Cause-specific death in heart failure across the ejection fraction spectrum: A comprehensive assessment of over 100 000 patients in the Swedish Heart Failure Registry.

AIM: To assess cause-specific death in patients with heart failure with preserved, mildly reduced, and reduced ejection fraction (HFpEF, HFmrEF, and HFrEF). METHODS AND RESULTS: Data were analysed from the Swedish Heart Failure Registry (SwedeHF) and the National Patient Register of patients enrolled in SwedeHF 2000-2021. Cox proportional hazards regression models were performed and adjusted for age, sex and time period. Among 100 584 patients (23% HFpEF, 23% HFmrEF, 53% HFrEF), median age (interquartile range) was 75 (66-82) and 36% were female. Of those who died within 5 years, most deaths were ascribed to cardiovascular (CV) causes across all ejection fraction (EF) categories. Within 5 years, HFpEF had higher adjusted risk of non-CV death (hazard ratio [HR] 1.33, 95% confidence interval [CI] 1.28-1.38, p < 0.001) and lower adjusted risk of CV death (HR 0.85, 95% CI 0.82-0.88, p < 0.001) compared to HFrEF. Ischaemic heart disease (IHD) and cancer were the most common causes of CV and non-CV death regardless of EF category. The incidence rate of CV death due to IHD was highest in HFrEF while incidence rates of CV death due to pulmonary vascular disease, stroke, valvular heart disease and atrial fibrillation increased with increasing EF. The incidence rates of non-CV deaths due to cancer, respiratory disease, and infections increased with increasing EF. CONCLUSION: Cardiovascular death was more common than non-CV death across all EF categories although the risk of non-CV death within 5 years was higher with increasing EF. IHD and cancer were the most common causes of CV and non-CV deaths, respectively, regardless of EF category.

Acyl ghrelin increases cardiac output while preserving right ventricular-pulmonary arterial coupling in heart failure.

AIM: Acyl ghrelin increases cardiac output (CO) in heart failure with reduced ejection fraction (HFrEF). This could impair the right ventricular-pulmonary arterial coupling (RVPAC), both through an increased venous return and right ventricular afterload. We aim to investigate if acyl ghrelin increases CO with or without worsening the right-sided haemodynamics in HFrEF assessed by RVPAC. METHODS AND RESULTS: The Karolinska Acyl ghrelin Trial was a randomized double-blind placebo-controlled trial of acyl ghrelin versus placebo (120-min intravenous infusion) in HFrEF. RVPAC was assessed echocardiographically at baseline and 120 min. ANOVA was used for difference in change between acyl ghrelin versus placebo, adjusted for baseline values. Of the 30 randomized patients, 22 had available RVPAC (acyl ghrelin n = 12, placebo n = 10). Despite a 15% increase in CO in the acyl ghrelin group (from 4.0 (3.5-4.6) to 4.6 (3.9-6.1) L/min, P = 0.003), RVPAC remained unchanged; 5.9 (5.3-7.6) to 6.3 (4.8-7.5) mm·(m/s)-1 , P = 0.372, while RVPAC was reduced in the placebo group, 5.2 (4.3-6.4) to 4.8 (4.2-5.8) mm·(m/s)-1 , P = 0.035. Comparing change between groups, CO increased in the acyl ghrelin group versus placebo (P = 0.036) while RVPAC and the right ventricular pressure gradient remained unchanged. CONCLUSION: Treatment with acyl ghrelin increases CO while preserving or even improving RVPAC in HFrEF, possibly due to increased contractility, reduced PVR and/or reduced left sided filling pressures. These potential effects strengthen the role of acyl ghrelin therapy in HFrEF with right ventricular failure.

What determines who gets cardiac resynchronization therapy in Europe? A comparison between ESC-HF-LT registry, SwedeHF registry, and ESC-CRT Survey II.

AIMS: Cardiac resynchronization therapy (CRT) is effective in heart failure with reduced ejection fraction (HFrEF) and dyssynchrony but is underutilized. In a cohort study, we identified clinical, organizational, and level of care factors linked to CRT implantation. METHODS AND RESULTS: We included HFrEF patients fulfilling study criteria in the ESC-HF-Long Term Registry (ESC-HF-LT, n = 1031), the Swedish Heart Failure Registry (SwedeHF) (n = 5008), and the ESC-CRT Survey II (n = 11 088). In ESC-HF-LT, 36% had a CRT indication of which 47% had CRT, 53% had indication but no CRT, and the remaining 54% had no indication and no CRT. In SwedeHF, these percentages were 30, 25, 75, and 70%. Median age of patients with CRT indication and CRT present vs. absent was 68 vs. 65 years with 24% vs. 22% women in ESC-HF-LT, 76 vs. 74 years with 26% vs. 26% women in SwedeHF, and 70 years with 24% women in CRT Survey II (all had CRT). For ESC-HF-LT, independent predictors of having CRT were guideline-directed medical therapy (GDMT), atrial fibrillation (AF), prior HF hospitalization, and NYHA class. For SwedeHF, they were GDMT, age, AF, previous myocardial infarction, lower NYHA class, enrolment at university hospital, and follow-up at HF centre/Hospital. In SwedeHF, above median income and higher education level were also independently associated with having CRT. In the ESC-CRT Survey II (n = 11 088), all patients received CRT but with differences in the clinical characteristics between countries. CONCLUSION: CRT was used in a minority of eligible patients and more used in ESC-HF-LT than in SwedeHF.

Acyl ghrelin improves cardiac function in heart failure and increases fractional shortening in cardiomyocytes without calcium mobilization.

BACKGROUND AND AIMS: Ghrelin is an endogenous appetite-stimulating peptide hormone with potential cardiovascular benefits. Effects of acylated (activated) ghrelin were assessed in patients with heart failure and reduced ejection fraction (HFrEF) and in ex vivo mouse cardiomyocytes. METHODS AND RESULTS: In a randomized placebo-controlled double-blind trial, 31 patients with chronic HFrEF were randomized to synthetic human acyl ghrelin (0.1 µg/kg/min) or placebo intravenously over 120 min. The primary outcome was change in cardiac output (CO). Isolated mouse cardiomyocytes were treated with acyl ghrelin and fractional shortening and calcium transients were assessed. Acyl ghrelin but not placebo increased cardiac output (acyl ghrelin: 4.08 ± 1.15 to 5.23 ± 1.98 L/min; placebo: 4.26 ± 1.23 to 4.11 ± 1.99 L/min, P < 0.001). Acyl ghrelin caused a significant increase in stroke volume and nominal increases in left ventricular ejection fraction and segmental longitudinal strain and tricuspid annular plane systolic excursion. There were no effects on blood pressure, arrhythmias, or ischaemia. Heart rate decreased nominally (acyl ghrelin: 71 ± 11 to 67 ± 11 b.p.m.; placebo 69 ± 8 to 68 ± 10 b.p.m.). In cardiomyocytes, acyl ghrelin increased fractional shortening, did not affect cellular Ca2+ transients, and reduced troponin I phosphorylation. The increase in fractional shortening and reduction in troponin I phosphorylation was blocked by the acyl ghrelin antagonist D-Lys 3. CONCLUSION: In patients with HFrEF, acyl ghrelin increased cardiac output without causing hypotension, tachycardia, arrhythmia, or ischaemia. In isolated cardiomyocytes, acyl ghrelin increased contractility independently of preload and afterload and without Ca2+ mobilization, which may explain the lack of clinical side effects. Ghrelin treatment should be explored in additional randomized trials. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05277415.

Eligibility for Dapagliflozin and Empagliflozin in a Real-world Heart Failure Population.

BACKGROUND: We investigated eligibility for dapagliflozin and empagliflozin in a real-world heart failure (HF) cohort based on selection criteria of DAPA-HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure), DELIVER (Dapagliflozin Evaluation to Improve the Lives of Patients with Preserved Ejection Fraction Heart Failure), and EMPEROR (Empagliflozin Outcome Trial in Patients with Chronic Heart Failure with Reduced Ejection Fraction and Empagliflozin Outcome Trial in Patients with Chronic Heart Failure with APreserved Ejection Fraction) trials. METHODS AND RESULTS: Selection criteria were applied to the Swedish HF registry outpatient population according to 3 scenarios: (i) a "trial scenario" applying all selection criteria; (ii) a "pragmatic scenario" applying the most clinically relevant criteria; and (iii) a "label scenario" following the regulatory agencies labels. Of the 49,317 patients, 55% had an ejection fraction of less than 40% and were assessed for eligibility based on DAPA-HF and EMPEROR-Reduced, 45% had ejection fraction of 40% or greater and were assessed based on EMPEROR-Preserved and DELIVER. Eligibility using trial, pragmatic, and label scenarios was 35%, 61%, and 80% for DAPA-HF; 31%, 55%, and 81% for EMPEROR-Reduced; 30%, 61%, and 74% for DELIVER; and 32%, 59%, and 75% for EMPEROR-Preserved, respectively. The main selection criteria limiting eligibility were HF duration and N-terminal pro-B type natriuretic peptide levels. Eligible patients had more severe HF, more comorbidities, higher use of HF treatments and higher mortality and morbidity.Clinical Highlights: Large clinical trials for the approval of new drugs in heart failure often apply numerous selection criteria, limiting the generalizability of trial findings to real-world populations. We assessed eligibility for dapagliflozin and empagliflozin according to trial criteria, the more practical criteria usually applied in daily practice for treatment selection, and the criteria mandated by regulatory agencies, in a real-word heart failure population. Our results from the Swedish Heart Failure Registry show that a great number of patients with heart failure might be candidates for these therapies, which have been shown to significantly decrease morbidity and mortality; therefore, their use should be implemented in clinical practice. LAY SUMMARY: When strictly applying selection criteria used in clinical trials, only one-third of a real-world heart failure population is eligible for treatment with empagliflozin and dapagliflozin. Adopting approaches that consider the most meaningful criteria, that is, those most clinically relevant or those mandated by regulatory agencies, significantly broadened eligibility. These results might contribute to future trial design taking into consideration the characteristics of real-world populations, feasibility, and potential cost benefits. CONCLUSIONS: In a real-world HF setting, eligibility for sodium glucose co-transporter-2 inhibitors was similar whether selection criteria from DAPA-HF or EMPEROR-Reduced were applied in HFrEF, or EMPEROR-Preserved or DELIVER in HFpEF. These data might help stakeholders assessing the consequences of future trial eligibility.

Use of evidence-based therapy in heart failure with reduced ejection fraction across age strata.

AIMS: In older patients, guideline-directed medical therapy (GDMT) for heart failure (HF) with reduced ejection fraction (<40%; HFrEF) is not contraindicated, but adherence to guidelines is limited. We investigated the implementation of GDMT in HFrEF across different age strata in a large nationwide cohort. METHODS AND RESULTS: Patients with HFrEF and HF duration ≥3 months registered in the Swedish HF Registry between 2000-2018 were analysed according to age. Multivariable logistic and multinomial regressions were fitted to investigate factors associated with underuse/underdosing. Of 27 430 patients, 31% were <70 years old, 34% 70-79 years old, and 35% ≥80 years old. Use of treatments progressively decreased with increasing age. Use of renin-angiotensin system/angiotensin receptor-neprilysin inhibitors, beta-blockers and mineralocorticoid receptor antagonists was 80%, 88% and 35% in age ≥80 years; 90%, 93% and 47% in age 70-79 years; and 95%, 95% and 54% in age <70 years, respectively. Among patients with an indication, use of implantable cardioverter defibrillator and cardiac resynchronization therapy (CRT) was 7% and 23% in age ≥ 80 years; 22% and 42% in age 70-79 years; and 29% and 50% in age <70 years, respectively. Older patients were less likely treated with target doses or combinations of HF medications. Except for CRT, after extensive adjustments, age was inversely associated with the likelihood of GDMT use and target dose achievement. CONCLUSION: In HFrEF, gaps persist in the use of medications and devices. In disagreement with current recommendations, older patients remain undertreated. Improving strategies and a more individualized approach for implementing use of GDMT in HFrEF are required, particularly in older patients.

Non-cardiology vs. cardiology care of patients with heart failure and reduced ejection fraction is associated with lower use of guideline-based care and higher mortality: Observations from The Swedish Heart Failure Registry.

BACKGROUND: Patients with heart failure (HF) are often cared for by non-cardiologists. The implications are unknown. METHODS: In a nationwide HF cohort with reduced ejection fraction (HFrEF), we compared demographics, clinical characteristics, guideline-based therapy use and outcomes in non-cardiology vs. cardiology in-patient and out-patient care. RESULTS: Between 2000 and 2016, 36,076 patients with HFrEF were enrolled in the Swedish HF registry (19,337 [54%] in-patients overall), with 44% of in-patients and 45% of out-patients managed in non-cardiology settings. Predictors of treatment in non-cardiology were age > 75 years (adjusted odds ratio for non-cardiology 1.20; 95% confidence interval 1.14-1.27), lower education level (0.71; 0.66-0.76 for university vs. compulsory), valve disease (1.24; 1.18-1.31) and systolic blood pressure (SBP) >120 mmHg (1.05; 1.00-1.10). Non-cardiology care was significantly associated with lower use of beta-blockers (0.80; 0.74-0.86) and devices (intracardiac defibrillator [ICD] and/or cardiac resynchronization therapy [CRT]: 0.63; 0.56-0.71), and less frequent specialist follow-up (0.61; 0.57-0.65). Over 1-year follow-up the risk of all-cause mortality (adjusted hazard ratio 1.09; 1.03-1.15) was higher but the risk of first HF (re-) hospitalization was lower (0.93; 0.89-0.97) in non-cardiology vs. cardiology care. CONCLUSIONS: In HFrEF, non-cardiology care was independently associated with older ageand lower education. After covariate adjustment, non-cardiology care was associated with lower use of beta-blockers and devices, higher mortality, and lower risk of HF hospitalization. Access to cardiology care may not be equitable and this may have implications for use of guideline-based care and outcomes.

Electrostatic Discharge Causing Pump Shutdown in HeartMate 3.

Left ventricular assist devices (LVADs) improve symptoms and outcomes in advanced heart failure. Although device malfunction has decreased significantly with later generation LVADs, it has not been eliminated. We describe the clinical course of a patient with HeartMate 3 LVAD who experienced device malfunction, involving temporary pump shutdown suspected to be caused by electrostatic discharge. (Level of Difficulty: Advanced.).

Congestion and Diuretic Resistance in Acute or Worsening Heart Failure.

Hospitalisation for acute heart failure (AHF) is associated with high mortality and high rehospitalisation rates. In the absence of evidence-based therapy, treatment is aimed at stabilisation and symptom relief. The majority of AHF patients have signs and symptoms of fluid overload, and, therefore, decongestion is the number one treatment goal. Diuretics are the cornerstone of therapy in AHF, but the treatment effect is challenged by diuretic resistance and poor diuretic response throughout the spectrum of chronic to worsening to acute to post-worsening HF. Adequate dosing and monitoring and evaluation of diuretic effect are important for treatment success. Residual congestion at discharge is a strong predictor of worse outcomes. Therefore, achieving euvolaemia is crucial despite transient worsening renal function.

Comorbidities and cause-specific outcomes in heart failure across the ejection fraction spectrum: A blueprint for clinical trial design.

BACKGROUND: Comorbidities may differently affect treatment response and cause-specific outcomes in heart failure (HF) with preserved (HFpEF) vs. mid-range/mildly-reduced (HFmrEF) vs. reduced (HFrEF) ejection fraction (EF), complicating trial design. In patients with HF, we performed a comprehensive analysis of type 2 diabetes (T2DM), atrial fibrillation (AF) chronic kidney disease (CKD), and cause-specific outcomes. METHODS AND RESULTS: Of 42,583 patients from the Swedish HF registry (23% HFpEF, 21% HFmrEF, 56% HFrEF), 24% had T2DM, 51% CKD, 56% AF, and 8% all three comorbidities. HFpEF had higher prevalence of CKD and AF, HFmrEF had intermediate prevalence of AF, and prevalence of T2DM was similar across the EF spectrum. Patients with T2DM, AF and/or CKD were more likely to have also other comorbidities and more severe HF. Risk of cardiovascular (CV) events was highest in HFrEF vs. HFpEF and HFmrEF; non-CV risk was highest in HFpEF vs. HFmrEF vs. HFrEF. T2DM increased CV and non-CV events similarly but less so in HFpEF. CKD increased CV events somewhat more than non-CV events and less so in HFpEF. AF increased CV events considerably more than non-CV events and more so in HFpEF and HFmrEF. CONCLUSION: HFpEF is distinguished from HFmrEF and HFrEF by more comorbidities, non-CV events, but lower effect of T2DM and CKD on events. CV events are most frequent in HFrEF. To enrich for CV vs. non-CV events, trialists should not exclude patients with lower EF, AF and/or CKD, who report higher CV risk.

Validation of non-invasive ramp testing for HeartMate 3.

AIMS: Ramp testing in the postoperative period can be used to optimize left ventricular assist device (LVAD) speed for optimal left ventricular (LV) unloading. We tested the hypothesis that a non-invasive echocardiographic ramp test post-HeartMate 3 implantation improves LV unloading immediately after and 1-3 months after as compared with before the test. We also tested a secondary hypothesis that speed adjustments during echocardiography-guided ramp testing do not worsen right ventricular (RV) function immediately after and 1-3 months after. METHODS AND RESULTS: We retrospectively reviewed data from patients who underwent an echocardiographic ramp test. A total of 14 out of 19 patients were clinically stable and were enrolled. Adequate LV unloading was defined as no more than mild mitral regurgitation, and intermittent aortic valve (AV) opening or closed AV, and reduction of left ventricular end-diastolic diameter (LVEDD); and for the follow-up measurement, decreased NT-proBNP. Median (interquartile range) time from implantation to ramp test was 27 (16; 56) days, and median time from ramp test to follow-up echocardiography was 55 (47; 102) days. Median LVAD speed achieved during ramp testing was 5550 (5375; 6025) revolutions per minute (rpm), and median final LVAD speed was 5200 (5000; 5425) rpm. Ramp testing resulted in final LVAD speed increase in 11 (79%) patients and a median net change of 200 (200; 300) rpm. Speed adjustments after ramp testing resulted in improved LVAD unloading that was achieved in additional 3 (21%) patients who were not originally optimized. RV function did not worsen significantly during ramp testing or at final LVAD speed. CONCLUSIONS: The echocardiographic ramp test allowed LVAD speed adjustment and optimization and improved LV unloading during ramp testing and at final speed with no evidence of worsening of RV function.

Focusing on Referral Rather than Selection for Advanced Heart Failure Therapies.

Despite advances in heart failure treatment, advanced heart failure affects 5-10% of people with the condition and is associated with poor prognosis. Selection for heart transplantation and left ventricular assist device implantation is a rigorous and validated process performed by specialised heart failure teams. This entails comprehensive assessment of complex diagnostic tests and risk scores, and selecting patients with the optimal benefit-risk profile. In contrast, referral for advanced heart failure evaluation is an arbitrary and poorly studied process, performed by generalists, and patients are often referred too late or not at all. The study elaborates on the differences between selection and referral and proposes some simple strategies for optimising timely referral for advanced heart failure evaluation.

Controller and battery changes due to technical problems related to the HVAD® left ventricular assist device - a single center experience.

BACKGROUND: The use of left ventricular assist devices (LVADs) has increased in the last decade. Major complications have been well described, but there is no data on device alarms and actual or threatening malfunction which impair quality of life and may impair outcomes. This study describes the technical problems related to the use of the HVAD® left ventricular assist device in a single center. METHODS: We retrospectively reviewed device malfunctions and outcomes in 22 patients with HVAD® left ventricular assist device followed at Karolinska University Hospital between 2011 and 2016. Device malfunction was defined by INTERMACS as a failure of one or more of the components of the LVAD system. The primary outcome was defined as death or hospitalization or unplanned urgent clinic visit due to device alarm of unknown significance or actual or threatening malfunction. Separate secondary outcomes were malfunction resulting in controller exchange and malfunction resulting in battery change. Exploratory outcomes were death, transplantation, or explantation because of recovery. RESULTS: Median age was 59 years and 19% were women. Over a mean follow-up time of 1.7 years (37 patient-years), the primary outcome occurred 30 times (0.8 events per patient-year; 0 deaths, 2 hospitalizations and 28 un-planned clinic visits). Secondary outcomes were 41 device malfunctions for 14 patients requiring 45 controller exchanges in 12 patients (1.1 events per patient-year) and 128 battery changes in 12 patients (3.5 events per patient-year). Exploratory outcomes were 8 deaths (36.4%), 7 transplantations (31.8%) and 2 explants due to recovery (9.1%). CONCLUSION: The use of HVAD® was associated with technical problems requiring frequent un-planned clinic visits and changes of controller and/or batteries. There were no deaths due to device malfunction. Further studies are warranted to evaluate the risk of device malfunction and associated reductions in quality of life and cost.

Predicting Risk in Patients Hospitalized for Acute Decompensated Heart Failure and Preserved Ejection Fraction: The Atherosclerosis Risk in Communities Study Heart Failure Community Surveillance.

BACKGROUND: Risk-prediction models specifically for hospitalized heart failure with preserved ejection fraction are lacking. METHODS AND RESULTS: We analyzed data from the ARIC (Atherosclerosis Risk in Communities) Study Heart Failure Community Surveillance to create and validate a risk score predicting mortality in patients ≥55 years of age admitted with acute decompensated heart failure with preserved ejection fraction (ejection fraction ≥50%). A modified version of the risk-prediction model for acute heart failure developed from patients in the EFFECT (Enhanced Feedback for Effective Cardiac Treatment) study was used as a composite predictor of 28-day and 1-year mortalities and evaluated together with other potential predictors in a stepwise logistic regression. The derivation sample consisted of 1852 hospitalizations from 2005 to 2011 (mean age, 77 years; 65% women; 74% white). Risk scores were created from the identified predictors and validated in hospitalizations from 2012 to 2013 (n=821). Mortality in the derivation and validation sample was 11% and 8% at 28 days and 34% and 31% at 1 year. The modified EFFECT score, including age, systolic blood pressure, blood urea nitrogen, sodium, cerebrovascular disease, chronic obstructive pulmonary disease, and hemoglobin, was a powerful predictor of mortality. Another important predictor for both 28-day and 1-year mortalities was hypoxia. The risk scores were well calibrated and had good discrimination in the derivation sample (area under the curve: 0.76 for 28-day and 0.72 for 1-year mortalities) and validation sample (area under the curve: 0.73 and 0.71, respectively). CONCLUSIONS: Mortality after acute decompensation in patients with heart failure with preserved ejection fraction is high, with one third of patients dying within a year. A prediction tool may allow for greater discrimination of the highest risk patients. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00005131.

Use of evidence-based therapy and survival in heart failure in Sweden 2003-2012.

AIMS: In heart failure with reduced ejection fraction, drug and device therapy improve survival. We studied contemporary trends in utilization of evidence-based therapy and associated survival. METHODS AND RESULTS: We studied 5908 patients with NYHA class II-IV heart failure, EF <30%, and duration of heart failure ≥6 months registered in the Swedish Heart Failure Registry between 2003 and 2012. Regression using generalized estimation equations was used to examine temporal trends in crude and risk-adjusted rates of utilization of evidence-based heart failure therapy and 30-day, 1-year, and 3-year survival. In 2003 vs. 2012, the risk-adjusted use of therapy and P-values for trends were as follows: renin-angiotensin system antagonists, 88% vs. 86% (P = 0.091); beta-blockers, 85% vs. 93% (P = 0.008); mineralocorticoid receptor antagonists, 53% vs. 42% (P < 0.001); CRT, 2.4% vs. 8.2% (P = 0.074); and implantable cardioverter-defibrillators, 4.0% vs. 10.7% (P = 0.004). During the same period, the risk-adjusted 30-day, 1-year, and 3-year survival was 92% vs. 94% (P = 0.532), 81% vs. 77% (P = 0.260), and 58% vs. 54% (P = 0.425), respectively. CONCLUSIONS: In this large nationwide registry, over the last decade the use of evidence-based drug therapy was high and remained stable over time, but, despite an increased use of device therapy, the absolute use was poor. This was associated with an absence of improvement in survival. The improvements in therapy and prognosis over the last generation may be levelling off, and efforts should be directed at improving implementation of evidence-based therapy.

Planned repetitive use of levosimendan for heart failure in cardiology and internal medicine in Sweden.

BACKGROUND/OBJECTIVES: Levosimendan is used in acute heart failure (HF) and increasingly as planned repetitive infusions in stable chronic HF, but the extent of this practice is unknown. The aim was to assess the use of levosimendan vs. conventional inotropes and the use as planned repetitive vs. acute treatment, in Sweden. METHODS: We performed a descriptive study with individual patient validation assessing the use of levosimendan and conventional intravenous inotropes, indications for levosimendan, clinical characteristics and survival in the Swedish Heart Failure Registry between 2000 and 2011. For repetitive levosimendan, we assessed potential indications for alternative interventions. RESULTS: Of 53,548 total registrations, there were 655 confirmed with inotrope use (597 levosimendan, 37 conventional, 21 both) from 22 hospitals responding to validation, and 6069 in-patient controls with New York Heart Association III-IV and ejection fraction <40%. The indications for levosimendan were acute HF in 384 registrations (306 patients), and planned repetitive in 234 registrations (87 patients). Planned repetitive as a proportion of total levosimendan registrations ranged 0-65% and of total levosimendan patients ranged 0-54% in different hospitals. Of planned repetitive patients without existing cardiac resynchronization therapy, implantable cardioverter defibrillator, transplant and/or assist device, 46-98% were potential candidates for such interventions. CONCLUSION: In HF in cardiology and internal medicine in Sweden, levosimendan was the overwhelming inotrope of choice, and the use of planned repetitive levosimendan was extensive, highly variable between hospitals and may have pre-empted other interventions. Potential effects of and indications for planned repetitive levosimendan need to be evaluated in prospective studies.

Triage of patients with moderate to severe heart failure: who should be referred to a heart failure center?

OBJECTIVES: The purpose of this study was to evaluate simple criteria for referral of patients from the general practitioner to a heart failure (HF) center. BACKGROUND: In advanced HF, the criteria for heart transplantation, left ventricular assist device, and palliative care are well known among HF specialists, but criteria for referral to an advanced HF center have not been developed for generalists. METHODS: We assessed observed and expected all-cause mortality in 10,062 patients with New York Heart Association (NYHA) functional class III to IV HF and ejection fraction <40% registered in the Swedish Heart Failure Registry between 2000 and 2013. Next, 5 pre-specified universally available risk factors were assessed as potential triggers for referral, using multivariable Cox regression: systolic blood pressure ≤90 mm Hg; creatinine ≥160 µmol/l; hemoglobin ≤120 g/l; no renin-angiotensin system antagonist; and no beta-blocker. RESULTS: In NYHA functional class III to IV and age groups ≤65 years, 66 to 80 years, and >80 years, there were 2,247, 4,632, and 3,183 patients, with 1-year observed versus expected survivals of 90% versus 99%, 79% versus 97%, and 61% versus 89%, respectively. In the age ≤80 years group, the presence of 1, 2, or 3 to 5 of these risk factors conferred an independent hazard ratio for all-cause mortality of 1.40, 2.30, and 4.07, and a 1-year survival of 79%, 60%, and 39%, respectively (p < 0.001). CONCLUSIONS: In patients ≤80 years of age with NYHA functional class III to IV HF and ejection fraction <40%, mortality is predominantly related to HF or its comorbidities. Potential heart transplantation/left ventricular assist device candidacy is suggested by ≥1 risk factor and potential palliative care by multiple universally available risk factors. These patients may benefit from referral to an advanced HF center.