Advanced Systolic Heart Failure Research Articles

Optimizing Triage of Ambulatory Patients With Advanced HeartFailure: 2-Year Outcomes From REVIVAL.

Left ventricular assist device (LVAD) use remains uncommon in advanced heart failure (HF) patients not dependent on inotropes. Before considering a randomized trial comparing a strategy of earlier use of LVAD to continued medical therapy, a better understanding is needed of the clinical trajectory of ambulatory patients with advanced systolic HF on optimal guideline-directed medical therapy (GDMT). REVIVAL enrolled 400 patients with advanced ambulatory systolic HF,≥1 HF mortality risk marker (≥2 HF hospitalizations past year; or HF hospitalization and high natriuretic peptide; or no HF hospitalizations but low peak oxygen consumption, 6-minute walk, serum sodium, HF survival score or Seattle HF model predicted survival), and no LVAD contraindication at 21 LVAD centers from July 2015 to June 2016. Patients were followed for 2 years or until a primary outcome (death, durable ventricular assist device, or urgent transplant). Clinical outcomes and health-related quality of life were evaluated. Mean baseline left ventricular ejection fraction was 21%, median 6-minute walk was 341 m, and 92% were Interagency Registry for Mechanically Assisted Circulatory Support profiles 5 to 7. Adherence to GDMT and electrical device therapies was robust. Composite primary outcome occurred in 22% and 37% at 1 and 2 years, with death alone in 8% and 16%, respectively. Patients surviving for 2 years maintained GDMT intensity and had no decline in health-related quality of life. Structured, serial follow-up at programs with expertise in caring for advanced ambulatory systolic HF patients facilitates triage for advanced therapies. Better strategies are still needed to avoid deaths in a small but significant group of patients who die without advanced therapies. REVIVAL patients not selected for VAD or transplant have robust survival and patient-reported outcomes, which challenges advocacy for earlier VAD implantation. (RegistryEvaluation of Vital Information for VADs in Ambulatory Life [REVIVAL]; NCT01369407).

Behavior of coronary sinus oxygen saturation and cardiac output in systolic heart failure

Abstract Background CRT implantation is indicated in advanced systolic heart failure (LV-EF < 35%) on optimal medical therapy and left bundle branch block with wide QRS complex (QRS > 150 ms). This study investigates the influence of different variables on venous saturation in the coronary sinus during HFrEF. Methods In this study, blood gas analyses (BGA) of patients undergoing CRT implantation were performed at our center. Patients with an electrophysiological study but without structural heart disease served as a control group. In all patients a BGA from the coronary sinus was performed. Arterial and central venous saturation were used to determine cardiac output (CO) according to Fick's principle. Oxygen uptake was calculated from body surface area and age. Results In total, the study population included 19 patients in the CRT and 18 patients in the control group. The median age of the CRT group was 75 years (54-87 years) and in the control group 58 years (36-81 years). In the CRT group 53% had ischaemic cardiomyopathy. The saturation in the coronary sinus was 30.3% in CRT patients and was therefore significantly lower than in the control group (40.0%, p = 0.02). However, CO at rest did not differ in both groups (CRT 6.8 L/min vs. control 7.4 L/min.). It was observed that the coronary sinus saturation was independent of CO and the genesis of heart failure. In contrast, QRS width before CRT implantation was negatively correlated with saturation in the coronary sinus (r = - 0.58, p = 0.01). Conclusion In patients with systolic heart failure and despite a normal CO, a decreased oxygen saturation in the coronary sinus at rest was found compared to cardiac healthy subjects. CS saturation correlates negatively with the width of the QRS complex. It is not dependent on age, LV function and the genesis of heart failure.

Restoration of Cardiac Myosin Light Chain Kinase Ameliorates Systolic Dysfunction by Reducing Superrelaxed Myosin.

Cardiac-specific myosin light chain kinase (cMLCK), encoded by MYLK3, regulates cardiac contractility through phosphorylation of ventricular myosin regulatory light chain. However, the pathophysiological and therapeutic implications of cMLCK in human heart failure remain unclear. We aimed to investigate whether cMLCK dysregulation causes cardiac dysfunction and whether the restoration of cMLCK could be a novel myotropic therapy for systolic heart failure. We generated the knock-in mice (Mylk3+/fs and Mylk3fs/fs) with a familial dilated cardiomyopathy-associated MYLK3 frameshift mutation (MYLK3+/fs) that had been identified previously by us (c.1951-1G>T; p.P639Vfs*15) and the human induced pluripotent stem cell-derived cardiomyocytes from the carrier of the mutation. We also developed a new small-molecule activator of cMLCK (LEUO-1154). Both mice (Mylk3+/fs and Mylk3fs/fs) showed reduced cMLCK expression due to nonsense-mediated messenger RNA decay, reduced MLC2v (ventricular myosin regulatory light chain) phosphorylation in the myocardium, and systolic dysfunction in a cMLCK dose-dependent manner. Consistent with this result, myocardium from the mutant mice showed an increased ratio of cardiac superrelaxation/disordered relaxation states that may contribute to impaired cardiac contractility. The phenotypes observed in the knock-in mice were rescued by cMLCK replenishment through the AAV9_MYLK3 vector. Human induced pluripotent stem cell-derived cardiomyocytes with MYLK3+/fs mutation reduced cMLCK expression by 50% and contractile dysfunction, accompanied by an increased superrelaxation/disordered relaxation ratio. CRISPR-mediated gene correction, or cMLCK replenishment by AAV9_MYLK3 vector, successfully recovered cMLCK expression, the superrelaxation/disordered relaxation ratio, and contractile dysfunction. LEUO-1154 increased human cMLCK activity ≈2-fold in the Vmax for ventricular myosin regulatory light chain phosphorylation without affecting the Km. LEUO-1154 treatment of human induced pluripotent stem cell-derived cardiomyocytes with MYLK3+/fs mutation restored the ventricular myosin regulatory light chain phosphorylation level and superrelaxation/disordered relaxation ratio and improved cardiac contractility without affecting calcium transients, indicating that the cMLCK activator acts as a myotrope. Finally, human myocardium from advanced heart failure with a wide variety of causes had a significantly lower MYLK3/PPP1R12B messenger RNA expression ratio than control hearts, suggesting an altered balance between myosin regulatory light chain kinase and phosphatase in the failing myocardium, irrespective of the causes. cMLCK dysregulation contributes to the development of cardiac systolic dysfunction in humans. Our strategy to restore cMLCK activity could form the basis of a novel myotropic therapy for advanced systolic heart failure.

The serum concentration of brain‑derived neurotrophic factor is lower in ambulatory and clinically stable patients with more advanced systolic heart failure.

Brain‑derived neurotrophic factor (BDNF) is decreased in heart failure (HF), but whether serum BDNF concentration is related to the severity of HF with reduced left ventricular (LV) ejection fraction (LVEF) below 50% is uncertain. We aimed to compare cardiac structure and function in ambulatory and clinically stable patients with HF and LVEF below 50% for lower and higher BDNF serum concentrations. A total of 361 ambulatory patients with a compensated HF and LVEF below 50% underwent cardiac evaluation and measurement of serum BDNF and N‑terminal pro-B‑type natriuretic peptide (NT‑proBNP). Patients from the lower (below median) and higher (equal to or above median) BDNF serum concentration groups were compared by analysis of covariance (ANCOVA) adjusted for age, sex, body mass index, resting heart rate, and systolic blood pressure. The patients were at a median age of 63.8 (interquartile range [IQR], 57.7-71.5) years and had a median LVEF of 31.0% (IQR, 23.0-37.4). Individuals with lower BDNF (<23.5 ng/ml) had significantly (P ≤0.05) more dilated right and left atria both before and after emptying, larger right ventricular end-diastolic diameter, LV end-systolic diameter, lower tricuspid annulus plane systolic excursion, shorter pulmonary acceleration time, higher mitral E to A waves ratio and mitral E wave to tissue Doppler e' wave ratio, and higher concentration of NT‑proBNP. HF patients with LVEF below 50% and lower serum BDNF concentration present more advanced cardiac remodeling and dysfunction than individuals with higher BDNF. Potential mechanisms and clinical consequences of these findings require further investigation.

Skeletal Muscle Mass Recovery Early After Left Ventricular Assist Device Implantation in Patients With Advanced Systolic Heart Failure.

Patients with advanced systolic heart failure are at risk of unintentional weight loss and muscle wasting. It has been observed that left ventricular assist device (LVAD) recipients gain weight after device implantation, although it is unknown whether this represents skeletal muscle mass gains. We aimed to determine whether skeletal muscle mass increases early during LVAD support. We prospectively recruited 30 adults with systolic heart failure ±21 days from LVAD implantation. Participants underwent whole-body dual X-ray absorptiometry to measure fat free mass, appendicular lean mass (ALM, lean mass in the arms and legs) and fat mass. Dual X-ray absorptiometry imaging was repeated at 3 and 6 months after LVAD implantation, with participation ending after the 6-month visit or heart transplantation, whichever occurred first. Changes in body composition were evaluated using mixed effects linear regression models. The cohort was 87% male, with mean age 56±12 (SD) years, and mean body mass index 26.4±5.4 kg/m2. Per sarcopenia ALM criteria, 52% of participants had muscle wasting at baseline. At baseline, mean fat free mass and ALM were 56.4±11.7 and 21.0±5.3 kg, respectively. Both measures increased significantly (P<0.001) over 6 months of LVAD support: mean fat free mass change at 3 and 6 months: 2.3 kg (95% CI, 1.0-3.5) and 4.2 kg (95% CI, 2.2-6.1); mean ALM change at 3 and 6 months: 1.5 kg (95% CI, 0.7-2.3) and 2.3 kg (95% CI, 0.9-3.6). Among LVAD recipients with advanced systolic heart failure and high baseline prevalence of muscle wasting, there were significant gains in skeletal muscle mass, as represented by dual X-ray absorptiometry fat free mass and ALM, over the first 6 months of LVAD support.

First signs of reverse cardiac remodeling following one-month, low dose add-on sacubitril-valsartan therapy in patients with advanced systolic heart failure

We investigated the early effects of low dose sacubitril/valsartan (S/V) on cardiac reverse remodeling (CRR). Methods: In 37 patients (45- excluded 8pts,mean age 64.5±17.5 years, five females), 24/26 mg S/V BID was started, and the second evaluation was performed after month. Results: Following CRR parameters improved: LVEDD (-∆2,9±2.6 mm; Student’s t-test: p =0.0098), LVESD (-∆2,4±2.5 mm; Student’s t-test: p=0.0092), LVEDV (-∆14.6±33.1 mL; Wilcoxon test: p = 0.0412), LVESV (-∆13.4±30.6 mL; Wilcoxon test: p =0.0442), LAVI (-∆8.7±37.7 mL/m2; Wilcoxon test: p = 0.0012), and EROA (-∆0.09±0.01 cm2; Student’s t-test: p = 0.0318). In opposite to LVEF, global longitudinal strain (GLS) changed from -6.6% to -7.9% (absolute improvement of 16%, Wilcoxon test: p=0.0013). Other parameters improving: 6-MWT (+∆65.4±75.8 m; Wilcoxon test: p = 0.0013) and the quality of life (MLHFQ 22 vs 16 scores; Student’s t-test: p= 0.0098), NT-pro BNP (-∆1203.1±3121.4 pg/mL; Student’s t-test: p = 0.0348) and troponin T (-∆ 4.7±9.4 pg/mL, Wilcoxon test: p = 0.0041). Correlation between GLS and LVESV (Pearson's correlation coefficient: r = -0,4596, p = 0.0239) was found. ROC curve analysis showed that in the group with severe systolic dysfunction (GLS&lt; -8%) clinical improvement (6MWT: AUC = 0.692, p = 0.0383) and CRR (MRvol: AUC = 0.736, p = 0.0062; LAVI: AUC = 0.710, p = 0.0414) are more likely to occur. Conclusions: Low-dose (24/26 mg BID) S/V therapy initiates CRR. S/V should be started in patients with less impaired LV systolic function (GLS &lt; -8%) because CRR and clinical improvement are more likely to develop.

Right heart catheterization in advanced systolic heart failure. What are the most useful haemodynamic parameters for risk stratification?

Previous studies have shown that pulmonary hypertension is a predictor of mortality in patients with systolic heart failure (SHF). Persistent pulmonary hypertension after a reactivity test is associated with a worse outcome after transplantation. Recent studies have shown the utility of different haemodynamic parameters. To define best haemodynamic parameters for risk stratification in patients with advanced systolic heart failure. We included 425 consecutive patients who underwent a right heart catheterization with an inotropic challenge if indicated. During a median (interquartile range) follow-up of 1.67 (0.49-4.49) years, there were 151 major cardiac events (126 cardiovascular deaths and 25 postoperative deaths after ventricular assist device implantation or heart transplantation). The most powerful independent predictors of major cardiac events were baseline right atrial pressure (RAP) (hazard ratio [HR]: 1.09, 95% confidence interval [CI]: 1.06-1.12; P<0.0001) and baseline pulmonary vascular resistance (PVR) (HR: 1.10; 95% CI: 1.03-1.17; P=0.002). After inotropic challenge, the only independent predictor was mean pulmonary arterial pressure (mPAP) (HR: 1.06; 95% CI: 1.03-1.09; P<0.0001). The combination of PVR (≤or>3 Wood units), RAP (<or≥9mmHg) and mPAP after the inotropic challenge (≤or>30mmHg) was the best predictor of major events. We suggest using a simple algorithm based on baseline PVR, baseline RAP and mPAP after the inotropic challenge for the risk stratification of stable patients with advanced systolic heart failure.

Predictors and prognosis of RV function in pulmonary hypertension due to heart failure with reduced ejection fraction

Abstract Background and aims Failure of right ventricular (RV) function worsens outcome in pulmonary hypertension (PH). The adaptation of RV contractility to afterload, the RV-pulmonary artery (PA) coupling, is defined by the ratio of RV end-systolic to PA elastances (Ees/Ea). Using pressure volume loop (PV-L) technique we aimed to identify an Ees/Ea cutoff predictive for overall survival and to assess hemodynamic and morphologic conditions for adapted RV function in secondary PH due to Heart Failure with Reduced Ejection Fraction (HFREF). Methods This post hoc analysis is based on 112 patients of the prospective Magdeburger Resynchronization Responder Trial. All patients underwent right and left heart echocardiography, and a baseline PV-L and RV catheter measurement. A subgroup of patients (n=50) without a pre-implanted cardiac device underwent MRI at baseline. Results The analysis revealed that 0.68 is an optimal Ees/Ea cutoff (area under the curve: 0.697, p&amp;lt;0.001) predictive for overall survival (median follow up = 4.7 years, Ees/Ea ≥0.68 vs. &amp;lt;0.68, log-rank 8.9, p=0.003. In patients with PH (n=76, 68%) Multivariate Cox-regression demonstrated the independent prognostic value of RV-Ees/Ea in PH patients (HR 0.2, p&amp;lt;0.038). Patients without PH (n=36, 32%) and those with PH but RV-Ees/Ea ≥0.68 showed comparable RV-Ees/Ea ratios (0.88 vs. 0.9, p=0.39), RV size/function, and survival. In contrast, secondary PH with RV-PA coupling ratio Ees/Ea &amp;lt;0.68 corresponded extremely close to cut-off values that define RV dilatation/remodeling (RVEDV &amp;gt;160ml, RV-mass/volume-ratio &amp;lt;0.37 g/ml) and dysfunction (RVEF &amp;lt;38%, TAPSE &amp;lt;16mm, FAC &amp;lt;42%, and stroke-volume/end-systolic volume ratio &amp;lt;0.59) and is associated with a dramatically increased short and medium-term all-cause mortality. Independent predictors of prognostically unfavorable RV-PA coupling (Ees/Ea &amp;lt;0.68) in secondary PH were a preexistent dilated RV (end-diastolic volume &amp;gt;171ml, odds ratio, OR 0.96, p=0.021), high pulsatile load (PA compliance &amp;lt;2.3 ml/mmHg, OR 8.6, p=0.003), and advanced systolic left heart failure (left ventricular (LV) ejection fraction &amp;lt;30%, OR 1.23, p=0.028). Conclusions The RV-PA coupling ratio Ees/Ea predicts overall survival in PH due to HFREF and is mainly affected by pulsatile load, RV remodeling and LV dysfunction. Prognostically favorable coupling (RV-Ees/Ea ≥0.68) in PH was associated with preserved RV size/function and mid-term survival, comparable to HFREF without PH. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Boston Scientific

Myosin Modulation in Hypertrophic Cardiomyopathy and Systolic Heart Failure: Getting Inside the Engine.

Myosin Modulation in Hypertrophic Cardiomyopathy and Systolic Heart Failure: Getting Inside the Engine.

Impact of Sleep Apnea, Daytime Sleepiness, Comorbidities, and Depression on Patients' Heart Failure Health Status.

There is a gap in current research on common factors that impact patients with advanced heart failure (HF). The purpose of this secondary data analysis was to explore associations of those factors with three empirically verified measures of HF-related clinical, physical, and mental health status. Baseline data of 198 advanced systolic HF (EF < 40%) patients were analyzed. Patients were 61.6% male, with a mean age of 62.3 (SD = 13.2) years. The multivariable general linear modeling results indicated that patients who had poorer scores on HF-related clinical status were those who had sleep apnea (β = -6.6, p < .05), daytime sleepiness (β = -9.4, p < .01), four or more comorbidities (β = -11.8, p < .001), and depression (β = -18.7, p < .001). Depression was associated with all three measures of HF-related health status. These findings alert nurses to assess for sleep apnea and to use known screening measures for daytime sleepiness, depression, and comorbidities.

Effect of Radiation in Patients with HeartMate 3 LVAD Therapy

Introduction Radiation therapy in patients with axial flow left ventricular assist devices (LVAD) has not been associated with significant device malfunction. However, the effects of radiation on the fully magnetically levitated HeartMate 3 (Abbott, Abbott Park, IL) LVAD are not well known. We report two cases of stereotactic bone radiation therapy (SBRT) in patients with a HeartMate 3 LVAD implantation. Case Report Patient 1 71-year-old woman with history of chronic systolic heart failure status post HeartMate 3 LVAD and history of left upper lobe non-small cell lung cancer status post lobectomy was found to have an incidental left lateral thorax wall mass on CT imaging with subsequent biopsy consistent for recurrent oligometastatic lung adenocarcinoma. She consequently underwent 5 fractions of 600 cGy SBRT to her left lateral chest wall over a period of 10 days. Mild fatigue was reported following radiation, however LVAD log files sent subsequent to each fraction were unremarkable. On follow up, no cardiac symptoms were reported and LVAD parameters were normal with flow 4.6 L/min, speed 5600 rpm, pulse index 2.8 and power 4.4 watts. Device malfunction has not been witnessed during 1 year follow up. Patient 2 70-year-old man with history of advanced systolic heart failure status post HeartMate 3 LVAD implantation was found to have a right upper lobe nodule and mediastinal lymphadenopathy on CT imaging. Ensuing biopsy diagnosed squamous cell lung cancer without metastatic disease. SBRT was initiated and 5 treatments of 1000 cGy were delivered to the right upper lobe lesion within 10 days. No LVAD complications or symptoms of heart failure were witnessed during treatment. On follow up, patient denied any symptoms and LVAD function remained normal with observed with flow 4.3 L/min, speed 5200 rpm, pulse index 4.8 and power 3.8 watts. Device malfunction has not been witnessed during 1 year follow up. Summary Our 2 cases suggests that SBRT in patients with HeartMate 3 LVAD implantation may be safe and likely not associated with device malfunction. Larger studies are required to better evaluate this relationship and to determine long term safety profile.

Patient-Reported Health Status in Relation to Change in Skeletal Muscle Mass and Function during Left Ventricular Assist Device Support

Purpose Patients with heart failure (HF) frequently experience loss of skeletal muscle mass and strength. It is unknown if loss of muscle mass and/or strength in patients with HF is associated with quality of life (QoL) reductions. Understanding the relationship between loss of muscle mass, strength and HF-specific patient reported health status is essential in defining the clinical importance of skeletal muscle wasting. Methods We retrospectively analyzed data collected prospectively between 5/2016-3/2020 from patients with advanced systolic HF requiring left ventricular assist device (LVAD) support. There were 3 visits: 0 (baseline), 3 and 6 months of LVAD support. Each visit included whole-body dual X-ray absorptiometry (DXA) to calculate appendicular lean mass (ALM), a hydraulic hand dynamometer for handgrip strength, and a Kansas City Cardiomyopathy Questionnaire (KCCQ). KCCQ is a HF-specfic measure of patient-reported health status, symptoms, physical/social functioning and QoL, with summary scores ranging 0-100 (higher indicates better health status) and domain-specific subscores. Linear mixed effects models were used to evaluate relationships between ALM, handgrip strength and KCCQ scores over time, adjusted for potential confounders. Results The cohort was 90% (36/40) male with mean age 57 ±12 years. The median HF duration was 50 months. From baseline to 6 months, there was a significant increase in KCCQ scores (baseline: 46.6 ±19.0, n=40; 3 months: 65.4 ±18.3, n=35, p Conclusion Among patients with advanced HF, skeletal muscle mass and patient-reported health status are positively associated and both significantly increase over the first 6 months of LVAD support. While muscle strength does not significantly change with time, it is significantly associated with patient-reported health status. Further research is necessary to fully evaluate the significance of restoring muscle mass and function to optimize patient-reported QoL.

Prognostic value of 6-minute walk test and cardiopulmonary exercise test in acute heart failure (from the ESCAPE trial)

IntroductionWe aim to study the utility of 6-minute walk distance (6MWD) and cardiopulmonary exercise testing (CPET) in patients with acute systolic heart failure (HF) in predicting post-discharge outcomes. MethodsThe ESCAPE trial data was utilized to examine the prognostic role of 6MWD and CPET in predicting 6-month all-cause mortality and rehospitalization in acute HF. ResultsThe average 6MWD recorded in 271 and 292 patients on admission and discharge was 597 and 765 ft., respectively. Compared with non-survivors, survivors had significantly higher 6MWD on admission (624 vs. 463 ft., P = 0.006) and discharge (789 vs. 636 ft., P = 0.006). Admission and discharge 6MWD had an AUC of 0.629 (P = 0.0047) and 0.628 (P = 0.0093) in predicting mortality. The combination of optimal 6MWD cutoff values of >288 ft. on admission and > 320 ft. on discharge was associated with significantly lower mortality (11.1% vs. 28.3%, OR 0.316, P = 0.002). When dividing the sample into quartiles of increasing walking distance, patients in the 1st quartile had significantly higher mortality on admission (OR 3.59, 95% CI 1.396–9.282, P = 0.008) and discharge (OR 3.66, 95% CI 1.357–9.839, P = 0.01) compared with 4th quartile. P-value for the trend in mortality across quartiles of 6MWD on admission and discharge was 0.016 and 0.047, respectively. Cox proportional hazard analysis revealed that admission (HR 0.632, 95% CI 0.449–0.890, P = 0.009) and discharge 6MWD (HR 0.657, 95% CI 0.467–0.926, P = 0.016) were independent mortality determinants after adjustment for age, creatinine, sodium, systolic blood pressure and NYHA class, all on admission. CPET-derived variables did not predict either outcomes. Conclusion6MWD is an independent mortality determinant in advanced systolic HF.

Ambulatory advanced heart failure patients: timing of mechanical circulatory support - delaying the inevitable?

Current indications for continuous-flow left ventricular assist device (cfLVAD) implantation is for patients in cardiogenic shock or inotrope-dependent advanced heart failure. Risk stratification of noninotrope dependent ambulatory advanced heart failure patients is a subject of registries designed to help shared-decision making by clinicians and patients regarding the optimal timing of mechanical circulatory support (MCS). The Registry Evaluation of Vital Information for VADs in Ambulatory Life enrolled ambulatory noninotrope dependent advanced systolic heart failure patients who had 25% annualized risk of death, MCS, or heart transplantation (HT). Freedom from composite clinical outcome at 1-year follow-up was 23.5% for the entire cohort. Seattle Heart Failure Model Score and Natriuretic pepides were predictors with modest discriminatory power. Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) profile 4 patients had the highest risk (3.7-fold) of death, MCS or HT compared to INTERMACS profile 7. We propose individualized risk stratification for noninotrope dependent ambulatory advanced heart failure patients and include serial changes in end-organ function, nutritional parameters, frailty assessment, echocardiographic and hemodynamic data. The clinical journey of a patient with advanced heart failure should be tracked and discussed at each clinic visit for shared decision-making regarding timing of cfLVAD.

Abstract 16239: Skeletal Muscle Mass Recovery Early After Left Ventricular Assist Device Implantation in Patients With Advanced Systolic Heart Failure

Introduction: Patients with advanced systolic heart failure (HF) are at risk of unintentional weight loss and muscle wasting. It has been observed that left ventricular assist device (LVAD) recipients gain weight after device implantation, although it is unknown whether this represents skeletal muscle or fat mass gains. Hypothesis: We hypothesized that LVAD recipients would gain skeletal muscle mass during the first 6 months of LVAD support. Methods: We prospectively recruited 28 adults with systolic HF ±21 days from LVAD implantation. Participants underwent whole-body dual X-ray absorptiometry (DXA) to calculate fat free mass (FFM, representing all lean mass), appendicular lean mass (ALM, lean mass in the arms and legs) and fat mass (FM). DXA was repeated at 3 and 6 months after LVAD implantation (±14 days), with study participation ending after either the 6 month visit or heart transplantation, whichever occurred first. Paired t-testing and mixed effects models were used to evaluate changes over time each for FFM, ALM and FM. Results: The cohort was 86% (24/28) male, with mean age 56 ±12 years and mean BMI 26.6 ±5.5 kg/m 2 at baseline. The median Intermacs class was 2 and duration of HF 50 months. Per European Working Group on Sarcopenia in Older People (EWGSOP) criteria, 41% of participants had muscle wasting at baseline. There was a significant increase from baseline to 3 months and then 6 months of LVAD support for FFM (Fig 1A; baseline: 56.6 ±11.8 kg, n=27; 3 months: 57.9 ±11.3 kg, n=23; 6 months: 62.7 ±11.1 kg, n=17; p-value for change=0.025) and for ALM (Fig 1B; 22.2 ±5.6 kg; 23.2 ±5.0 kg; 25.4 ± 4.5 kg; p&lt;0.001). There was no increase in FM over the same period (p=0.36). Amongst 22 participants with comparison DXAs, 81% had a ≥5% ALM gain by either 3 or 6 months. Conclusions: Among patients with advanced systolic HF and a high baseline prevalence of muscle wasting, there was a significant gain in skeletal muscle mass, as represented by both FFM and ALM, over the first 6 months of LVAD support.

Guideline-based and personalized treatment approach to reduce hospitalizations and mortality for high risk advanced chronic systolic heart failure

Abstract The aim of our research was to evaluate mortality and rehospitalizations rates in patients with high risk subtype of heart failure (advanced HF) during 12 months of intensive monitoring after discharge on the basis of guidelines recommendations and personalized approach in treatment with frequent outpatient monitoring to reveal subcompensation/worsening of HF. Methods High risk advanced subtype of systolic HF was determined based on at least two hospitalizations during last year, severely reduced EF&amp;lt;30%, right and left atria hypertension echo patterns, pseudonormal/restrictive diastolic dysfunction, frequent outpatient deterioration of euvolemic state. Patients were randomized into two groups: 143 patients who underwent personalized intensive outpatient monitoring with care and 71 patients who underwent standard monitoring with regular guideline based treatment Intensive monitoring in ambulatory settings included frequent attending protocol of clinical evaluation (from OPTIMIZE -HF multicenter study), body mass, heart rate, GFR controls and additional echo evaluation of pressures in right and left atria at every outpatient visit, lung ultrasound with detection of B-lines. Results Cumulative number of CV and HF deaths was 11% (16 out of 143 in intensive monitoring group) and 36% (26 out of 71 patients) in standard monitoring group. Kaplan-Meier curve showed survival benefit in patients with personalized monitoring and treatment compared to those who were on standard care (Picture 1). Conclusions A strong trend towards decline in mortality and rehospitalizations, when personalized outpatient monitoring was implemented was observed (P&amp;lt;0,001) at 12 months in patients with advanced systolic heart failure. Kaplan-Meier survival curves groups Funding Acknowledgement Type of funding source: None

Myocardial work – new insights from deformation imaging in patients with advanced heart failure

Abstract Background The evaluation of myocardial contractility appears to be a major determinant for the prognosis and allocation of treatment strategies in advanced systolic heart failure (HFrEF). Non-invasive measurement of myocardial work is currently emerging as a new promising method for the assessment of myocardial contractility, as it additionally accounts for hemodynamic loading conditions of the ventricle. Objectives This study sought to assess the prognostic impact of myocardial work in patients with advanced heart failure and to compare it with routinely used deformation imaging parameters. Methods We included 234 patients with HFrEF under guideline directed therapy and comprehensively assessed myocardial work, as well as global longitudinal strain (GLS) by speckle tracking echocardiography. The primary endpoint was all-cause mortality. Results Median age of the patients was 68 years (IQR 60–75) and 78% were male. Over a 5-year follow-up period, 107 patients died. Median GWI was 526 mmHg% (IQR 366–779) and median GCW was 730 mmHg% (IQR 523–988). Parameters of myocardial work displayed a strong and independent association with long-term mortality, even after careful adjustment for clinical and echocardiographic confounders (Table 1). Additionally, we observed a significantly better calibration towards long-term mortality for GCW compared to GLS as the current golden standard for myocardial deformation imaging (AUC 0.63 vs. 0.60; P=0.007). Conclusion This is the first study to comprehensively assess global myocardial work in patients with advanced heart failure. Important treatment decisions rely on the assessment of myocardial contractility and risk stratification, specifically in late stages of the disease where exact guiding of treatment success and timely allocation of more aggressive treatment strategies are warranted. By incorporating loading conditions, myocardial work seems to be able to sensitively detect changes in myocardial contractility thath predict a dismal course of the disease. Furthermore, our data suggests that global constructive work is a more sensitive parameter to predict long-term outcome compared to the currently used echocardiographic deformation imaging parameters (i.e. GLS). Funding Acknowledgement Type of funding source: None

Catheter Ablation for Persistent Atrial Fibrillation in Class IV Systolic Heart Failure: A Single-Center Case Series.

Questions remain as to how aggressively catheter ablation for atrial fibrillation may be applied to patients with advanced systolic congestive heart failure, owing to a historic under-representation in multicenter clinical ablation trials. We sought to describe the experience of catheter ablation for persistent atrial fibrillation in Class IV systolic heart failure patients at our institution. All Class IV systolic heart failure patients (left ventricular assist device patients excluded) between 2017 and 2020 referred for radiofrequency ablation were included. Out of 10 patients, 7 agreed to proceed, had restoration of normal sinus rhythm upon completion of the catheter ablation procedure, and of which five (71%) remain in normal rhythm at a mean follow-up of 23 months. Catheter ablation for atrial fibrillation in patients with Class IV chronic systolic heart failure, even on advanced heart failure therapies, is feasible, and can improve heart failure status with maintenance of NSR.

Levosimendan in the treatment of patients with acute cardiac conditions: an expert opinion of the Association of Intensive Cardiac Care of the Polish Cardiac Society.

Levosimendan is a new inodilator which involves 3 main mechanisms: increases the calcium sensitivity of cardiomyocytes, acts as a vasodilator due to the opening of potassium channels, and has a cardioprotective effect. Levosimendan is mainly used in the treatment of acute decompensated heart failure (class IIb recommendation according to the European Society of Cardiology guidelines). However, numerous clinical trials indicate the validity of repeated infusions of levosimendan in patients with stable heart failure as a bridge therapy to heart transplantation, and in patients with accompanying right ventricular heart failure and pulmonary hypertension. Due to the complex mechanism of action, including the cardioprotective and anti- -aggregating effect, the use of levosimendan may be particularly beneficial in acute coronary syndromes, preventing the occurrence of acute heart failure. There are data indicating that levosimendan administered prior to cardiac surgery may improve outcomes in patients with severely impaired left ventricular function. The multidirectional mechanism of action also affects other organs and systems. The positive effect of levosimendan in the treatment of cardiorenal and cardiohepatic syndromes has been shown. It has a safe and predictable profile of action, does not induce tolerance, and shows no adverse effects affecting patients survival or prognosis. However, with inconclusive results of previous studies, there is aneed for awell-designed multicenter randomized placebo-‑controlled study, including an adequately large group of outpatients with chronic advanced systolic heart failure.

Impact of Socioeconomic Factors on Patient Desire for Early LVAD Therapy Prior to Inotrope Dependence

Worsening heart failure (HF) and health-related quality of life (HRQOL) have been shown to impact the decision to proceed with left ventricular assist device (LVAD) implantation, but little is known about how socioeconomic factors influence expressed patient preference for LVAD. Ambulatory patients with advanced systolic HF (n=353) reviewed written information about LVAD therapy and completed a brief survey to indicate whether they would want an LVAD to treat their current level of HF. Ordinal logistic regression analyses identified clinical and demographic predictors of LVAD preference. Higher New York Heart Association (NYHA) class, worse HRQOL measured by Kansas City Cardiomyopathy Questionnaire, lower education level, and lower income were significant univariable predictors of patients wanting an LVAD. In the multivariable model, higher NYHA class (OR [odds ratio]: 1.43, CI [confidence interval]: 1.08-1.90, P = .013) and lower income level (OR: 2.10, CI: 1.18 - 3.76, P = .012 for <$40,000 vs >$80,000) remained significantly associated with wanting an LVAD. Among ambulatory patients with advanced systolic HF, treatment preference for LVAD was influenced by level of income independent of HF severity. Understanding the impact of socioeconomic factors on willingness to consider LVAD therapy may help tailor counseling towards individual needs.