted a prospective registry of consecutive patients discussed in the Heart Team meeting of a single centre, between January 2018 and June 2021. All patients with severe AS were included. For each patient we recorded demographic data, blood test results, echocardiogram parameters, and MACEs (a composite of death, HF hospitalization, non-fatal acute myocardial infarction, and non-fatal stroke). MACEs were recorded until the patient underwent AVR. The median follow-up time was 187 days (IQR 59-352). Results Overall, 235 patients were included (mean age 76.7±10.7 years, 48.1% male). Previous HF hospitalization (HR 2.77, 95% CI 1.66 – 4.62), HF symptoms with New York Heart Association (NHYA) class ≥3 (HR 2.64, 95% CI 1.58–4.39), and the presence of left ventricular dysfunction (HR 2.86, 95% CI 1.71–4.78) were independent predictors of MACE (Figure 1). The presence of pulmonary hypertension (HR 2.16, 95CI 1.27–3.66), but not right ventricular dysfunction (HR 2.34, 95CI 0.45–12.08, p=0.31), was associated with MACE until AVR. Concomitant moderate to severe tricuspid regurgitation (HR 10.88, 95CI 1.41–83.94) and moderate to severe mitral regurgitation (HR 5.91, 95CI 1.50–23.34) were associated with a worse prognosis, even when adjusted for other relevant MACE predictors. Laboratory data such as serum creatinine, haemoglobin, and NT-proBNP levels were not associated with the occurrence of MACE in this population (HR 1.00). Past medical history of hypertension, diabetes, chronic kidney disease, and chronic obstructive pulmonary disease were not associated with MACE. Age was a limited predictor of MACE (HR 1.03, 95CI 1.00 – 1.06, p=0.04). Conclusion Previous HF hospitalization, NYHA class ≥3 symptoms, left ventricular dysfunction, and pulmonary hypertension were independent predictors of MACE in patients with severe AS awaiting AVR. Additionally, concomitant moderate to severe tricuspid and mitral regurgitation were also associated with worse prognosis. These findings may help identify those at high risk of MACE who would benefit most from early intervention and close monitoring.

Effect of dapagliflozin in patients in Asia with heart failure with mildly reduced or preserved ejection fraction: insights from DELIVER

Abstract Background A large and growing fraction of the global heart failure (HF) population lives in Asia. One-fifth of participants in the DELIVER (Dapagliflozin Evaluation to Improve the Lives of Patients with Preserved Ejection Fraction Heart Failure) trial were enrolled from Asia, providing a rich source of contemporary data to understand their unique clinical profiles and responses to sodium-glucose cotransporter 2 (SGLT2) inhibition. Purpose To assess the differences in clinical characteristics, outcomes, and response to dapagliflozin in patients from Asia vs outside Asia among patients with HF with mildly reduced or preserved ejection fraction in the DELIVER trial. Methods DELIVER was a global randomized clinical trial enrolling across 353 sites in 20 countries. Baseline clinical characteristics from patients enrolled in DELIVER trial were compared between patients in Asia vs outside Asia. The primary outcome was a composite of worsening HF or cardiovascular (CV) death. The effect of dapagliflozin on primary and secondary outcomes were compared in patients in Asia vs outside Asia. Results Among 6,263 participants in the DELIVER trial, 1,226 (19.6%) were enrolled in Asia (310 in China, 422 in Japan, and 318 in Taiwan, and 176 in Vietnam). Compared to patients outside Asia, participants from Asia were similar in age, more likely to be men with previous HF hospitalization, less likely to have obesity, diabetes, hypertension, or history of myocardial infarction, and had lower symptom burden despite similar natriuretic peptide levels (Figure 1). After adjusting for age, sex, and baseline LVEF, those in Asia faced similar risks of HF events but lower risk of mortality compared with those enrolled outside Asia (all-cause mortality Asia vs. outside Asia: HR 0.60, 95% confidence interval [CI] 0.49 – 0.72, Table 1). Within Asia, all-cause mortality was highest in Vietnam (6.8 per 100 person-year [py]), followed by Taiwan (6.7 per 100 py), Japan (3.5 per 100 py) and China (3.3 per 100 py). Dapagliflozin reduced the primary outcome in participants enrolled in Asia (hazard ratio [HR] 0.89, 95% CI 0.67-1.18) and outside Asia (HR 0.80, 95% CI 0.71 – 0.92) to a similar extend (P-interaction = 0.54, Figure 1). Similarly, region did not modify the treatment effect of dapagliflozin on CV death, HF hospitalization, all-cause death, CV death and recurrent HF events, or changes in Kansas City Cardiomyopathy Questionnaire scores (P-interaction &amp;gt; 0.30 for all). Serious adverse events and rates of drug discontinuation were also balanced in both treatment arms, irrespective of enrollment in Asia vs. outside Asia. Conclusions In the global DELIVER trial, dapagliflozin reduced the risk of CV death or HF events and was well tolerated both among participants enrolled in Asia and other geographic regions.Figure 1Table 1

Impact of a clinician-to-clinician electronic consultation in heart failure patients with previous hospital admissions.

To evaluate the impact of an outpatient care management programme that includes a clinician-to-clinician e-consultation on delay time in care, hospital admissions, and mortality in a high-risk group of patients with heart failure (HF) and previous episodes of HF hospitalization (HFH). We selected 6444 HF patients who visited the cardiology service at least once between 2010 and 2021. Of these, 4851 were attended in e-consult, and 2230 had previous HFH. Using an interrupted time series regression model, we analysed the impact of incorporating e-consult into the healthcare model in the group of patients with HFH and evaluated the elapsed time to cardiology care, HF, cardiovascular (CV), and all-cause hospital admissions and mortality, calculating the incidence relative risk (iRR). In the group of patients with HFH, the introduction of e-consult substantially decreased waiting times to cardiology care (8.6 [8.7] vs. 55.4 [79.9] days, P < 0.001). In that group of patients, after e-consult implantation, hospital admissions for HF were reduced (iRR [95%CI]: 0.837 [0.840-0.833]), 0.900 [0.862-0.949] for CV and 0.699 [0.678-0.726] for all-cause hospitalizations. There was also lower mortality (iRR [95%CI]: 0.715 [0.657-0.798] due to HF, 0.737 [0.764-0.706] for CV and 0.687 [0.652-0.718] for all-cause). The improved outcomes after e-consultation implementation were significantly higher in the group of patients with previous HFH. In patients with HFH, an outpatient care programme that includes an e-consult significantly reduced waiting times to cardiology care and was safe, with a lower rate of hospital admissions and mortality in the first year.

Associations between baseline heart rate and blood pressure and time to events in HFrEF patients: data from the QUALIFY international registry.

A high resting heart rate (RHR) and low systolic blood pressure (SBP) are a risk factor and a risk indicator, respectively, for poor heart failure (HF) outcomes. This analysis evaluates the associations between baseline RHR and SBP with outcomes and treatment patterns in HF patients with reduced ejection fraction (HFrEF) in the QUALIFY international registry. Between September 2013 and December 2014, 7317 HFrEF patients with a previous HF hospitalization within 1-15 months were enrolled in the QUALIFY registry (Quality of Adherence to Guideline Recommendations for Life-Saving Treatment in Heart Failure Survey). Complete follow-up data were available for 5138 patients. The relationships between RHR and SBP and outcomes were assessed using a Cox proportional hazards model and were analyzed according to baseline values as high RHR (H-RHR) ≥ 75 vs. low RHR (L-RHR) < 75 bpm) and high SBP (H-SBP): ≥ 110 vs. low SBP (L-SBP): <110 mmHg and analyzed according to each of the following 4 phenotypes: (H-RHR/L-SBP, L-RHR/L-SBP, H-RHR/H-SBP and L-RHR/H-SBP (reference group). Compared to the reference group, H-RHR/L-SBP was associated with the worst outcomes for the combined primary endpoint of CV death and HF hospitalization (HR 1.83, CI 1.51-2.21, p<0.001), CV death (HR 2.7, CI 1.69-4.33, p <0.001), and HF hospitalization (HR 1.62, CI 1.30-2.01, p<0.001). Low-risk patients with L-RHR/H-SBP achieved more frequently >=50% of target doses of ACEIs and BBs than the other groups. However, 48% and 46% of low-risk patients were not well treated with ACEIs and BBs, respectively (<=50% of target dose or no treatment). In patients with HFrEF and recent hospitalisation, elevated RHR and lower SBP identify patients at increased risk for CV endpoints. While SBP and RHR are often recognized as barriers that deter physicians from treating with high doses of recommended drugs, they are not the only reason leaving many patients suboptimally treated. This article is protected by copyright. All rights reserved.

Baroreflex activation therapy in patients with heart failure with reduced ejection fraction: a single-centre experience.

Heart failure with reduced ejection fraction (HFrEF) is associated with excessive sympathetic and impaired parasympathetic activity. The Barostim Neo™ device is used for electronical baroreflex activation therapy (BAT) to counteract autonomic nervous system dysbalance. Randomized trials have shown that BAT improves walking distance and reduces N-terminal prohormone of brain natriuretic peptide (NT-proBNP) levels at least in patients with only moderate elevation at baseline. Its impact on the risk of heart failure hospitalization (HFH) and death is not yet established, and experience in clinical routine is limited. We report on patient characteristics and clinical outcome in a retrospective, non-randomized single-centre registry of BAT in HFrEF. Patients in the New York Heart Association (NYHA) Classes III and IV with a left ventricular ejection fraction (LVEF) <35% despite guideline-directed medical therapy were eligible. Symptom burden, echocardiography, and laboratory testing were assessed at baseline and after 12months. Clinical events of HFH and death were recorded at routine clinical follow-up. Data are shown as number (%) or median (inter-quartile range). Between 2014 and 2020, 30 patients were treated with BAT. Median age was 67 (63-77) years, and 27 patients (90%) were male. Most patients (83%) had previous HFH. Device implantation was successful in all patients. At 12months, six patients had died and three were alive but did not attend follow-up. NYHA class was III/IV in 26 (87%)/4 (13%) patients at baseline, improved in 19 patients, and remained unchanged in 5 patients (P<0.001). LVEF improved from 25.5 (20.0-30.5) % at baseline to 30.0 (25.0-36.0) % at 12months (P=0.014). Left ventricular end-diastolic diameter remained unchanged. A numerical decrease in NT-proBNP [3165 (880-8085) vs. 1001 (599-3820) pg/mL] was not significant (P=0.526). Median follow-up for clinical events was 16 (10-33) months. Mortality at 1 (n=6, 20%) and 3years (n=10, 33%) was as expected by the Meta-Analysis Global Group in Chronic Heart Failure risk score. Despite BAT, event rate was high in patients with NYHA Class IV, NT-proBNP levels >1600pg/mL, or estimated glomerular filtration rate (eGFR) <30mL/min at baseline. NYHA class and eGFR were independent predictors of mortality. Patients with HFrEF who are selected for BAT are in a stage of worsening or even advanced heart failure. BAT appears to be safe and improves clinical symptoms and-to a modest degree-left ventricular function. The risk of death remains high in advanced disease stages. Patient selection seems to be crucial, and the impact of BAT in earlier disease stages needs to be established.

What determines who gets cardiac resynchronization therapy in europe?

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Supported by Swedish Heart and Lung foundation and Stockholm County Council. Background/Introduction Cardiac resynchronization therapy (CRT) is a valuable treatment in selected patients with heart failure (HF) but is still underutilized. Aim We compared three informative data sources, which enrolled patients with HF at different organization setting and identified clinical, organizational, and level of care factors linked to CRT implantation in these cohorts. Methods Data from three large cohorts of patients with HF were compared. Patients with HF with reduced ejection fraction (HFrEF) in an ESC HF-Long Term Registry (ESC-HF-LT, n=25,621), a National HF Registry - Swede HF (n=156,621) and in the ESC-CRT Survey II (n=11088, all receiving CRT across 42 ESC countries), contributed data to the analysis. The ESC Survey II recruited patients at implanting centers, ESC-HF-LT at HF centers, whereas SwedeHF enrolled HF patients at different levels of care. Firstly, we compared patient characteristics, socio-economic and organizational factors between cohorts as well as between overlapping countries participating both in CRT Survey II and ESC HF LT. Secondly, we identified independent predictors of CRT use in the two registries using multivariable logistic regressions. Results Of the 1031 patients in ESC-HF-LT and the 5008 patients in Swede-HF, CRT was not used in 53-75 % of guideline- indicated patients. Women constituted 22% and median age ranged between 68-72 years. Guideline Directed Medical Therapy (GDMT), atrial fibrillation, previous myocardial infarction (SwedeHF) and HF hospitalization (ESC-HF-LT) was associated with more CRT use as was enrollment at university hospital and follow-up at HF center/Hospital. In Swede-HF above median income and higher education level were also independently associated with use of CRT. In the ESC-CRT Survey II (n=11.088) all patients received CRT with differences in the clinical indications between countries. Conclusion(s) CRT is an important treatment option for eligible patients with HF, which is still largely underused. The findings reported demonstrate that awareness of CRT indications as well as demographics, organizational and economic factors play an important role in CRT utilization.

Empagliflozin in heart failure with preserved ejection fraction with and without atrial fibrillation.

Atrial fibrillation/flutter (AF) is common in heart failure (HF) with preserved left ventricular ejection fraction (LVEF) and associated with worse outcomes. Empagliflozin reduces cardiovascular death or HF hospitalizations and slows estimated glomerular filtration rate (eGFR) decline in patients with HF and LVEF >40%. We aimed to assess the efficacy and safety of empagliflozin in improving outcomes in patients with HF and LVEF >40% with and without AF. In this pre-defined secondary analysis of EMPEROR-Preserved, we compared the effects of empagliflozin versus placebo on the primary and secondary endpoints and safety outcomes, stratified by baseline AF, defined as AF reported in any electrocardiogram before empagliflozin initiation or in medical history. Among 5988 patients randomized, 3135 (52%) had baseline AF; these patients were older, with worse functional class, more previous HF hospitalizations and higher natriuretic peptides compared to those without AF (all p < 0.001). After a median of 26 months, empagliflozin reduced cardiovascular death or HF hospitalization compared to placebo to a similar extent in patients with and without AF (hazard ratio [HR] 0.78 [95% confidence interval 0.66-0.93] vs. 0.78 [0.64-0.95], interaction p = 0.96). Empagliflozin also reduced total HF hospitalizations (HR 0.73 [0.57-0.94] vs. 0.72 [0.54-0.95], interaction p = 0.94) and annual eGFR decline (difference = 1.368 vs. 1.372 ml/min/1.73 m2 /year, interaction p = 0.99) consistently in patients with and without AF. There was no increase in serious adverse events with empagliflozin versus placebo in patients with and without AF. In patients with HF and ejection fraction >40%, empagliflozin reduced the risk of serious HF events and slowed the eGFR decline regardless of baseline AF.

Hemodynamic-Guided Heart Failure Management in Patients With Either Prior HF Hospitalization or Elevated Natriuretic Peptides

BackgroundIn patients with symptomatic heart failure (HF) and previous heart failure hospitalization (HFH), hemodynamic-guided HF management using a wireless pulmonary artery pressure (PAP) sensor reduces HFH, but it is unclear whether these benefits extend to patients who have not been recently hospitalized but remain at risk because of elevated natriuretic peptides (NPs). ObjectivesThis study assessed the efficacy and safety of hemodynamic-guided HF management in patients with elevated NPs but no recent HFH. MethodsIn the GUIDE-HF (Hemodynamic-Guided Management of Heart Failure) trial, 1,000 patients with New York Heart Association (NYHA) functional class II to IV HF and either previous HFH or elevated NP levels were randomly assigned to hemodynamic-guided HF management or usual care. The authors evaluated the primary study composite of all-cause mortality and total HF events at 12 months according to treatment assignment and enrollment stratum (HFH vs elevated NPs) by using Cox proportional hazards models. ResultsOf 999 evaluable patients, 557 were enrolled on the basis of a previous HFH and 442 on the basis of elevated NPs alone. Those patients enrolled by NP criteria were older and more commonly White persons with lower body mass index, lower NYHA class, less diabetes, more atrial fibrillation, and lower baseline PAP. Event rates were lower among those patients in the NP group for both the full follow-up (40.9 per 100 patient-years vs 82.0 per 100 patient-years) and the pre–COVID-19 analysis (43.6 per 100 patient-years vs 88.0 per 100 patient-years). The effects of hemodynamic monitoring were consistent across enrollment strata for the primary endpoint over the full study duration (interaction P = 0.71) and the pre–COVID-19 analysis (interaction P = 0.58). ConclusionsConsistent effects of hemodynamic-guided HF management across enrollment strata in GUIDE-HF support consideration of hemodynamic monitoring in the expanded group of patients with chronic HF and elevated NPs without recent HFH. (Hemodynamic-Guided Management of Heart Failure [GUIDE-HF]; NCT03387813)

Timing of cardiac resynchronization therapy implantation.

The optimum timing of cardiac resynchronization therapy (CRT) implantation is unknown. We explored long-term outcomes after CRT in relation to the time interval from a first heart failure hospitalization (HFH) to device implantation. A database covering the population of England (56.3 million in 2019) was used to quantify clinical outcomes after CRT implantation in relation to first HFHs. From 2010 to 2019, 64 968 patients [age: 71.4 ± 11.7 years; 48 606 (74.8%) male] underwent CRT implantation, 57% in the absence of a previous HFH, 12.9% during the first HFH, and 30.1% after ≥1 HFH. Over 4.54 (2.80-6.71) years [median (interquartile range); 272 989 person-years], the time in years from the first HFH to CRT implantation was associated with a higher risk of total mortality [hazard ratio (HR); 95% confidence intervals (95% CI)] (1.15; 95% CI 1.14-1.16, HFH (HR: 1.26; 95% CI 1.24-1.28), and the combined endpoint of total mortality or HFH (HR: 1.19; 95% CI 1.27-1.20) than CRT in patients with no previous HFHs, after co-variate adjustment. Total mortality (HR: 1.67), HFH (HR: 2.63), and total mortality or HFH (HR: 1.92) (all P < 0.001) were highest in patients undergoing CRT ≥2 years after the first HFH. In this study of a healthcare system covering an entire nation, delays from a first HFH to CRT implantation were associated with progressively worse long-term clinical outcomes. The best clinical outcomes were observed in patients with no previous HFH and in those undergoing CRT implantation during the first HFH. The optimum timing of CRT implantation is unknown. In this study of 64 968 consecutive patients, delays from a first heart failure hospitalization (HFH) to CRT implantation were associated with progressively worse long-term clinical outcomes. Each year from a first HFH to CRT implantation was associated with a 21% higher risk of total mortality and a 34% higher risk of HFH. The best outcomes after CRT were observed in patients with no previous HFHs and in those undergoing implantation during their first HFH.

Hyperuricemia predicts increased cardiovascular events in patients with chronic coronary syndrome after percutaneous coronary intervention: A nationwide cohort study from Japan.

The causal relationship between hyperuricemia and cardiovascular diseases is still unknown. We hypothesized that hyperuricemic patients after percutaneous coronary intervention (PCI) had a higher risk of major adverse cardiovascular events (MACE). This was a large-scale multicenter cohort study. We enrolled patients with chronic coronary syndrome (CCS) after PCI between April 2013 and March 2019 using the database from the Clinical Deep Data Accumulation System (CLIDAS), and compared the incidence of MACE, defined as a composite of cardiovascular death, myocardial infarction, and hospitalization for heart failure, between hyperuricemia and non-hyperuricemia groups. In total, 9,936 patients underwent PCI during the study period. Of these, 5,138 patients with CCS after PCI were divided into two group (1,724 and 3,414 in the hyperuricemia and non-hyperuricemia groups, respectively). The hyperuricemia group had a higher prevalence of hypertension, atrial fibrillation, history of previous hospitalization for heart failure, and baseline creatinine, and a lower prevalence of diabetes than the non-hyperuricemia group, but the proportion of men and age were similar between the two groups. The incidence of MACE in the hyperuricemia group was significantly higher than that in the non-hyperuricemia group (13.1 vs. 6.4%, log-rank P < 0.001). Multivariable Cox regression analyses revealed that hyperuricemia was significantly associated with increased MACE [hazard ratio (HR), 1.52; 95% confidential interval (CI), 1.23-1.86] after multiple adjustments for age, sex, body mass index, estimated glomerular filtration rate, left main disease or three-vessel disease, hypertension, diabetes mellitus, dyslipidemia, history of myocardial infarction, and history of hospitalization for heart failure. Moreover, hyperuricemia was independently associated with increased hospitalization for heart failure (HR, 2.19; 95% CI, 1.69-2.83), but not cardiovascular death or myocardial infarction after multiple adjustments. Sensitive analyses by sex and diuretic use, B-type natriuretic peptide level, and left ventricular ejection fraction showed similar results. CLIDAS revealed that hyperuricemia was associated with increased MACE in patients with CCS after PCI. Further clinical trials are needed whether treating hyperuricemia could reduce cardiovascular events or not.