Treatment Of Heart Failure Research Articles

A graded association between mobility limitation and prognosis in patients with heart failure

Abstract Background In the era of an aging population worldwide, geriatric conditions have become a high-priority clinical concern in treating heart failure (HF). Although mobility limitation is one of the most common geriatric conditions, no study has quantified the dose-response relationship between the level of mobility limitation and the risk of adverse clinical outcomes in patients with HF. Purpose This study aimed to characterize the association between the level of mobility limitation and prognosis in patients with HF. Methods This study was conducted as a patient-level pooled analysis of data from two prospective multicenter cohort studies. The analysis included consecutive patients hospitalized for HF without any exclusion criteria, with a total of 2103 participants. We categorized the patients into four groups based on their level of mobility limitation: Category I, independent outdoor walking; Category II, independent indoor walking; Category III, indoor walking with assistance; and Category IV, abasia. The primary endpoint was a 2-year composite outcome of re-hospitalization for HF or all-cause mortality after hospital discharge. Results During the 2820.7 person-year follow-up period, 998 patients experienced the composite outcome. The cumulative incidences of the composite outcome for Categories I to IV were 24.9, 47.0, 59.3, and 84.8 per 100 person-years, respectively (Figure). After adjusting for potential confounders, a 1-point increase in the mobility limitation category was associated with a 19% higher risk of the composite outcome (hazard ratio: 1.19; 95% CIs: 1.10–1.29; p<0.001). Conclusions A strong and graded association exists between the level of mobility limitation and prognosis in patients with HF. Even among patients with mobility limitations, the risk of adverse clinical outcomes varies in a dose-response manner depending on the magnitude of mobility limitation. Our findings contribute to a more individualized approach for managing older patients with HF.Figure

Safety and effectiveness of sodium-glucose co-transporter 2 inhibitors in active cancer patients with heart failure: results of the observational TOSCA trial

Abstract Background Sodium-glucose co-transporter 2 inhibitors (SGLT2i) currently represent a pillar of heart failure (HF) treatment. However, cancer patients have not been included in landmark randomized controlled trials (RCTs), and data on safety and effectiveness in this population are lacking. Purpose Purpose of present study was to evaluate safety and effectiveness of SGLT2i in active cancer patients with HF. Methods TOSCA is a multi-centre observational trial including patients (≥ 18 years) with active cancer (diagnosis < 3 years) receiving SGLT2i for HF treatment. Patients were enrolled in two (prospective and retrospective) cohorts. The primary endpoint was safety (incidence of known and unexpected side effects). The secondary endpoint was effectiveness (ejection fraction (EF) increase, New York Heart Association (NYHA) class change, HF-related events). Exploratory endpoints included drug-drug interactions with anticancer and supportive care drugs, treatment of cancer therapy-related cardiac dysfunction (CTRCD), and changes in NT-proBNP. Results Eighty-three pts were enrolled (59 prospective - 24 retrospective). Median age was 71 (range 44-92) yrs, M/F 48/52%. The main cancer sites were breast, gastrointestinal tract, and hematological malignancies. Most cases (62%) received an active treatment (mainly chemotherapy) while on SGLT2i. Prevalent aetiology was drug-induced HF (37%) with reduced EF as the prevalent clinical presentation (39%). Prescribed agents were dapagliflozin in 60% and empagliflozin in 40% of cases on top of conventional guideline-directed medical therapy, with a median treatment duration of 3 (range 3-25) months. The incidence of urinary tract infection was 2.5%. No cases of genital infection, hypoglycemia, diabetic ketoacidosis, acute renal injury, thrombosis, and bone fractures were reported. Mean overall EF slightly increased (44.1% vs. 46.6%), and NYHA class improved (class improvement in 16%). Unplanned cardiology visits (1.2%), i.v. diuretics (1.2%), coronary angiography (5%), emergency access (2.5%), and new HF episodes (3.7%) rates were low. SGLT2i appeared effective in 31 cases of CTRCD. A relative reduction in mean NT-proBNP levels (2748 vs 1125pg/mL) was observed. No drug-drug interactions were reported. Conclusions SGLT2i appear to be safe and effective in active cancer patients with HF, with potential cardioprotective effect. No new safety warnings were recorded.

What does routinely-collected electronic health record data tell us about the use of heart failure medication among older people in Wales? Making progress but could do better

Abstract Background European Society of Cardiology 2021 guidelines recommend 4 pillars of treatment to reduce mortality for those with heart failure (HF) and reduced ejection fraction (HFrEF): pillar 1) angiotensin converting enzyme inhibitor (ACE-I)/angiotensin receptor blocker (ARB)/angiotensin receptor-neprilysin inhibitor (ARNI), pillar 2) beta-blocker (BB), pillar 3) mineralocorticoid receptor antagonist (MRA), pillar 4) sodium-glucose co-transporter 2 inhibitor (SGLT2i). When there is heart failure with preserved ejection fraction (HFpEF), guidelines recommend diuretics to alleviate congestion and treatment of risk factors such as hypertension and diabetes. Prior to 2021, United Kingdom guidelines did not include SGLT2i. Purpose To examine how HF treatment is recorded in routinely-collected electronic health record (EHR) data for older people in Wales, and to explore how that has changed since 2015. Methods We conducted a retrospective, population-level, observational study using linked anonymised EHR data in Wales (2015-22). 737,230 individuals were aged 65y+ in the study period (21.5% of population in 2022). Of these, 65,010 had a code for heart failure in their primary or secondary care records. We excluded 13,990 individuals with fewer than 12 months data pre- or post-diagnosis. We looked forward, from HF diagnosis, for codes associated with specific medications. Results The final cohort comprised 51,020 individuals aged 65y and over with a diagnosis of heart failure between 2015-2022. Incidence and prevalence of heart failure increased across the study period (1.4-1.5% and 8.5-9.1% respectively). Preceding cardiovascular diagnoses included hypertension (69.5%), atrial fibrillation (36.7%), myocardial infarction (30.5%), coronary artery disease (25.7%), and valve disease (17.7%). Diabetes (41.7%), chronic kidney disease (30.9%) and cancer (26.4%) were the most common comorbidities. The subtype of HF (HFrEF or HFpEF) was only evident in 5,850. Treatments recorded most often were loop diuretics, ACE-I, and BB (Table 1). SGLT2i codes increased in 2020/2021(Figure 1). At 10-12 months post diagnosis, the proportion with simultaneous pillar combinations was; 27.4% 1 + 2, 12.5% 1, 2 + 3, and only 2% 1, 2, 3 + 4. Conclusions In Wales, there is a need to improve the coding of HF subtype in primary care records. We suggest interpreting data with the assumption that approximately half of the cohort are likely to have HFrEF. While the cohort proportion on ACE-I or beta-blockers may be appropriate, the proportion with more than 1 simultaneous pillar of treatment recorded appears low. The use of SGLT2i in codes is increasing. These results are important in evaluating health service delivery and in establishing baseline data from which to monitor improvements.

Modern heart failure treatment is superior to conventional treatment across the left ventricular ejection spectrum: Real-life data from the Swedish Heart Failure Registry 2013-2020

Abstract Background Heart failure (HF) is a clinical syndrome characterized by high mortality and morbidity. In 2016, Sacubitril/valsartan, an angiotensin receptor-neprilysin inhibitor (ARNI), was recommended as a new treatment option for HF in patients with HFrEF. In the 2021 European Society of Cardiology guidelines for treatment of HFrEF patients Sodium-glucose cotransporter 2 inhibitors (SGLT2i) were introduced because they demonstrated significantly reduced HF events or cardiovascular (CV) mortality. Since ARNI and SGLT2i were introduced to treat HF, its therapeutic regimen has modernized from previous treatment with beta-blocker (BB) and angiotensin-converting enzyme inhibitor (ACEi)/angiotensin II receptor blocker (ARB) with mineralocorticoid receptor antagonist (MRA) as added-on in HF with reduced ejection fraction (HFrEF). Purpose This study is aimed to compare effectiveness of modern therapy including ARNI and SGLT2i with conventional heart failure treatment. Conventional HF treatment includes (BB, ACEi/ARB, with or without MRA) and modern heart failure treatment (BB, ACEi/ARB, MRA, SGLT2i or BB, ARNI, MRA with/without SGLT2i) in real-world. Methods This observational study (2013-2020), using the Swedish HF Registry, involved 20,849 HF patients. Patients received either conventional (BB, ACEi/ARB, with/without MRA, n=20,140) or modern (BB, ACEi/ARB, MRA, SGLT2i or BB, ARNI, MRA with/without SGLT2i, n=709) treatment at the index visit. The endpoints were all-cause and cardiovascular (CV) mortality. Results Modern HF therapy was associated with a significant 28% reduction in all-cause mortality compared to conventional HF treatment (adjusted HR [aHR]: 0.72 (95% CI 0.54 - 0.96), p=0.024), and had 33% reduced all-cause mortality (aHR: 0.67 (95% CI 0.48 - 0.94), p=0.019) within 2 years of index registration. Similarly, modern HF therapy was associated with a significant 62% reduction in CV mortality compared to conventional HF treatment (aHR: 0.38 (95% CI 0.21 - 0.68), p=0.0013). In addition, we found a 58% reduced CV mortality (aHR 0.42 (95% CI 0.22 - 0.79), p=0.0067) within 2 years of index registration. In the propensity score 1:1 matched cohort in which ARNI was included in the matching procedure, i.e., no ARNI was used in any of the two treatment groups and the effect of SGLT2i was the target assessment. The results were associated with a statistically significant risk reduction of 42% in all-cause mortality in the modern HF treatment group compared to the conventional treatment group (aHR: 0.58 (95% CI 0.36 - 0.94), p=0.028), and a 49% (aHR: 0.51 (95% CI 0.29 - 0.89), p=0.018) risk reduction within 2 years of index registration. Conclusion This study demonstrates that modern HF therapy in a real-world Swedish HF population is associated with a statistically significant risk reduction in all-cause and CV mortality, regardless of EF, sex, age, eGFR, and etiology of HF compared to conventional HF therapy.Central Illustration

Stress memory of heart failure in hematopoietic niche promotes recurrence via adipocytic skewing of mesenchymal stromal cells

Abstract Background Heart failure (HF) is marked by recurrent acute decompensations, which poses significant treatment challenges in advanced stages. Our preceding work demonstrated that hematopoietic stem cells (HSCs) from HF-experienced mice induce cardiac fibrosis and dysfunction when transplanted, as a result of epigenetic alterations favoring myeloid hematopoiesis and impeding the differentiation of monocytes into cardiac mature macrophages. These findings hint at epigenetic modifications in HSCs as potential drivers of HF recurrence, suggesting their manipulation as a novel therapeutic strategy. However, the exact mechanisms by which HF-associated stress leads to these epigenetic changes remain unclear. Given the crucial role of bone marrow mesenchymal stromal cells (MSCs) in maintaining HSC stemness, this study explores the impact of cardiac stress on MSC function and its subsequent effect on HSCs. Purpose This study aims to elucidate the mechanisms behind the phenotypic changes in HSCs and to identify novel therapeutic targets to mitigate HF recurrence by investigating the role of MSCs in the hematopoietic niche under cardiac stress. Methods & Results Initially, we examined MSC phenotypic changes during HF using bulk and single-cell RNA sequencing. Results from transverse aortic constriction (TAC) model mice revealed a shift towards adipocyte differentiation under cardiac stress. Histological analyses confirmed an increase in adipocytes in TAC mice compared to controls, suggesting a stress-induced predisposition of MSCs towards adipocytic lineage commitment. This trend was further supported by ex vivo models using MSCs isolated from TAC mice. Notably, the proportion of adipocyte lineage-specific MSCs correlated with cardiac dysfunction severity. Subsequently, we assessed the impact of HF-conditioned MSCs on HF development by transplanting healthy HSCs with MSCs from control or TAC mice. Mice receiving HF-conditioned MSCs developed HF, evidenced by reduced ejection fraction and cardiac fibrosis. In these mice, a notable increase in HSC proliferation and a relative increase of myeloid cells within the peripheral blood were observed, along with an increase in proinflammatory cardiac macrophages. These findings suggest HF induces a "stress memory" in bone marrow MSCs. To test the potential of inhibiting adipocyte differentiation of MSCs in erasing this stress memory, we administered MSC phenotype-modulating agents to TAC mice, resulting in improved cardiac function and the disappearance of adipocytes from the bone marrow. Conclusions This study sheds light on how cardiac stress affects the bone marrow niche, leading to adipocytic skewing of MSCs and subsequent alterations in HSCs, thereby exacerbating cardiac dysfunction. The potential of targeting bone marrow niche components in HF treatment is highlighted.

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.

Effects of sodium-glucose cotransporter 2 inhibitors on pulmonary hemodynamics in chronic heart failure patients with a pulmonary artery pressure sensor

Abstract Background Approximately 50% of patients with chronic heart failure (HF), either with preserved or reduced left ventricular ejection fraction (LVEF), have secondary pulmonary hypertension, which results in poorer prognosis. In previous studies, sodium-glucose cotransporter 2 inhibitors (SGLT2i) have shown a reduction in cardiovascular death, HF hospitalization and pulmonary artery pressure (PAP) in patients with HF, regardless of LVEF, but exact mechanisms remain unclear. Purpose The main objective of this study is to analyse effects of SGLT2i on PAP in patients with chronic HF followed by a PAP sensor (CardioMEMS HF system). The secondary objective is to analyse effects in subgroups of LVEF. Methods We included chronic HF patients (regardless of LVEF) with previously implanted a PAP sensor, from July 2019 to February 2023. SGLT2i had been added in fourth position in patients with reduced LVEF, since they were previously on optimal HF treatment as chronic patients. Changes in PAP, renal function and N-terminal pro B-type natriuretic peptide (NTproBNP) were compared between two periods of time: "30 days before" and "30 days after" SGLT2i initiation. Patients were then classified in two groups: group 1 (LVEF ≤40%) and group 2 (LVEF >40%) and repeated same analyses. Results Overall, 61 patients were screened, and 17 finally were included, mean age 71.7 ± 9.6 years, 64.7% were men, mean LVEF was 49.4 ± 17.5%, 23.5% had ischaemic aetiology and 64.7% were in NYHA class III (Table 1). There were more men in group 1 than in group 2 (p=0.043), without other differences in basal characteristics between groups (Table 1). Dapagliflozin (10mg daily) was initiated in 14 patients (82.4%), 5 from group 1 and 9 from group 2 (p=1.000), and empagliflozin (10mg daily) in 3 patients (17.6%), 1 from group 1 and 2 from group 2 (p=1.000). Before SGLT2i, mean diastolic PAP (dPAP) was 17.3 ± 5.6 mmHg and median NTproBNP was 2841.5 (289-10515) pg/mL. SGLT2i significantly reduced dPAP; average dPAP ("30 days after" period) was 1.5 mmHg lower (95% CI, 0.26-2.74; p=0.021) compared to "30 days before" period (Figure 1). SGLT2i also reduced systolic PAP (-2.2 mmHg), mean PAP (-1.7 mmHg), NTproBNP (-183 pg/mL) and creatinine (-0.2 mg/dL), but not statistically significant. SGLT2i reduced PAP, NTproBNP and creatinine too in group 1 (6 patients), but did not achieve statistical significance. Reductions were as well observed in group 2 (11 patients), and SGLT2i significantly reduced dPAP (-2.04 mmHg) (95% CI, 0.31-3.77; p=0.025). Conclusions In patients with chronic HF and a PAP sensor, SGLT2i, added to previous HF treatment, significantly reduced dPAP. PAP reductions were observed regardless LVEF, but results were more robust in patients with LVEF >40%.Figure 1

National trends of left ventricular assist device therapy in Germany

Abstract Background The prevalence of advanced heart failure (HF) is increasing and prognosis remains poor. Although heart transplantation is still considered to be the gold standard for the treatment of advanced HF in selected patients, its use is limited by organ donor shortage and a growing burden of cormorbidities among potential recipients. The 2021 European Society of Cardiology (ESC) guidelines recommend consideration of long-term mechanical circulatory support with a left ventricular assist device (LVAD) in eligible patients with advanced heart failure (HF) who are refractory to medical/device therapy. Purpose The purpose of this study was to evaluate the national trends of LVAD in Germany. The main hypothesis was that LVAD therapy is still underutilized. Methods From the national database of the German Federal Statistical Office (DESTATIS), we identified all patients who underwent LVAD implantation in Germany between January 2011 and December 2022 (n = 9,232). We compared temporal trends and in-hospital outcomes. Results From 2011 to 2022, number of LVAD implantation was highest in the year 2017 (n = 914) and steadily decreased over the following years (2022: n = 617). Mean age of LVAD recipients was 56.2 years (2011-2015) and increased to 58.4 years (2020-2022). The majority of LVAD recipients are male (84,8 %), and this trend has been stable during the entire time period. In-hospital mortality after LVAD remains high, but has been decreasing (25.8% during 2011-2015 compared to 20.2% during 2020-2022). Conclusion Although LVAD is recommended in eligible patients with advanced HF, our study suggests an underutilization of LVAD in this patient population and especially in female patients.

Survival and predictors of mortality in patients with heart failure in the cardiology department of the Center Hospitalier Basse Terre in Guadeloupe: historical cohort study

BackgroundDespite the progress made in recent years in the treatment of Acute Heart Failure (AHF), its prognosis remains poor in the developing country. The objective of this study is to analyze the survival and predictors of mortality of patients with acute heart failure in the cardiology department of the Basse Terre Hospital Center in Guadeloupe.Methodsthis was a historical cohort study carried out over a period from June 2021 to June 2022, targeting all acute heart failure patients undergoing cardiac monitoring in the cardiology department of the Basse Terre Hospital Center in Guadeloupe. Sociodemographic, clinical, biological characteristics and outcome (recovery or death) were studied. Survival was described using the Kaplan Meier method α = 5%.Resultsthis study involved 242 acute heart failure patients whose median age was 75 years and the majority were male (sex ratio 2 M/1F). Among these patients, 14.9% died, the most common cause of death was cardiogenic shock (52.8%). After adjustment, tobacco consumption (aHR: 2.90; 95% CI: 1.36–8.09), Chronic Kidney Disease (aHR: 2.52; 95% CI: 1.22–5.20), infection (aHR: 2.14; 95CI %: 1.99–4.58), hyponatremia (aHR: 1.90; 95% CI: 1.10–2.86), mitral regurgitation (aHR: 3.04; 95% CI: 1.98–9.47) and N-terminal pro Brain Natriuretic Peptide > 10000ng/ml (aHR: 2.57; 95% CI: 1.21–5.49) were independently associated with the risk of death in heart failure patients.ConclusionAcute heart failure leads to high mortality, mainly due to cardiogenic shock and factors of multiple organ failure.

Prognostic impact of mitral valve geometry in patients with secondary mitral regurgitation: a secondary analysis of the MITRA-FR trial

Abstract Background Mitral valve (MV) transcatheter edge-to-edge repair (TEER) has emerged as a second line therapy on top of guidelines-directed medical treatment (GDMT) in heart failure (HF) patients with severe secondary mitral regurgitation (SMR). Following the disparate results of the COAPT and MITRA-FR pivotal trials, echocardiographic markers of LV remodeling and MR severity have been proposed to select patients most likely to benefit from MV-TEER. The characterization of MV geometry arises as a potential tool to stratify risk of outcomes in SMR patients, who underwent classical surgery or MV-TEER intervention. However, it remains unknown whether MV geometry parameters were associated with prognosis in MITRA-FR patients and whether MV-TEER could modulate their impact on outcomes. Purpose To evaluate the association between MV geometry and outcomes of HF patients with SMR in the MITRA-FR trial, as well as the impact of SMR treatment modality. Methods Thirteen MV geometry parameters were assessed from baseline transthoracic echocardiograms in patients from the MITRA-FR trial. The prognostic impact of MV geometry parameters was studied on top of the baseline clinical variables used in the primary analysis of MITRA-FR (i.e. age, atrial fibrillation [AF], ischemic cardiomyopathy, myocardial infarction, left ventricular ejection fraction [LVEF] and effective regurgitant orifice area [EROA]). The primary endpoint was the composite of all-cause mortality or HF hospitalization (HFH) within 2 years. The effect of treatment arms (MV-TEER plus GDMT vs. GDMT alone) on this association was also evaluated. Results Among the 307 patients included in the pivotal trial, 272 were analyzed in the present study (i.e. 135 from the GDMT group and 137 from the GDMT + MV-TEER group). Mean age was 70±10, 74% male. 50% had ischemic cardiomyopathy and 34% AF. LVEF was 33±7% and EROA was 31±11 mm². MV geometry parameters were presented for the whole population and according to the randomization group in the Table. Among these parameters, only MV tenting area remained independently associated with the primary endpoint (Hazard Ratio (HR) = 1.22 per 1 cm², Confidence Interval (CI) = 1.01-1.47; p=0.041) after multivariate analysis (Figure). Tenting height was independently associated with the risk of HFH (HR=1.07 per 1 mm, CI=1.00-1.14, p=0.037), but no MV geometry variable was associated with all-cause death. These findings remained consistent in both treatment arms (p>0.20 for interaction). Conclusion In HF patients with SMR included in the MITRA-FR trial, MV tenting area and MV tenting height were independently associated with the risk of HFH or all-cause mortality and HFH respectively, without any difference according to treatment arms. These data suggest that MV tethering provides an incremental prognostic value beyond classical echocardiographic variables, including EROA, and then should be considered in the risk stratification of patients with HF and SMR.Table of MV geometry parameters featuresMultivariate analysis (Forrest-plots)

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.

Impact of mitral transcatheter edge-to-edge repair in patients with advanced heart failure evaluated for heart transplantation

Abstract Background Heart transplantation is sometimes the only therapeutic option in patients with advanced heart failure (HF), impaired ventricular function and significant functional or secondary mitral regurgitation (MR). The shortage of organs and the limitations of the recipient make it necessary to consider other therapeutic alternatives in these patients, such as mitral transcatheter edge-to-edge repair (M-TEER). The MitraBridge registry has recently been published in which they analyze the potential effect of M-TEER in patients with advanced HF and moderate-severe MI who are candidates for heart transplantation (mean age 59 years, left ventricular ejection fraction (LVEF) 27%); after a mean follow-up of 24 months, complete in 82.4%, they report an overall survival of 78.5%, a combined event-free survival of 47%, with a 6.5 % need for urgent transplantation and an HF hospitalization rate after M-TEER of 44/100 patient-years. The aim of our study is to assess the impact of M-TEER on mortality and the combined events of death, HF rehospitalization and the need for urgent transplantation or a ventricular assistance device in patients with moderate-severe functional MI and advanced HF who have also been evaluated for cardiac transplantation in our hospital. Methods This is a retrospective analysis of a prospective registry. Of the patients treated by M-TEER for severe MI, we selected those with advanced HF (defined as LVEF≤35%, and/or advanced functional class (NYHA III-IV)) who had also been evaluated as possible candidates for inclusion in the heart transplant list. Results From November 2011 to December 2023, 191 patients were treated by M-TEER, of whom 38 patients met the established criteria (median age 59 years [48-65], 31 (81%) males, mean LVEF was 26 ± 6%). All patients had at least one previous hospitalization for HF and optimal medical treatment according to guidelines; the rest of the baseline clinical characteristics are listed in Table 1. During the follow-up after M-TEER, with a median of 34 months [7-70], the probability of overall survival at 2 years was 75.6%. The combined endpoint of death, need for urgent transplantation or a ventricular assist device, and rehospitalization for heart failure occurred in 26 patients with a 2-year event-free survival probability of 48% (Figure 1). Five patients (13%) were transplanted, one (2.6%) urgently. Prior to M-TEER therapy, the rate of HF hospitalization was 108 hospitalizations/100 patient-years, which was significantly reduced after the procedure to 33 hospitalizations/100 patient-years (rate ratio 0.31 [95% CI 0.21-0.45, p<0.0005]). Conclusions In patients with advanced HF and severe functional MR who are candidates for cardiac transplantation, M-TEER is an effective therapeutic alternative, achieving a survival rate of more than three-quarters of the patients at 2 years of follow-up, a significant reduction in HF hospitalizations, and a low rate of need for cardiac transplantation.

Vericiguat in heart failure patients: analyzing safety, tolerability, and quality of life via meta-analysis of randomized controlled trials

Abstract Background Heart failure (HF) poses a significant burden on global healthcare systems, necessitating effective therapeutic interventions. Vericiguat, a novel agent targeting soluble guanylate cyclase, has emerged as a potential treatment for HF. Purpose To understand its impact on patient outcomes, including safety, tolerability, and quality of life (QoL). Methods A comprehensive meta-analysis was conducted, encompassing four randomized controlled trials (RCTs) identified through Cochrane CENTRAL, Ovid Medline R, Pubmed, and Web of Science databases up to December 1, 2023. The primary efficacy outcome, Kansas City Cardiomyopathy Questionnaire (KCCQ) Overall Summary Score (OSS), and the primary safety outcome, drug-related serious adverse events (AEs), were analyzed. Pooled mean differences (MD) and risk ratios (RR) were calculated using inverse variance common-effect model. Results The meta-analysis encompassed 5947 patients across the four RCTs. Our findings indicated that vericiguat did not demonstrate a significant beneficial effect on KCCQ-OSS (MD -0.13, 95% CI -1.32 to 1.05), suggesting no substantial impact on overall QoL, despite a statistically significant improvement in the KCCQ-Physical Limitation Score (PLS) (MD 3.74, 95% CI 0.24 to 7.24) compared to placebo. Notably, vericiguat exhibited a favorable safety and tolerability profile, with comparable risk for AEs leading to death (RR 1.32, 95%CI, 0.58 to 3.03), withdrawal due to AEs (RR 1.08, 95% CI 0.88 to 1.32) or serious AEs (RR 1,18, 95%CI, 0,50; 2,80), renal and urinary disorders (RR 0.99, 95% CI 0.88 to 1.11), symptomatic hypotension (RR 1.17, 95% CI 0.98 to 1.40), and acute kidney injury (RR 1.04, 95% CI 0.83 to 1.31) compared to placebo. Conclusion Vericiguat demonstrates promising safety and tolerability profiles in patients with HF. While our analysis reveals significant improvement in KCCQ-PLS, indicating enhanced physical limitation scores, the lack of statistically significant impact on overall QoL raises questions about its comprehensive efficacy. These findings underscore the need for further research to elucidate the holistic impact of vericiguat on patient-reported outcomes in heart failure management.Forest plot of quality of life outcomesForest plot of safety outcomes

Beyond telehealth in heart failure, how a nurse-led mobile team unit improves management and reduces re-admission in elderly patients living in a rural area

Abstract Introduction Telehealth plays a crucial role in improving access to healthcare for elderly patients with heart failure (HF), particularly those who live in under-resourced geographic areas, have physical disabilities, or have difficulties with transportation. However, extending and improving telehealth faces significant obstacles, primarily due to its inadequacy to fully assess a patient's clinical status. While some components of HF can be measured remotely, others, such as cardiac and lung examinations, require in-person clinical evaluation. This leads to imprecise assessments of HF severity, excessive medical consultations, and inappropriate emergency transfers or hospitalization. We conducted an evaluation of a specialized mobile team unit (MTU) for HF care in a rural area. The team consisted of nurses trained in performing electrocardiograms (ECGs) and point-of-care ultrasound (POCUS) to extend telemonitoring services to elderly patients with HF in the comfort of their homes. This approach offers a direct and optimal evaluation of the patient's condition. Purpose This study aimed to evaluate the added value of an MTU in assessing and optimizing treatment for HF in elderly patients, ultimately leading to decreased hospitalization or medical request rates. Materials and methods This retrospective analysis examined data from elderly patients diagnosed with HF, who participated in a 6-month telemonitoring program, and received MTU visits. MTU was activated by the telemonitoring team, in patients presenting signs of decompensation, with an imprecise assessment of severity based on digital data only. Results During six months, 165 elderly patients were included in the telemonitoring platform after index HF hospitalization. The mobile team traveled over 3,040 kilometers in a rural area with limited cardiological care. They visited 84 patients (50.9%), offering personalized education and physical assessments to all of the patients, 45% received additional imaging (EKG, POCUS). This resulted in 30% therapeutic adjustments, 90% fewer General practitioner (GP) /Cardiologist consultations and 54% avoided readmissions: 20% of hospitalizations were avoided immediately and 34% likely avoided in the near future, demonstrating the intervention's 80% effectiveness. Conclusion Monitoring heart failure (HF) in elderly patients can be challenging, especially in rural areas with limited access to care, few caregivers, cognitive impairments, or difficulty using e-health platforms. This study emphasizes the benefits of a nurse-led mobile team unit in providing a reliable direct assessment of HF severity. This home intervention provides education, strengthens the decision-making capacity of the remote monitoring platform, assists with patient management, and significantly reduces the readmission rate.

Impact on healthcare costs of adding telemedicine to a multidisciplinary disease management program for heart failure: a sub-analysis of the iCOR trial

Abstract Background Impact of telemedicine on heart failure outcomes has shown conflicting results. Little is known about the effect of these programs on mid-term healthcare costs. Purpose To evaluate the cost-efficacy of a comprehensive telemonitoring program within the vulnerable post-discharge period after an acute heart failure admission. Methods The insuficiència cardiaca Optimizació Remota (iCOR) trial was a single-centre, randomized, open-label study designed to evaluate the efficacy of the addition of telemonitoring and teleintervention to a specialized multidisciplinary nurse-led heart failure (HF) program. Adult patients with a recent hospital admission for acute HF and an acceptable social support and cognitive ability were recruited. This sub-analysis evaluates the effect of telemedicine on mid-term healthcare costs, including clinical events, drugs and devices, technology purchase and maintenance, outpatient care, days of hospitalization, procedures and complementary tests. t-test via bootstrap estimation is used to compare differences between the telemedicine (TM) and the usual care (UC) groups. Results 81 patients were assigned to the TM group and 97 patients to the UC group. Mean age was 74 years, more than 50% had HF with preserved ejection fraction and 25% were frail. Baseline characteristics were well-balanced between groups. Among the TM subgroup, adherence was very high (< 1% of missed biometric daily transmissions). During 6 months of follow-up, mean total healthcare cost per patient was 7949 euros (€) in the UC cohort and 4383 € in the TM cohort (relative risk reduction [RRR] of 45%; between-group differences 3546 €, 95% confidence interval 627-6464 €, bootstrap achieved significance level 0.022). This result was consistent across several subgroups (age, sex, frailty, left ventricular ejection fraction, educational level) and mainly driven by a 63% RRR in costs of hospitalization (which accounted for two-thirds of the total costs) in the TM cohort. 20 patients required HF admissions in the TM group, compared to 51 patients in the TM group (p < 0.001). This was associated with a 59% RRR in the need for diagnostic procedures. Total number of days of hospitalization per patient decreased from 12.2 in the UC group to 4.2 days in the TM group (p = 0.003), impelled by a reduction in HF and cardiovascular days of hospital stay. On the contrary, ambulatory care costs increase two-fold in the TM group compared to UC group. Nevertheless, these costs only accounted for a 19% of the total costs. Cost of devices needed to implement TM supposed 698 € per patient. Use of TM was associated with a 355 € increase in the cost of ambulatory neurohormonal treatment for HF. Conclusions TM implementation during the vulnerable phase after an acute HF admission was associated to a 45% RR reduction in mean total healthcare cost per patient. This result was driven by an almost two-thirds decrease in costs of hospitalization.UC and TM total healthcare costs

Associations between cardiac rehabilitation and clinical outcomes in patients with heart failure and cognitive frailty

Abstract Introduction Patients with heart failure (HF) often contend with various comorbidities, including cognitive impairment. Cognitive impairment has been increasingly recognised as cognitive frailty, which is reportedly associated with poor outcomes. On the other hand, cardiac rehabilitation (CR) for HF contributes to improved clinical outcomes. However, very few reports have examined whether CR is effective in patients with HF who have cognitive frailty. Purpose The present study aimed to investigate whether CR is associated with clinical outcomes in patients with HF, even in the presence of cognitive frailty. Methods This observational study analysed 1404 consecutive patients who admitted to a university hospital for the treatment of HF and received CR during hospitalisation. Patients who had dementia, did not perform the cognitive function evaluation, or died during hospitalisation were excluded from this study. All patients were encouraged to continue outpatient CR after hospital discharge. Cognitive function was assessed using the Mini-Cog© and a score ≤2 points was defined as the cognitive frailty. As physical function, quadriceps isometric strength (QIS) and 6-min walking distance (6MWD) were measured at the discharge and at the end of outpatient CR. The primary outcome was composite events, comprising all-cause death and re-admission due to HF. The secondary outcome was the change in physical function (ΔQIS and Δ6MWD) following outpatient CR. The association between participation in outpatient CR and composite events was assessed using the multivariate Cox proportional hazard models. We also compared the physical function changes between the presence or absence of cognitive frailty using analysis of covariance. Results The median age of the patients was 75 (interquartile range [IQR]: 66–81) years and 62.3% were males. Among them, 23.4% were identified as cognitive frailty. While 45.1% of overall population participated in outpatient CR, the cognitive frailty was relevant to a lower participation rate (P <0.001). Over a median follow-up period of 1.0 years (IQR: 0.3–2.4 years), a total of 544 composite events occurred. Participation in outpatient CR was associated with a reduced incidence of composite events in both the cognitive frailty and non-cognitive frailty, as well as in the overall patient population (Figure 1). Additionally, ΔQIS and Δ6MWD did not significantly differ between the cognitive frailty status (P = 0.655 and 0.573, respectively). Conclusions Participating in outpatient CR was linked to reduced rates of composite events and improved physical function in patients with HF, regardless of the presence or absence of cognitive frailty. Encouraging active participation in outpatient CR, even among patients with cognitive frailty, is essential as it is associated with favourable clinical outcomes.Survival analysisANCOVA

Transcatheter valve replacement as rescue treatment for heart failure in infective endocarditis. A multinational series.

Abstract Background Transcatheter valve replacement (TVR) could be a therapeutic alternative for refractory heart failure in patients with infective endocarditis (IE) unsuitable for open surgery. However, evidence of tis use in this scenario is limited to isolated case reports. Purpose We aimed to describe the clinical characteristics and outcome of IE patients in whom a TVR was performed during the active phase of infection in a multinational case series. Methods This retrospective study was conducted in 23 referral hospitals for IE and TVR procedure in 8 countries. All consecutive adult patients (≥18 y) with definite IE in whom a TVR was performed during antimicrobial treatment of within the 3 three months after its withdrawal were included. The inclusion period was between July 2011 and July 2023. Baseline, IE-related, TVR-related, outcome and follow-up (min. 3 months) variables were collected. Results Forty-five patients [median age 74 years (IQR 64 – 82), 35 males (78%), median Charlson comorbidity index 6 (4 – 7) points] were included in the study: 42 aortic TVR, 2 mitral TVR and 1 tricuspid TVR. In 20 patients (44%) TVR was performed on a native valve and in 25 on a prosthetic valve. The most frequent microorganisms causing IE were streptococci (n=16, 36%), staphylococci (n=13, 29%) and enterococci (n=5, 11%). Acute heart failure was present in 41 (91%). Of them, 23 (51%) developed acute pulmonary oedema or cardiogenic shock. The main reasons for excluding open surgery were: high surgical risk [n=39, 87%; median EuroSCORE 17 (9 – 28)] and technical impossibility (n=3, 7%). TVR was performed during antimicrobial treatment in 27 cases (60%) [median 25 (13 – 54) days after initiation] and within the first three months after its completion in 18 (40%) [median 25 (17 – 68) days after discontinuation]. Four patients (9%) died during admission. Over a median follow-up of 10 (6 -30) months, 7/41 patients (17%) died and there were 2/41 (5%) relapses, one of which required open valve replacement surgery 17 days after TVR procedure. Two other patients underwent open surgery due to paravalvular leaks (11 and 44 days after TVR). All cases of relapse and open surgery occurred when TVR was performed during antibiotic treatment. Conclusion TVR could be an option as rescue treatment for heart failure in selected IE patients unsuitable for open surgery. This represents a paradigm shift in the management of IE and may change the natural history of the disease in patients who would otherwise die.

Nicorandil activates lkb1-ampk signaling pathway to ameliorate cardiac remodeling after myocardial ischemia/reperfusion injury by upregulating mt2

Abstract Background Cardiomyocyte apoptosis is a crucial event underlying the development of cardiac abnormalities and dysfunction after myocardial ischemia reperfusion (MI/R) injury. A better understanding of the cell signaling pathways involved in cardiac remodeling may support the development of new therapeutic strategies for the treatment of heart failure (HF) after MI/R. Nicorandil, an ATP-sensitive potassium channel opener, could improve mitochondrial damage and reduce oxidative stress，which reduce cardiomyocyte apoptosis. Metallothionein (Mt), reactive oxygen species (ROS) scavenger, which can reduce oxidative stress, also attenuated MI/R-induced autophagy and cell apoptosis. Except as a potassium channel opener, nicorandil may play a cardioprotective role by regulating metallothionein, and its specific mechanism remains to be elucidated. Objective To clarify the protective effect of nicorandil in myocardial ischemia/reperfusion injury, and elucidate the specific mechanism which nicorandil regulate the expression of metallothiosin to reduce myocardial ischemia/reperfusion injury, so as to provide new drug targets or new measures for clinical prevention and treatment of MI/R. Methods A cardiac MI/R injury model was constructed by the ligation of the left anterior descending coronary artery to investigate the underlying molecular mechanisms. The apoptosis of myocardial tissue cells was detected by TUNEL staining. The ultrastructural changes of myocardial tissue were observed by transmission electron microscopy. The expressions of Mt family, mitochondrial dynamics and Glucose metabolism-associated genes were measured by Western blotting and qPCR. The content of ATP was determined by ELISA in heart tissue. AutodockVina was used to evaluate binding energy and interaction patterns between drug candidates and their targets. The protein-protein interaction model was predicted by ZDOCK software. Results Treatment with nicorandil mitigated left ventricular enlargement, improved cardiac dysfunction,reduced myocardial infarcation area and decreased cardiomyocyte apoptosis after I/R. Nicorandil up-regulated the expression of Mt2 and decreased the expressions of Drp-1,p-Drp-1(ser616), while enhanced the expression of Mfn1/2,GLUT4,HK II and MPC II in myocardium. Knockdown of Mt2 decreased the effects of nicorandil on apoptosis and mitochondrial dysfunction after I/R. Mechanistically, nicorandil significantly upregulated the expression of Mt2, which could bound to LKB1 and cause phosphorylation of LKB1, resulting in AMPK-dependent activation. Conclusions Nicorandil significantly upregulated the expression of Mt2, which interacted with LKB1 to promote LKB1 protein phosphorylation, resulting in AMPK-dependent activation and subsequently alleviating I/R-induced mitochondrial dysfunction and energy metabolism disorder, and thereby reducing cardiomyocyte apoptosis, eventually improving I/ R-induced cardiac remodeling and dysfunction.

KardioNet Digital - a structured care model involving digital tools for intersectoral communication and a patient-focused strategy for treatment of heart failure

Abstract Introduction Inefficiencies and discontinuities in care at the interfaces within Germany's healthcare system, especially between acute and outpatient care, present significant challenges in managing patients with heart failure (HF). The management complexity of HF has increased with the advent of new digital tools, though patient acceptance of these tools remains contentious. The prevention of loss of diagnostic and therapeutic information for this complex disease is crucial for cross-sectoral communication (hospital - office-based cardiologist - general practitioner) and quality of care. Purpose Our goal was to examine the impact of digital app-supported coordination of HF management across different healthcare providers from hospital discharge to the ambulatory sector and to assess patients' acceptance of a structured care program. A patient-focused digital strategy, supported by a Heart Failure Nurse (HFN), aimed to facilitate structured follow-up and patient empowerment, focusing on patient-reported outcomes and experiences (refer to Table 1). Results Out of 401 patients screened during their hospital stay for HF, only 57 (14.9% male, 12.6% female) participated in the KardioNet Digital (KND) program. NYHA classifications were I (3.5%), II (49.1%), III (40.4%), and IV (7.1%); Diagnoses included CMP (26, 45.6%), CAD (19, 33.3%), valvular HF (8, 14.0%), and others (4, 7.0%). The mean age was 55.03 years, with a notable difference in participation based on age (≥70 years: 9.5% male, 33.3% female; <70 years: 90.5% male, 66.7% female). Age was a significant determinant of program participation. Patients who regularly used the app benefited from several features: A total of 35 alerts (17 patients) were triggered for reasons such as bodyweight increase (2kg or more) and device-induced alerts (i.e. false shock delivery, 3x slow-VT, Syncope), leading the HFN to contact the patients. This early intervention prevented rehospitalization due to decompensation of heart failure in 11 patients (64.7%) and addressed device-related alarms for organizing an emergency hospital visit by HFN. Despite substantial incentives, such as support from an HFN and expedited appointments with specialists for follow-up therapy, refusal rates were high (refer to Table 2). Conclusion A structured, digitally supported cross-sectoral care model for heart failure patients can potentially improve care coordination and outcomes. However, the success of such programs critically depends on patient willingness and the seamless integration into existing healthcare structures. Despite valuable incentives, we observed low acceptance of the program. Even among motivated participants (14.1%), there is a significant need for substantial support and education on digital literacy for the widespread implementation of digital tools in real-world settings for the treatment of heart failure.Workflow of structured digital supportReasons for Declining Participation

Survival benefit of guideline-directed medical therapy in elderly patients with heart failure with reduced ejection fraction: a systematic review and meta-analysis

Abstract Background Heart failure is a major cause of mortality in the elderly and heart failure-related mortality in elderly patients has increased since 2012. The evidence of guideline-directed medical therapy (GDMT), the four pillars of treatment of heart failure with reduced ejection fraction (HFrEF), remains insufficient in this population. Aim The objective of this study was to assess the survival benefit of the four pillars of GDMT in elderly patients aged ≥ 65-years-old with HFrEF. Methods MEDLINE, EMBASE and the Cochrane Library were searched from inception to 21 July 2023. The inclusion criteria were studies comparing survival between patients ≥ 65-years-old with left ventricular systolic dysfunction receiving and not receiving GDMT. Pooled prevalence, hazard ratio (HR) and risk ratio (RR) were calculated with 95% confidence interval (CI). Heterogeneity was explored through subgroup analyses based on the number of GDMT, age cut-off, sample size, ejection fraction cut-off, study type and study publication date. Results Thirty studies with 86,941 patients from 1994 to 2019 were included. The GDMT group received three drug classes in three studies, two drug classes in four studies, and at least one class in the remaining studies. There were no reported studies on elderly patients receiving four classes of GDMT. Over 5% of the elderly HFrEF patients were frail (Pooled prevelance 7%, 95%CI 2.0–14.0, I2 98%). Frail elderly patients were less likely to receive GDMT (RR 0.63, 95%CI 0.45–0.89, I2 50%, p = 0.009). There was a survival benefit of GDMT in elderly patients with HFrEF (HR 0.70, 95%CI 0.65-0.76, I2 75%, p < 0.001). Elderly patients receiving BB were more likely to develop bradycardia (RR 3.96, 95%CI 2.71-5.80, p < 0.001, I2 0%). There was no difference in the incidence of hypotension, acute renal impairment, and hypoglycemia between the GDMT and control group. The funnel plot appeared asymmetrical which suggests possible publication bias. Conclusion The use of GDMT in elderly HFrEF patients was associated with a survival benefit. Frailty may interfere with the implementation of GDMT. High quality studies are needed to guide the safety and efficacy of GDMT, and the development of guidelines on HFrEF management the in elderly according to frailty status.Forrest plot of overall survival