Heart Failure Status Research Articles

Cost-effectiveness of immediate initiation of dapagliflozin in patients with a history of heart failure.

To compare the cost-effectiveness of immediate and 12-month delayed initiation of dapagliflozin treatment in patients with a history of hospitalization for heart failure (HHF) from the UK, Canadian, German, and Spanish healthcare perspectives. A cost-utility analysis was conducted using a decision-analytic Markov model with health states defined by Kansas City Cardiomyopathy Questionnaire scores, type 2 diabetes mellitus status and incidence of heart failure (HF) events. Patient-level data for patients with prior HHF from the Dapagliflozin And Prevention of Adverse-outcomes in Heart Failure (DAPA-HF) trial were used to inform the model inputs on clinical events and utility values. Healthcare costs were sourced from the relevant national reference databases and the published literature. Compared to standard therapy, immediate initiation of dapagliflozin decreased HHF (187 events), urgent HF visits (32 events) and cardiovascular mortality (18 events). Standard therapy was associated with lifetime costs of £13 224 and 4.02 quality-adjusted life years (QALYs). Twelve-month delayed initiation of dapagliflozin was associated with total discounted lifetime costs and QALYs of £16 660 and 4.61, respectively, compared to £16 912 and 4.66, respectively, for immediate initiation. Compared to standard therapy, immediate and 12-month delayed initiation of dapagliflozin yielded an incremental cost-effectiveness ratio (ICER) of £5779 and £5821, respectively. Compared to 12-month delayed initiation, immediate initiation of dapagliflozin had an ICER of £5263. Results were similar from the Canadian, German, and Spanish healthcare perspectives. Both immediate and 12-month delayed initiation of dapagliflozin are cost-effective. However, immediate initiation provides greater clinical benefits, with almost 10% additional QALYs gain, compared to 12-month delayed initiation of dapagliflozin and should be considered standard of care.

Effects of sodium glucose cotransporter 2 inhibitors on the risk of hyperkalemia in patients on mineralocorticoid receptor antagonist: a systematic review and meta-analysis

Abstract Funding Acknowledgements Type of funding sources: None. Background Occurrence of hyperkalemia has been a great limitation in the full implementation of a guideline-directed medical therapy especially in patients with heart failure. Recent developments have exhibited the positive role of SGLT2 inhibitors, not only on the cardiovascular outcomes but also conferred renal protection. Purpose We explored the effects of SGLT2i and MRA combination on the risk of developing hyperkalemia. Methods Randomized controlled trials on SGLT2i versus placebo in patients already on MRA regardless of heart failure status reporting outcomes of potassium homeostasis were searched using Pubmed, CENTRAL, and ScienceDirect. Outcome of interest was the effects on the risk of hyperkalemia. Pooled hazard ratios with 95% confidence intervals were used as effect estimates using fixed-effects model. Results Five studies were included with a total of 11,123 patients. There was a significant reduction on the risk of hyperkalemia in the MRA with SGLT2i group (HR 0.61, 95% CI 0.50-0.75, p<0.00001) compared to MRA without SGLT2i group. Conclusion SGLT2i provides significant risk reduction on the development of hyperkalemia in patients already on a mineralocorticoid receptor antagonist.

Effects of Ertugliflozin on Kidney Outcomes in Patients With Heart Failure at Baseline in the Evaluation of Ertugliflozin Efficacy and Safety Cardiovascular Outcomes (VERTIS CV) Trial

In the eValuation of ERTugliflozin effIcacy and Safety CardioVascular outcomes (VERTIS CV) trial (NCT01986881), patients with type 2 diabetes mellitus (T2DM) and atherosclerotic cardiovascular disease (ASCVD) were randomized (1:1:1) to placebo, ertugliflozin 5 mg or 15 mg (doses pooled for analyses as prospectively planned). In this post hoc analysis, the effects of ertugliflozin on kidney outcomes were assessed in analyses stratified by baseline heart failure (HF). Baseline HF was defined as a history of HF or prerandomization left ventricular ejection fraction≤45%. Outcomes included estimated glomerular filtration rate (eGFR) over time, total 5-year eGFR slopes and time to first event of a prespecified exploratory kidney composite outcome of sustained≥40% decrease from baseline eGFR, chronic kidney replacement therapy, or kidney death. All analyses were stratified by baseline HF status. Compared with no-HF at baseline (n= 5807; 70.4%), patients with HF (n= 2439; 29.6%) had a notably faster rate of eGFR decline, which is unlikely to be explained by the slightly lower baseline eGFR in that group. Ertugliflozin treatment resulted in a slower rate of eGFR decline in both subgroups; total placebo-adjusted 5-year eGFR slopes (ml/min per 1.73 m2 per year [95% confidence intervals; CI]) were 0.96 (0.67-1.24) and 0.95 (0.76-1.14) for HF and no-HF subgroups, respectively. The placebo HF (vs. placebo no-HF) subgroup had a higher incidence of the composite kidney outcome (35/834 [4.20%] vs. 50/1913 [2.61%]). Hazard ratios (95% CI) for the effect of ertugliflozin on the composite kidney outcome did not differ significantly between HF and no-HF subgroups: 0.53 (0.33-0.84) and 0.76 (0.53-1.08), respectively (P interaction = 0.22). Although patients with HF at baseline had a faster rate of eGFR decline in VERTIS CV, the beneficial effects of ertugliflozin on kidney outcomes did not differ when stratified by baseline HF.

PS-C17-4: ASSOCIATION BETWEEN SERUM INSULIN LEVELS AND HEART FAILURE-RELATED PARAMETERS IN PATIENTS WITH TYPE 2 DIABETES AND HEART FAILURE

Background: Insulin resistance and hyperinsulinemia in patients with type 2 diabetes (T2D) are adversely associated with the development and worsening of heart failure (HF). Herein, we sought to investigate the effect of canagliflozin on insulin concentrations and the associations of changes in insulin concentrations with HF-related clinical parameters in patients with T2D and HF. Methods: This was a post hoc analysis of the investigator-initiated, multicenter, open-label, randomized, controlled CANDLE trial for patients with T2D and chronic HF (UMIN000017669). The endpoints were the effects of 24 weeks of canagliflozin treatment, relative to glimepiride treatment, on insulin concentrations and the relationship between changes in insulin concentrations and clinical parameters of interest, including New York Heart Association (NYHA) classification. The effects of canagliflozin on those parameters were also analyzed by baseline insulin level. Results: Among the participants in the CANDLE trial, a total of 129 patients (canagliflozin, n = 64; glimepiride, n = 65) who were non-insulin users with available serum insulin data both at baseline and week 24 were included in this analysis. Overall, the mean age was 69.0 ± 9.4 years; 75% were male; the mean HbA1c was 6.8 ± 0.7%; and the mean left ventricular ejection fraction was 59.0 ± 14.1%, with parameters roughly balanced between treatment groups. Canagliflozin treatment significantly reduced insulin concentrations at week 24 (p < 0.001), and the between-group difference (canagliflozin minus glimepiride) in those changes was -3.52 mU/L (95% confidence interval, -4.85 to -2.19; p < 0.001). Decreases in insulin concentrations, irrespective of baseline insulin level, were significantly associated with improvement in NYHA class in patients treated with canagliflozin. Conclusion: Our findings suggest that canagliflozin treatment in patients with T2D and HF ameliorated excess insulin overload, contributing to the improvement of clinical HF status.

Volume Status Assessment by Lung Ultrasound in End-Stage Kidney Disease: A Systematic Review.

Lung ultrasound is a noninvasive bedside technique that can accurately assess pulmonary congestion by evaluating extravascular lung water. This technique is expanding and is easily available. Our primary outcome was to compare the efficacy of volume status assessment by lung ultrasound with clinical evaluation, echocardiography, bioimpedance, or biomarkers. The secondary outcomes were all-cause mortality and cardiovascular events. We conducted a MEDLINE literature search for observational and randomized studies with lung ultrasound in patients on maintenance dialysis. From a total of 2363 articles, we included 28 studies (25 observational and 3 randomized). The correlation coefficients were pooled for each variable of interest using the generic inverse variance method with a random effects model. Among the clinical parameters, New York Heart Association Functional Classification of Heart Failure status and lung auscultation showed the highest correlation with the number of B-lines on ultrasound, with a pooled r correlation coefficient of .57 and .36, respectively. Among echocardiographic parameters, left ventricular ejection fraction and inferior vena cava index had the strongest correlation with the number of B-lines, with a pooled r coefficient of .35 and .31, respectively. Three randomized studies compared a lung ultrasound-guided approach with standard of care on hard clinical endpoints. Although patients in the lung ultrasound group achieved better decongestion and blood pressure control, there was no difference between the 2 management strategies with respect to death from any cause or major adverse cardiovascular events. Lung ultrasound may be considered for the identification of patients with subclinical volume overload. Trials did not show differences in clinically important outcomes. The number of studies was small and many were of suboptimal quality. The included studies were heterogeneous and of relatively limited quality.

New Classification for the Combined Assessment of the Fractional Excretion of Urea Nitrogen and Estimated Plasma Volume Status in Acute Heart Failure.

Background The fractional excretion of urea nitrogen (FEUN) has been used as a renal blood flow index related to cardiac output, and the estimated plasma volume status (ePVS) as a body fluid volume index. However, the usefulness of their combination in acute decompensated heart failure (HF) management is unclear. We investigated the effect of 4 hemodynamic categories according to the high and low FEUN and ePVS values at discharge on the long-term prognosis of patients with acute decompensated HF. Methods and Results Between April 2011 and December 2018, we retrospectively identified 466 patients with acute decompensated HF with FEUN and ePVS values at discharge. Primary end point was postdischarge all-cause death. Secondary end points were (1) the composite of all-cause death and HF readmission, and (2) HF readmission in a time-to-event analysis. The patients were divided into 4 groups according to the high/low FEUN (≥35%, <35%) and ePVS (>5.5%, ≤5.5%) values at discharge: high-FEUN/low-ePVS, high-FEUN/high-ePVS, low-FEUN/low-ePVS, and low-FEUN/high-ePVS groups. During a median follow-up period of 28.1 months, there were 173 all-cause deaths (37.1%), 83 cardiovascular deaths (17.8%), and 121 HF readmissions (26.0%). The Kaplan-Meier curve analysis showed that the high-FEUN/low-ePVS group had a better prognosis than the other groups (log-rank test, P<0.001). In the multivariable Cox regression analysis, the low-FEUN/high-ePVS group had a higher mortality than the high-FEUN/low-ePVS group (hazard ratio, 2.92 [95% CIs, 1.73-4.92; P<0.001]). Conclusions The new classification of the 4 hemodynamic profiles using the FEUN and ePVS values may play an important role in improving outcomes in patients with stable acute decompensated HF.

Hemodynamic Gain Index and Exercise Capacity in Heart Failure With Preserved Ejection Fraction

Decreased exercise capacity portends a poor prognosis in heart failure with preserved ejection fraction (HFpEF). The hemodynamic gain index (HGI) is an integrated marker of hemodynamic reserve measured during exercise stress testing and is associated with survival. The goal of this study was to establish the association of HGI with exercise capacity, serum biomarkers, and echocardiography features in subjects with HFpEF. In 209 subjects with HFpEF enrolled in the RELAX (Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in Diastolic Heart Failure) trial who underwent cardiopulmonary exercise testing, we calculated the HGI ([peak heart rate [HR]×peak systolic blood pressure [SBP]-[HR at rest×SBP at rest])/(HR at rest×SBP at rest) and tested associations with outcomes of interest. The median (interquartile range) HGI was 0.94 (0.5 to 1.3)beats per min/mm Hg. In multivariable-adjusted linear regression, higher HGI was associated with greater peak oxygen consumption (VO2), VO2 at anaerobic threshold, peak minute ventilation, and 6-minute walk distance (all p<0.001). Higher HGI was associated with lower serum high-sensitivity troponin I, pro-collagen III, N-terminal pro-B-type natriuretic peptide, and creatinine (all p<0.05) and with longer deceleration time, lower E/A ratio, and lower left atrial volume index by echocardiography (all p<0.05). In conclusion, higher HGI in stable HFpEF was associated with greater exercise capacity, a biomarker profile indicating less myocardial injury and fibrosis and less kidney dysfunction, and with less severe diastolic dysfunction. These results suggest that HGI, an easily calculated metric from routine exercise testing, is a marker of functional capacity and disease severity in HFpEF and may serve as a surrogate for VO2 parameters for use in treadmill testing without gas exchange capability.

Patient-Reported Versus Physician-Assessed Health Status in Heart Failure With Reduced and Preserved Ejection Fraction From ASIAN-HF Registry.

We aimed to assess if discordance between patient-reported Kansas City Cardiomyopathy Questionnaire (KCCQ)-overall summary (os) score and physician-assessed New York Heart Association (NYHA) class is common among patients with heart failure (HF) with reduced or preserved ejection fraction, and determine its association with outcomes. A total of 4818 patients with HF were classified according to KCCQ-os score (range 0-100, dichotomized by median value 71.9 into high [good] versus low [bad]) and NYHA class (I/II [good] or III/IV [bad]) as concordant good (low NYHA class, high KCCQ-os score), concordant bad (high NYHA class, low KCCQ-os score), discordant worse NYHA class (high NYHA class, high KCCQ-os score), and discordant worse KCCQ-os score (low NYHA class, low-KCCQ-os score). The composite of HF hospitalization or death at 1 year was compared across groups. There were 2070 (43.0%) concordant good, 1099 (22.8%) concordant bad, 331 (6.9%) discordant worse NYHA class, and 1318 (27.4%) discordant worse KCCQ-os score patients. Compared with concordant good, adverse outcomes were the highest in concordant bad (HR, 2.7 [95% CI, 2.2-3.5]) followed by discordant worse KCCQ-os score (HR, 1.8 [95% CI, 1.4-2.2]) and discordant worse NYHA class (HR, 1.5 [95% CI, 1.0-2.3]); with no modification by HF phenotype (preserved versus reduced ejection fraction, Pinteraction=0.52). At 6 months, 1403 (48%) experienced clinically significant improvement in KCCQ-os score (≥5 points increase over 6 months). Patients with improved KCCQ-os at 6 months (HR, 0.65 [95% CI, 0.47-0.92]) had better outcomes and the association was not modified by HF phenotype (Pinteraction=0.40). One-third of patients with HF had discordance between patient-reported and clinician-assessed health status, largely attributable to worse patient-reported outcomes. Such discordance, particularly in those with discordantly worse KCCQ, should alert physicians to an increased risk of HF hospitalization and death, and prompt further assessment for potential drivers of worse patient-reported outcomes relative to physicians' assessment.

Abstract 13420: Association of Digital ECG Biomarkers With Heart Failure Status

Introduction: Electrocardiography (ECG) may be useful as an adjunct method for evaluating heart failure (HF) severity, but few studies have systematically examined the electrocardiographic parameters associated with heart failure volume status. This may include effects of hypervolemia on thoracic impedance, autonomic function, and subendocardial ischemia. We hypothesized that ECG parameters related to these mechanisms co-vary over time with brain natriuretic peptide, a measure of HF severity. Methods: A retrospective cohort was obtained from the Emory Clinical Data Warehouse for patients who had &gt;2 ECGs performed &gt;3 days apart and repeated BNP measures within 24 hours of each ECG. We quantified the change in HF status by calculating the differences in BNP value between each ECG acquisition time point. A total of 37 metrics were extracted from digitized ECGs as primary predictors and evaluated using multiple linear regression. Results: We evaluated 10,376 pairs of ECGs from 7,171 unique patients. The mean age was 66.9 years, 48% were women, and 51.4% were black . The median absolute change in BNP over time was 178 pg/mL (IQR 52-532), and the median sampling interval was 106 days (IQR 27-357). We evaluated interval, duration, and axis metrics from the P, QRS, and T vectors from the raw digital ECG and found 8 co-varied with BNP changes, including heart rate, P wave axis, QRS amplitude, QRS duration, QRS axis, ST segment, T wave amplitude, and frontal T wave axis (see table). Conclusions: We found several ECG metrics that quantify autonomic activity, depolarization, and repolarization associated with changes in HF status as measured by BNP. These findings may help to understand the downstream effects of hypervolemia on cardiovascular risk and also understand the potential role for certain ECG metrics in helping determine volume status, especially in low-resource settings not offering BNP.

Abstract 13449: Patient-Triggered Symptomatic Events Poorly Predict Presence of Atrial Arrhythmia on Ambulatory Electrocardiogram Monitors in Heart Failure Patients

Introduction: Emerging evidence supports more aggressive rhythm control of atrial fibrillation (AF) among heart failure (HF) patients. Yet, the impact of AF on symptom status in HF and the relationship to rate control have not been well studied in the setting of prolonged, ambulatory monitoring. Hypothesis: Patient-triggered symptomatic events (PTSEs) can predict the simultaneous presence of atrial tachycardia/AF (ATAF) on cardiac event monitors(CEM) among HF patients with documented atrial arrhythmia. Methods: All UHealth HF patients with at least 1 ATAF event over ≥7 days on CEMs were retrospectively reviewed. Tetrachoric correlation analysis between PTSEs and ATAF events and t-tests of mean heart rates(HR) were performed. Results: A total of 3,162 events were analyzed among 185 HF patients. The mean age was 68 years and 43% were female; 61% had CAD; the mean ejection fraction was 54% (SD 16%); and 74% were on beta-blockers. There were 2347 ATAF events, 1031 PTSEs, and 216 symptomatic ATAF events. Of PTSEs, 21.0% were ATAF, and of ATAF events, 9.2% were symptomatic. Overall mean HR of PTSEs was 94bpm (SD 29), lower than asymptomatic events, 103bpm (SD 29, p&lt;0.001). Mean HR of symptomatic ATAF events was 117bpm (SD 35), compared with asymptomatic ATAF (110bpm, SD 31, p=0.008). See Figure 1. PTSEs were less likely to predict simultaneous ATAF compared to sinus rhythm, with a moderate inverse tetrachoric correlation of -0.69 (bootstrapped 95% CI -0.65, -0.72). Conclusion: Among patients with AF &amp; HF, symptoms are a poor marker of atrial arrhythmia. PTSEs on ambulatory monitoring are not correlated with ATAF events in a clinically meaningful association and are not adequately explained by the heart rate differences. Classic symptom-based treatment of AF and HF should give way to more comprehensive quality-of-life and substrate guides for therapy.

Abstract 9614: Association Between Myocardial Contraction Fraction and Heart Failure Subtypes in the Multi-Ethnic Study of Atherosclerosis (MESA)

Introduction: Myocardial contraction fraction (MCF) is a non-ejection fraction volumetric measure of myocardial shortening which has been associated with incident heart failure (HF) including in the Multi-Ethnic Study of Atherosclerosis (MESA) cohort. However, less is known regarding MCF’s prediction of HF subtypes. Methods: This analysis included men and women aged 45-84 free of clinical cardiovascular disease who underwent cardiac magnetic resonance imaging (cMRI) during the baseline MESA examination and who had data regarding incident adjudicated definite or probable HF events. MCF was calculated using cMRI measurements and defined as the ratio of stroke volume to myocardial volume. HF subtypes were divided into HF with ejection fraction (EF) &lt; 50% (HF EF &lt; 50%, including HF with reduced EF (EF ≤ 40%) and HF with mildly reduced EF (EF 41-49%) and HF with preserved EF (HFpEF, EF ≥ 50%). Cox proportional hazards regression was used to examine the association between MCF and incident HF subtype per decile increase in MCF. Event time was defined as time of first defined HF subtype, and censoring occurred at death or end of follow-up. After an incident HF event, participants were not at risk for another HF subtype. Covariates adjusted for were age, gender, race-ethnicity, education, body-mass index, tobacco and alcohol use, systolic blood pressure (BP), diabetes, physical activity, total cholesterol, and BP and lipid lowering drug use. Results: Among 4,983 participants (mean age 61, 52% female, 61% non-White) over a maximum of 18 years follow-up, there were 275 incident HF events (142 HF EF &lt; 50%, 113 HFpEF, 20 unknown EF). MCF differed across HF status (p&lt;0.001) . Participants without incident HF had a higher mean MCF (0.65) compared to HFpEF (0.62), HF EF &lt; 50% (0.53), and unknown EF (0.52). The adjusted risk of any HF was reduced (HR 0.86, 95% CI 0.82, 0.91) per decile increase of MCF. MCF was strongly associated with incident HF EF &lt; 50% (adjusted HR 0.80, CI 0.74, 0.86) but was not associated with HFpEF (adjusted HR 0.98, CI 0.91, 1.05). Conclusions: In a multi-ethnic cohort, increasing MCF is associated with a decreased risk of incident HF EF&lt;50%. MCF is not significantly associated with incident HFpEF, suggesting different etiologic pathways for these two HF subtypes.

Abstract 13774: Association Between Baseline Heart Failure During Acute Coronary Syndrome and Long-Term Cancer Risk. The ABC-9* Study on Heart Disease

Introduction: We aim to investigate the association between heart failure (HF) during hospitalization with acute coronary syndrome (ACS) and the long-term cancer risk. Methods: This prospective study included 571 patients admitted to 3 Italian hospitals and with ACS discharged alive and free from cancer. They were followed for 24 years or until death. Results: All except for three patients completed the follow-up, representing 6416 person-years. Patients' mean age was 66 ± 12 years and 70% were males. Baseline clinical HF was diagnosed in 192 (34%) patients. During follow-up, 129 patients (23%) developed cancer; of them, 103 with no HF [27% of patients without HF] and 26 had baseline HF [14% of patients with HF].The incidence rates for cancer were 21 and 18 per 1000 person-years for patients without and with baseline HF, respectively (p = 0.61).The risks for cancer associated with HF were (HR: 0.96; 95% CI: 0.62-1.47; p=0.84). Similar associations were observed among men, women, and patients younger than 75 years of age. Yet, in patients older than 75 years the unadjusted risk was (HR: 0.30; 95% CI: 0.09-0.92; p=0.04). Although, the fully adjusted risk was (HR: 0.39; 95% CI: 0.12-1.30; p=0.13). The unadjusted HRs for cancer development were (HR: 0.88; 95% CI: 0.45-1.74; p=0.73) and (HR: 0.91; 95% CI: 0.48-1.71; p=0.77) for patient with HFrEF and HFpEF respectively.We observed a positive interaction between age and LVEF for the risk of cancer onset (HR: 1.002; 95% CI: 1.0003 -1.004; p=0.02) in the unadjusted model. Results were the same in fully adjusted model. Conclusions: This prospective study of unselected ACS patients showed a lack of association between clinical heart failure at admission for ACS and the long-term cancer risk. A positive independent interaction between age and LVEF for the long-term risk of cancer was also observed. Figure 1: Cumulative hazards of cancer according to HF status (A) and interaction between age and LVEF for the risk of cancer (B) 24-years after ACS.

Abstract 12553: Adverse Cardiovascular Outcomes in Heart Failure (HF) With Preserved Systolic Function Associated With Atrial Fibrillation Are Due to Loss of Rhythm Control Impacting HF Status : A Propensity Score Matched Analysis of the TOPCAT Americas Study

Background: Atrial fibrillation (AF) is associated with excess mortality and cardiovascular (CV) hospitalizations in HF patients (pts) with preserved systolic function (pEF), Whether this is due to advanced co-morbidities or loss of atrioventricular (AV) synchrony &amp; rate control in AF is unclear. Hypothesis: To analyze the independent impact of AF on clinical outcomes of HFpEF pts in the TOPCAT AMERICAS study using propensity score matched (PSM) cohorts to account for confounding by other comorbidities. Methods: Study cohorts were matched for 20 clinical, demographic &amp; ECG variables. 3 matched cohorts based on baseline rhythm status at study entry were compared viz. subjects in sinus rhythm (SR), subjects in AF on baseline ECG &amp; subjects with Any AF event by history or ECG. We analyzed CV mortality, adjudicated modes of death &amp; morbidity during a mean follow up period of 2.9 yrs. Results: 418 subjects in SR (SR cohort) were PSM with 418 subjects in AF on baseline ECG (AF on ECG cohort) &amp; 418 pts with any AF event by history or ECG (Any AF cohort) at study entry. Any AF increased risk of CV death(D), pump failure death (PFD), CV and HF hospitalization(H) and HF progression. AF on ECG increased risk of CVD, CVH, HFH and PFD (Tables). Neither AF cohort increased risk of sudden death (SD) {Figure}. Conclusion: 1. AF is an independent risk factor for worsening CV outcomes in HFpEF. 2. This increased risk is due to a selective increase in HF worsening, HFH and PFD rather than SD. 3. Loss of AV synchrony &amp; rate control in AF can independently impact HF progression in HFpEF with consequent HFH and PFD. Restoration of SR may offer benefits for CV outcomes in HFpEF &amp; warrants evaluation.

Effects of sodium-glucose cotransporter-2 inhibitors on nutritional status in heart failure with reduced ejection fraction.

This study aimed to evaluate the effects of sodium-glucose cotransporter-2 inhibitors on nutritional status in patients with heart failure with reduced ejection fraction. The sodium-glucose cotransporter-2 inhibitor treatment was initiated in 153 patients with heart failure with reduced ejection fraction who were symptomatic despite optimal medical treatment and were followed up for 6 months. The Minnesota Living With Heart Failure Questionnaire scores, New York Heart Association functional class, NT-pro-BNP levels, and nutritional index scores of the patients were evaluated before sodium-glucose cotransporter-2 inhibitor treatment and at the 6-month follow-up. The nutritional status of the patients was evaluated with the COntrolling NUTritional Status score, Geriatric Nutritional Risk Index, and Prognostic Nutritional Index. After sodium-glucose cotransporter-2 inhibitor treatment, significant changes were observed in the mean scores of the three different nutritional indexes: COntrolling NUTritional Status (before: 2.76±2.43 vs. after: 1.12±1.23, p<0.001), Geriatric Nutritional Risk Index (before: 98.2±9.63 vs. after: 104.4±5.83, p<0.001), and Prognostic Nutritional Index (before: 37.9±4.63 vs. after: 42.9±3.83, p<0.001) scores. A significant decrease in the number of patients with malnutrition was observed according to the COntrolling NUTritional Status (before: 46.4% vs. after: 9.7%, p<0.001), Geriatric Nutritional Risk Index (before: 41.8% vs. after: 18.9%, p=0.006), and Prognostic Nutritional Index (before: 36.6% vs. after: 13.7%, p=0.007) scores. A significant functional improvement was observed in patients after sodium-glucose cotransporter-2 treatment: Minnesota Living With Heart Failure Questionnaire scores (before: 39.2±7.2 vs. after: 20.4±7.4, p<0.001), NT-pro-BNP levels (before: 2989±681 vs. after: 1236±760, p<0.001), and New York Heart Association class (before: class II-III: 95.5%; class IV: 4.5% vs. after: class II-III: 78%; class IV: 0%, p<0.001). In patients with heart failure with reduced ejection fraction who are symptomatic despite optimal medical treatment, the addition of an sodium-glucose cotransporter-2 inhibitor to treatment can significantly improve both the nutritional and functional statuses.

Patient autonomy in cardiac inpatient rehabilitation—A COVID-19-specific exploratory trend study

BackgroundThe COVID-19 outbreak has changed nearly all societal domains, including medical rehabilitation. Social distancing measures impacted patients as well as health professionals during the rehabilitation process. Enhancing patient participation should not be forgotten during exceptional situations, as restrictive measures are related to the self-determination of patients. AimIn this exploratory trend study, we aimed to examine the association between COVID-19 restrictions with patients’ motivation, their perception of the patient-provider-relationship, their participation in the rehabilitation process and their current state of health at the beginning of their rehabilitation. MethodsAdopting an exploratory approach, we compared data from a convenience sample of two different groups of patients, who stayed at a cardiac rehabilitation clinic at two different time periods: before the COVID-19 lockdown of rehabilitation clinics (n = 128) and after reopening during the COVID-19 period (n = 137). We used questionnaires on motivation for rehabilitation, patient-provider-relationship, patient activation and perceived state of health. We conducted t-tests and regression analysis to determine whether there were differences by gender, age, heart failure status, preferred form of decision-making (shared/not-shared) and time of rehabilitation (before/during COVID-19) related to the outcome variables. ResultsParticipants evaluated the quality of the patient-provider-relationship in a better way after the reopening of the rehabilitation clinics during the COVID-19 period (p < 0.05), their motivation, participation in the rehabilitation process and their current state of health at the beginning of their rehabilitation was comparable to the group before the COVID-19 lockdown of rehabilitation clinics. Differences in scepticism concerning the treatment and the quality of the patient-provider-relationship were related (p < 0.05) to age and the preferred form of decision-making. Differences in active participation were related (p < 0.05) to sex and differences in the perceived state of health (p < 0.05) to a heart failure diagnosis. ConclusionsTreatment providers could use the time patients spend in isolation after arrival to prepare them for virtual goal-setting conversations to enhance patient participation in exceptional situations.

Relationship between Cardiac Acoustic Biomarkers and Pulmonary Artery Pressure in Patients with Heart Failure.

Since an elevation of pulmonary artery pressure (PAP) often precedes clinical worsening of heart failure (HF), early and non-invasive detection of this sign is useful in HF care. This study aimed to assess whether cardiac acoustic biomarkers (CABs) are associated with the elevation of PAP in patients with HF. Patients with HF scheduled to undergo right heart catheterization were prospectively enrolled. CABs were concurrently recorded during catheterization at rest (baseline) and while applying a handgrip (exercise). Forty-nine patients were included in the analysis, and their mean PAP significantly increased after exercise compared to baseline. Several CABs correlated significantly with mean PAP by absolute values, among which S2 Width (r = 0.354; p = 0.014 and r = 0.363; p = 0.010) and S3 Strength (r = 0.375; p = 0.009 and r = 0.386; p = 0.007) were consistent throughout baseline and exercise. The response of CABs to exercise-induced PAP elevation was divided into two patterns: increasing and decreasing. The frequency of cardiac index below 2.2 mL/m2 was significantly higher in the decreasing pattern. CABs related to S2 and S3 showed significant correlations with absolute PAP values both at baseline and after exercise in patients with HF, but no significant correlations between their changes from baseline to post-exercise were observed in this study population. Further research is therefore needed to assess whether CABs can sensitively reflect changes in PAP according to HF status and underlying phenotypes.

Actualization of Positions of Gliflozins in Treatment Algorithms for Patients with Heart Failure: Chronology of Success

INTRODUCTION: Despite the efforts of the cardiologic communities to introduce approaches to treatment of heart failure (HF) based on the highest level of evidence, HF remains one of the least satisfied demands in the therapy of cardiovascular diseases due to high prevalence, poor prognosis and insufficient use of treatment methods with clinically proven effectiveness. The article considers chronology of study and introduction of sodium-glucose cotransporter 2 inhibitors (syn.: gliflozins; SGLT2is) in clinical practice from the moment of creation of the first drug of this group ― florizin ― and further, stepwise with the change of the therapeutic paradigm as the result of performed clinical trials. Thus, EMPAREG OUTCOME, CANVAS, DECLARE-TIMI 58 studies demonstrated that SGLT2is not only produce a glucosuric effect, but also reduce the development and progression of HF and increase the life expectancy of patients with type 2 diabetes mellitus (DM2) and with reduced left ventricular ejection fraction (LFEF). DAPA-HF, EMPEROR-Reduced studies proved a possibility of improving the outcomes for patients with HF with reduced LVEF irrespective of the presence or absence of DM2, thereby significantly expanding the potential target group for SGLT2is. EMPEROR-Preserved study is the only study of SGLT2is to date (the study drug ― empagliflozin) that has demonstrated high effectiveness of the drug in prevention of cardiovascular mortality and hospitalizations for HF, probably irrespective of LVEF and the existence of DM2. In result, on September 9, 2021, FDA (Food and Drug Administration, USА) assigned the breakthrough therapy status to Jardiance (empagliflozin) drug for treatment of HF with preserved LFEF. EMPA-REG OUTCOME, DAPA-HF, EMPEROR-Reduced, EMPEROR-Preserved, DAPA-CKD studies have shown SGLT2is to slow down the development of the terminal stage of chronic kidney disease. Finally, the main result of EMPULSE study completed in 2022, was the proven clinical benefit of empagliflozin in hospitalized and stabilized patients with acute HF decompensation irrespective of HF status and existence of DM2.&#x0D; CONCLUSION: From the moment SGLT2is have been introduced in the clinical practice, they rapidly and successfully passed the way from the second-line antidiabetic drugs for which it was just enough not to worsen the prognosis for serious cardiovascular complications, to independent and effective class of drugs for treatment of HF (with class I and IIa recommendations). The totality of clinical trials of empagliflozin showed that empaflorizin is so far the only drug of the SGLT2is group with the proven safety and clinical effectiveness including the influence on the prognosis, in patients with HF irrespective of the LVEF status, presence or absence of DM2, for use in outpatient treatment and in stabilized patients in hospital.

Coexistence of sarcopenia and osteoporosis in patients with heart failure: prevalence and association with functional status

Abstract Background Sarcopenia, the loss of muscle mass and function, and osteoporosis, a condition of low bone mass and micro-architectural deterioration of bone, frequently coexist and are associated with low functional status in heart failure (HF) patients. Aims We aimed to investigate the impact of coexistence of sarcopenia and osteoporosis on functional status in HF patients. Methods This cross-sectional study was conducted using data from patients who admitted to our institute for the diagnosis and management of HF from 1 November 2015 to 30 April 2021. All patients received the dual-energy X-ray absorptiometry (DEXA) method before discharge. The diagnosis of sarcopenia was made according to the criteria of Asia Working Group for Sarcopenia 2019 recommendation as follows: reduced skeletal muscle mass [appendicular skeletal muscle mass index (ASMI) by DEXA, &amp;lt;7.00 kg/m2 in males and &amp;lt;5.40 kg/m2 in females] plus lower muscle strength (handgrip strength, &amp;lt;28 kg in males and &amp;lt;18 kg in females) and/or poor physical performance (gait speed, &amp;lt;1.0 m/s; chair stand test time. ≥12 s; short physical performance battery ≤9 points). In addition, bone mineral densities (BMDs) at the lumbar spine, femoral neck, and total femur were measured by DEXA, and osteoporosis was diagnosed when BMDs at any of the three sites were less than 70% of Young Adult Mean (YAM). Functional status was assessed by the Barthel Index (BI) within three days before discharge, and patients with a BI score of &amp;lt;85 points was defined as having functional dependence (FD). The missing data were imputed using multiple imputation by chained -equations algorithm. Results Four hundred-thirty eight patients [median age of 74 years (interquartile range, 65–82 years), 37% females] were included in the analyses. Of these, percentage of HF patients with sarcopenia, osteoporosis, and sarcopenia and osteoporosis was 45%, 34%, and 20%, respectively (Figure 1A). The analysis of covariance showed a lower %YAM at any sites in patients with sarcopenia than those without sarcopenia (Figure 1B). When patients were divided into subgroups according to the presence or absence of sarcopenia and osteoporosis, the prevalence of FD was 32%, 34%, and 48% in patients with osteoporosis alone, sarcopenia alone, and sarcopenia and osteoporosis, respectively. Multivariate logistic regression analysis indicated that an increase in adjusted odds ratio (OR) for predicting FD was observed across subgroups in the following order: patients with osteoporosis alone [OR, 1.64; 95% confidence interval (CI), 0.63–4.24; p=0.31], those with sarcopenia alone (OR, 2.44; 95% CI, 1.13–5.25; p=0.02) and those with both conditions (OR, 3.34; 95% CI, 1.52–7.38; p&amp;lt;0.01) (Figure 2). Conclusion There was considerable overlap between sarcopenia and osteoporosis in HF patients, which appeared to be a risk factor for FD. Funding Acknowledgement Type of funding sources: None.

Effects of sodium glucose cotransporter 2 inhibitors on the risk of hyperkalemia in patients on mineralocorticoid receptor antagonist: a systematic review and meta-analysis

Abstract Background Occurrence of hyperkalemia has been a great limitation in the full implementation of a guideline-directed medical therapy especially in patients with heart failure. Recent developments have exhibited the positive role of SGLT2 inhibitors, not only on the cardiovascular outcomes but also conferred renal protection. Purpose We explored the effects of SGLT2i and MRA combination on the risk of developing hyperkalemia. Methods Randomized controlled trials on SGLT2i versus placebo in patients already on MRA regardless of heart failure status reporting outcomes of potassium homeostasis were searched using Pubmed, CENTRAL, and ScienceDirect. Outcome of interest was the effects on the risk of hyperkalemia. Pooled hazard ratios with 95% confidence intervals were used as effect estimates using fixed-effects model. Results Four studies were included with a total of 8,996 patients. There was a significant reduction on the risk of hyperkalemia in the MRA with SGLT2i group (HR 0.53, 95% CI 0.39–0.73, p&amp;lt;0.0001) compared to MRA without SGLT2i group. Conclusion SGLT2i provides significant risk reduction on the development of hyperkalemia in patients already on a mineralocorticoid receptor antagonist. Funding Acknowledgement Type of funding sources: None.

Implantable defibrillator-detected heart failure status predicts ventricular tachyarrhythmias

Abstract Background The occurrence of ventricular tachyarrhythmias is associated with increased mortality and hospitalizations for heart failure in implantable cardioverter defibrillator (ICD) patients. Nonetheless, the temporal relationship between heart failure worsening and ventricular tachyarrhythmias has been scarcely explored so far. Purpose We hypothesized that in patients with heart failure and reduced ejection fraction with ICDs, physiological sensor-based heart failure status, as reflected in the HeartLogic index, would predict appropriate device therapies for ventricular tachyarrhythmias (shocks and antitachycardia pacing). Methods and results 568 patients implanted with ICDs (n=410, 72%) or cardiac resynchronization therapy-defibrillators (CRT-D, n=158, 28%) endowed with the HeartLogic algorithm were included in this prospective observational multicenter analysis. Over a follow-up of 25 [25th-75th percentile: 15–35] months, 122 (21%) patients received an appropriate device therapy (shock, n=74, 13%), while the HeartLogic index crossed the threshold value 1200 times (0.71 alerts/patient-year) in 370 subjects (65%). The occurrence of at least one HeartLogic alert was significantly associated with both appropriate shocks (HR: 2.44, 95% CI: 1.49–3.97, p=0.003) and any ICD therapies (HR: 1.95, 95% CI: 1.37–2.85, p=0.003). Using a time-dependent Cox model, the weekly IN-alert state was the strongest predictor of ICD shocks (HR: 2.94, 95% CI: 1.73–5.01, p&amp;lt;0.001), after correction for age, secondary prevention, and use of CRT. As compared to clinically stable subjects with no therapies, patients experiencing shocks had significantly higher baseline values of the HeartLogic index, third heart sound amplitude, and respiratory rate. Beginning about one month prior to the arrhythmic event, we noticed further increase of the combined index and the third heart sound amplitude, a decrease of thoracic impedance, and higher resting heart rate (Figure 1). Conclusions The HeartLogic index is an independent predictor of appropriate defibrillator therapies. The combined index and its individual physiological components change well before the arrhythmic event, suggesting the existence of a window of opportunity to prevent shocks. Funding Acknowledgement Type of funding sources: None.