Advanced Chronic Heart Failure Research Articles

Comparison between acute and chronic refractory cardiogenic shock: is prognosis different?

Abstract Funding Acknowledgements None. Background Short-term mechanical circulatory support (ST-MCS) is essential to reverse refractory cardiogenic shock (RCS). Since compensatory mechanisms are differently activated depending on whether the cause of CS is acute injury or decompensation of advanced chronic heart failure, hypothetically, the prognosis could also be different. Purposes The aim of our study was to compare the prognosis of patients with RCS supported with ST-MCS (venoarterial-extracorporeal membrane oxygenation (VA-ECMO), Centrimag, Impella CP and Impella 5.0) according to whether the cause of cardiogenic shock was an acute myocardial injury (acute myocardial infarction, myocarditis...) or a worsening of advanced cardiomyopathy. Methods Consecutive patients ≥ 18 years with RCS requiring ST-MCS at a tertiary center from January 2020 to August 2023 were prospectively included. They were stratified according to whether the cause of shock was acute or chronic. Demographic, clinical characteristics before insertion, and outcomes were included in the analysis. Results A total of 86 patients with RCS were supported with ST-MCS in that period, 55 of them (64%) for acute injury and the rest (n=31; 36%) as decompensation of chronic heart failure, with a significantly higher Charlson Comorbidity Index in the chronic group (2(0-3) vs 3(2-4); p=0.01). Acute shock was predominantly supported with VA-ECMO (49.1%) and Impella CP (41.8%), while Impella 5.0 was the most commonly used device in chronic patients (32.2%). The severity of CS was significantly higher in the acute shock group, assessed by SCAI (p=0.005), VIS Score (55.1 (26.19-90.5) vs 8 (3.1-30); p=0.005) and lactate level (5.3 (3-10.3) vs 1.2 (1-2.2) mmol/l; p<0.005) and a higher but non-significant SOFA score (8 (6-10) vs 6 (4-9); p=0,06). However, no differences were found in prognosis, both in-hospital mortality, mortality during support and 30-day and 1-year mortality (Figure 1). Most patients with chronic shock were referred to cardiac transplantation (54.8%) while most patients with acute shock were weaned by myocardial recovery(30.9%), but there were no differences in the final destination of these patients (p=0.089). There were no differences in systemic and local complications between the three groups, except for the rate of device-related ischemia (21.8% vs. 6.4%, p=0.015). Conclusions In our center, most patients in CS who required short-term mechanical circulatory support debut after an acute cardiac injury. Percutaneous ST-MCS is preferentially selected in the acute group, probably because of its easy accessibility in emergency situations. Although patients with acute CS present a more severe overall situation than patients worsening due to advanced heart failure, there were no differences in the short- and long-term prognosis or in the destination treatment of these patients.Table of resultsFigure 1.Mortality in RCS

Treatment of Chronic Heart Failure in Advanced Chronic Kidney Disease: The HAKA Multicenter Retrospective Real-World Study

Plain Language SummaryPatients with advanced chronic kidney disease (aCKD) and heart failure (HF) are at high risk of poor outcomes including premature death and hospitalization. However, evidence on their management is scarce. Many pivotal clinical trials testing HF treatments have excluded patients with aCKD and there is a paucity of real-world data on the diagnosis and treatment of these patients. The cross-sectional and retrospective HAKA study has some novel findings. On the one hand, the large range in the prevalence of HF between centers suggests an underdiagnosed of HF in patients with aCKD cared for in some specialized aCKD units. On the other hand, foundational HF medications are markedly underprescribed in patients with HFrEF. The HAKA study results justify a call to action for clinicians to optimize the diagnosis and treatment of HF in patients with aCKD. In addition, they support that appropriate evidence-based pharmacological treatment of HF in patients with aCKD is an unmet medical need that urgently requires specific clinical trials.

TYG Index as a Novel Predictor of Clinical Outcomes in Advanced Chronic Heart Failure with Renal Dysfunction Patients.

The triglyceride-glucose (TYG) index is a novel and reliable marker reflecting insulin resistance. Its predictive ability for cardiovascular disease onset and prognosis has been confirmed. However, for advanced chronic heart failure (acHF) patients, the prognostic value of TYG is challenged due to the often accompanying renal dysfunction (RD). Therefore, this study focuses on patients with aHF accompanied by RD to investigate the predictive value of the TYG index for their prognosis. 717 acHF with RD patients were included. The acHF diagnosis was based on the 2021 ESC criteria for acHF. RD was defined as the eGFR < 90 mL/(min/1.73 m2). Patients were divided into two groups based on their TYG index values. The primary endpoint was major adverse cardiovascular events (MACEs), and the secondary endpoints is all-cause mortality (ACM). The follow-up duration was 21.58 (17.98-25.39) months. The optimal cutoff values for predicting MACEs and ACM were determined using ROC curves. Hazard factors for MACEs and ACM were revealed through univariate and multivariate COX regression analyses. According to the univariate COX regression analysis, high TyG index was identified as a risk factor for MACEs (hazard ratio = 5.198; 95% confidence interval [CI], 3.702-7.298; P < 0.001) and ACM (hazard ratio = 4.461; 95% CI, 2.962-6.718; P < 0.001). The multivariate COX regression analysis showed that patients in the high TyG group experienced 440.2% MACEs risk increase (95% CI, 3.771-7.739; P < 0.001) and 406.2% ACM risk increase (95% CI, 3.268-7.839; P < 0.001). Kaplan-Meier survival analysis revealed that patients with high TyG index levels had an elevated risk of experiencing MACEs and ACM within 30 months. This study found that patients with high TYG index had an increased risk of MACEs and ACM, and the TYG index can serve as an independent predictor for prognosis.

Artificial Intelligence Applied to Electrical and Non-Invasive Hemodynamic Markers in Elderly Decompensated Chronic Heart Failure Patients.

The first aim of this study was to assess the predictive power of Tend interval (Te) and non-invasive hemodynamic markers, based on bioimpedance in decompensated chronic heart failure (CHF). The second one was to verify the possible differences in repolarization and hemodynamic data between CHF patients grouped by level of left ventricular ejection fraction (LVEF). Finally, we wanted to check if repolarization and hemodynamic data changed with clinical improvement or worsening in CHF patients. Two hundred and forty-three decompensated CHF patients were studied by 5 min ECG recordings to determine the mean and standard deviation (TeSD) of Te (first study). In a subgroup of 129 patients (second study), non-invasive hemodynamic and repolarization data were recorded for further evaluation. Total in-hospital and cardiovascular mortality rates were respectively 19 and 9%. Te was higher in the deceased than in surviving subjects (Te: 120 ± 28 vs. 100 ± 25 ms) and multivariable logistic regression analysis reported that Te was related to an increase of total (χ2: 35.45, odds ratio: 1.03, 95% confidence limit: 1.02-1.05, p < 0.001) and cardiovascular mortality (χ2: 32.58, odds ratio: 1.04, 95% confidence limit: 1.02-1.06, p < 0.001). Subjects with heart failure with reduced ejection fraction (HFrEF) reported higher levels of repolarization and lower non-invasive systolic hemodynamic data in comparison to those with preserved ejection fraction (HFpEF). In the subgroup, patients with the NT-proBNP reduction after therapy showed a lower rate of Te, heart rate, blood pressures, contractility index, and left ventricular ejection time in comparison with the patients without NT-proBNP reduction. Electrical signals from ECG and bioimpedance were capable of monitoring the patients with advanced decompensated CHF. These simple, inexpensive, non-invasive, easily repeatable, and transmissible markers could represent a tool to remotely monitor and to intercept the possible worsening of these patients early by machine learning and artificial intelligence tools.

Nurse-based counselling on thirst in patients with advanced chronic heart failure : Study protocol for apilot before-after study and process evaluation.

Many patients with chronic heart failure (CHF) are critically ill and experience increased thirst. Study aims are to develop and evaluate anurse-based counselling intervention to promote self-care competencies related to thirst in hospitalised patients with advanced CHF eligible or listed for heart transplantation. Amixed-methods approach will be adapted with three study phases: (1)development of the nurse-based counselling intervention, (2)feasibility testing and training of nurses, and (3)implementation of the intervention and, evaluation of initial effects and process measures. In phase(1), interviews with hospitalised patients with advanced CHF listed for heart transplantation (n = 10), focus groups (n = 2) and aGermany-wide survey with nurses will be performed. In phase(2), experts experienced with caring for patients with advanced CHF and patients with advanced CHF will be consulted for content validation and pretest of the counselling intervention. The training concept for nurses will be evaluated using questionnaires. In phase(3), apilot before-after study will be conducted (n = 60). Primary patient-related outcome for the pilot study is thirst intensity using anumeric rating scale. Furthermore, aprocess evaluation (interviews with patients [n = 10], survey with nurses and physicians) will be performed. Quantitative data will be analysed descriptively, and qualitative data will be analysed using content analysis. Mean values of thirst intensity of the individual measurement points will be evaluated as interrupted time-series analysis using regression analyses. The development and implementation of acounselling intervention is influenced by various factors. Therefore, it is important to consider all factors throughout the process from development to evaluation.

Percutaneous Strategies in Structural Heart Diseases: Focus on Chronic Heart Failure.

Central Illustration : Percutaneous Strategies in Structural Heart Diseases: Focus on Chronic Heart Failure Transcatheter devices for monitoring and treating advanced chronic heart failure patients. PA: pulmonary artery; LA: left atrium; AFR: atrial flow regulator; TASS: Transcatheter Atrial Shunt System; VNS: vagus nerve stimulation; BAT: baroreceptor activation therapy; RDN: renal sympathetic denervation; F: approval by the American regulatory agency (FDA); E: approval by the European regulatory agency (CE Mark). Innovations in devices during the last decade contributed to enhanced diagnosis and treatment of patients with cardiac insufficiency. These tools progressively adapted to minimally invasive strategies with rapid, widespread use. The present article focuses on actual and future directions of device-related diagnosis and treatment of chronic heart failure.

Repetitive LevosimenDan infusions fOR patients with advanced chronic heart failure in the vulnerable post-discharge period: the multinational randomized LeoDOR trial

Abstract Background Studies of the repetitive use of intravenous levosimendan suggested a beneficial effect in patients with advanced heart failure (HF). It was the aim of the LeoDOR trial to test the efficacy and safety of intermittent levosimendan therapy in the vulnerable phase following a hospitalization for acute HF. Methods In this multicenter, double-blind, three-armed trial with an enrolment period from 3-2018 to 6-2021, patients with advanced HF were randomized 2:1 at the end of an index hospitalization for acute HF to intermittent levosimendan therapy or placebo for a period of 12 weeks. Levosimendan was administered according to center preference either as 6-hour infusion at a rate of 0.2 mcg/kg/min every 2 weeks, or as 24-hour infusion at a rate of 0.1 mcg/kg/min every 3 weeks. The primary efficacy assessment after 14 weeks was based on a global rank endpoint consisting of three hierarchical groups: Tier 1 = time to death or urgent heart transplantation or implantation of a ventricular assist device; Tier 2 = time to non-fatal HF requiring i.v. vasoactive therapy; Tier 3 = time-averaged proportional change in NTproBNP from baseline to week 14. Results Due to a forced interim interruption of the study as a result of the COVID-19 pandemic, the planned number of patients could not be recruited. The final modified intention-to-treat (mITT) analysis included 145 patients (93 in the combined levosimendan arm, 52 in the placebo arm). Patient characteristics were well balanced between treatment and placebo arms (mean age 69.3±9.7 vs 67.9±10.1, proportion of women 22.6% vs 21.2%, HF-hospitalizations in previous 12 months 1.9±1.4 vs. 1.7±1.1, NTproBNP at baseline 4740 ng/L (IQR 2235 – 9016) vs 5380 ng/L (IQR 2287 – 8204). There were no marked differences regarding HF medication and implanted devices. Compared with placebo, intermittent levosimendan had no significant effect on the primary endpoint (mean rank score 71.8 for the levosimendan group vs 75.1 for the placebo group; p = 0.65). However, there was a strong signal towards a higher incidence of the individual clinical components of the primary endpoint (tier 1 plus tier 2) in the levosimendan group vs the placebo group both after 14 weeks (HR 2.94, 95%CI 1.13–7.70; p = 0.028) and 26 weeks (HR 1.65 95%CI 0.87 – 3.12; p = 0.123). The number of investigator-reported adverse events during and immediately after drug application was 12.4% in the levosimendan group vs 11.8% in the placebo group (p = 0.905). Conclusion Our findings do not support the use of intermittent levosimendan to improve post-hospitalization clinical stability in patients who were recently hospitalized with HF and reduced LVEF. Further studies are warranted to find the correct use of levosimendan in advanced heart failure patients.

Applying the Rome Proposal on Exacerbations of Chronic Obstructive Pulmonary Disease: Does Comorbid Chronic Heart Failure Matter?

Chronic heart failure (CHF) is a common comorbidity among patients with chronic obstructive pulmonary disease (COPD). Both exacerbations of COPD (ECOPDs) and exacerbations of CHF (ECHFs) display worsening of breathlessness at rest (BaR) and breathlessness at physical activity (BaPA). Comorbid CHF may have an impact on the vital signs assessed, when the Rome proposal (adopted by GOLD 2023) is applied on ECOPDs. Thus, the aim of the present study was to investigate the impact of comorbid CHF on ECOPDs severity, particularly focusing on the influence of comorbid CHF on BaR and BaPA. We analysed data on COPD symptoms collected from the telehealth study The eHealth Diary. Patients with COPD (n = 43) and patients with CHF (n = 41) were asked to daily monitor BaR and BaPA, employing a digital pen and scales for BaR and BaPA (from 0 to 10). Twenty-eight patients of the COPD patients presented with comorbid CHF. Totally, 125 exacerbations were analysed. Exacerbations in the group with COPD patients and comorbid CHF were compared to the group with COPD patients without comorbid CHF and the group with CHF patients. Compared with GOLD 2022, the GOLD 2023 (the Rome proposal) significantly downgraded the ECOPD severity. Comorbid CHF did not interfere significantly on the observed difference. Comorbid CHF did not worsen BaR scores, assessed at inclusion and at the symptom peak of the exacerbations. In the present study, we find no evidence that comorbid CHF would interfere significantly with the parameters included in the Rome proposal (GOLD 2023). We conclude that the Rome proposal can be safely applied even on COPD patients with very advanced comorbid CHF.

Clinical Response and Safety of Angiotensin Receptor and Neprilysin Inhibitor Combination in Advanced Chronic Kidney Disease and Heart Failure with Reduced Ejection Fraction.

Though the combination of an angiotensin receptor blocker (ARB) and a neprilysin inhibitor (ARNi) has been shown to be useful in heart failure with reduced ejection fraction (HFrEF), its use has mostly been restricted to chronic kidney disease (CKD) patients with an estimated glomerular filtration rate (eGFR) &gt;30 mL/minute/1.73 m2 . We studied the role of ARNi in advanced CKD. Patients with HFrEF and advanced CKD with an eGFR of &lt;30 mL/ minute/1.73 m2 were given ARNi (sacubitril with valsartan) and prospectively studied for changes in hospitalization rate for HF, clinical symptoms, levels of N-terminal prohormone of brain natriuretic peptide (NT-proBNP), eGFR, and potassium. Of 34 patients who received ARNi, five were excluded due to hyperkalemia and three due to a decrease in eGFR &gt;30% occurring within 1 month. The remaining 26 patients included 17 with diabetes mellitus (DM) and 23 with underlying coronary artery disease. A total of eight patients had stage 4 and 18 stage 5 CKDs, amongst which eight required hemodialysis. Following ARNi, there was a significant decrease in the need for hospitalization for breathlessness (2.04 ± 1.03-0.23 ± 0.51; p &lt; 0,05), New York Heart Association (NYHA) and Kansas City Cardiomyopathy Questionnaire (KCCQ) scores (3.77 ± 0.43-2.19 ± 0.56 and 28.58 ± 9.04-64.81 ± 14.3, respectively, p &lt; 0.001) and NT-pro-BNP levels (24761 ± 12157.51-20149.92 ± 13555.269, p &lt; 0.05) without significant change in eGFR after 6 months. There were no significant differences in the need for hospitalization, changes in NT proBNP levels and eGFR between stages 4 and 5. Neprilysin inhibitor (ARNi) is effective and can be used with care even in patients with CKD stages 4 and 5 having HFrEF with monitoring of eGFR and potassium.

Impact of invasively determined cardiac power index on survival in patients with advanced chronic heart failure

Impact of invasively determined cardiac power index on survival in patients with advanced chronic heart failure

Association of Nutritional Risk Index With Continuous Flow Left Ventricular Assist Device Complications

Studies revealing the relationship between major surgery outcomes and nutritional parameters are increasing daily. Publications demonstrating the relationship between early postoperative success and surgical complications in patients with chronic heart failure and continuous flow left ventricular assist device (cf-LVAD) are limited. The vast majority of patients with advanced chronic heart failure are cachexic, and the reason for this is multifactorial. The aim of this study is to investigate the link between the modified nutritional risk index (NRI) and 6-month survival and complication rates in patients with a cf-LVAD. This study included statistical analysis of NRI and postoperative parameters of 456 patients with advanced heart failure who had cf-LVAD implantation between 2010 and 2020. The results of this study showed a statistically significant difference between mean NRI values and postoperative parameters such as 6-month survival (P=.001), right ventricular failure (P=.003), infection (P=.001), driveline infection (P=.000), and sepsis (P=.000). This study revealed that 6-month postoperative complications and mortality rates of patients with advanced heart failure in patients with cf-LVAD are closely related to malnutrition status. In these patients, nutrition specialist use would be beneficial both preoperatively and postoperatively to increase surveillance and reduce postoperative complications.

SCREENING RATES FOR PRIMARY ALDOSTERONISM ARE UNSATISFACTORY EVEN IN HYPERTENSION EXCELLENCE CENTERS. A CALL FOR COMPULSORY SCREENING FOR ALL HYPERTENSIVE PATIENTS

Objective: The Endocrine Society guidelines recommend screening for primary aldosteronism (PA) in high risk hypertensive patients. These include patients with sustained blood pressure (BP) above 150/100 mmHg, patients with resistant hypertension (HTN), hypertensive patients with spontaneous or diuretic-induced hypokalemia, adrenal incidentaloma, sleep apnea, family history of early onset HTN or cerebrovascular accident at a young age and all hypertensive first-degree relatives of patients with PA. Even though guidelines are clear and screening is simple, compliance rates among clinicians are extremely low ranging between 0.1% to 2.7%. This results in underdiagnosis of early disease, leading to an enormous extra-burden of advanced chronic kidney disease, heart failure, atrial fibrillation, and stroke. We aimed to examine the screening rate, according to the abovementioned guidelines, at our recently recognized Hypertension Excellence Center in Assuta Ashdod University Hospital. Design and method: A retrospective cohort study. We analyzed all hypertensive patients, eligible for screening between 01/18 and 12/20. We calculated screening rates and in univariate and multivariate regression analyses, looked at parameters that influence screening. Results: Of 661 patients over 18 years of age with HTN, 218 patients (33%) met the Endocrine Society guidelines for PA screening. However only 46 of them (21.1%), were referred for screening. A multivariate regression analysis, demonstrated that advanced age and male gender were associated with lower rates of screening referral. Odds ratio for age was 0.945 for every year (95% CI 0.915-0.975). Conclusions: A 21% screening rate in a Hypertension Excellence Center, although higher than prior published studies, suggests that many cases of PA are likely missed, more often in elderly population in whom adrenal micro as well as macronodular-hyperplasia is extremely common and can be the cause of secondary HTN. We therefore advocate for PA screening at least once of all hypertensive patients, preferably before the patient is started on multiple anti-hypertensive medications. This should be done regardless of patients’ age and gender, as the absolute risk for cardiovascular events in both hypertensive and PA patients increases with rising age, and treatment with mineralocorticoid receptor antagonists can be lifesaving.

Stent Implantation and Thromboendarterectomy for the Common Femoral Artery in Real-World Practice.

To compare the outcomes of thromboendarterectomy (TEA) and endovascular therapy (EVT) with stenting for patients with atherosclerotic common femoral artery (CFA) occlusive disease. From a retrospective registry of 1193 consecutive patients with CFA treatment performed between 2018 and 2020 at 66 institutions in Japan, we identified patients who underwent TEA (n=432) or stent implantation (n=157). The primary outcome measures were the 1-year primary patency of TEA versus stenting with propensity score matching. The secondary outcome measures were perioperative complications, length of hospital stay, any reintervention, limb salvage, and overall survival. Interaction analysis for primary patency was performed with propensity score stratification to determine the appropriate target population for CFA stenting. Propensity score matching extracted 101 pairs (101 patients in the EVT group and 253 patients in the TEA group). The 1-year primary patency rate was significantly higher in the TEA cohort (92.8% vs 84.6%, p=0.006). The freedom from reintervention rate was also significantly higher in the TEA cohort (94.0% vs 89.9%, p=0.030). However, the 1-year limb salvage (98.7% vs 100.0%, p=0.32), 1-year overall survival (90.8% vs 85.0%, p=0.14), and frequency of perioperative complications were not significantly different between the cohorts (6.9% vs 14.2%, p=0.10). Based on interaction analysis, the superiority of TEA over EVT in terms of patency was less apparent in patients with advanced age and chronic heart failure. Thromboendarterectomy was superior to stenting in terms of primary patency and freedom from revascularization at 1 year. There was no significant difference in the incidence of perioperative complications between both groups. Thromboendarterectomy may be recommended as the standard treatment strategy for patients with atherosclerotic CFA disease, whereas stenting may be considered for patients with advanced age and chronic heart failure. Thromboendarterectomy compared to stenting was the preferred revascularization strategy for patients with CFA disease in terms of primary patency and freedom from target lesion revascularization during the 1st year. The difference was attenuated in subgroups with advanced age (85 years or older) or chronic heart failure, thus stenting may be considered in patients with these backgrounds.

Comparison of immediate changes of repolarization parameters after left bundle branch area pacing and traditional biventricular pacing in heart failure patients.

Comparison of immediate changes of repolarization parameters after left bundle branch area pacing and traditional biventricular pacing in heart failure patients.

143 ESTIMATION OF RIGHT ATRIAL PRESSURE BY ULTRASOUND-ASSESSED JUGULAR VEIN DISTENSIBILITY IN PATIENTS WITH CHRONIC ADVANCED HEART FAILURE

Abstract Aims In patients with chronic advanced heart failure (HF) signs of congestion are not always evident on clinical examination. We aim to validate the ultrasound (US)-assessed jugular vein distensibility (JVD), as a non-invasive tool to identify patients with normal right atrial pressure (RAP≤7 mmHg). Methods and Results In a single-center prospective study, we assessed chronic HF patients with a left ventricular ejection fraction (LVEF)&amp;lt;50% who underwent a pulmonary artery catheterization in the setting of advanced HF therapies workup. We first identify the JVD threshold (Valsalva/rest ratio of the vein diameter) of 1.6 that allowed the most accurate discrimination between patients with RAP≤7 vs. &amp;gt;7 mmHg (area under the curve [AUC] of 0.74; p&amp;lt;0.0001) in a calibration cohort of 100 patients (mean age 53 years, median LVEF 25%). Based on this JVD threshold, we defined patients with low JVD (≤1.6; n=58; median RAP 8 mmHg) and high JVD (&amp;gt;1.6, n=42; median RAP 4 mmHg). Then, we tested the threshold in 101 patients (validation cohort), where we found comparable results (AUC of 0.82; p&amp;lt;0.0001). The JVD threshold had 0.86 and 0.94 predictive positive values to identify patients with RAP≤7 mmHg in the calibration and validation cohorts. Finally, the low JVD vs. high JVD group had a 42.7% vs. 16.1% incidence of major cardiac events at 2 years (log-rank p=0.006), showing its prognostic value. Conclusion US-assessed JVD is an accurate diagnostic tool to identify advanced HF patients with normal RAP. This tool could be tested in the ambulatory setting to modulate diuretic/vasodilator therapies.

Distinct Transcriptomic and Proteomic Profile Specifies Patients Who Have Heart Failure With Potential of Myocardial Recovery on Mechanical Unloading and Circulatory Support.

Extensive evidence from single-center studies indicates that a subset of patients with chronic advanced heart failure (HF) undergoing left ventricular assist device (LVAD) support show significantly improved heart function and reverse structural remodeling (ie, termed "responders"). Furthermore, we recently published a multicenter prospective study, RESTAGE-HF (Remission from Stage D Heart Failure), demonstrating that LVAD support combined with standard HF medications induced remarkable cardiac structural and functional improvement, leading to high rates of LVAD weaning and excellent long-term outcomes. This intriguing phenomenon provides great translational and clinical promise, although the underlying molecular mechanisms driving this recovery are largely unknown. To identify changes in signaling pathways operative in the normal and failing human heart and to molecularly characterize patients who respond favorably to LVAD unloading, we performed global RNA sequencing and phosphopeptide profiling of left ventricular tissue from 93 patients with HF undergoing LVAD implantation (25 responders and 68 nonresponders) and 12 nonfailing donor hearts. Patients were prospectively monitored through echocardiography to characterize their myocardial structure and function and identify responders and nonresponders. These analyses identified 1341 transcripts and 288 phosphopeptides that are differentially regulated in cardiac tissue from nonfailing control samples and patients with HF. In addition, these unbiased molecular profiles identified a unique signature of 29 transcripts and 93 phosphopeptides in patients with HF that distinguished responders after LVAD unloading. Further analyses of these macromolecules highlighted differential regulation in 2 key pathways: cell cycle regulation and extracellular matrix/focal adhesions. This is the first study to characterize changes in the nonfailing and failing human heart by integrating multiple -omics platforms to identify molecular indices defining patients capable of myocardial recovery. These findings may guide patient selection for advanced HF therapies and identify new HF therapeutic targets.

Systemic immune-inflammation index as a prognostic marker for advanced chronic heart failure with renal dysfunction.

We aim to investigate the correlation between high levels of the systemic immune-inflammation index (SII) and long-term mortality and major cardiovascular adverse events in advanced chronic heart failure patients with renal dysfunction. Seven hundred seventeen advanced chronic heart failure patients with renal dysfunction, who visited the First affiliated hospital of Zhengzhou University from September 2019 to December 2020, were included. All-cause mortalities (ACM) were selected as primary endpoints and major cardiovascular adverse events (MACEs) as the secondary endpoints. Based on the receiver operating characteristic (ROC) curve and the Youden index, the optimal cut-off values of SII for ACM and MACEs were 1228 and 1406. In the group where ACM were the primary endpoint, patients were categorized into the low-SII group (n=479) and the high-SII group (n=238). Patients in the group using MACEs as the secondary endpoint were also categorized into the low-SII groups (n=514) and the high-SII groups (n=203). Univariate and multivariate COX regression were used to screen the independent predictors for ACM and MACEs, revealing the relationship between SII levels and endpoints. According to the univariate COX analysis, SII was the risk factor (hazard ratio [HR]=2.144, 95% confidence interval [CI]: 1.565-2.938, P<0.001) for the ACM subgroup. It was also the risk factor (HR=1.625, CI: 1.261-2.905, P<0.001) for the MACEs subgroup. Multivariate COX regression analysis indicated that the occurrence of ACM and MACEs in high-level SII and low-level SII patients had statistical differences. The incidence of ACM increased by 70.3% (HR=1.703; 95% CI: 1.200-2.337; P=0.002) in patients of the high SII level group, the incidence of MACEs increased by 58.3% (HR=1.583, 95% CI: 1.213-2.065, P=0.001). Kaplan-Meier (K-M) survival analysis further suggested that patients with a high SII level had an increased risk of having ACM (log-rank P<0.001) and MACEs (log-rank P<0.001) within 30months. SII could be considered as a novel predictor of the occurrence of ACM and MACEs for patients with advanced chronic heart failure and renal dysfunction. This study suggested that SII is a novel independent predictor of mortality in advanced chronic heart failure patients with renal dysfunction, and it should be considered in current clinical management.

Comprehensive care for people living with heart failure and chronic obstructive pulmonary disease-Integration of palliative care with disease-specific care: From guidelines to practice.

Heart failure (HF) and chronic obstructive pulmonary disease (COPD) are the leading global epidemiological, clinical, social, and economic burden. Due to similar risk factors and overlapping pathophysiological pathways, the coexistence of these two diseases is common. People with severe COPD and advanced chronic HF (CHF) develop similar symptoms that aggravate if evoking mechanisms overlap. The coexistence of COPD and CHF limits the quality of life (QoL) and worsens symptom burden and mortality, more than if only one of them is present. Both conditions progress despite optimal, guidelines directed treatment, frequently exacerbate, and have a similar or worse prognosis in comparison with many malignant diseases. Palliative care (PC) is effective in QoL improvement of people with CHF and COPD and may be a valuable addition to standard treatment. The current guidelines for the management of HF and COPD emphasize the importance of early integration of PC parallel to disease-modifying therapies in people with advanced forms of both conditions. The number of patients with HF and COPD requiring PC is high and will grow in future decades necessitating further attention to research and knowledge translation in this field of practice. Care pathways for people living with concomitant HF and COPD have not been published so far. It can be hypothesized that overlapping of symptoms and similarity in disease trajectories allow to draw a model of care which will address symptoms and problems caused by either condition.

Tolerability of Sacubitril/Valsartan in Patients With Advanced Heart Failure: Analysis of the LIFE Trial Run-In

BackgroundThe LIFE (LCZ696 In Hospitalized Advanced Heart FailurE) trial, which evaluated sacubitril/valsartan in patients with advanced heart failure (HF) with reduced ejection fraction and recent New York Heart Association functional class IV symptomatology, did not require tolerance to a renin angiotensin system antagonist before initiating sacubitril/valsartan, thus affording an opportunity to study the tolerability of sacubitril/valsartan in advanced HF with reduced ejection fraction. ObjectivesThe goal of this analysis of the LIFE trial is to characterize the tolerability of initiating sacubitril/valsartan in patients with chronic advanced HF with reduced ejection fraction. MethodsIn the LIFE trial, 445 subjects with advanced HF entered an unblinded run-in period of 3-7 days with sacubitril/valsartan 24/26 mg twice a day. The authors compared characteristics of subjects completing and failing run-in, performed multivariable analysis of clinical parameters associated with run-in failure, and developed a predictive model for short-term intolerance to sacubitril/valsartan. ResultsOf 445 subjects entering run-in, 73 (18%) were intolerant of sacubitril/valsartan. Reasons for intolerance included systolic blood pressure <90 mm Hg (59%), symptoms of hypotension/dizziness with systolic blood pressure >90 mm Hg (19%), and renal dysfunction (creatinine >2.0 mg/dL) (12%). Multivariable predictors of intolerance included lower mean arterial pressure, lower serum chloride, presence of an implantable cardioverter-defibrillator and/or cardiac resynchronization device, moderate or greater mitral regurgitation, nonuse of angiotensin-converting enzyme inhibitor or angiotensin receptor blocker at the screening visit, and use of insulin at screening. Subjects with 4 or more predictors had a 48.9% probability of sacubitril/valsartan intolerance. ConclusionsIntolerance to low doses of sacubitril/valsartan is common in patients with advanced chronic HF with reduced ejection fraction and may be predicted by the presence of certain risk factors. (EntrestoTM [LCZ696] in Advanced Heart Failure [LIFE Study] [HFN-LIFE] NCT02816736)

Pleural Effusions in Patients With Congestive Heart Failure: Frequency, Pathogenesis, Diagnosis, and Implications.

Patients with cardiac disease frequently develop pleural effusions; the incidence is approximately 500,000 cases per year in the United States. These effusions often represent important clinical events for patients, indicating that either there has been an acute change in the patient's clinical status or the patient's chronic management program needs review. These effusions usually develop in both the right and left hemithorax but can be unilateral. The pathogenesis involves increased fluid transfer from parietal pleural capillaries into the pleural space and possibly decreased pleural fluid uptake into parietal pleural lymphatic structures. The increased fluid transfer develops due to increased capillary pressure secondary to elevated venous outflow pressure and secondary to decreased lymphatic flow into central vessels secondary to heart failure. Most pleural effusions associated with heart failure are transudates, but 20% to 25% have increased protein and lactate dehydrogenase levels suggesting an exudative process. Additional testing can clarify the situation and requires calculation of the serum albumin to pleural fluid albumin gradient or measurement of N-terminal pro-brain natriuretic peptide in the pleural fluid. An albumin gradient of greater than 1.2 g/dL suggests that the fluid is a transudate. The presence of a pleural effusion in a hospitalized patient at discharge is associated with an increased likelihood of rehospitalization and mortality within the next year. Patients with large symptomatic pleural effusions may require therapeutic thoracentesis. Recurrence of symptomatic effusions presents a management dilemma that might require repeated thoracenteses, indwelling intrapleural catheter placement, or other management steps used in advanced chronic heart failure.