Decompensated Heart Failure Research Articles

Feasibility and efficacy of acetazolamide in the treatment of acute decompensated heart failure

Abstract Background The ADOVAR trial showed that the addition of acetazolamide to loop diuretics could be expected to result in more rapid diuresis and shorter hospital stays in patients with acute decompensated heart failure (ADHF). However, tolvaptan and SGLTII inhibitors are often added for patients with ADHF in Japan. Method An inception cohort of patients with ADHF admitted between January 2022 and June 2023 was assessed. We studied baseline characteristics and divided the patients into "acetazolamide-use" and "no-use" groups. After three days of admission, the endpoint was the reduction rate of body weight, urine output, and the Congestion Score Index (CSI) improvement rate. Results A total of 222 patients were included (73 of the use group and 149 of the no-use group). Baseline characteristics showed the use of catecholamines, PDE III inhibitors, and SGLTII inhibitors were higher in the use group (30.1% vs. 14.8%; P<0.05, 37.0% vs. 8.1%; P<0.05, and 75.3% vs. 38.3%; P<0.05). The reduction rate of body weight, the amount of urine output, and the CSI improvement rate were higher in the use group (6.5% vs. 4.1%; P<0.05, 2745.8ml/day vs. 2004.8ml/day; P<0.05, and 27.8% vs. 19.2%; P<0.05). A hierarchical multiple regression analysis showed the use of acetazolamide and SGLT II inhibitors were the factors that contributed to the reduction of body weight, the amount of urine output, and the improvement of the CSI (P<0.05). Conclusion The addition of acetazolamide to daily medical therapy in patients with ADHF in Japan resulted in a greater incidence of successful decongestion.

Increased frailty is associated with risk of hospital-acquired infections and death during heart failure hospital admissions

Abstract Background Frailty is common in patients admitted with acute decompensation of heart failure (ADHF) and it is unclear how the frailty syndrome affects heart failure (HF) patients during their acute hospital admission. Understanding the interplay between frailty, impaired renal function, hospital-acquired infections (HAI), and death may be useful in optimising patient care and prognosis. Purpose The aim of this analysis was to explore the relationship between admission frailty levels and the incidence of HAI, acute kidney injury (AKI), and mortality in acute HF hospital admissions. Methods This is a retrospective analysis of data submitted from a single centre to the National HF audit between January and June 2023. Additional frailty and baseline renal function data was retrospectively collected from electronic patient health records. Patients were categorised into three groups according to their Rockwood Clinical Frailty Scale (CSF) (1): no/mild frailty (CFS 1-3), moderate frailty (CFS 4-6) and severe frailty (CFS 7-9). AKI was defined based on baseline and admission creatinine, as per KDIGO guidelines (2). Chi-squared and t-tests were used to compare baseline characteristics between frailty groups. Chi-squared tests were used to compare frailty groups in terms of: HAI, AKI, mortality. Results Between 1st January and 22nd June 2023, there were 344 acute HF hospital admissions in our centre. Most patients had moderate frailty on admission (n=256, 74.4%). Frail patients were significantly older, had a lower admission mean haemoglobin and more were female, compared to non-frail patients (Figure 1A). Patients who were more frail were more likely to experience HAI during their admission; p=0.035 (figure 1B). Furthermore, patients with HAI had a greater risk of mortality, at a median follow-up of 171 (IQR 100.25) days after admission, compared to those without HAI (p>0.001). 41.9% of acute HF admissions were associated with an AKI, and although numerically more frail patients had an AKI, this did not achieve statistical significance (p=0.084). Patients who were more frail were more likely to die, both during hospital admission and at 3 months following discharge; p<0.001 (Figure 1B). Furthermore, this trend persisted after follow-up; p<0.001 (Figure 2). Conclusions Patients with moderate or severe frailty are at greater risk of adverse events (HAI, death) during an acute HF hospital admission, than patients with no or mild frailty. It is imperative to consider the frailty status of all patients with ADHF, to be aware of the frailty-associated risks, and act proactively with targeted interventions (screen for infections, daily bloods, early conversations with patients and their families about treatment escalation plans and patient priorities) to improve outcomes and enhance the quality of care for this vulnerable patient population. Further research is warranted to explore potential interventions to address frailty-related risks in HF management.

Heart failure and advanced chronic kidney disease: differences in characteristics, treatment and outcomes in patients with glomerular filtration rate greater or less than 30 ml/minute/m2

Abstract Introduction Heart failure (HF) is a serious health problem and continues to have a high mortality and incidence of decompensation, despite advances in its management. Chronic kidney disease (CKD) is very prevalent in patients with HF, hinders their treatment and worsens their prognosis, especially when it is advanced CKD (glomerular filtration rate-GFR <30 ml(min/m2). It is important to know the differential characteristics of these patients to improve their management. Purpose To analyze in a contemporary registry of HF patients followed in specialized HF units in Spain the differences in clinical characteristics and treatment between patients with HF and advanced CKD. Methods We analyzed data from the registry of the SEC-Excelente-IC quality accreditation program of the Spanish Society of Cardiology, with 1716 patients with HF included between 2019 and 2021 by 45 specialized HF units accredited by the SEC. Patients were included consecutively in two 1-month cutoffs (March and October) in that period. The clinical and demographic characteristics and comorbidities of the patients were compared according to GFR < or > 30ml/min/m2. Results Of the 1,716 patients, 11.1% had a GFR<30 and 88.9% >30 mL/min/m2. Figure 1 shows the main clinical characteristics and comorbidities of the 2 groups. Median LVEF was similar in both groups: 42 (30-58) vs 38% (29-54). The group with advanced CKD was older (77±9.6 vs 70.5±12.6 years; p<0.001), had greater HF severity (more admissions for HF in the last year, worse NYHA functional class and longer evolution time), and a higher prevalence of coronary heart disease, hypertension, diabetes mellitus, cognitive impairment, anemia, iron deficiency and hyponatremia. There were no differences in sex, BMI, serum potassium or other comorbidities (Figure 1). Figure 2 shows the treatment received in each group. Patients with GFR <30 received in a significantly lower proportion all drugs for HF (p<0.001), except diuretics and potassium binders (ACEI/ARA, sacubitril-valsartan, MRA, beta-blockers, digoxin and SLGT2 inhibitors), and less cardiac rehabilitation (5.2 vs 10.4%; p=0.029). Incidence of one-year mortality was significantly higher in patients with GFR<30 ml/min/m2 (37.2 vs 14.4 per 100 persons-year, p<0.001), as were HF hospitalizations (61.3 vs 33.0; p<0.001) and HF decompensations without hospitalization (24.1 vs 11; p<0.001). Conclusions In our contemporary cohort of real-life HF patients, the prevalence of advanced CKD was 11.1%. These patients had a higher severity of HF, despite which, the utilization of HF drugs, including SGLT2 inhibitors was much lower than in those with GFR >30 ml/min/m2. One-year mortality, HF hospitalization and HF decompensations were almost 3-times higher. This treatment trend needs to be modified to improve the prognosis of these patients.

Daily Subcutaneous injections of Relaxin is a therapy for heart failure with preserved ejection fraction

Abstract Background and Significance: Relaxin (RLX), a hormone of pregnancy has engendered a great deal of excitement as a therapy for cardiovascular diseases. Clinical trials treated patients with acute decompensated Heart Failure (HF) with RLX (i.v. 30µg/kg/day-2 days) and reported a 37% decrease in mortality during a 6-months follow up. This led the FDA to declare RLX a ‘break-through’ therapy. However, a larger trial failed to meet the sought-after end points. Here, we propose that periodic subQ RLX pulses are more effective. We measured the pharmacokinetics of serum RLX following subQ injections of RLX in Sprague Dawley rats. Further, we treated rats with confirmed HFpEF with daily subQ RLX (2-weeks) to reverse the diastolic dysfunction (DD), arrhythmia and fibrotic profile. Methods Sprague-Dawley (250 g, n=20, either sex) received 2-subQ injections 12 hrs apart of RLX (from Relaxera) or the vehicle. Serial blood samples were drawn following each injection to measure [RLX]. ZSF1 rats (9-weeks old, either sex) were placed on a high fat diet (HFD) and serial echos tracked the DD. Once severe DD was established (25-35 weeks of HFD), rats received daily subQ injections of RLX (100µg/kg) or vehicle. After 2-weeks, hearts were perfused to optically map action potentials and Ca2+ transients, and analyze the arrhythmia profile. IF and Westerns were used to measure changes in fibrosis (collagen 1), Nav1.5, connexin 43, Wnt1 and β-catenin. Results After an injection, RLX reached a peak in ~60 min, fell to 50% in 5-6 hours. Injections of 0, 30, 100 or 500 µg/kg yielded peak levels of 0, 11.26±3.52, 58.33±16.10, and 209.42±29.04 ng/ml and residual levels after 24-hrs of 0, 4.9, 45.1 and 156 pg/ml, respectively. The 30µg/kg injections had no effect and 100 µg/kg increased Nav1.5 (25%), Cx43 (30%) and β-catenin (90%). The 500 µg/kg injections increased Nav1.5 and Cx43 but upregulated β-catenin, only slightly. In ZSF1 HFpEF rats that received the vehicle (n=12), a premature stimulus (at 30 ms) elicited arrhythmia in 67% of the hearts. RLX injections reversed DD, suppressed sustained atrial and ventricular arrhythmias (n=0/12) but not self-terminating arrhythmias, lasting < 10sec. RLX improved the conduction velocity (CV), particularly at fast rates (100ms) from 0.74 to 0.9 m/s (p<0.001, n=12). RLX significantly increased Cx43 expression, Nav1.5 and β-catenin at intercalated disks. RLX reduced collagen deposition in HFpEF rats, to normal levels and increased Wnt1 compared to control HFpEF rats. Conclusions The ZSF1 diabetic rat on a HFD recapitulates human HFpEF, high blood pressure, fibrosis, DD, AF and VF. SubQ RLX injections reversed DD i.e. enlarged Left Atrium, E/e’ ratio, fibrosis, and the arrhythmia vulnerability by increasing CV, Cx43, and Nav1.5. Daily subQ RLX injections were highly effective as a therapy for HFpEF.Echo parameterHFpEF + RLX

Transferrin saturation is a superior prognostic biomarker for iron deficiency after acute decompensated heart failure: a retrospective clinical real-world cohort study

Abstract Background Iron deficiency (ID) is the most common extracardiac comorbidity in heart failure (HF) and associated with worse outcomes. While a uniform definition of ID in HF remains lacking, several biomarkers for ID, including ferritin and transferrin saturation (TSAT), are used in both clinical trials and clinical practice. However, which biomarker is a superior prognostic predictor for ID in HF remains unsettled. In addition, real-world clinical data on ID screening and intravenous (IV) iron treatment is largely missing. Purpose To determine which biomarker is a superior prognostic predictor for the composite endpoint of HF rehospitalisation (HHF) and all-cause mortality in a real-world cohort of patients with HF and coexisting ID, and to investigate frequency and predictors of ID screening and IV iron treatment. Methods In this retrospective cohort study, all patients aged 18-85 years hospitalised at a tertiary university hospital with new onset HF with reduced ejection fraction (HFrEF) in 2016-2020 were consecutively included from medical records by ICD-10 code I50.0-I50.9 and followed until 31 December 2021. Patient characteristics, comorbidities, medications, laboratory results and data on follow-up, including if ID was tested for, IV iron administration, HHF and all-cause mortality was collected. First available iron status after admission for index hospitalisation was used. Predictors for ID screening and IV iron use were identified with univariate logistic regression. The association between ID markers and the composite endpoint was analysed with Cox regression adjusted for age, sex, baseline anemia, estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2 and N-terminal pro-B type natriuretic peptide (NT-proBNP) below median value with median ferritin and TSAT values set as references respectively. Results In all, 753 patients were included (66.5 ± 12.7 years, 508 (67.5%) men, ejection fraction 29.5 ± 6.9% and mean NT-proBNP 6241 ± 7183 ng/L). Of these, 484 (64.3%) were screened for ID and 235 (48.6%) fulfilled criteria for ID. Of these, 94 (40.0%) received IV iron. Of screened patients, 28.6% had ID with anemia and 20.8% ID without anemia (Table 1). Factors associated with screening for ID were follow-up at hospital, anemia, eGFR <30 mL/min/1.73 m2 and ischemic heart disease, and for IV iron additionally chronic kidney disease and peripheral artery disease. Median ferritin was 140 µg/L and TSAT 0.2. Both ferritin and TSAT displayed an inversely linear association with outcomes, while TSAT <0.2 showed a stronger association with increased risk of HHF and all-cause mortality compared to median values (Figure 1-2). Conclusions In a real-world clinical setting, TSAT was a superior prognostic biomarker for worse outcomes compared to ferritin in patients hospitalised for acute HF. While both ID screening and IV iron use remained greatly underutilised in clinical practice, identification of a reliable biomarker for ID is critical.

Effect of nutritional guidance on mortality and composite endpoints in patients with acute myocardial infarction: a single center retrospective cohort study

Abstract Background/Introduction Acute myocardial infarction (AMI) stands as a major global cause of mortality. Various intervention strategies, such as pre-hospital care, reperfusion therapies, pharmacological interventions, dietary modifications, and exercise therapies, have been researched to improve patient prognosis (1,2). While reports suggest the efficacy of the Mediterranean diet, there remains a lack of evidence regarding the impact of nutritionist-led dietary guidance on the prognosis of AMI patients. Purpose This study aimed to elucidate whether nutritional guidance by nutritionists who have national qualifications would improve the mortality and the primary composite endpoint (including acute decompensated heart failure, stroke, and acute coronary syndrome) of patients following an acute myocardial infarction. Methods A retrospective cohort study was conducted, enrolling 446 consecutive AMI patients who underwent emergency coronary angiography and percutaneous coronary interventions between September 1, 2015, and October 31, 2023. Patients meeting the universal definition of myocardial infarction were included (3). After excluding 37 in-hospital deaths, evaluations for all-cause mortality, cardiovascular mortality, and composite endpoints were performed during follow-up in 409 patients. Nutritionists guided 223 patients (54.5%) during hospitalization in this study. The nutritional guidance used in our study was also based on the definition of adequate caloric intake of 25–30 kcal per ideal body weight (kg). Under an appropriate total energy intake, a fat energy ratio of 20–25% and a carbohydrate energy ratio of 50–60% are recommended, with protein and lipid restrictions depending on the disease state. Results During a median follow-up of 39 months, 24 cases of all-cause mortality (5.9%) and 6 cases of cardiovascular mortality (1.5%) were recorded. Additionally, 15 cases of nonfatal stroke (3.7%), 17 cases of nonfatal acute coronary syndrome (4.2%), and 20 cases of hospitalizations for acute decompensated heart failure (4.9%) were observed. Kaplan–Meier curves demonstrated significantly higher incidence rates of death and primary composite endpoints among patients without nutritional guidance. The multivariate Cox regression model incorporated all variables exhibiting statistically significant associations with long-term mortality, and the primary composite endpoints. The multivariate Cox regression model revealed nutritional guidance as a significant predictor for long-term mortality but not for primary composite endpoints. Conclusion Nutritional guidance for AMI patients may improve overall mortality. Further research is warranted to explore the physiological impacts of improved diets resulting from such guidance and their effects on enhancing prognosis.

Multiple comorbidities are associated with poor prognosis in patients with ADHF-HFpEF and non-frailty or mild frailty but not moderate-severe frailty -PURSUIT-HFpEF Registry-

Abstract Background A variety of comorbidities are frequently observed and represent a major problem in the management of patients with heart failure. Frailty is a strong predictor of poor clinical outcome in patients with heart failure, which may be partially attributable to the presence of multiple comorbidities. However, it remains to be clarified whether frailty is prognostically useful in relation to multiple comorbidities in patients with acute decompensated heart failure and preserved ejection fraction (ADHF-HFpEF). Purpose The purpose of this study is to investigate the relationship between frailty, multiple comorbidities and prognosis in patients with ADHF-HFpEF. Methods We prospectively studied 1028 patients with ADHF-HFpEF. Frailty was assessed using Clinical Frailty Scale (CFS). Multiple comorbidities were defined as the presence of 4 or more factors from the following 11 groups: diabetes, obesity, lung disease, anemia, renal dysfunction, electrolyte disorder, dyslipidemia, depression, hypertension, stroke and cancer. The primary outcome of this study was the composite endpoint of all-cause mortality and rehospitalization for worsening heart failure. Results During a mean follow-up period of 1.6±1.3 years, 454 patients underwent primary outcome. CFS (p<0.001) and the number of comorbidities (p=0.006) were significantly independently associated with primary outcome after multivariate adjustment. Kaplan-Meier analysis revealed that patients with multiple comorbidities had significantly higher risk for primary outcome than those without multiple comorbidities in the group with non-frailty (defined as CFS of 1 or 2, p=0.019) and mild frailty (CFS of 3 or 4, p=0.036). However, there was no significant difference in the group with moderate or greater frailty (CFS of 5 or more) in patients with ADHF-HFpEF. Conclusion(s) Multiple comorbidities would be associated with poor prognosis in patients with ADHF-HFpEF and non-frailty or mild frailty but not in patients with moderate or greater frailty.Multiple comorbidities and MACE risk

Prognostic impact of left atrial reverse remodeling in patients with ADHF-HFpEF regardless of atrial fibrillation -PURSUIT-HFpEF Registry-

Abstract Background Left atrial (LA) dilatation is associated with increased mortality in patients with cardiovascular disease including heart failure (HF) and LA reverse remodeling (LARR) was reported to be associated with favorable outcomes in patients with HF. However, it remains to be clarified whether LARR could have prognostic value in patients with HF with preserved ejection fraction (HFpEF). Purpose The purpose of this study is to elucidate whether LARR is associated with clinical outcome in patients with HFpEF in relation to the presence of atrial fibrillation (AF). Methods We prospectively studied 492 patients with acute decompensated heart failure with preserved ejection fraction (ADHF-HFpEF) without the poor outcome during the first year postdischarge. Echocardiography was performed just before discharge and at 1 year after discharge. LARR was defined as the reduction of 15% or more in left atrial end-systolic volume (LAV). The primary outcome was rehospitalization for worsening heart failure. Results All study patients were divided into 2 groups according to the presence of AF at discharge (AF group, n=182 and non-AF group, n=310). During a mean follow-up period of 1.4±1.2 years, 78 patients were rehospitalized for worsening heart failure (37 patients in AF group and 41 in non-AF group). ΔLAV, the degree of reduction in LAV during the first year postdischarge, was significantly independently associated with primary outcome after multivariable adjustment both in AF group (p=0.033, HR 0.992 [0.984-0.999]) and non-AF group (p=0.021, HR 0.986 [0.974-0.998]). Kaplan-Meier analysis revealed that patients with LARR had significantly lower risk for primary outcome than those without LARR not only in the whole study patients (8% vs 20%, p=0.001) but also both in AF group (9% vs 24% p=0.013) and in non-AF group (8% vs 16% p=0.043). Among clinical characteristics during the index hospitalization, the presence of AF and prior HF hospitalization were significantly independently associated with LARR at multivariate Cox logistic regression analysis (p=0.006, OR 0.554 [0.364-0.843] and p=0.007, OR 0.491 [0.292-0.826], respectively). Conclusion(s) The left atrial reverse remodeling could have the prognostic impact in patients with ADHF-HFpEF regardless of the presence of atrial fibrillation.Kaplan-Meier curves in AF and non-AF

Changes in N-terminal pro b-type natriuretic peptide according to SGLT2 inhibitor utilization patterns in patients hospitalized for decompensated heart failure: a prospective cohort study

Abstract Introduction Sodium-glucose cotransporter-2 (SGLT2) inhibitors have found success in treating patients with chronic heart failure (HF) across the entire spectrum of left ventricular ejection fraction (EF). Their benefits may also extend to patients with acute HF decompensation, as they may aid effective decongestion. Purpose This study aims to present the various patterns in changes of N-terminal pro b-type natriuretic peptide (NT-proBNP) according to SGLT2 inhibitor use in patients hospitalized for acute HF decompensation. Methods In this prospective cohort study, we enrolled consecutive patients hospitalized for HF decompensation during a 4-month period in a cardiology department. Prior medical history and cardiovascular risk factors were recorded. The patterns in SGLT2 inhibitor use were noted and patients were classified into three groups; Group 1 (No SGLT2 inhibitor use/Discontinuation), Group 2 (Prior SGLT2 inhibitor use and continuation), and Group 2 (SGLT2i-naïve and initiation). Categorization according to left ventricular (EF) to HF with reduced EF (HFrEF), HF with mildly reduced EF (HFmrEF), and HF with preserved EF (HFpEF) was also performed. Moreover, estimated glomerular filtration rate (eGFR) was used as an estimate of renal function. Results In this analysis, 159 patients were included (median age: 79 years old, male sex: 64.8%, median duration of hospitalization: 6 days). In this population, 67.9% of the patients were not receiving a SGLT2 inhibitor on admission. Concerning demographic and clinical variables (Figure 1), there were no major differences in age, sex distribution, history of diabetes mellitus, dyslipidemia, and atrial fibrillation, as well as in renal function. Group 2 patients had a lower prevalence of arterial hypertension compared to Group 3 (36.6% vs. 52.6%, p<0.05). Moving to the changes in NTproBNP (Figure 2), we observed that patients who did not use SGLT2 inhibitors and did not initiate them during hospitalization had negligible changes in NTproBNP, either as an absolute change (Group 1: 506 (8792) pg/ml vs. Group 2: -5610 (9461) pg/ml vs. Group 3: -3602 (4409) pg/ml, p=0.001) or as percentage change (Group 1: -2.1 (63.4) % vs. Group 2: -30.3 (39.0) % vs. Group 3: -38.3 (41.5) %, p=0.001), compared to the rest of the study population who were already taking SGLT2 inhibitors or initiated them during hospitalization. Conclusion In this study we found NTproBNP, a widely used biomarker of congestion and prognosis in HF, was significantly reduced in decompensated HF patients receiving SGLT2 inhibitors, with the greatest change being observed in those being treatment-naïve prior to admission. These findings further highlight the role of this drug class even in the acute phase of the disease.Figure 1Figure 2

Effect of renin-angiotensin system inhibitors in elderly patients with heart failure and reduced ejection fraction

Abstract Background More than half of the patients admitted for acute decompensated heart failure (ADHF) in Japan are over 80 years of age. Both Japanese and European heart failure guidelines recommend the use of renin-angiotensin system inhibitors (RASIs) in patients with heart failure with reduced ejection fraction (HFrEF). However, there is a paucity of data on the effect of RASIs in elderly patients with HFrEF, because elderly patients have been excluded from large clinical trials. Purpose The purpose of the current study was to clarify the effect of RASIs in elderly patients with HFrEF. Methods This was a post-hoc analysis of a prospective, observational, multicentre cohort study that enrolled consecutive patients admitted with ADHF to 19 secondary and tertiary hospitals in Japan between October 2014 and March 2016. Patients who were ≥ 80 years old, with left ventricular ejection fraction (LVEF) < 40% and discharged alive were included in the present study. RASIs were defined as either ACE inhibitors or angiotensin II receptor blockers. The primary endpoint was a composite of all-cause death and heart failure (HF) hospitalisation. Results Among 518 patients enrolled, 288 patients received RASIs at discharge and 230 patients did not. The median follow-up period was 335 days (interquartile range; 124 – 499 days). Patients receiving RASIs were younger (85.7 ± 4.4 vs. 86.5 ± 4.4 years of age, p=0.03), had a higher body mass index (BMI; 21.4 ± 3.3 vs. 20.6 ± 3.7 kg/m², p=0.01) and better renal function (eGFR; 45.4 ± 21.5 vs. 38.2 ± 19.2 ml/min/1.73m², p<0.001). Patients receiving RASIs had a higher LVEF (30.9 ± 6.3 vs. 28.5 ± 7.1%, p<0.001). The use of beta-blockers at discharge was more prevalent in patients receiving RASIs (77.8% vs. 60.4%, p<0.001), but the use of mineralocorticoid receptor antagonists was not (50.0% vs. 42.2%, p=0.08). The cumulative incidence of all-cause death or HF hospitalisation one year after discharge was significantly lower in patients receiving RASIs (40.1% vs. 59.5%, p<0.001). Even after adjusting for confounders, the risk of a composite of all-cause death and HF hospitalisation was significantly lower in patients receiving RASIs (adjusted hazard ratio 0.59, 95% confidence interval 0.45-0.77, p<0.001). There was no interaction between the effect of RASIs and subgroup factors such as age, BMI, dementia, malignancy, frailty, and renal function. Conclusion Use of RASIs at discharge was associated with lower incidence of all-cause death or HF hospitalisation in elderly patients with HFrEF.

Impact of inhaled nitric oxide therapy in patients with cardiogenic shock treated with veno-arterial extracorporeal membrane oxygenation combined with Impella

Abstract Background Mortality rates remain high in patients with cardiogenic shock (CS) requiring veno-arterial extracorporeal membrane oxygenation (VA-ECMO) combined with Impella (ECPELLA) support. Early weaning from VA-ECMO may be the first step in reducing mortality in these patients. Inhaled nitric oxide (iNO) therapy improves right ventricular function by decreasing pulmonary arterial resistance, resulting in increased Impella flow rate, which may facilitate early withdrawal of VA-ECMO and improve survival. Purpose The purpose of this study was to investigate the prognostic impact of iNO therapy on ECPELLA patients. Methods We retrospectively studied consecutive patients with CS due to acute myocardial infarction (AMI-CS) or decompensated heart failure (ADHF-CS) supported with ECPELLA from September 2019 to January 2024 at our hospital. The VA-ECMO withdrawal rate, time to withdrawal, and 30-day survival were compared for ECPELLA patients with and without iNO therapy. Results A total of 47 patients were included (AMI-CS, n=26, and ADHF-CS, n=21). Of these, 21 patients (44.7%) were treated with iNO therapy. Patient characteristics were not significantly different between those with and without iNO therapy, including age, gender, percentage of cardiopulmonary arrest or acute coronary syndrome, and lactate levels at mechanical circulatory support induction. Patients receiving iNO therapy had significantly higher VA-ECMO withdrawal rates (90% vs. 50%, P=0.003) and shorter time to VA-ECMO withdrawal (5.0±1.3 vs. 7.8±5.6 days, P=0.04) than those not receiving iNO therapy. Furthermore, Kaplan-Meier analysis demonstrated that the 30-day survival rate was significantly higher in patients receiving iNO therapy than those without (P=0.003, Figure). Conclusion Adjuvant iNO therapy for CS patients supported by ECPELLA facilitates early withdrawal of VA-ECMO and improve survival representing a useful therapeutic option.Figure

Continuation of beta-blockers at discharge is associated with improved outcome in patients with HFpEF and concomitant moderate aortic stenosis

Abstract Background In patients with severe aortic stenosis or decompensated heart failure with preserved ejection fraction (HFpEF), beta-blockers are usually discontinued despite the absence of unequivocal evidence. The data on the effect of beta-blockers in patients with moderate aortic stenosis (MAS) are scarce. Aim To investigate the relationship between beta-blocker use and outcome in patients with MAS, who were hospitalized for decompensated HFpEF. Methods The current study includes 61 patients admitted for decompensated HFpEF with concomitant MAS. The mean age of the population was 82.7±7.59 years old and 41% were females. The diagnosis MAS was established on criteria including aortic valve area between 1-1.5 cm², mean gradient - 20-39 mmHg, and max velocity between 3-3.9 m/s. For those with borderline measurements, the Doppler Velocity Index (DVI) was calculated (DVI < 0.25 indicates severe aortic stenosis). All echocardiographic data were assessed by an experienced echocardiographer. Patients with previous aortic valve replacement and a severe mixed of multivalvular disease were excluded. Result The median follow-up was 52 months (interquartile range 34-63 months). During this period 38 patients (62.3%) died from any cause while 42 (68.9%) individuals experienced a composite endpoint, of all-cause death or hospitalization due to worsening HFpEF. In survivors, we observed higher prescription of beta-blockers at hospital discharge (66% vs. 34%, p<0,05) and better diastolic function than in patients with endpoints. In multivariate Cox regression analysis the use of beta-blockers (HR = 0,27; 95% CI 0,13-0,57; p<0.01) and better diastolic function, defined as higher septal e` (HR=0,76; 95% CI 0,61-0,94; p=0.01) were identified as independent predictors for both - survival and composite endpoint (Figure 1). Advanced age was recognized as an associated factor for outcomes. Conclusion In the present study, continuation of beta-blockers at discharge was independently associated with better survival in patients with decompensated HFpEF and concomitant MAS. It remains to be addressed in future studies, whether or not beta-blockers should be started in these patients or if there is any prognostic interaction between beta-blockers and aortic valve intervention for MAS.Figure 1.Kaplan-Meier survival curve

The 5-Item Modified Frailty Index (mFI-5) for risk stratification of patients with infective endocarditis undergoing cardiac surgery

Abstract Background population aging has led to an increased burden of frailty as an emerging global health issue, and variables for its quantification in patients with infective endocarditis (IE) are lacking in current surgical risks scores. The 5-item modified frailty index (mFI-5) score has shown to be effective in the prediction of surgical outcomes in other medical scenarios. Purpose this study aimed to assess the role of the mFI-5 in the prediction of surgical outcomes in patients with left-sided IE undergoing cardiac surgery. Methods a total of 112 cases of confirmed left-sided IE undergoing surgery, were consecutively collected and followed during one year after diagnosis in two tertiary hospitals between 2016 and 2021. The mFI-5 score included 5 baseline patient-specific comorbidities: diabetes, congestive heart failure, non-independent functional status (Barthel index <80), hypertension and chronic obstructive pulmonary disease (range 0-5), and patients were categorised as mFI-low (<2, n=65), and mFI-high (>=2, n=47). Results mean age was 66 [SD 15] years, 67% were men and community-acquired infections were 75%. As shown in Table 1, mFI-high patients were older and, aside from the specific comorbidities included in the score, with more chronic kidney disease. The most isolated pathogen was S. viridans (n=32), predominantly in mFI-low, in contrast to enterococcal and polymicrobial IEs, which were more frequent in mFI-high. Larger vegetations were reported in mFI-high [16 (10) vs 13 (9) mm, p 0.03], with no differences regarding infection site or periannular complications. Acute kidney injury, decompensated heart failure and higher natriuretic peptides were more common in mFI-high. Regarding mortality, in-hospital deaths were more frequent in mFI-high group. When analyzing mFI-score as a discrete variable, in-hospital mortality was associated with higher median scores values [2 (2) vs 1(1) points, p 0.02], being 2 points the optimal cutoff point for prediction [AUC 0.64 (95% CI 0.54-0.73), Fig.1A]. Among survivors who completed follow-up (n=82), rehospitalization and all-cause mortality rates in mFI-high exceeded those from mFI-low. Predictors of in-hospital and 1-year mortality were assessed by logistic regression (Fig. 1B), confirming the independent prognostic association of mFI-5-score in patients with IE undergoing surgery. Conclusions patients with IE undergoing cardiac surgery with higher mFI-5 scores were older, more predisposed to enterococcal and polymicrobial infections, and had a greater comorbidity burden with a more complicated clinical course. The mFI-score was independently associated with in-hospital mortality as well as rehospitalizations and 1-year mortality, positioning itself as an additional tool for risk stratification in this cluster of patients.Table 1Figure 1

Anemia and sideropenia in patients with decompensated heart failure

Abstract Introduction Anemia is highly prevalent in patients with heart failure (HF). In the latest ESC guidelines, intravenous. iron supplementation is recognized as substantial for improving quality of life, exercise capacity and reducing the risk of future hospitalizations in patients diagnosed with HF of reduced ejection fraction (HFrEF). We hypothesized that patients diagnosed with HF of preserved EF (HFpEF) and midly reduced EF (HFmrEF), who also exhibit iron deficiency, may benefit from intravenous iron supplementation. Method We evaluated the prevalence and parameters of anemia from medical histories of hospitalized patients with HFrEF and HFmrEF/HFpEF, from March 2023 to January 2024, and compared them to NTproBNP levels. Results We included 134 hospitalized patients with HF, mean age 71 ± 10 (41% women). Of total 134, 77 patients exhibited acute worsening of chronic HFrEF or were newly diagnosed HFrEF (group A), whereas 57/134 patients had decompensated HFmrEF/HFpEF (11 and 46, respectively - group B) whose iron status was analyzed on admission. General prevalence of anemia in all HF patients was 50.8% (cut off value - hemoglobin concentration less than 12 g/dL in women, and less than 13 g/dL in men), 54.4% of HFpEF/HFmrEF group and 48.1% of HFrEF group had anemia, 46.6% patients with anemia had EF>40%, without any statistical difference among groups (hemoglobin concentration group A/group B – 12.33±2.54/11.89­±2.63 g/dL, CV 0.2). Reduced transferrin saturation, which is defined as less than 20.0%, had 44.0% of all HF patients, and that was more common in HFrEF patients (62.0%), but statistically insignificant (group A/group B - 0.1843±0.10/0.1877±0.11, CV 0.6). Among group A and group B - 63.6% and 62.5% had transferrin saturation less than 0.2, respectively. There was no difference in the prevalence of serum ferritin <100 μg/L in group A and B (41.6% and 47.4% respectively; group A/group B – 177.26±176.7/137.01±126.6, CV 0.9). Spearman’s rank test implied no correlation between NTproBNP levels and serum ferritin or transferrin saturation. Serum iron had a mild negative (coefficient -2.8) correlation with NTproBNP levels (p<0.01). Hemoglobin concentration was associated with strong negative correlation with NTproBNP levels but with less statistical significance (coefficient -0.9 p<0.05). Conclusion Results of our study suggest that anemia and sideropenia are common in our HF population, with no difference between the spectrum of HF subgroups based on EF. There seems to be a correlation between anemia and serum iron and level of NTproBNP which may imply that anemia and low iron worsen the degree of HF decompensation.

Home alone on milrinone: a novel way to deliver home inotropes as a bridge to heart transplantation

Abstract Continuous ambulatory intravenous inotropes can be successfully used as a bridge to decision or heart transplant in patients with end-stage heart failure. The traditional model at our institute involved the Hospital in the Home (HITH) team, with daily nurse-led visits to the patients’ home, to safely maintain this treatment, which is otherwise largely restricted to the intensive care setting. In response to the COVID-19 pandemic, delivery of healthcare underwent a paradigm shift. Our model was changed to a patient led continuous intravenous inotrope program at home which obviated the need for a daily nurse visit. We describe our process and our early outcomes. Fifteen patients were deemed suitable for the Independent at Home program. All patients needed to complete ambulatory intravenous inotrope education, pass competency testing and have implantable cardioverter-defibrillators inserted prior to discharge. Competencies included proficiency for troubleshooting the inotrope ambulatory delivery pump, monitoring of vital signs and ability to report decompensated heart failure symptoms. Weekly outpatient visits to our heart failure clinic with nursing, medical and pharmacy reviews were scheduled. Emergency action plans were provided to patients. 73.3% of our cohort were male. The average age was 51 years. 46.6% had a diagnosis of dilated cardiomyopathy. 53.3% were listed for heart transplant and were bridge to transplant (BTT) and 46.7% were bridge to decision (BTD) for heart transplant. Over a study period of 35 months, seven (46.7%) patients were weaned off inotropes, three (20.0%) were escalated to durable mechanical circulatory support (one due to decompensated heart failure and two due to persistently elevated pulmonary pressures), four (26.7%) were transplanted and one (6.7%) chose to be palliated. Six patients had one admission, five patients had two admissions. Five readmissions were due to decompensated heart failure, four admissions were planned to optimize pulmonary hypertension following a right heart catheterization, three had peripherally inserted central catheter (PICC) line complications and two had non-cardiac admissions (refer to table 1). The median length of days on the Independent at Home program was 112 days with an interquartile range of 120 days. A comparative group consisting of consecutive patients treated under the previous Hospital in the Home model are presented in table 2; the Independent at Home cohort shows reduced unplanned admissions. The independent at home inotrope program is an effective and safe option to bridge to decision or bridge to cardiac transplantation.HITH vs Independent admission reasonHITH vs Independent admissions

Elderly patients with decompensated heart failure: prospective analysis from the LECRA-HF registry

Abstract Background/Introduction Heart failure (HF) presents as a clinical syndrome associated with an adverse prognosis, increased mortality risk, and recurrent hospitalizations for HF (HHF). In Poland, there has been a persistent increase in the overall prevalence and hospitalizations of HF among patients. Each subsequent HHF is associated with progressively worsening prognosis. In Europe, HF is most prevalent in elderly individuals, rendering this patient group particularly susceptible to HF exacerbations. Purpose The aim of this study was to conduct a comprehensive analysis of the oldest patients (≥80 years) hospitalized due to HF decompensation, compared to the rest of the evaluated cohort, including overall mortality after median 46 months of observation. Methods The prospective registry of patients with HF decompensation (LECRA-HF) is an ongoing registry conducted at a tertiary cardiology center specializing in HF treatment. Patients enrolled in the registry (n=1394) were evaluated for the presence of cardiovascular risk factors, HF phenotype, laboratory, and echocardiographic findings, as well as overall mortality. Due to the frequent occurrence of HF in elderly patients, we arbitrarily chose to compare two cohorts of patients: those above (n=306) vs. below 80 years of age (n=1088). Results Median age of elderly patients was 84 [82-86] years, of which only 7.8% were >90 years of age. HFrEF was the most common HF phenotype, which, occurred less frequently in the elderly (54.4 vs 74.4%, P<0.001). In turn, HFpEF was more prevalent in elderly group (39.2 vs 17.7%, P<0.001). Elderly patients were more often female (45.1 vs 30.2%, P<0.001) and had more comorbidities: arterial hypertension (85.6 vs 78.6%, P=0.007), atrial fibrillation (61.1 vs 45.7%, P<0.001), renal failure (49.7 vs 28.5%, P<0.001) as well as peripheral arterial disease (17 vs 9.8%, P=0.005). Those patients had more frequently implanted cardiac pacemakers (28.6 vs 12.6%, P<0.001), but less often implantable cardioverter-defibrillators (7.9 vs 14.3%, P=0.003). During HHF they were less often qualified to elective coronary angiography (24.2 vs 31.5%, P=0.039). At discharge mineralocorticoid receptor antagonist were less often prescribed in that group (42.4 vs 50.3%, P=0.010). During long-term observation patients ≥80 years had a higher all-cause mortality (81 vs 67.4%, P<0.001, Panel A). Moreover, it was also higher elderly with NT-proBNP>4497 pg/mL (P<0.001) and LVEF<41% (P=0.014) (Panel B). Conclusion(s) Patients aged ≥80 years were characterized by a higher burden of comorbidities. They were more often qualified to cardiac pacemakers, but less often to implantable cardioverter-defibrillators and invasive coronary procedures. The most common HF phenotype was HFrEF, however with a significant increase in HFpEF. They exhibited significantly higher overall mortality compared to those <80 years old, which was associated with both LVEF and NT-proBNP levels.

Incidence of 1-year mortality, heart failure admissions and decompensation in patients with heart failure followed in HF units in Spain. Differences according to type of units

Abstract Introduction Heart failure is a serious health problem and continues to have a high mortality and incidence of decompensation, despite advances in its management. The introduction of specific multidisciplinary HF units has improved the management of patients with this disease, thanks to better organization and management of available diagnostic and therapeutic resources. The HF Association of the ESC and the Spanish Society of Cardiology have defined 3 types of HF units (community, specialized, and advanced) according to their structure, complexity, and portfolio of services. Purpose To analyze in a contemporary registry of patients with HF followed up in HF units in Spain whether the results in terms of mortality and HF decompensations during follow-up are similar or different between the 3 types of units. Methods We analyzed data from the registry of the SEC-Excelente-IC quality accreditation program of the Spanish Society of Cardiology, with 1,716 patients with HF included between 2019 and 2021 by 45 SEC-accredited HF units. Patients were included consecutively in two 1-month cutoffs (March and October) in that period. Units were defined as community, specialized, and advanced according to ESC HFA and SEC criteria. We compared the incidence of death, HF admissions and total decompensations at 1-year follow-up between community and specialized/advanced units. Results Of the 1716 patients, 55.5% were treated in community units, 65.9% in advanced units, and 20.9% in advanced HF units. Figure 1 shows the main characteristics and treatment used in the 3 types of units. The community units treated older patients and more HFpEF, and the use of NRA and AID was lower, with no differences in the remaining characteristics, comorbidities, or treatments (Figure 1). Figure 2 shows the incidence of events at 1 year. Total mortality was 27.5% in community and 15.5% in specialized/advanced (p<0.001). HF admissions (39.7 vs 29.2%; p=0.019), HF decompensations without admission (16.4 vs 11.3%; p=0.074), total decompensations (56.1 vs 40.5%; p=0.003), and combined HF death/admissions (45.2 vs 31.4%; p=0.005) were statistically higher in community units. Control in specialized/advanced units was an independent protector factor for all events (mortality: HR 0.59, 0.43-0.82; p=0.002; HF admissions: HR 0.61, 0.42-0.90; p=0.012; total HF decompensations: HR 0.58, 0.42-0.81; p=0.001). Conclusions One-year prognosis of HF patients continues to be poor, with high rates of mortality and decompensations. Patients attended in community HF units was significantly worse in our country during the study period. Although this may be due in part to the small differences between the characteristics of the patients followed in the different types of units, it seems necessary to improve the network organization of HF care with the aim of achieving greater equity in the treatment of HF in Spain.

Clinical value of multiple sensors contributing to a composite heart failure ICD monitoring index

Abstract Background The HeartLogic algorithm integrates data from various implantable defibrillator (ICD) sensors to predict impending heart failure (HF) decompensation. The algorithm computes worsening in its sensors and weighs them based on a risk level. These sensors include accelerometer-based first (S1) and third (S3) heart sounds, intrathoracic impedance (TI), respiration rate (RR), the ratio of respiration rate to tidal volume (RSBI), and night heart rate (NHR). Objective This study assessed the relative worsening of ICD sensors at the onset of HeartLogic alerts, their association with patient characteristics and subsequent outcomes. Methods The HeartLogic feature was activated in 568 ICD patients (410 with CRT-D) across 26 centers, with a median follow-up of 26 months [25th–75th percentile: 16–37]. Results During the follow-up, 1200 HeartLogic alerts were recorded in 370 patients. The sensor with the highest worsening (SHW) at the alert onset was S3 (27% of alerts), followed by S3/S1 (25%), TI (16%), RR (15%), and NHR (11%), RSBI (6%). Patients with atrial fibrillation (AF) at implantation and those with chronic kidney disease (CKD) had higher alert prevalence (AF 84% vs. no-AF 58%, CKD 72% vs. no-CKD 59%; both p <0.05) and higher alert rates (AF 1.51/patient-year vs. no-AF 0.88/patient-year, CKD 1.30/patient-year vs. no-CKD 0.89/patient-year; both p <0.05). AF patients had alerts with every sensor as SHW, while CKD patients had alerts primarily with TI, RR, and RSBI as SHW (Figure). In 85% of cases among 247 patients with >1 alert, the SHW changed between successive alerts. Of the 88 (7%) alerts resulting in HF hospitalizations or deaths, a greater proportion featured RR or RSBI (11%) and NHR (11%) as SHW, followed by heart sounds (5%) (both p <0.05). Clinical events were more common with the first alert (12.6%) than subsequent alerts (5.2%, p <0.001). Conclusion HeartLogic alerts are predominantly associated with the highest worsening in heart sounds. Nevertheless, recurrent alerts often involve other sensors, suggesting varied HF progression mechanisms and potential divergent outcomes. The frequency of alerts and the pattern of worsening in ICD sensors are linked to patient characteristics.

Extending the window in clinical decision making: the role for Impella 5.5 in cardiogenic shock

Abstract Background Acute decompensated heart failure (HF) refractory to medical management deteriorates quickly to cardiogenic shock, ultimately requiring mechanical circulatory support (MCS). These devices aim to provide circulatory support as a bridge to advanced therapies. We report patient outcomes with the latest minimally invasive temporary MCS device: Impella 5.5 with SmartAssist. Methods All patients who underwent Impella 5.5 implantation between January 2020 and December 2023 were analyzed. Duration of Impella support and peri-implant parameters were collected from electronic medical records. ANOVA was performed and utilized a p-value of <0.05 as significant for statistical analysis. Results During our review period, a total of 99 patients were supported with Impella 5.5 in the setting of cardiogenic shock. 92 were bridged to heart transplant (BTT), of which 17 also received combined kidney transplantation. Two underwent durable VAD implantation (BTVAD), and 3 had native heart recovery (BTR) and explant. Two patients died, yielding a survival rate of 98%. For BTT group, the median age was 60 years (52-65) at implant and a median BMI of 27 kg/m² (24-31) with a mean support duration of 29 days (SD ±24). Baseline GFR was 49 mL/min/1.73m² (35-65). In the BTVAD group, the median BMI was 43 kg/m² (39-46) with an average duration of support of 22 days (SD ±8) with a GFR of 55 mL/min/1.73m² (38-73). The BTR group had a median BMI of 29 kg/m² (27-30) with an average duration of support of 15 days (SD ±7) and a lower baseline GFR of 36 mL/min/1.73m² (26 – 37) compared to BTT or BTVAD. The two patients that died were supported for an average of 42 days (SD ±9.2) and expired due to non-candidacy in the setting of newly detected prostate cancer in one patient and multi-organ failure in another. All BTVAD and BTT patients did not have a stroke or major vascular complications before terminal therapy. Conclusion Our center highlights the role of early Impella 5.5 placement in the stabilization of patients in cardiogenic shock, thereby providing both patients and providers time for decision-making while optimizing end-organ perfusion beyond the accepted duration of 14 days.Impella Data - Entire CohortImpella Data - Stratified by Outcome

Impact of household income on acute decompensated heart failure outcomes: national representative sample

Abstract Background The clinical outcomes of ADHF have been extensively studied; however, the impact of household income still needs to be better understood. This study aimed to elucidate the relationship between household income and outcomes in patients with ADHF. Methods This national retrospective cohort study used data from the 2016-2020 National Inpatient Database, focusing on patients admitted with ADHF. We stratified the cohort into two groups based on the median household income: below $50k and above $86k. The selection criteria included patients aged ≥ 18 years diagnosed with ADHF, excluding those with incomplete income data. The primary outcome was all-cause inpatient mortality, with a length of stay (LOS) and total hospital charges as secondary outcomes. Statistical analysis employed logistic and linear regressions adjusted for confounders, with the significance level set at p<0.05. We accounted for missing data using multiple imputation analyses. Results 1,123,024 patients admitted with ADHF met the inclusion criteria. We divided the groups into two cohorts: low-income (64%, N=718,735) and high-income (36%, N=404,289). No increase in mortality was identified (adjusted aOR: 1.05; p = 0.212). The study revealed that high-income patients had marginally longer average LOS (5.62 days vs. 5.35 days, p < 0.0001) and higher hospital charges ($62,512.46 vs. $49,440.14, p < 0.0001) compared to their low-income counterparts. Low-income patients exhibited a higher prevalence of hypertension and obesity, whereas high-income individuals were more affected by atrial fibrillation and hyperlipidemia (hypertension and obesity, p < 0.0001; atrial fibrillation, p < 0.0001). Conclusion In this national retrospective cohort of patients admitted for ADHF over five years, income did not affect mortality. However, LOS and total charges were affected by the median household income.