Abstract Background Exercise training (ET) is an effective therapy to improve peak oxygen consumption (V̇O2) in patients with heart failure with preserved ejection fraction (HFpEF). However, it remains unknown if such an intervention has a sustainable effect beyond the active study period. Purpose To investigate peakV̇O2 in the long-term period after completing a one-year ET intervention in HFpEF. Methods This is a long-term follow-up (FU) study of patients enrolled in the OptimEx-Clin or Ex-DHF trial, the two largest randomised controlled trials of ET over one year in HFpEF. In the OptimEx-Clin trial, 180 patients (mean age: 70 years; 67% women) with HFpEF were randomised to high-intensity interval training, moderate continuous training or usual care (UC). In the Ex-DHF trial, 322 patients (mean age: 70 years; 60% women) were randomised to endurance plus resistance training or UC. All patients who were randomised in one centre and completed the respective trial were contacted to participate in this FU. Baseline assessments were conducted between May 2013 and April 2017 with the last active study visit in May 2018. Patients were reassessed for FU between December 2021 and August 2022. Primary endpoint was the absolute change in peakV̇O2 between the baseline and FU visit. All exercise and both control groups were combined into one ET and one UC group. PeakV̇O2 was assessed during symptom-limited cardiopulmonary exercise testing (CPET) on a cycle ergometer at baseline, 3, 6, 12 months and at FU. PeakV̇O2 was defined as the highest 30-second average within the last minute of CPET. Statistical analyses were performed using dependent and independent t-tests with α = 0.05. Results Among 142 initially randomised patients, 75 were recruited for FU and 67 (40 ET; 27 UC) had available CPET data both at baseline and FU (75% women; mean [SD] age at baseline: 66±7 years). Mean time between baseline and FU was 6.3 ± 1.3 and 6.6 ± 0.8 years in the ET and UC groups, respectively. During the active study phase, ET patients significantly increased peakV̇O2 from baseline to 3, 6 and 12 months (mean change [95% CI]: 1.5 [0.6 to 2.3], 1.5: [0.5 to 2.4] and 1.4: [0.3 to 2.5] mL/kg/min, respectively; Fig. 1). However, a statistically significant difference between groups was only observed at 3 months (P=0.03). The change in peakV̇O2 from baseline to FU was not significantly different between both groups (ET: -2.7 ± 3.3 mL/kg/min; UC: -2.5 ± 3.6 mL/kg/min; P=0.87) (Fig. 1). Finally, between 12 months and FU, change in peakV̇O2 was -4.2 ± 3.6 mL/kg/min for ET, and -3.4 ± 3.3 mL/kg/min for UC patients (P=0.35). Conclusions While patients with HFpEF had significantly improved peakV̇O2 between 3 and 12 months of ET (~1.5 mL/kg/min), these effects were not sustainable beyond the active study period. This finding highlights the importance of incorporating behavioural strategies to ensure long-term adherence to ET is maintained for optimal benefits in peakV̇O2 over time. Change in peakV̇O2 (mean and 95% CI)

Abstract Background Elevated filling pressures and subsequent left atrial (LA) dilation are common findings in heart failure with preserved ejection fraction (HFpEF), reflecting a chronic state of the disease and holding prognostic value. HFpEF is thought to develop through a long-term pro-inflammatory state triggered by comorbidities, such as obesity and type 2 diabetes mellitus (T2DM). Emerging biomarkers have shown associations with structural remodeling, but also increased myocardial stiffness. Purpose To elucidate the relationship between LA volume and function, and prognostic biomarkers (NT-proBNP, BNP-32, IL1R1, Galectin-3, and Pentraxin-3) in an obese cohort with T2DM or HFpEF and T2DM, versus healthy obese controls. Methods We conducted a prospective cohort study of 35 obese participants, divided into three groups: T2DM (n=16), HFpEF with T2DM (NYHA II-III, n=13), and healthy obese controls (n=6). Each subject underwent comprehensive CMR at a 3T scanner to assess LA strain and volume. Atrial strain was assessed on 2- and 4-chamber view cine images by experienced CMR investigators using dedicated software. Routine labs and serum levels of biomarkers were measured. If labs or images were repeated, the average was calculated. Statistical significance was determined through ANOVA and student’s t-test for group comparisons and Pearson correlation for associations between LA parameters and biomarker levels. Results Cohorts were evenly matched in terms of demographics, vital signs, and ventricular volumes and functions, as depicted in Table 1. Only one patient in the HFpEF subgroup reported history of atrial fibrillation. Both minimum and maximum LA volumes were significantly elevated in the HFpEF group compared to the T2DM and control groups (p < 0.018). LA strain (conduit, reservoir, and booster) was notably compromised in the HFpEF cohort, contrasting with the obese T2DM group where LA strain values did not differ significantly from those observed in obese controls (Figure 1). Biomarker analysis revealed a marked increase of NT-proBNP, BNP-32, Galectin-3, and Pentraxin-3 in the HFpEF cohort. In the HFpEF cohort, IL1R1 was the only biomarker that was strongly associated with higher left ventricular enddiastolic (r=0.69, p=0.003) and endsystolic volumes (r=0.75, p=0.009). Moreover, IL1R1 was the only biomarker associated with atrial functional changes (booster strain, r=-0.57, p=0.043) in the HFpEF patients. Our findings indicate that ILR1 plays a crucial role in the cardiometabolic (obesity-T2DM) HFpEF phenotype, with its activation leading to advanced cardiac remodeling. Conclusion Obese HFpEF patients with T2DM showed severely altered left atrial morphology and function compared to those that are only obese or obese with T2DM. Moreover, our findings revealed that atrial remodeling in this population is driven by pro-fibrotic inflammatory pathways.Characteristics of the study cohortLeft atrial strain analysis

AIMS:In VICTORIA, vericiguat compared with placebo reduced the risk of cardiovascular death (CVD) and heart failure hospitalization (HFH) in patients enrolled after a worsening heart failure (WHF) event. We examined clinical outcomes and efficacy of vericiguat as it relates to background use of loop diuretics in patients with WHF. METHODS AND RESULTS:We calculated the total daily loop diuretic dose equivalent to furosemide dosing at randomization and categorized these as: no loop diuretic, 1-39, 41-80, 40, and >80 mg total daily dose (TDD). The primary composite outcome of CVD/HFH and its components were evaluated based on TDD loop diuretic and expressed as adjusted hazard ratios with 95% confidence intervals. Post-randomization rates of change in TDD were also examined. Of 4974 patients (98% of the trial) with diuretic dose information available at randomization, 540 (10.8%) were on no loop diuretic, 647 (13.0%) were on 1-39, 1633 (32.8%) were on 40, 1185 (23.8%) were on 41-80, and 969 (19.4%) were on >80 mg TDD. Patients with higher TDD had a higher rate of primary and secondary clinical outcomes. There were no significant interactions with TDD at randomization and efficacy of vericiguat versus placebo for any outcome (all pinteraction > 0.5). Post-randomization diuretic dose changes for vericiguat and placebo showed similar rates of up-titration (19.6 and 20.2/100 person-years), down-titration (16.8 and 18.1/100 person-years), and stopping diuretics (22.9 and 24.2/100 person-years). CONCLUSIONS:Loop diuretic TDD at randomization was independently associated with worse outcomes in this high-risk population. The efficacy of vericiguat was consistent across the range of diuretic doses.

Abstract Introduction and Aim Exercise intolerance is a hallmark feature of patients with heart failure with preserved ejection fraction (HFpEF).While clinical evidence suggests potential benefits of exercise training in HFpEF, its mechanisms remain largely unknown.In this study, we used a translationally relevant murine model of cardiometabolic HFpEF(1) to assess whether moderate intensity continuous training(MICT) can ameliorate the HFpEF phenotype in mice and promote cardiometabolic health. Methods Twenty-five adult, male C57BL/6N were fed with the combination of high fat diet(HFD;D12492,Research diet)and L-NAME(0.5 g/L,in drinking water) for 15 weeks to elicit HFpEF as previously described(1).After the establishment of the HFpEF phenotype, mice were randomized in two groups:sedentary(SED,n= 10) and exercised(MICT,n=15)mice.MICT was carried out according to the protocol:running on 10-degree positive inclination treadmill for 8 consecutive weeks,5 times/week,60 minutes/day,at a speed gradually increasing from 0.1 to 0.2 m/sec on a weekly basis.Morphometry, echocardiography(TTE),isoproterenol-induced stress echocardiography(SE),time domain nuclear magnetic resonance, and treadmill exhaustion tests were performed at the beginning and end of MICT.Additionally, at the end of MICT blood and tissues were collected for proteomics analysis(Fig1).Non-trained male C57BL/6N mice(37w) were used as controls for the HFpEF mice. Results Before randomization, all HFpEF mice were similar in terms of phenotypic characteristics. Compared to SED mice, MICT induced a significantly decrease in body weight driven by a reduction of total fat mass with an increased in lean mass(Fig2A+B).Interestingly, MICT had no impact on skeletal muscle mass for all different muscle groups evaluated (extensor digitorum longus, soleus and tibialis anterior).Importantly, MICT led to a significant improvement in exercise capacity in HFpEF mice, as shown by increased running distance and time, surpassing even the running distance seen in non-HFpEF mice (SED:62.8±18.7,MICT:305.7±13.9,non-HFpEF mice: 129.72±15.2meters,p<0.001).Preclinical surrogate of HFpEF such as pulmonary congestion, evaluated by index lung weights, improved after aerobic training.Following MICT there was a marked improvement in diastolic dysfunction(measured by E/E’ratio) both at rest(SED:36.5±3.3,MICT:23.3±5.09,p<0.001) and after isoproterenol challenge(SED:42.6±15.1,MICT:26.09±3.75,p<0.001)(Fig2C).Moreover, the wet cardiac mass was lower in the MICT group(Fig2A), suggesting potential amelioration in cardiac hypertrophy following aerobic training. Conclusion Eight weeks of supervised MICT on treadmill improves functional status, exercise capacity, and diastolic function in a cardiometabolic HFpEF murine model.The most significant effects were seen on weight loss and fat mass reduction.Our findings suggest a beneficial impact of aerobic exercise in mitigating HFpEF by improving metabolic fitness in the preclinical HFpEF model.Fig1-Study DesignFig2-Characteristics SED vs MICT groups

Abstract Background In patients with heart failure with preserved ejection fraction (HFpEF), ventilatory inefficiency is associated with worse prognosis, and may indicate co-existing pulmonary hypertension (PH) or a higher risk of developing PH. While different exercise training modes [e.g., moderate continuous training (MCT), high-intensity interval training (HIIT)] have been shown to improve peak oxygen uptake in HFpEF over 3-6 months, the effects on ventilatory efficiency are largely unknown. Purpose To investigate the effects of HIIT, MCT or usual care (UC) over 12 months on ventilatory efficiency in HFpEF. Methods In the OptimEx-Clin trial, 180 stable patients with HFpEF were randomly assigned to 12 months of HIIT (3×38 min/week with 4×4 min at 80-90% heart rate reserve [HRR]), MCT (5×40 min/week at 35-50% HRR) or UC (one-time advice on physical activity). Ventilatory efficiency parameters were assessed during symptom-limited cardiopulmonary exercise testing on a bicycle ergometer at baseline and follow-up. Ventilation to carbon dioxide production (V̇E/V̇CO2) slope and y-intercept were calculated between one minute of cycling and the second ventilatory threshold. The nadir of the ventilatory equivalent for CO2 (EqCO2) was defined as the lowest 60-second average during exercise. PetCO2 values were calculated as the lowest 60-second average at rest and the highest 60-second average during exercise. Statistical analyses were performed using dependent t-tests for within-group changes from baseline to 12 months, and analysis of variance and independent t-tests to compare the changes between groups. Analyses were done in R Statistical Software with α=0.05 and without adjusting for multiple testing. Results Among 180 randomized patients, 138 who had available CPET data both at baseline and 12-month follow-up (66% female; mean age, 70 years) were included in this secondary analysis. In the HIIT group, all investigated ventilatory efficiency parameters (V̇E/V̇CO2 slope, V̇E/V̇CO2 slope y-intercept, EqCO2 nadir, PetCO2 at rest and during exercise) significantly worsened from baseline to 12 months (P<0.05), while none were significantly altered following MCT or UC (Tab. 1). Group comparisons revealed significant differences between HIIT and MCT for change in V̇E/V̇CO2 slope [mean difference, +2.6 (95% CI, 0.8 to 4.5), global P=0.04)], V̇E/V̇CO2 slope y-intercept [-1.4 (95% CI, -2.5 to -0.3); global P=0.02)] and PetCO2 at rest [-2.0 mmHg (-3.5 to -0.5); global P=0.001)]. Moreover, change in PetCO2 at rest was also significantly different between HIIT and UC [-2.7 mmHg (-4.1 to -1.2)]. Conclusions In patients with HFpEF, ventilatory efficiency significantly worsened after 12 months of HIIT, which could be indicative of worsened heart failure prognosis and/or a shift towards PH – a frequent sequela of HFpEF.

Abstract Introduction Patients with heart failure with preserved ejection fraction represent half of the heart failure patients nowadays, an at least steady trend due to the aging of the population. We investigated whether the parameters obtained from cardiopulmonary exercise testing (CPET) correlated with the prognosis of these patients. This prospective observational cohort study looks into the relationship between the CPET parameters peak VO2 and VE/VCO2 slope and the heart failure hospitalizations or cardiovascular death of these patients. Methods From August 2016 until May 2019, 99 patients of our outpatient clinic with newly diagnosed with heart failure with preserved ejection fraction underwent cardiopulmonary exercise testing. Median follow-up was 30 months (interquartile range, 24-38.5). We selected peak VO2 <14 ml/min/kg and a VE/VCO2 slope > 34 as threshold values for our primary endpoint, a composite of hospitalization for heart failure or cardiovascular death. Results The mean age was 75.07 ± 7.31 years, 48.5% were women, 24.2% were at NYHA class III and mean NTproBNP was 511 pg/mL. Mean peakVO2 was 15.09 ± 4.75 and mean VE/VCO2 was 36.05 ± 6.60. During follow-up, they were 67 hospitalizations, 53 cardiovascular hospitalizations, 24 heart failure hospitalizations and 4 deaths. Over a median follow-up of 30 months, the primary outcome event occurred in 5 of 40 patients (12.5%) with a VE/VCO2 Slope ≤ 34 and in 19 of 59 patients (32.2%) with a VE/VCO2 Slope > 34 (hazard ratio, 2.688; 95% confidence interval (CI); P 0.04). On multivariate analysis, accounting for heart failure hospitalization or cardiovascular death as a terminal event, VE/VCO2 slope was independently associated with the risk of admission due to heart failure worsening. Conclusion In patients with heart failure with preserved ejection fraction, a VE/VCO2 Slope > 34 predicts heart failure hospitalizations and cardiovascular death.Primary Endpoint

Aim An echocardiographic algorithm derived by machine learning (e′VM) characterizes pre‐clinical individuals with different cardiac structure and function, biomarkers, and long‐term risk of heart failure (HF). Our aim was the external validation of the e′VM algorithm and to explore whether it may identify subgroups who benefit from spironolactone. Methods and results The HOMAGE (Heart OMics in AGEing) trial enrolled participants at high risk of developing HF randomly assigned to spironolactone or placebo over 9 months. The e′VM algorithm was applied to 416 participants (mean age 74 ± 7 years, 25% women) with available echocardiographic variables (i.e. e′ mean, left ventricular end‐diastolic volume and mass indexed by body surface area [LVMi]). The effects of spironolactone on changes in echocardiographic and biomarker variables were assessed across e′VM phenotypes. A majority (>80%) had either a ‘diastolic changes’ (D), or ‘diastolic changes with structural remodelling’ (D/S) phenotype. The D/S phenotype had the highest LVMi, left atrial volume, E/e', natriuretic peptide and troponin levels (all p < 0.05). Spironolactone significantly reduced E/e' and B‐type natriuretic peptide (BNP) levels in the D/S phenotype ( p < 0.01), but not in other phenotypes ( p > 0.10; p interaction <0.05 for both). These interactions were not observed when considering guideline‐recommended echocardiographic structural and functional abnormalities. The magnitude of effects of spironolactone on LVMi, left atrial volume and a type I collagen marker was numerically higher in the D/S phenotype than the D phenotype but the interaction test did not reach significance. Conclusions In the HOMAGE trial, the e′VM algorithm identified echocardiographic phenotypes with distinct responses to spironolactone as assessed by changes in E/e' and BNP.

Abstract Background Prognosis in HFpEF is determined by risk factor control and treatment of comorbidities. Industrially processed TFA (IP-TFA) from partially hydrogenated oils have been linked to altered lipoprotein metabolism, endothelial dysfunction, increased biomarkers of inflammation and increased NTproBNP. In patients with heart failure with preserved ejection fraction (HFpEF), associations of TFA blood levels with patient characteristics are unknown. Purpose To evaluate associations of blood TFA with cardiovascular risk factors, aerobic capacity and cardiac function in patients with HFpEF. Methods This is a secondary analysis from the Aldo-DHF-RCT. From 422 patients, individual blood TFA were analyzed at baseline in n=404 using the HS-Omega-3-Index® methodology. Patient characteristics were; 67±8 years, 53% female, NYHA II/III (87/13%), ejection fraction ≥50%, E/e' 7.1±1.5; median NT-proBNP 158 ng/L (IQR 82–298). Multiple linear regression analyses, using sex and age as covariates, were used to describe associations of TFA with metabolic phenotype, functional capacity, echocardiographic markers for left ventricular diastolic function (LVDF), and neurohumoral activation at baseline and after 12-months-follow-up (12mFU). To account for randomization group, all analyses were repeated as sensitivity analysis with group as covariate. A significance level of α=5% was used for all tests. As all tests were hypothesis generating without confirmatory interpretation, no correction was applied to counteract the problem of multiple comparisons. Results Higher blood levels of the naturally occurring TFA C16:1n-7t were broadly associated with a more favorable lipid profile, lower body weight/central adiposity, lower white blood cell count and lower biochemical markers of non-alcoholic fatty liver disease at baseline/12mFU. Conversely, blood levels of the IP-TFA C18:1n9t were directly associated with lipid risk markers [triglycerides (β=19.7, p<0,001), non-HDL-C (β=7.9, p=0,001), and LDL-C (β=5.4, p=0,011)]. The two IP-TFA C18:2n6 isomers C18:2n6tt and C18:2n6ct were positively associated with HbA1c [(β=14.6, p=0,003) and (β=4.2, p=0,014) respectively]. The IP-TFA C18:2n6tt/-ct isomers were associated with lower submaximal aerobic capacity (distance covered in the 6MWT) at baseline/12mFU. No significant association was found between TFA blood levels and left ventricular filling pressures, left ventricular relaxation or neurohumoral activation. Significant effects of group allocation (spironolactone +/−) were found for the 12mFU outcomes systolic/diastolic blood pressure (all p<0.001), heart rate, E/e$'$ and HbA1c. Conclusions In HFpEF patients, higher blood levels of industrially processed TFA, but not of the TFA C16:1n-7t in full fat dairy and meat, were associated with a higher risk phenotype and lower aerobic capacity. Our findings support efforts to remove IP-TFA from the food supply for improving risk factor control in HFpEF patients. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): German Foundation of Heart Research

Abstract Introduction In heart failure with preserved ejection fraction (HFpEF), moderate continuous training (MCT) and high-intensity interval training (HIIT) are both effective in increasing peak oxygen uptake (peak V̇O2). Purpose The aim of this study was to investigate the association of training characteristics (i.e. average sessions/week, average duration/week, mean intensity) and change in peak V̇O2 following 3 months of MCT and HIIT in patients with HFpEF. Methods Among 120 patients who were randomized to MCT (5x40 min/week at 35–50% heart rate reserve [HRR]) or HIIT (3x38 min/week at 80–90% HRR), those who completed 3-month follow-up (N=107) were considered for this analysis. Training duration and heart rates [HR] were recorded with a smartphone application, evaluated with a customized software and manually checked for plausibility. If HR measurements were classified as invalid/unreliable (e.g. very strong fluctuations), patients were excluded from analysis. Intensities were calculated as average % HRR of total sessions in MCT and the average of the highest % HRR values of all intervals in HIIT. Associations between training characteristics and change in peak V̇O2 were evaluated using univariate and multivariate regression analyses. Individual HR-V̇O2 relationships were used to calculate and compare energy expenditure (MET-minutes) in MCT and HIIT. Results After excluding 16 patients due to invalid/unreliable HR data, 91 patients (67% female, 69±7 years) were included in this analysis. On average, MCT patients (N=45) performed 4.0±1.2 sessions/week (162±52 min/week) at 47.4±6.7% HRR, while HIIT patients (N=46) performed 2.4±0.8 sessions/week (96±40 min/week) at 81.8±11.8% HRR. Peak V̇O2 was improved by 1.70±2.35 ml/kg/min in MCT and 1.46±2.98 ml/kg/min in HIIT (difference: 0.24 [95% CI, −0.87 to 1.34], p=0.67). The associations between training characteristics and change in peak V̇O2 are shown in Fig.1. Mean % HRR was not significantly associated with the change in peak V̇O2 in the HIIT group, whereas in MCT, mean duration/week and mean intensity were of similar relative importance (standardized coefficients) and explained up to 26% of the variation in change in peak V̇O2 (Table 1). Average weekly MET-minutes above rest were 451±260 for MCT and 389±375 for HIIT (difference: 62 [95% CI, −71 to 195], p=0.36). After adjustment for MET-minutes, the difference in change in peak V̇O2 between groups diminished to 0.09 ml/kg/min (95% CI, −0.97 to 1.16; p=0.98). Conclusions Weekly duration and mean % HRR had a similar predictive ability for the change in peak V̇O2 following MCT with, interestingly, lower change in peak V̇O2 with increasing intensity. In HIIT, mean % HRR was not significantly associated with the change in peak V̇O2. After adjusting for energy expenditure, the difference in change in peak V̇O2 between training modes diminished, suggesting that MCT and HIIT were similarly effective. Funding Acknowledgement Type of funding sources: Public grant(s) – EU funding. Main funding source(s): European Commission, Framework Program 7

Abstract Background In the VICTORIA trial (n=5050) the reduction in the primary composite endpoint of cardiovascular death (CVD) or heart failure hospitalization (HFH) was similar whether or not patients received sacubitril/valsartan. The distribution of those patients who received sacubitril/valsartan after randomization (drop-ins) and the relationship to the efficacy and safety of vericiguat is unknown. Purpose We assessed the efficacy and safety of vericiguat in patients who were or were not treated with sacubitril/valsartan at baseline in the VICTORIA trial and the implications of post- randomization use of sacubitril/valsartan. Methods A total of 5040 patients were analyzed according sacubitril/valsartan use at randomization or initiated after randomization. The efficacy of vericiguat on the primary composite endpoint and its components, time to first HF hospitalization or all-cause mortality, were assessed according to sacubitril/valsartan use. Safety outcomes included symptomatic hypotension, syncope, worsening renal function, and hyperkalemia. Results Overall, 731 patients (360 on vericiguat and 371 on placebo) received sacubitril/valsartan at randomization. Patients treated with sacubitril/valsartan were twice as likely to be from Western Europe or North America, to have a lower ejection fraction and systolic and diastolic blood pressures, were more often on triple therapy (65.9 vs 58.6%), and more likely to have received biventricular pacing (17.9 vs 14.1%) or ICDs (42.3 vs 25.3%). For patients on sacubitril/valsartan at baseline, the adjusted hazard ratios for vericiguat's treatment effect on the primary composite outcome, CVD, and HFH was 0.94 (95% CI 0.74–1.20), 0.81 (95% CI 0.55–1.20) and 0.99 (95% CI 0.76–1.30), respectively. For those patients not on sacubitril/valsartan (2161 vericiguat; 2148 on placebo), the corresponding adjusted hazard ratios for vericiguat's treatment effect on the primary composite outcome, CVD, and HFH were 0.89 (0.80–0.98), 0.95 (0.82–1.11), and 0,87 (0.78–0.98), respectively. There was no significant interaction on the treatment effect of vericiguat based on the use of sacubitril/valsartan. More placebo patients (n=238) received drop-in use of sacubitril/valsartan than vericiguat group (n=187; p=0.007) post-randomization during follow-up (Figure). Overall, adverse events in the 992 patients receiving sacubitril/valsartan (at either baseline or drop-in for at least 3 months) were not significantly different according to those on placebo vs vericiguat for symptomatic hypotension (21.0% vs 23.1), renal dysfunction (8.0 vs 9.0%), and hyperkalemia (10.3 vs 7.9%). Conclusions Sacubitril/valsartan use was initiated more frequently after randomization in patients on placebo than on vericiguat. Concomitant use of sacubitril/valsartan did not alter the efficacy of vericiguat and was similarly tolerated in both study arms. Funding Acknowledgement Type of funding sources: Other. Main funding source(s): Merck & Co., Inc. and Bayer

Heart failure (HF) patients represent one of the most prevalent as well as one of the most fragile population encountered in the cardiology and internal medicine departments nowadays. Estimated to account for around 26 million people worldwide, diagnosed patients present a poor prognosis and quality of life with a clinical history accompanied by repeated hospital admissions caused by an exacerbation of their chronic condition. The frequent hospitalizations and the extended hospital stays mean an extremely high economic burden for healthcare institutions. Meanwhile, the number of chronically diseased and elderly patients is continuously rising, and a lack of specialized physicians is evident. To cope with this health emergency, more efficient strategies for patient management, more accurate diagnostic tools, and more efficient preventive plans are needed. In recent years, telemonitoring has been introduced as the potential answer to solve such needs. Different methodologies and devices have been progressively investigated for effective home monitoring of cardiologic patients. Invasive hemodynamic devices, such as CardioMEMS™ , have been demonstrated to be reducing hospitalizations and mortality, but their use is however restricted to limited cases. The role of external non-invasive devices for remote patient monitoring, instead, is yet to be clarified. In this review, we summarized the most relevant studies and devices that, by utilizing non-invasive telemonitoring, demonstrated whether beneficial effects in the management of HF patients were effective.

In patients undergoing decongestive therapy for acute heart failure (AHF), endogenous filtration markers such as serum creatinine (SCr) or cystatin C (CysC) are used to monitor kidney function. We tested whether dynamics of endogenous filtration markers and estimated GFR (eGFR) based on these markers appropriately reflect changes of measured GFR (mGFR) patients with AHF.