Heart Failure Status Research Articles

Association between modified frailty index and surgical outcomes in intradural skull base surgery

The objective of this study is to evaluate the impact of preoperative frailty on short-term outcomes following intradural resection of skull base lesions. The 2005–2017 ACS-NSQIP database was queried for 30-day post-operative outcomes of patients undergoing intradural resection of the skull base, extracted by CPT codes 61601, 61606, 61608, and 61616. Five-item modified frailty index (mFI) was calculated based on the history of diabetes mellitus, chronic obstructive pulmonary disease, congestive heart failure, chronic hypertension, and functional status. A total of 701 patients (58.8% female, 72.0% white) were included with a mean age of 51.8 ± 14.7 years. Compared to patients with mFI = 0 (n = 403), patients with mFI ≥ 1 (n = 298) were more likely to have higher rates of reoperation (13.4% vs. 8.7%, p = 0.045), medical complications (20.5% vs. 9.2%, p < 0.001), surgical complications (13.8% vs. 8.4%, p = 0.024), discharge to non-home facility (DNHF) (24.8% vs. 13.3%, p < 0.001), and prolonged length of hospitalization (7.3 ± 6.8 days vs. 5.6 ± 5.0, p = 0.003). Moreover, mFI = 1–3 was also associated with higher BMI, non-white race, high ASA, and older age (all p < 0.05). Upon adjusting for age, BMI, race, ASA score, and surgical site, multivariate regression analysis demonstrated that higher mFI (treated as a continuous variable) was associated with higher odds of medical complications (OR = 1.630, CI = 1.153–2.308, p = 0.006), surgical complications (OR = 1.594, CI = 1.042–2.438, p < 0.031), and LOS ≥ 10 days (OR = 1.609, CI = 1.176–2.208, p = 0.003). In conclusion, the 5-item mFI can be an independent predictor of several important short-term surgical outcomes following intradural resection of skull base lesions, warranting further investigations into its clinical utility.

Heart failure following transcatheter aortic valve replacement

ABSTRACT Introduction: Over the past decade, the number of transcatheter aortic valve replacement (TAVR) procedures has increased exponentially. Despite major improvements in both device and successes, the rate of hospital readmission after TAVR remains high, with heart failure (HF) decompensation being one of the most important causes. Areas covered: This review provides an overview of the current status of HF following TAVR, including details about its incidence, clinical impact, contributing factors, and current and future treatment perspectives. Expert opinion: HF decompensation has been identified as the most common cause of rehospitalization following TAVR, and it has been associated with a negative prognosis. Multiple preexisting factors including low flow status, cardiac amyloidosis, myocardial fibrosis, multivalvular disease, pulmonary hypertension, coronary artery disease, and atrial fibrillation have been associated with an increased risk of HF events. Also, multiple post-procedural factors like the occurrence of significant paravalvular leaks, severe prosthesis-patient mismatch, and conduction disturbances have also contributed to increase this risk . Thus, reducing HF events in TAVR recipients would require a multifactorial and multidisciplinary effort including the optimization of the medical treatment and close follow-up and treatment of residual or concomitant valvular disease and conduction disturbance issues. Future studies in this challenging group of patients are warranted.

The significance of heart failure in hospitalised patients with pulmonary embolism. A gender-specific analysis.

Heart failure (HF) is a risk factor for the development of pulmonary embolism (PE). Few studies have examined sex differences in risk of PE among HF patients. (a) To examine the incidence, characteristics and in-hospital outcomes among patients hospitalised with PE according to HF status; (b) to compare the in-hospital mortality (IHM) after PE between HF and non-HF patients and (c) to identify variables associated with IHM. All analyses were stratified by sex. We included all adult patients hospitalised for PE from 1 January 2016 to 31 December 2018. Data were collected from the Spanish National Hospital Discharge Database. Poisson regression models were constructed to quantify the difference in the incidences between HF and non-HF populations. Propensity score matching (PSM) was used to obtain comparable subgroups by sex and HF status. We identified 46,835 PE hospitalisations, 11.4% with HF. Adjusted incidence of PE was higher in HF patients than in those without HF (Incidence Rate Ratio 1.11; 95% CI 1.08-1.13). Crude and PSM adjusted IHM were significantly higher in men and women hospitalised with PE suffering HF than in men and women without HF (P<.001). Women with HF who suffered a PE had lower IHM than men with this condition (P<.001) after adjusting. Adjusted incidence of PE was higher in HF patients than in those without HF. After PSM suffering, HF was associated to higher IHM in men and women. Women with PE and HF had lower IHM than men with these conditions.

Temporal changes of cardiac acoustic biomarkers and cardiac function in acute decompensated heart failure.

AimsRelationships between cardiac acoustic biomarkers (CABs) measured by acoustic cardiography and clinical outcomes have been reported in heart failure (HF) patients. However, no studies have investigated the temporal change of CABs and the corresponding changes in HF status. The purpose of this study was to assess whether the temporal changes of CABs in patients with acute decompensated heart failure (ADHF) reflect changes in cardiac function and status.Methods and resultsSixty ADHF patients were enrolled prospectively. CABs and echocardiography data were collected at admission, before discharge, and at the first clinic visit. CABs included electromechanical activation time (EMAT); the time interval from Q wave onset on electrocardiography to the first heart sound (S1), QoS2; the time interval from Q wave onset on electrocardiography to the second heart sound (S2); and third heart sound (S3) and fourth heart sound (S4) intensities, defined as the peak‐to‐peak amplitudes of S3 and S4. EMATc (EMAT/RR) (P = 0.001), S3 intensity (P < 0.001), and S4 intensity (P < 0.001) were significantly decreased, and QoS2 (P = 0.005) was significantly increased from admission to discharge. The change in S3 intensity was significantly correlated with that of E/A (ρ = 0.571, P < 0.001), and the extended QoS2 was also significantly correlated with the increase in the stroke volume index (ρ = 0.383, P = 0.004).ConclusionsSome CABs in ADHF patients changed significantly in the normal direction throughout the treatment course and could be useful biomarkers in ADHF management.

The impact of diabetes and osteoarthritis on the occurrence of stroke, acute myocardial infarction, and heart failure among older adults with non-valvular atrial fibrillation in Hawaii: a retrospective observational cohort study

BackgroundTo date, little is known about cardiovascular disease risks among older adults with non-valvular atrial fibrillation by their association with diabetes and osteoarthritis status, based on longitudinal data with substantial amounts of non-white individuals. The objective of this study was to examine the risks for three cardiovascular diseases: stroke, acute myocardial infarction (AMI), and heart failure (HF), by diabetes and osteoarthritis status among older adults with non-valvular atrial fibrillation in Hawaii.MethodsWe conducted a retrospective observational cohort study for older adults (65 years and older) with non-valvular atrial fibrillation using the Hawaii Medicare data 2009–2017. Their risks for the three cardiovascular diseases by diabetes and osteoarthritis status (diabetes, osteoarthritis, diabetes and osteoarthritis, and without diabetes and osteoarthritis) were examined by multivariable Cox proportional hazard regression models.ResultsThe analysis included 19,588 beneficiaries followed up for a maximum of 3288 days (diabetes: n = 4659, osteoarthritis: n = 1978, diabetes and osteoarthritis: n = 1230, without diabetes and osteoarthritis: n = 11,721). Among them, those diagnosed with the cardiovascular diseases were identified (stroke: diabetes n = 837, osteoarthritis n = 315, diabetes and osteoarthritis n = 184, without diabetes and osteoarthritis n = 1630)(AMI: diabetes n = 438, osteoarthritis n = 128, diabetes and osteoarthritis n = 118, without diabetes and osteoarthritis n = 603)(HF: diabetes n = 2254, osteoarthritis n = 764, diabetes and osteoarthritis n = 581, without diabetes and osteoarthritis n = 4272). After adjusting for age, sex, race/ethnicity, and other potential confounders, those with diabetes and osteoarthritis had higher risks for HF (hazard ratio: 1.21 95% confidence interval: 1.10–1.33) than those without diabetes and osteoarthritis. They also had higher risks than those with osteoarthritis for HF. Those with diabetes had higher risks for all three cardiovascular diseases than the other three groups.ConclusionsVariation in cardiovascular disease risks for older adults with non-valvular atrial fibrillation in Hawaii exists with diabetes and osteoarthritis status.

Systemic iron deficiency does not affect the cardiac iron content and progression of heart failure

Chronic heart failure (HF) is often accompanied by systemic iron deficiency (ID). However, effects of ID on cardiac iron status and progression of HF are unknown. To investigate these effects rats underwent LAD ligation to induce post-myocardial infarction HF or sham operation. After 3 weeks the animals from both groups were randomized into three subgroups: control, moderate ID and severe ID+anemia (IDA) by a combination of phlebotomy and low iron diet for 5 weeks. Serum and hepatic iron content were reduced by 55% and 70% (ID) and by 80% and 77% (IDA), respectively, while cardiac iron content was unchanged in HF rats. Changes in expression of all cardiomyocyte iron handling proteins indicating preserved cardiomyocytes iron status in HF and ID/IDA. Contractile function of LV cardiomyocytes, Ca2+ transient amplitude, sarcoplasmic reticulum Ca2+ release and SERCA2a function was augmented by ID and IDA and it was accompanied by an increase in serum catecholamines. Neither ID nor IDA affected left ventricular (LV) systolic or diastolic function or dimensions. To sum up, systemic ID does not result in cardiac ID and does not affect progression of HF and even improves contractile function and Ca2+ handling of isolated LV cardiomyocytes, however, at the cost of increased catecholamine level. This suggests that intravenous iron therapy should be considered as an additional therapeutic option in HF, preventing the increase of catecholaminergic drive with its well-known long-term adverse effects.

Yes-Associated Protein (Yap) Is Up-Regulated in Heart Failure and Promotes Cardiac Fibroblast Proliferation

Left ventricular (LV) heart failure (HF) is a significant and increasing cause of death worldwide. HF is characterized by myocardial remodeling and excessive fibrosis. Transcriptional co-activator Yes-associated protein (Yap), the downstream effector of HIPPO signaling pathway, is an essential factor in cardiomyocyte survival; however, its status in human LV HF is not entirely elucidated. Here, we report that Yap is elevated in LV tissue of patients with HF, and is associated with down-regulation of its upstream inhibitor HIPPO component large tumor suppressor 1 (LATS1) activation as well as upregulation of the fibrosis marker connective tissue growth factor (CTGF). Applying the established profibrotic combined stress of TGFβ and hypoxia to human ventricular cardiac fibroblasts in vitro increased Yap protein levels, down-regulated LATS1 activation, increased cell proliferation and collagen I production, and decreased ribosomal protein S6 and S6 kinase phosphorylation, a hallmark of mTOR activation, without any significant effect on mTOR and raptor protein expression or phosphorylation of mTOR or 4E-binding protein 1 (4EBP1), a downstream effector of mTOR pathway. As previously reported in various cell types, TGFβ/hypoxia also enhanced cardiac fibroblast Akt and ERK1/2 phosphorylation, which was similar to our observation in LV tissues from HF patients. Further, depletion of Yap reduced TGFβ/hypoxia-induced cardiac fibroblast proliferation and Akt phosphorylation at Ser 473 and Thr308, without any significant effect on TGFβ/hypoxia-induced ERK1/2 activation or reduction in S6 and S6 kinase activities. Taken together, these data demonstrate that Yap is a mediator that promotes human cardiac fibroblast proliferation and suggest its possible contribution to remodeling of the LV, opening the door to further studies to decipher the cell-specific roles of Yap signaling in human HF.

RNA-seq profiling of the atrial transcriptome reveals gender-specific patterns and interactions with atrial fibrillation and heart failure

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): TRAIN-HEART Innovative Training Network, funded by the European Union’s Horizon 2020 research and innovation program (under the Marie Sklodowska-Curie grant agreement no. 813716) Characterizing Atrial fibrillation by Translating its Causes into Health Modifiers in the Elderly (CATCH ME), funded by the European Union’s Horizon 2020 research and innovation program (under the grant agreement no. 633196) Background Atrial fibrillation (AF) is the most common cardiac arrhythmia and is associated with heart failure (HF) and stroke. Clinical and experimental data from previous studies suggest gender differences in mechanisms and phenotypes of AF: women may have more atrial fibrosis, worse outcomes after catheter ablation, and some women carry a higher risk for thromboembolic complications than men. The molecular mechanisms underlying these differences are still poorly understood. Methods Gender-based transcriptional patterns were assessed using paired-end, directional RNA sequencing data generated from atrial tissue biopsies in 199 patients either in sinus rhythm or with paroxysmal or persistent AF as part of the CATCH-ME project. Transcript counts were compared between genders separately in the left and right atria using the DESeq2 package in R. The models were adjusted for potential sources of confounding (age, atrial fibrillation status, heart failure status and sequencing batch). Interaction models were implemented using DESeq2 to compare gender*morbidity interactions for persistent AF and HF. Significance was assessed using likelihood ratio tests comparing models with and without the interaction terms. Results with an adjusted P-value 0.05 were considered significant and utilized for subsequent downstream assessments. Differentially expressed (DE) genes were tested for enrichment of gene ontology (GO) terms and KEGG pathways using the WebGestalt toolkit. Results Transcriptome-wide profiling across the cohort identified 33 sex-differentiated genes in the left atria and 51 in the right atrial samples, with 21 of these showing bilateral differences. Interestingly, 36 (44%) of the results from these analyses were comprised of non-coding transcripts, including long non-coding RNAs (lncRNAs), antisense RNAs and pseudogenes. GO and pathway enrichment analyses for these genes revealed their involvement in critical pathways such as the complement and coagulation cascades and RNA transport. Interaction analyses between gender and AF identified two genes (MPP2 &amp; GNAS-AS1) that were differentially transcribed in the right atria and one gene (MYL2) that was DE in the left atria by gender in persistent AF samples. A similar analysis comparing gender*HF morbidity also revealed evidence of DE. Four transcripts (HLA-DQB1-AS1, EIF1AY, UTY and ZFY-AS1) showed gender-specific differences in expression by HF status in left atria, while HLA-DQB1-AS1 was differentially regulated by gender and HF status in right atrial samples. Conclusions These RNA-seq analyses provide novel insights into gender-related differences in the transcriptional landscape of right and left adult human atrial appendages. Moreover, interaction analyses identified three genes DE in female atria in persistent AF and four DE genes in female atria in heart failure, providing a molecular anchor for the observed differences in atrial diseases phenotypes between men and women.

Plasma Renin Activity after Diuretic Treatment in Patients with Stable Heart Failure: With Special Reference to its Association with Electrolyte Chloride

A recent study reported an intimate association between urinary chloride (Cl) and plasma renin activity (PRA) in acute heart failure (HF) status, reflecting normal functioning of the ‘tubulo-glomerular feedback’ mechanism. Whether the ‘tubuloglomerular feedback’ mechanism functions normally in stable HF status, however, is unclear. This study examined whether the ‘tubulo-glomerular feedback’ mechanism functions normally under resolution of worsening HF after decongestive therapy. Data from 26 patients with acute HF and its recovery after decongestive therapy were analyzed. Clinical tests included measurement of peripheral blood tests, serum and spot urinary electrolytes, plasma neurohormones, and fractional urinary excretions of electrolytes. In a total of 26 patients, PRA increased after acute HF treatment (from 1.64±2.0 to 5.48±6.1 ng/ mL/h, p=0.002). Changes in the serum logPRA and urinary Cl concentration from worsening to its recovery tended to be inversely correlated (R2 =0.12, p=0.085) and logPRA and the serum Cl concentration at recovery were inversely correlated (R2 =0.23, p=0.01). When divided into 2 groups (n=13 in each) according to the median PRA, the group with greater PRA changes showed a larger decrease in the urinary Cl concentration (from 110±44 to 72.8±38, p=0.03). The group with higher PRA at recovery showed a lower serum Cl concentration than the group with lower PRA at recovery (102±6.5 vs 107±4.2 mEq/L, p=0.04). In conclusion, the association between PRA and the serum/urinary Cl concentration is blunted in stable HF under-decongestive therapy, possibly due to the physiologic status under full cardiovascular medication compared with that in acute HF status.

De-Intensification of Antidiabetic Treatment Using Canagliflozin in Patients with Heart Failure and Type 2 Diabetes: Cana-Switch-HF Study.

Canagliflozin is a sodium-glucose co-transporter 2 inhibitor that reduces glycemia as well as the risk of cardiovascular events. Our main objective was to analyze antidiabetic treatment de-intensification and the glycemic efficacy of replacing antidiabetic agents (excluding metformin) with canagliflozin in patients with heart failure and type 2 diabetes with poor glycemic control. In this observational, retrospective, real-world study, we selected patients treated with metformin in combination with ≥2 non-insulin antidiabetic agents or metformin in combination with basal insulin plus ≥1 non-insulin antidiabetic agent. Non-insulin antidiabetic agents were replaced with canagliflozin. Patients were followed-up on at three, six, and 12 months after the switch and a wide range of clinical variables were recorded. A total of 121 patients were included. From baseline to 12 months, the number of antidiabetic agents (3.1 ± 1.0 vs. 2.1 ± 0.8, p < 0.05), basal insulin dose (20.1 ± 9.8 vs. 10.1 ± 6.5 units, p < 0.01), and percentage of patients who used basal insulin (47.9% vs. 31.3%, p < 0.01) decreased. The proportion of patients who used diuretics also declined significantly. In addition, we observed improvement in glycemic control, with an increase in the proportion of patients with glycated hemoglobin <7% from 16.8% at three months to 63.5% at 12 (p < 0.001). Canagliflozin use was also beneficial in terms of body weight, blood pressure, heart failure status, functional class, and cardiovascular-renal risk. There were also reductions in the number of emergency department visits and hospitalizations for heart failure. Moreover, canagliflozin was well-tolerated, with a low rate of drug-related discontinuation. Mounting evidence from randomized controlled trials and real-world studies point to the beneficial profile of sodium-glucose co-transporter type 2 inhibitors such as canagliflozin in patients with heart failure.

A novel hybrid dimension reduction technique for efficient selection of bio-marker genes and prediction of heart failure status of patients

This study highlighted and provided a conceptual framework of a hybridized dimension reduction by combining Genetic Algorithms (GA) and Boruta Algorithm (BA) with Deep Neural Network (DNN). Among questions left unanswered sufficiently by both computational and biological scientists are: which genes among thousand of genes are statistically relevant to the prediction of patients’ heart rhythm? and how they are associated with heart rhythm? A plethora of models has been proposed to reliably identify core informative genes. The premise of this present work is to address these limitations. Five distinct micro-array data on heart diseases have been taken into consideration to observe the prominent genes. We form three distinct set two-way hybrids between Boruta Algorithm and Neural Network (BANN); Genetic Algorithm and Deep Neural Network (GADNN) and Boruta Algorithm and Deep Neural Network (BADNN), respectively, to extract highly differentially expressed genes to achieve both better estimation and clearer interpretation of the parameters included in these models. The results of the filtering process were observed to be impressive since the technique removed noisy genes. The proposed BA algorithm was observed to select minimum genes in the wrapper process with about 80% of the five datasets than the proposed GA algorithm with 20%. Moreover, the empirical comparative results revealed that BADNN outperformed other proposed algorithms with prediction accuracy of 97%, 87%, and 100% respectively. Finally, this study has successfully demonstrated the utility, versatility, and applicability of hybrid dimension reduction algorithms (HDRA) in the realm of deep neural networks.

Cluster Analysis Identifies Phosphatidylcholine Species in the Liver and Heart as Prediction Hubs in Ossabaw Swine with Cardio‐Metabolic Heart Failure

We recently developed an Ossabaw swine model (Western Diet and aortic banding; WD-AB) that exhibits features consistent with cardio-metabolic heart failure (HF). This pre-clinical model has a pattern of findings possibly useful for enhancing our understanding of the interactions between metabolic syndrome and HF. The aim of this study is to use advanced quantitative methods to reveal novel relationships and candidate predictors we hypothesize may be important to cardio-metabolic HF. A large-scale data repository was created containing 142 hemodynamic, structural, and functional cardiovascular measures, 413 lipid species identified using shotgun lipidomics, and 28,386 mRNA-transcripts revealed by RNA-seq. Repository data was generated from heart, vascular, hepatic, and blood samples collected from 2 groups of intact female Ossabaw swine: 1) lean control (CON; N=5); and 2) WD-AB (N=4). Logistic regression models with AUC scores identified a subset of measurements predictive of HF status that included 1,237 measurements (4.3%). Log2 fold changes were then calculated and statistically significant changes (p<0.05) with absolute value log2 fold changes >1 were considered. Pearson correlations for these 153 measurements were analyzed to identify redundant information using k-medoids clustering analysis with an average silhouette approach. Twenty-eight left ventricle (LV) genes and 125 lipids in 2 clusters (Fig. 1 Circos plot) with center points were identified. Cluster 1 (7 mRNA-transcripts, 70 lipids) was composed of strong correlations with center point phosphatidylcholine (PC) alkyl ether (a) species 32 from the liver (LIVER_PC­_32.0a_754) that increased 10-fold in the WD-AB group (P<0.05; 25±4 CON vs. 277±56 WD-AB pmols/mg). Cluster 2 (21 mRNA-transcripts, 55 lipids) had center point PC species 38.4a from the LV (HEART_PC_38.4a_830) that increased ~3-fold in the WD-AB group (P<0.05; 37±3 CON vs. 102±3 WD-AB pmols/mg). Identified PCa species containing arachidonic acid are storage depots for bioactive oxylipids (eicosanoids) and a precursor for platelet activating factor production. Increased alkyl ether phospholipids may also indicate increased peroxisome proliferation (the site of alkyl ether biosynthesis) and the potential to increase unknown peroxisome proliferator-activated receptor (PPAR) endogenous ligands. In conclusion, PCa species identified from the heart and liver of WD-AB animals may be underappreciated and have predictive significance for cardio-metabolic HF. Ongoing work includes enrichment analysis to determine biological processes underlying clusters.

Not all fluid overloads are the same: some practical considerations for better decongestion

Not all fluid overloads are the same: some practical considerations for better decongestion

Cardiac rehabilitation after catheter ablation of atrial fibrillation in patients with left ventricular dysfunction.

Few studies have examined the efficacy and safety of cardiac rehabilitation in patients with atrial fibrillation (AF) who underwent AF ablation. We explored the feasibility of additional cardiac rehabilitation after AF ablation in patients with a reduced left ventricular ejection fraction (LVEF). Fifty-four patients with heart failure (HF) and a reduced LVEF (HFrEF) (LVEF < 50%; 67.1 ± 11.6years; 43 men) who underwent initial AF ablation procedures were included. Fourteen (25.9%) patients underwent cardiac rehabilitation (rehabilitation-group) and the remaining 40 (74.1%) did not (non-rehabilitation-group) after the procedure. The rehabilitation-group patients were relatively older, more likely female (p = 0.024), and had more likely a history of an HF hospitalization (p < 0.01) and cardiac device implantation (p = 0.041). The baseline LVEF was significantly lower (p = 0.043) and brain natriuretic peptide (BNP) (p < 0.01) and C-reactive protein (CRP) (p < 0.01) values were significantly higher in the rehabilitation-group. The 6-min walk distance significantly improved after 21.4 ± 11.5days of cardiac rehabilitation during hospitalization (226.1 ± 155.9 vs. 398.1 ± 77.5m, p = 0.016) without any adverse events. During an 18.9 ± 6.3month follow-up period, the freedom from AF recurrence (p = 0.52) and re-hospitalizations due to HF (p = 0.63) were similar between the 2 groups. No death or strokes were observed. During the follow-up period, the LVEF significantly improved similarly in both groups, and the change in the BNP and CRP values significantly decreased in the rehabilitation-group. Despite the rehabilitation-group patients having a more severe HF status, the clinical outcomes and AF freedom were similar between the 2 groups, suggesting the favorable impact of cardiac rehabilitation after AF ablation in HFrEF patients.

A META-ANALYSIS ASSESSING THE EFFECT OF SODIUM-GLUCOSE CO-TRANSPORTER-2 INHIBITORS ON SURROGATE ENDPOINTS IN PATIENTS WITH HEART FAILURE WITH REDUCED EJECTION FRACTION

Objective: Heart failure (HF) is a main contributor of cardiovascular morbidity and mortality among patients with type 2 diabetes mellitus (T2DM), while T2DM among patients with HF with reduced ejection fraction (HFrEF) represents an independent risk factor for 1-year all-cause mortality and HF re-admission. Design and method: For this meta-analysis, we identified the hallmark cardiovascular outcome trials (CVOTs) and we searched the two major electronic databases, PubMed and Cochrane Central Register of Controlled Trials (CENTRAL), for sub-analyses of these trials according to HF status of enrolled participants at baseline. Results: Besides the dedicated HFrEF trials (DAPA-HF and EMPEROR-Reduced), only researchers of the DECLARE-TIMI 58 trial provided data regarding the effect of dapagliflozin on “hard” outcomes in patients with HFrEF. Therefore, we pooled data in a total of 9,145 patients with HFrEF. SGLT-2 inhibitor treatment resulted in a significant decrease in the odds for HF hospitalization compared to placebo, equal to 31% [OR = 0.69, 95% confidence interval (CI); 0.61 to 0.78, I2 = 0%]. In addition, SGLT-2 inhibitor treatment decreased the odds for cardiovascular death by 18% (OR = 0.82, 95% CI; 0.68 to 0.99, I2 = 40%). Odds for the composite outcome of cardiovascular death or HF hospitalization was significantly decreased by 28% with SGLT-2 inhibitor treatment (OR = 0.72, 95% CI; 0.65 to 0.80, I2 = 0%). Finally, SGLT-2 inhibitor treatment resulted in marginally non-significant decrease in the odds for all-cause death by 17% (OR = 0.83, 95% CI; 0.68 to 1.00, I2 = 53%). Conclusions: SGLT-2 inhibitor treatment provides substantial cardiovascular benefits in patients with HFrEF, decreasing the odds for HF hospitalization and cardiovascular death, while it might reduce the odds for all-cause death, compared to placebo.

Commentary: Sodium Glucose Cotransporter 2 Inhibitors Reduce the Risk of Heart Failure Hospitalization in Patients With Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

We read with interest a meta-analysis (1) recently published in “Frontiers in Endocrinology” conducted by Zhang et al. In this study (1), Zhang and colleagues included eight randomized controlled trials (RCTs) comparing sodium-glucose cotransporter 2 inhibitors (SGLT2is) with placebo in patients with type 2 diabetes (T2D), and performed a meta-analysis to produce a pooled risk ratio (RR) and 95% confidence interval (CI) of SGLT2is versus placebo in reducing four cardiovascular endpoints. The authors in this study (1) concluded that SGLT2is would be an ideal choice for T2D patients with heart failure (HF) because they found that SGLT2is significantly reduced hospitalization for heart failure (HHF), major adverse cardiovascular events (MACE, a composite of cardiovascular death, myocardial infarction, or stroke), and cardiovascular death (CVD) versus placebo in T2D patients. On the other hand, they concluded that SGLT2is did not significantly affect all-cause death (ACD) because they produced the nonsignificant 95% CI of RR (SGLT2is versus placebo: RR 0.77, 95% CI 0.59-1.01) for ACD. In my opinion, these two conclusions are not rigorous. First, they cannot conclude that SGLT2is are an ideal choice for T2D patients with HF until they assess the efficacy of SGLT2is in this T2D subgroup of concomitant HF and identify the obvious effectiveness. Second, using RR as drug effect is not accurate enough; all the original studies included in the meta-analysis (1) used hazard ratio (HR) as drug effect and RR only contains the status of the occurrence of events, but fails to contain the time when events happen. HR, on the other hand, contains both. Thus, to validate and further extend the findings in the meta-analysis by Zhang et al. (1), we implemented this further quantitative synthesis study by carrying out a meta-analysis stratified by the status of HF based on the data of HRs and 95% CIs as reported in the original studies. Moreover, we additionally incorporated the recently published SOLOIST-WHF trial (2), in addition to the eight RCTs included in the study by Zhang et al. (1), because this trial (2) contributed to the relevant data of the T2D subgroup of concomitant HF.

Socioeconomic Status and Outcomes in Heart Failure With Reduced Ejection Fraction From Asia.

Little is known regarding the impact of socioeconomic factors on the use of evidence-based therapies and outcomes in patients with heart failure with reduced ejection fraction across Asia. We investigated the association of both patient-level (household income, education levels) and country-level (regional income level by World Bank classification, income disparity by Gini index) socioeconomic indicators on use of guideline-directed therapy and clinical outcomes (composite of 1-year mortality or HF hospitalization, quality of life) in the prospective multinational ASIAN-HF study (Asian Sudden Cardiac Death in Heart Failure). Among 4540 patients (mean age: 60±13 years, 23% women) with heart failure with reduced ejection fraction, 39% lived in low-income regions; 34% in regions with high-income disparity (Gini ≥42.8%); 64.4% had low monthly household income (<US$1000); and 29.5% had no/only primary education. The largest disparity in treatment across regional income levels pertained to β-blocker and device therapies, with patients from low-income regions being less likely to receive these treatments compared with those from high-income regions and even greater disparity among patients with lower education status and lower household income within each regional income strata. Higher country- and patient-level socioeconomic indicators related to higher quality of life scores and lower risk of the primary composite outcome. Notably, we found a significant interaction between regional income level and both household income and education status (Pinteraction <0.001 for both), where the association of low household income and low education status with poor outcomes was more pronounced in high-income compared with lower income regions. These findings highlight the importance of socioeconomic determinants among patients with heart failure in Asia and suggest that attention should be paid to address disparities in access to care among the poor and less educated, including those from wealthy regions. Registration: URL: https://clinicaltrials.gov; Unique Identifier: NCT01633398.

Association between Pre-Albumin and Malnutrition in Children with Advanced Heart Failure

<h3>Purpose</h3> Malnutrition is an important complication of heart failure (HF) and associated with significant mortality. The serum pre-albumin level is often performed to evaluate patient nutritional status in HF, however its association with clinical malnutrition severity has not been determined. We sought to evaluate the association between pre-albumin and malnutrition severity using contemporary definitions of malnutrition. <h3>Methods</h3> All children listed for heart transplant (HT) between 2014 and 2017 were identified using a hospital database at a single center. Clinical malnutrition severity was determined by a certified pediatric dietitian using the American Society of Parenteral and Enteral Nutrition (ASPEN) guidelines. The pre-albumin level drawn around the time of the nutritional assessment was recorded. ANOVA for K groups with the Bonferroni correction was used to compare groups. <h3>Results</h3> Among 73 children who met the inclusion criteria, the median age at nutrition evaluation was 7.8 (Q1-Q3 1.3-12.6) years, the median weight-for-age Z-score was -1.5 (-2.3, 0.1), 36% were female, and 68% had congenital heart disease. Overall, malnutrition status by ASPEN guidelines was mild (25%), moderate (30%), severe (21%), or normal or obese (24%). Among the 73 subjects, the mean pre-albumin level was 20 (SD 10) mg/dl including 50% classified as normal. By ANOVA, there was no association between pre-albumin and clinical nutrition severity in children with HF (<b>Figure).</b> Variation within individual patients was high. <h3>Conclusion</h3> Pre-albumin does not appear to be a meaningful marker of malnutrition status in children with advanced heart failure. Pre-albumin levels vary markedly across malnutrition groups and within individual patients at a constant nutrition status, variability which may reflect its tendency to rise and fall as an acute phase reactant. Alternative strategies for estimating nutritional status are warranted.

A Hemolytic Event in a Heartmate 3 Patient in the Setting of Polycythemia

Introduction The Heartmate 3 (HM3) LVAD has significantly reduced hemocompatibility events. We present a case of a hemolytic event in a HM3 patient likely related to underling polycythemia. Case Report A 49-year-old man with multisystem sarcoidosis (pulmonary and cardiac) complicated by stage D systolic heart failure status post HeartMate 3 left ventricular assist device (LVAD) implantation and secondary polycythemia attributed to chronic hypoxic respiratory disease and pulmonary hypertension presented with symptoms of left arm numbness and tingling followed by severe substernal chest pain. Initial examination was unremarkable. EKG revealed nonspecific intraventricular conduction delay. Troponin I was elevated at 6.1. Hemoglobin was elevated to 19. LDH was elevated to LDH 568 from baseline of 300s. INR was 1.6 upon arrival. LVAD interrogation revealed speed 5600 rpm, flow 4.5 L/min, power 4.4 Watts and pulsatility index of 4.8. Heparin drip, aspirin and statin were initiated for presumed NSTEMI. LDH remained elevated to 600s. Left heart catherization revealed an acute clot in mid-circumflex associated with 50% stenosis consistent with partial resolution of thrombosis. Further workup revealed normal haptoglobin, erythropoietin and total bilirubin levels however plasma free hemoglobin was elevated to 63.1. Urine hemoglobin was not detected. A JAK2 mutation was excluded. Slow therapeutic phlebotomies with replacement of 125cc of blood with equivalent normal saline were initiated given concern for hemolytic event in the setting of worsening polycythemia. Renal imaging was negative and pretest probability for hematologic malignancies remained low. Of note, the patient reported non-compliance with home oxygen therapy used only at the time of exertion. Compliance was reinforced. Subsequently, LDH trended down to baseline following successful heparin bridge to therapeutic warfarin level. The patient was discharged in stable condition. Summary An acute hemolytic event (and possible cardioembolic NSTEMI) was seen in our patient evidenced by an elevation of LDH, plasma hemoglobin and new coronary thrombus in the setting of worsening polycythemia. Despite a remarkable low rate of pump thrombosis, HM3 recipients with acquired pro-thrombotic states such as polycythemia maybe at risk for adverse hemocompatibility events. Close surveillance is warranted for these special populations.

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.