HF Cohort Research Articles

Obesity paradox in patients with reduced ejection fraction eligible for device implantation - an observational study.

Patients with obesity have an overall higher cardiovascular risk, at the same time obesity could be associated with a better outcome in a certain subgroup of patients, a phenomenon known as the obesity paradox. Data are scarce in candidates for cardiac resynchronization therapy (CRT). We aimed to investigate the association between body mass index (BMI) and all-cause mortality in patients eligible for CRT. Altogether 1,585 patients underwent cardiac resynchronization therapy between 2000-2020 and were categorized based on their BMI, 459 (29%) patients with normal weight (BMI<25kg/m2), 641 (40%) patients with overweight (BMI 25-<30kg/m2) and 485 (31%) with obesity (BMI≥30kg/m2). The primary endpoint was all-cause mortality, heart transplantation, and left ventricular assist device implantation. We assessed periprocedural complications and 6-month echocardiographic response. Normal-weight patients were older compared to patients with overweight or obesity (70years vs. 69years vs. 68years; P ‹0.001), respectively. Sex distribution, ischaemic aetiology, and CRT-D implantation rates were similar in the three patient groups. Diabetes mellitus (BMI<25kg/m2 26% vs. BMI 25-<30kg/m2 37% vs. BMI≥30kg/m2 48%; P ‹0.001) and hypertension (BMI<25kg/m2 71% vs. BMI 25-<30kg/m2 74% vs. BMI≥30kg/m2 82%; P ‹0.001) were more frequent in patients with overweight and obesity. During the mean follow-up time of 5.1years, 973 (61%) reached the primary endpoint, 66% in the BMI<25kg/m2 group, 61% in the BMI 25-<30kg/m2 group and 58% in the BMI≥30kg/m2 group (log-rank P‹0.05). Patients with obesity showed mortality benefit over normal-weight patients (HR 0.78; 95%CI 0.66-0.92; P=0.003). The obesity paradox was present in patients free from diabetes, atrial fibrillation, and ischemic events. Periprocedural complication rates did not differ in the three groups (BMI<25kg/m2 25% vs. BMI 25-<30kg/m2 28% vs. BMI≥30kg/m2 26%; P=0.48). Left ventricular ejection fraction improved significantly in all patient groups (BMI<25kg/m2 median -LVEF 7% vs. BMI 25-<30kg/m2 median -LVEF 7.5% vs. BMI≥30kg/m2 median -LVEF 6%; P<0.0001) with a similar proportion of developing reverse remodeling (BMI<25kg/m2 58% vs. BMI 25-<30kg/m2 61% vs. BMI≥30kg/m2 57%; P=0.48); P=0.75). The obesity paradox was present in our HF cohort at long-term, patients underwent CRT implantation with obesity and free of comorbidities showed mortality benefit compared to normal weight patients. Patients with obesity showed similar echocardiographic response and safety outcomes compared to normal weight patients.

Cost-effectiveness analysis of sodium zirconium cyclosilicate for hyperkalemia among patients with chronic kidney disease or heart failure in Kuwait

Introduction Our model was conducted from Kuwaiti payer’s perspective to provide evidence on the cost-effectiveness of Sodium zirconium cyclosilicate (SZC) versus patiromer to correct and maintain serum potassium (K+) in combination with renin‐angiotensin‐aldosterone system inhibitors (RAASis) with different dose titration in patients with chronic kidney disease/heart failure (CKD/HF) with/without renal replacement therapy (RRT). Methodology The model was developed as a patient-level, fixed-time increment stochastic simulation to simulate the complexity of disease, including multiple coexisting and competing conditional risks. This model was established to compare SZC versus patiromer as a treatment for hyperkalemia (HK) among adult populations with underlying conditions of advanced CKD stages 3a–5 or HF to correct and maintain serum K + over a lifetime horizon. The clinical outcomes of SZC and patiromer were demonstrated through arm-specific K + trajectories extracted from the HARMONIZE trial and OPAL-HK trial, respectively. The utility data was captured from different studies. Direct medical cost was captured from local data from Kuwaiti hospitals. Sensitivity analyses were conducted to assess the uncertainty in the model. Results Within different scenarios of CKD/HF, SZC was a cost-saving option, with/without RRT, whether one-off administration or repeated administration, except for one-off treatment administration among the HF cohort, which generated an incremental cost effectiveness ratio of KWD 331/quality adjusted life year (QALY). The incremental QALY of SZC ranged from 0.007 to 0.202. In addition, the savings observed with SZC fall within a range of KWD −60 to KWD −1,235 at serum K+ ≥ 5.1 mmol/L. Conclusion The evidence generated by our model recommends the inclusion of SZC as a treatment option to correct HK and maintain normal serum K + level for CKD/HF patients within the Kuwaiti healthcare system. The costs saved from reducing frequent HK episodes, RAASis discontinuation/down titration, major cardiovascular events, and hospitalization offset the drug acquisition cost of SZC.

Public Health Impact and Cost-Effectiveness of Empagliflozin (JARDIANCE®) in the Treatment of Patients with Heart Failure with Preserved Ejection Fraction in France, Based on the EMPEROR-Preserved Clinical Trial.

The efficacy and safety of empagliflozin in the treatment of heart failure with preserved ejection fraction (HFpEF) were demonstrated in the EMPEROR-Preserved trial, which showed a 21% reduction in combined risks of cardiovascular death or HF hospitalization [hazard ratio (HR) 0.79; 95% confidence interval (CI) 0.69-0.90, p<0.001] and a 27% reduction in the total number of HF hospitalizations (HR 0.73; 95% CI 0.61-0.88, p<0.001) compared with placebo. On the basis of these results, the present study aimed to assess the cost-effectiveness of empagliflozin + standard of care (SoC) compared with SoC alone in the treatment of HFpEF. A published Markov model was adapted to compare the health and economic outcomes in France, considering a collective perspective, in patients treated with empagliflozin in addition to SoC versus patients treated by SoC alone. The model simulated the intention-to-treat (ITT) population of the trial, transitioning between four mutually exclusive health states representing the quartiles of the Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score (KCCQ-CSS). For each arm, the model estimated (over a lifetime time horizon) the economics and the health outcomes (HF hospitalizations avoided, and life years and quality-adjusted life years (QALYs) gained) to calculate the incremental cost-effectiveness ratios (ICERs). The resources used were derived by pairing the FREnch Survey on HF (FRESH) cohort data to French health insurance claims data, and the utilities were derived on the basis of the EQ-5D-5L questionnaire valued on the French tariff. Both economic and health outcomes were discounted at a 2.5% annual rate. The model predicted that treatment of HFpEF patients with empagliflozin would prevent, for 1000 patients treated, 74 HF hospitalizations and 15 deaths attributable to cardiovascular events, resulting on average in a gain of 1 month in overall survival (7.24 versus 7.16years with placebo) and 0.11 QALYs (6.14 versus 6.03 with placebo). Empagliflozin costs were partially offset by the cost savings from avoided hospitalizations. The ICERs were €18,597 per life year gained and €13,980 per QALY gained. The sensitivity analyses conducted showed that empagliflozin has a 65% probability to be cost-effective under the €25,000/QALY threshold. The base-case results showed that empagliflozin is a cost-effective strategy for management of HFpEF, in addition to the impact on public health by preventing HF-hospitalizations and deaths in France. Sensitivity analyses suggest that 65% of simulations are under the €25,000/QALY threshold.

Meta-analysis on the effectiveness of SGLT2 inhibitors in heart failure

Abstract Funding Acknowledgements Type of funding sources: None. Aims We aimed to carry out a meta-analysis on the effectiveness of sodium-glucose co transporter 2 (SGLT2) inhibitors in heart failure patients (HF) with preserved and reduced ejection fraction. Methods and results From their inception till September 2022, MEDLINE, Scopus, Cochrane CENTRAL, and ClinicalTrials.gov were searched for placebo-controlled randomized controlled trials of SGLT2 inhibitors. Randomized controlled studies were chosen if they included HF patients and reported at least one of the predetermined outcomes. A random effects model was used to pool hazard ratios (HRs) or risk ratios together with the appropriate 95% confidence intervals. There were fourteen trials in total, with 42409 HF patients participating (N = 21678 in the SGLT2 inhibitor arms and N = 20731 in the placebo arms). In the overall HF cohort, SGLT2 inhibitors significantly reduced the composite of first HF hospitalization or cardiovascular death [HR: 0.75 (0.71–0.79); P &amp;lt;0.001; I2 = 0%]. Also resulted in a significant reduction in total hospitalizations for heart failure [HR: 0.70 (0.66–0.75); P &amp;lt; 0.001; I2 = 0%] and reduced the occurrence of cardiovascular death [HR: 0.86 (0.81–0.92); P &amp;lt; 0.001; I2 = 43%]. Sub-group analysis was conducted to based on HF status at baseline, ejection fraction, diabetes status at baseline, and gender. SGLT2 inhibitors significantly reduced the composite heart failure hospitalization and cardiovascular death for all the subgroups except for patients with HFpEF at baseline [HR: 0.87 (0.74–1.03); P = 0.11; I2 = 60%] and no diabetes status at baseline [HR: 0.92 (0.73–1.16); P = 0.50; I2 = 78%]. SGLT2 inhibitors seemed to have no risk of hypovolaemia, hyperkalaemia, or hypotension when compared to the placebo. Conclusions In patients with HF, SGLT2 inhibitors substantially increase cardiovascular outcomes, including all-cause and cardiovascular mortality. In this meta-analysis, SGLT2 inhibitors did not show reduction in composite heart failure in patients with heart failure with preserved ejection fraction (HFpEF) at baseline.

Real-World Evaluation of Demographics, Treatment Pattern, and Economic Burden of Heart Failure and Kidney Disease in Type 2 Diabetes Mellitus Patient Population in Dubai, United Arab Emirates

Aims: The current study evaluated the demographics, clinical characteristics, treatment patterns, and economic burden of patients with type 2 diabetes mellitus (T2DM) with comorbidities (heart failure [HF], chronic kidney disease [CKD], and cardiovascular disease [CVD] without HF) in Dubai, United Arab Emirates (UAE). Methods: This observational, retrospective study collected data from January 01, 2014, to December 31, 2019, from the Dubai Real-World Claims Database (adults ≥18 years; at least 1 T2DM diagnosis claim). Patients were stratified into 5 cohorts: T2DM alone (cohort 1), T2DM and CKD (cohort 2), T2DM and CVD without CKD and HF (cohort 3), T2DM and HF (cohort 4), and T2DM with HF and CKD (cohort 5). An evaluation of demographics and clinical characteristics during pre-index period, as well as treatment patterns, healthcare resource utilization, and costs during the post-index period was conducted. Results: The sample had 374,271 patients with T2DM (age 43–56 years; male [72–84%]). Patients in cohorts 4 and 5 had Deyo-Charlson Comorbidity Index scores of 4.4 and 5.8, respectively. General practitioners (GPs) routinely prescribed biguanides for patients in cohorts 1–4 (24–38%), and insulin to patients in cohort 5 (27.7%). Prescription rates of novel antihyperglycemic drugs, such as glucagon-like peptide-1 (GLP-1 RA), were very low (∼2–8%) even in cohorts with cardiovascular and renal comorbidities (cohorts 2–5). A similar observation was noted with prescribing rates (0.6–4.4%) of sodium-glucose cotransporter-2 inhibitors (SGLT-2i) in cohorts 2–5. Endocrinologists preferred to prescribe GLP-1 RA and SGLT2i to T2DM patients with comorbidities. During the 5-year study period, median outpatient claims were the highest in cohort 5 (8.0 [range, 1.0–168.0]), followed by cohort 2 (5.5 [range, 1.0–52.0]). The median cost for inpatient claims was higher in cohort 5 (16,429 [range, 3,732–29,126] AED) compared to other cohorts. The median cost for drugs and procedures was highest in cohort 5 (4,525 [range, 38–31,546] AED and 2,297 [range, 56–105,074] AED, respectively). Conclusion: Continued and increased usage of drugs such as SGLT2i and GLP-1 RA with proven cardiorenal benefits could improve long-term outcomes and reduce associated healthcare costs in patients with T2DM and comorbidities in Dubai, UAE.

Pulsatile Pressure Delivery of Continuous-Flow Left Ventricular Assist Devices Is Markedly Reduced Relative to Heart Failure Patients.

Although continuous-flow left ventricular assist devices (CF-LVADs) provide an augmentation in systemic perfusion, there is a scarcity of in vivo data regarding systemic pulsatility on support. Patients supported on CF-LVAD therapy (n = 71) who underwent combined left/right catheterization ramp study were included. Aortic pulsatility was defined by the pulsatile power index (PPI), which was also calculated in a cohort of high-output heart failure (HOHF, n = 66) and standard HF cohort (n = 44). PPI was drastically lower in CF-LVAD-supported patients with median PPI of 0.006 (interquartile range [IQR], 0.002-0.012) compared with PPI in the HF population at 0.09 (IQR, 0.06-0.17) or HOHF population at 0.25 (IQR, 0.13-0.37; p < 0.0001 among groups). With speed augmentation during ramp, PPI values fell quickly in patients with higher PPI at baseline. PPI correlated poorly with left ventricular ejection fraction (LVEF) in all groups. In CF-LVAD patients, there was a stronger correlation with LV dP/dt (r = 0.41; p = 0.001) than LVEF (r = 0.21; p = 0.08; pint < 0.001). CF-LVAD support is associated with a dramatic reduction in arterial pulsatility as measured by PPI relative to HOHF and HF cohorts and decreases with speed. Further work is needed to determine the applicability to the next generation of device therapy.

Protein signatures of heart failure mortality in the community

Abstract Background Heart failure (HF) is a complex clinical syndrome that affects over 60 million persons worldwide.1 The 5-year survival rate of HF is less than 50% irrespective of ejection fraction (EF) and the limitations of EF in sufficiently phenotyping HF are recognized.2,3 High throughput proteomics assays are an attractive option for precision phenotyping.4 Purpose To explore the proteomic profiles and biomarker pathways associated with death in an HF community cohort. Methods We measured proteomics in plasma specimens collected from an HF cohort (2003–2012) of patients predominantly of European Ancestry (92%). The relative concentrations of circulating plasma proteins were measured using an aptamer-based assay containing 7335 human protein targets. Proteins significantly associated with mortality were selected while adjusting for age, sex, and eGFR. These proteins were employed in clustering analysis and subjected to 10-fold cross-validation. We quantified and corrected the clustering bias via bootstrapping and subsequently validated the results via semi-supervised clustering. Multivariable Cox regression was implemented for the cluster variable while adjusting for the Meta-analysis Global Group in Chronic Heart Failure (MAGGIC) risk score. Additionally, we performed enrichment and pathway analysis of the outcome-associated proteins considering significance thresholds of −log10(P-value) &amp;gt;2, FDR corrected P&amp;lt;0.05 (regulator analysis) and Z-scores of &amp;gt;2 and &amp;lt;−2 as thresholds for activation and inhibition of proteins/pathways. Results From a total of 1,388 patients (mean age 75±13; 52% male), 2 distinct clusters, (HR: 2.04; 95% CI [1.78–2.34]; p-value: &amp;lt;0.0001 independent of MAGGIC) were identified, cluster 1; n=722, mean age 72±14; NYHA class III/IV: 41%/26%; EF: 47%±17 and cluster 2; n=666, mean age 79±11; NYHA class III/IV: 41%/31%, EF: 48%±16 based on the 447 proteins [354 positively and 93 negatively] significantly associated with mortality (1,158 events). Gene-set enrichment analysis of all 447 proteins revealed cell adhesion, extracellular matrix organization, enzyme-linked protein/tyrosine kinase signaling pathways, humoral immune response, tissue development, growth factor signaling, post-translational protein modification, and platelet degranulation as the dominant biological themes. Finally, we found 18 upstream regulators predicted to be driving the expressions of the proteins in the dataset including a predicted outcome-associated protein-Transforming Growth Factor Beta 1 – TGFB1 (p=7.46E-09), Interleukin 1B, IL1B (p=9.40E-08), and oncostatin M, OSM (p=6.61E-05) as the top 3 regulators (predicted activation) based on FDR-corrected statistical significance of P&amp;lt;0.05 (Figure 1) Conclusion We identified distinct clusters based on proteomic profiles associated with HF mortality independently of clinical prognostic makers. Further, we delineated protein regulators driving the major pathways associated with HF survival. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Department of Intramural Research, NIH/NHLBI

Pulsatile Pressure Delivery of Continuous Flow LVAD is Speed Dependent and Markedly Reduced Relative to Heart Failure Patients

<h3>Purpose</h3> Although continuous flow left ventricular assist devices (CF-LVADs) provide an augmentation in systemic perfusion, there is a scarcity of in-vivo data regarding systemic pulsatility on support. <h3>Methods</h3> A retrospective cohort study was performed in patients supported on CF-LVAD therapy (n=67) who underwent a combined left and right heart catheterization ramp protocol. Aortic pulsatility was defined by the pulsatile power index (PPI), a quantity derived from the amplitudes of the harmonics of the pressure waveform. PPI was calculated in a cohort of high-output heart failure (HOHF, n=66) and standard HF cohort (n=44) and invasive hemodynamics and pulsatility were compared. <h3>Results</h3> Systemic, pulmonary artery, and pulmonary capillary wedge pressures were lower in the LVAD cohort (<i>P</i>≤.04 for each) compared with HOHF or HF. PPI was drastically lower in CF-LVAD supported patients with median PPI .006 (IQR .002-.012) vs PPI .09 (IQR .06-.17) in HF and PPI .25 (IQR .13-.37) in HOHF (<i>P</i><.0001 among groups). PPI more significantly differed between groups than aortic pulse width. With speed augmentation during ramp, PPI values fell more quickly in centrifugal flow pumps than axial flow (slopes -3.3 × 10⁻⁵ and -1.1 × 10⁻⁵ vs -6.9 × 10⁻⁶ for HW, HM3, and HMII respectively). PPI correlated poorly with LV ejection fraction (LVEF) in CF-LVAD patients and HOHF (<i>P</i>>.05) and modestly (r=.38, <i>P</i>=.01) in HF but in CF-LVAD patients, there was a stronger correlation with LV dP/dt (r=.41, <i>P</i>=.002) than LVEF (r=.21, <i>P</i>=.09, <i>P_int</i> <.001). <h3>Conclusion</h3> CF-LVAD support is associated with a dramatic reduction in arterial pulsatility as measured by PPI relative to HOHF and HF cohorts and decreases with increasing speed. Further work is needed to determine the applicability to the next generation of device therapy.

Cryoballoon Ablation for the Treatment of Atrial Fibrillation in Patients With Concomitant Heart Failure and Either Reduced or Preserved Left Ventricular Ejection Fraction: Results From the Cryo AF Global Registry.

BackgroundHeart failure (HF) and atrial fibrillation (AF) often coexist; yet, outcomes of ablation in patients with AF and concomitant HF are limited. This analysis assessed outcomes of cryoablation in patients with AF and HF.Methods and ResultsThe Cryo AF Global Registry is a prospective, multicenter registry of patients with AF who were treated with cryoballoon ablation according to routine practice at 56 sites in 26 countries. Patients with baseline New York Heart Association class I to III (HF cohort) were compared with patients without HF. Freedom from atrial arrhythmia recurrence ≥30 seconds, safety, and health care utilization over 12‐month follow‐up were analyzed. A total of 1303 patients (318 HF) were included. Patients with HF commonly had preserved left ventricular ejection fraction (81.6%), were more often women (45.6% versus 33.6%) with persistent AF (25.8% versus 14.3%), and had a larger left atrial diameter (4.4±0.9 versus 4.0±0.7 cm). Serious procedure‐related complications occurred in 4.1% of patients with HF and 2.6% of patients without HF (P=0.188). Freedom from atrial arrhythmia recurrence was not different between cohorts with either paroxysmal AF (84.2% [95% CI, 78.6–88.4] versus 86.8% [95% CI, 84.2–89.0]) or persistent AF (69.6% [95% CI, 58.1–78.5] versus 71.8% [95% CI, 63.2–78.7]) (P=0.319). After ablation, a reduction in AF‐related symptoms and antiarrhythmic drug use was observed in both cohorts (HF and no‐HF), and freedom from repeat ablation was not different between cohorts. Persistent AF and HF predicted a post‐ablation cardiovascular rehospitalization (P=0.032 and P=0.001, respectively).ConclusionsCryoablation to treat patients with AF is similarly effective at 12 months in patients with and without HF.RegistrationURL: https://www.clinicaltrials.gov; Unique Identifier: NCT02752737.

Abstract 10062: Administrative Data Algorithms Can Identify Patients with Advanced Heart Failure

Introduction: Advanced or “Stage D” heart failure (Adv HF) patients are at high risk of poor outcomes. However, recognition of Adv HF is limited as diagnostic criteria are complex. Administrative algorithms to identify Adv HF could enable better understanding of who has advanced HF and lead to enhanced therapeutics development, dissemination, and outcomes. Methods: In a population-based cohort of all Olmsted County, Minnesota residents with ≥1 HF billing code 2007-2017 (n=9881), we identified all patients with Adv HF (n=753) by applying the gold standard European Society of Cardiology Adv HF criteria via manual medical review by a HF cardiologist. The Adv HF index date was the date the patient first met all ESC criteria. We then developed candidate algorithms to identify Adv HF using only administrative data (billing codes and HF prescriptions or comorbidities known to affect HF outcomes), applied them to the entire HF cohort and assessed their ability to identify patients with Adv HF on or after their Adv HF index date. Results: A single hospitalization (Hsp) for HF or ventricular arrhythmias (VA, 2007-2017) identified all patients with Adv HF (sensitivity 100%), but the PPV was low (36.4%). Requiring more Hsp, other signs of Adv HF such as hyponatremia, acute kidney injury, hypotension or high-dose diuretic use decreased the sensitivity but improved specificity and PPV. As Adv HF was relatively uncommon, negative predictive values (NPV) were high regardless of algorithm characteristics. Conclusions: Algorithms using administrative data can identify patients with Adv HF with clinically useful accuracy.

Machine Learning Based Analysis of Heart and Cardiac Substructures for Radiation-Induced Cardiac Toxicity From Breast Cancer Radiotherapy

Radiation-induced cardiac toxicity is an importantissue of breast RT. Although a relationship between mean heart dose and acute coronary event (ACE) risk was reported in previous study, the specific relationships between doses to cardiac structures or their sub-regions and subsequent toxicity have not been well defined. In this study, we studied the effect of radiation on specific heart segments on subsequent cardiac toxicity.From the 1294 patients with breast cancer where previously demonstrated a relationship between mean heart dose and ACE, 21 patients who developed HF following breast RT and 39 with ACE were identified after an independent review by cardiologists. The study included 21 and 39 controls for respective toxicity who were matched according to age, comorbidities, and physical activity. For each patient who received radiotherapy, substructures were manually drawn, and then dose-distribution parameters of heart and substructures (Mean, Maximum (Max) dose, Relative volume at least given dose from 5-50 Gy in 5 Gy increments) were collected from CT planning data. To specify most critical regions for developing ACE, analysis using High-dimensional Cox regression model (SNet) was performed to reveal the effect of radiation on specific heart segments on subsequent cardiac toxicity.In HF (n = 42) and ACE (n = 78) cohorts, characteristics between case and control were well matched. Mean time to develop heart failure, acute coronary events were 40.0 months and 42.2 months, respectively. In HF cohort, there was no significant difference not only in the mean heart dose (3.7 Gy vs 3.1 Gy, P = 0.652), but also in the mean left ventricle (LV) (5.0 Gy vs 4.1 Gy, P = 0.587), mean right ventricle (RV) (4.8 Gy vs 3.6 Gy, P = 0.473). On the other hand, in ACE cohort, there was significant difference in mean dose of heart (2.9 Gy vs 1.3 Gy, P = 0.015), left atrium (LA) (1.0 Gy vs 0.5 Gy, P = 0.008), LV (3.7 Gy vs 1.5 Gy, P = 0.028), left anterior descending artery (LAD) (6.6 Gy vs 2.4 Gy, P = 0.028) and right atrium (RA) (1.5 Gy vs 0.9 Gy, P = 0.025). In univariate analysis, mean dose of heart, LA, LV, LAD and RA was significant factors for acute coronary event free survival. ((Heart; P = 0.006, Hazard ratio (HR) 1.139, 95% Confidence Interval (CI) 1.035-1.253) (LA; P = 0.002, HR 1.735, 95% CI 1.209-2.490), (LV; P = 0.018, HR 1.079, 95% CI 1.012-1.150), (LAD; P = 0.031, HR 1.032, 95% CI 1.002-1.064), (RA; P = 0.008, HR = 1.307, 95% CI 1.068-1.598)). For predicting ACE risk for breast cancer patients, SNet model suggested nomogram based on mean and max LA dose, LAD V10, 15, 20, mean heart dose, mean RA dose and RV V35 in the order of higher predicted point variation. Based on this risk stratification model, event free survival significantly showed difference (P = 0.013).There was significant difference between cardiac substructure dose parameters in ACE cohort, but not in HF cohort. Further analysis using convolution neural network will be performed to specify most critical region to be spared.

Healthcare utilization after cryoballoon ablation for treatment of atrial fibrillation in patients with heart failure: real-world results from the Cryo AF Global Registry

Abstract Funding Acknowledgements Type of funding sources: Private company. Main funding source(s): Medtronic, Inc. OnBehalf Cryo AF Global Registry Investigators Background Heart failure (HF) concomitant to atrial fibrillation (AF) can exacerbate the risk of hospitalization, morbidity, mortality, and impairment in quality of life posed by each condition alone. While the reciprocal relationship between HF and AF challenges effective treatment for these patients, catheter ablation for treatment of AF is reasonable for select patients with AF and HF according to guidelines. Purpose: Assess real-world usage and healthcare utilization outcomes of cryoablation for patients with AF and HF. Methods: The Cryo AF Global Registry (NCT02752737) is an ongoing, prospective, multicenter registry. Patients with AF were enrolled and treated with cryoballoon ablation (Arctic Front Advance, Medtronic) according to clinical practice at 56 sites in 26 countries world-wide. Subjects with NYHA class I-III at baseline comprised the HF cohort and were compared to patients without HF (No-HF). Freedom from atrial arrhythmia recurrence ≥30 sec, adverse events associated with the AF ablation procedure, repeat ablations, AAD usage, and cardiovascular rehospitalization over a 12-month follow-up were compared between cohorts. Results: A total of 1,303 patients (318 HF, 985 No-HF) were included. The HF cohort included patients with NYHA Class I (56.3%) and II/III (43.7%) with either preserved (81.6%) or mid/reduced (18.4%) left ventricular ejection fraction. HF patients were more often female (45.6% vs 33.6%) with persistent AF (25.8% vs 14.3%), larger left atrial diameter (4.4 ± 0.9 vs 4.0 ± 0.7 cm), and higher rates of hypertension (67.9% vs 49.1%) and prior myocardial infarction (3.8% vs 1.7%; all, P &amp;lt; 0.05). The rate of serious procedure-related complications was 5.3% in HF and 3.0% in No-HF (P = 0.08). Freedom from atrial arrhythmia recurrence at 12-months was not different between HF and No-HF patients with either paroxysmal (84.2% (95% CI:78.6-88.4) vs 86.8% (95% CI: 84.2 – 89.0)) or persistent AF (69.6% (95% CI: 58.1 – 78.5) vs 71.8% (95% CI: 63.2-78.7)), respectively (p = 0.32, HF vs No-HF). AF-related symptoms and antiarrhythmic drug use were significantly reduced after cryoablation in the HF and No-HF cohorts (P &amp;lt; 0.05). Freedom from repeat ablation at 12-months was similar between HF and No-HF patients. Of patients who had a cardiovascular rehospitalization after cryoablation, 78% presented with a supraventricular tachyarrhythmia. Persistent AF and HF at baseline both increased the risk of cardiovascular rehospitalization after cryoballoon ablation (P &amp;lt; 0.05). Conclusion: Cryoablation is used to treat patients with AF and concomitant HF in real-world practice and is similarly safe and effective at 12-months in patients with and without HF.

Dynamic 31P-MRI and 31P-MRS of lower leg muscles in heart failure patients

Impaired oxidative metabolism is one of multi-variate factors leading to exercise intolerance in heart failure patients. The purpose of the study was to demonstrate the use of dynamic 31P magnetic resonance spectroscopy (MRS) and 31P magnetic resonance imaging (MRI) techniques to measure PCr resynthesis rate post-exercise as a biomarker for oxidative metabolism in skeletal muscle in HF patients and controls. In this prospective imaging study, we recruited six HF patients and five healthy controls. The imaging protocol included 31P-MRS, spectrally selective 3D turbo spin echo for 31P-MRI, and Dixon multi-echo GRE for fat–water imaging on a 3 T clinical MRI scanner. All the subjects were scanned pre-exercise, during plantar flexion exercise, and post-exercise recovery, with two rounds of exercise for 31P -MRS and 31P-MRI, respectively. Unpaired t-tests were used to compare 31P-MRS and 31P-MRI results between the HF and control cohorts. The results show that PCr resynthesis rate was significantly slower in the HF cohort compared to the controls using 31P-MRS (P = 0.0003) and 31P-MRI (P = 0.0014). 31P-MRI showed significant differences between the cohorts in muscle groups (soleus (P = 0.0018), gastrocnemius lateral (P = 0.0007) and gastrocnemius medial (P = 0.0054)). The results from this study suggest that 31P-MRS/31P-MRI may be used to quantify lower leg muscle oxidative metabolism in HF patients, with 31P-MRI giving an additional advantage of allowing further localization of oxidative metabolism deficits. Upon further validation, these techniques may serve as a potentially useful clinical imaging biomarker for staging and monitoring therapies in HF-patients.

Regulation of Angiopoietin-2 Before and After Mechanical Circulatory Support Therapy.

Gastrointestinal bleeding (GIB) during mechanical circulatory support (MCS) is a major unsolved comorbidity. Inadequate activation of angiopoietin-2-related systems is considered as a major cause of GIB. However, the regulation of angiopoietin-2 remains unknown. Consecutive 20 patients who received continuous-flow MCS therapy (MCS group) and 12 with advanced heart failure (HF; HF group) were prospectively enrolled and their angiopoetin-2 levels were compared. Angiopoietin-2 level had a moderate correlation with log10 B-type natriuretic peptide (BNP; r = 0.39, p < 0.001). The MCS group had significantly higher angiopoietin-2 level divided by log10 BNP compared with the HF group (2.80 ± 0.20 vs. 1.88 ± 0.17, p < 0.001). Angiopoetin-2 had a moderate correlation with central venous pressure and C-reactive protein during the MCS support (r = 0.51 and r = 0.45, respectively). Higher angiopoietin-2 level divided by log10 BNP (> 4.3) was significantly associated with the occurrence of GIB with a hazard ratio of 296 (95% confidence interval 2.24-38620, p = 0.0224). Angiopoietin-2 was already elevated in the HF cohort and more elevated following MCS initiation. Among the MCS cohort, angiopoietin-2 was particularly elevated in patients with systemic congestion and inflammation and was associated with higher incidence of GIB.

A network analysis to identify pathophysiological pathways distinguishing ischaemic from non-ischaemic heart failure.

AimsHeart failure (HF) is frequently caused by an ischaemic event (e.g. myocardial infarction) but might also be caused by a primary disease of the myocardium (cardiomyopathy). In order to identify targeted therapies specific for either ischaemic or non‐ischaemic HF, it is important to better understand differences in underlying molecular mechanisms.Methods and resultsWe performed a biological physical protein–protein interaction network analysis to identify pathophysiological pathways distinguishing ischaemic from non‐ischaemic HF. First, differentially expressed plasma protein biomarkers were identified in 1160 patients enrolled in the BIOSTAT‐CHF study, 715 of whom had ischaemic HF and 445 had non‐ischaemic HF. Second, we constructed an enriched physical protein–protein interaction network, followed by a pathway over‐representation analysis. Finally, we identified key network proteins. Data were validated in an independent HF cohort comprised of 765 ischaemic and 100 non‐ischaemic HF patients. We found 21/92 proteins to be up‐regulated and 2/92 down‐regulated in ischaemic relative to non‐ischaemic HF patients. An enriched network of 18 proteins that were specific for ischaemic heart disease yielded six pathways, which are related to inflammation, endothelial dysfunction superoxide production, coagulation, and atherosclerosis. We identified five key network proteins: acid phosphatase 5, epidermal growth factor receptor, insulin‐like growth factor binding protein‐1, plasminogen activator urokinase receptor, and secreted phosphoprotein 1. Similar results were observed in the independent validation cohort.ConclusionsPathophysiological pathways distinguishing patients with ischaemic HF from those with non‐ischaemic HF were related to inflammation, endothelial dysfunction superoxide production, coagulation, and atherosclerosis. The five key pathway proteins identified are potential treatment targets specifically for patients with ischaemic HF.

Impact of left ventricular assist devices and heart transplants on acute myocardial infarction and heart failure mortality and readmission measures.

Concern has been raised about consequences of including patients with left ventricular assist device (LVAD) or heart transplantation in readmission and mortality measures. We calculated unadjusted and hospital-specific 30-day risk-standardized mortality (RSMR) and readmission (RSRR) rates for all Medicare fee-for-service beneficiaries with a primary diagnosis of AMI or HF discharged between July 2010 and June 2013. Hospitals were compared before and after excluding LVAD and heart transplantation patients. LVAD indication was measured. In the AMI mortality (n = 506,543) and readmission (n = 526,309) cohorts, 1,166 and 1,016 patients received an LVAD while 3 and 2 had a heart transplantation, respectively. In the HF mortality (n = 1,015,335) and readmission (n = 1,254,124) cohorts, 789 and 931 received an LVAD, while 212 and 202 received a heart transplantation, respectively. Less than 2% of hospitals had either ≥6 patients who received an LVAD or, independently, had ≥1 heart transplantation. The AMI mortality and readmission cohorts used 1.8% and 2.8% of LVADs for semi-permanent/permanent indications, versus 73.8% and 78.0% for HF patients, respectively. The rest were for temporary/external indications. In the AMI cohort, RSMR for hospitals without LVAD patients versus hospitals with ≥6 LVADs was 14.8% and 14.3%, and RSRR was 17.8% and 18.3%, respectively; the HF cohort RSMR was 11.9% and 9.7% and RSRR was 22.6% and 23.4%, respectively. In the AMI cohort, RSMR for hospitals without versus with heart transplantation patients was 14.7% and 13.9% and RSRR was 17.8% and 17.7%, respectively; in the HF cohort, RSMR was 11.9% and 11.0%, and RSRR was 22.6% and 22.6%, respectively. Estimations changed ≤0.1% after excluding LVAD or heart transplantation patients. Hospitals caring for ≥6 patients with LVAD or ≥1 heart transplantation typically had a trend toward lower RSMRs but higher RSRRs. Rates were insignificantly changed when these patients were excluded. LVADs were primarily for acute-care in the AMI cohort and chronic support in the HF cohort. LVAD and heart transplantation patients are a distinct group with differential care requirements and outcomes, thus should be considered separately from the rest of the HF cohort.

Bi-directional association between depression and HF: An electronic health records-based cohort study.

Objective:To determine whether a bi-directional relationship exists between depression and HF within a single population of individuals receiving primary care services, using longitudinal electronic health records (EHRs).Methods:This retrospective cohort study utilized EHRs for adults who received primary care services within a large healthcare system in 2006. Validated EHR-based algorithms identified 10,649 people with depression (depression cohort) and 5,911 people with HF (HF cohort) between January 1, 2006 and December 31, 2018. Each person with depression or HF was matched 1:1 with an unaffected referent on age, sex, and outpatient service use. Each cohort (with their matched referents) was followed up electronically to identify newly diagnosed HF (in the depression cohort) and depression (in the HF cohort) that occurred after the index diagnosis of depression or HF, respectively. The risks of these outcomes were compared (vs. referents) using marginal Cox proportional hazard models adjusted for 16 comorbid chronic conditions.Results:2,024 occurrences of newly diagnosed HF were observed in the depression cohort and 944 occurrences of newly diagnosed depression were observed in the HF cohort over approximately 4–6 years of follow-up. People with depression had significantly increased risk for developing newly diagnosed HF (HR 2.08, 95% CI 1.89–2.28) and people with HF had a significantly increased risk of newly diagnosed depression (HR 1.34, 95% CI 1.17–1.54) after adjusting for all 16 comorbid chronic conditions.Conclusion:These results provide evidence of a bi-directional relationship between depression and HF independently of age, sex, and multimorbidity from chronic illnesses.

P5008Empagliflozin in a real-world chronic heart failure population

Abstract Introduction Heart Failure (HF) is a burdensome syndrome with significant mortality, morbidity and costs. Its prognosis is further aggravated by diabetes mellitus (DM). The EMPA-REG OUTCOME trial suggested that empagliflozin significantly reduced HF hospitalizations compared to placebo in patients with DM. Purpose We aimed to investigate which patients with chronic HF and DM in the outpatient setting could have been enrolled in the main empagliflozin trial. Methods This analysis is based on a retrospective cohort enrolling chronic HF patients who consecutively attended the HF appointment between January and July 2018. Of these, those with concomitant DM were selected and further analysed. The key EMPA-REG OUTCOME trial inclusion criteria [(i.e., hemoglobin A1c 7–10%, high cardiovascular (CV) risk and glomerular filtration rate [GFR] ≥30mL/min/1,73m2) were considered. Further, the European Medicine Agency (EMA) restriction (GFR&gt;60mL/min/1,73m2) was also considered in an additional analysis. Results Of 316 patients with HF, 114 (36%) concomitantly had DM. Mean age was 74±10 years, 63% were male and most (54%) had preserved left ventricular ejection fraction. Ischemic (51%) and hypertensive (27%) HF were the most often observed etiologies. According to the inclusion criteria, 21 (18.4%) (or 5.3% when further considering the EMA restriction) HF patients could have been potentially enrolled in the main trial and derive a HF hospitalization reduction benefit from starting empagliflozin. The remainder would be excluded due to GFR&lt;30mL/min/1.73m2 (2.6%), absence of “high CV risk” as per trial's definition (7%), HbA1c off target (18,4%) or a combination of the above criteria (53.6%). In light of the new Standards of Medical Care in Diabetes 2019, controlled patients with HbA1c off target (i.e., &lt;7% or &gt;10%) could be switched to a SGLT2 inhibitors, hence possibly expanding the indication to start empagliflozin to 36.8% of our HF cohort. Figure 1 Conclusions Roughly 1 in every 5 patients with HF and DM could have been enrolled in the main empagliflozin trial, as per key inclusion criteria, and potentially derive CV benefit from it. Thus, only a minority of our cohort shared the features for EMPA-REG OUTCOME trial inclusion, limiting the extrapolation of the trial's observed CV benefits to our HF cohort. Indeed, whether these benefits also expand to overall HF cohort is eagerly awaited by ongoing trials. Acknowledgement/Funding None

Skeletal muscle alterations in HFrEF vs. HFpEF.

Severe exercise intolerance and early fatigue are hallmarks of heart failure patients either with a reduced (HFrEF) or a still preserved (HFpEF) ejection fraction. This review, therefore, will provide a contemporary summary of the alterations currently known to occur in the skeletal muscles of both HFrEF and HFpEF, and provide some further directions that will be required if we want to improve our current understanding of this area. Skeletal muscle alterations are well documented for over 20years in HFrEF, and during the recent years also data are presented that in HFpEF muscular alterations are present. Alterations are ranging from a shift in fiber type and capillarization to an induction of atrophy and modulation of mitochondrial energy supply. In general, the molecular alterations are more severe in the skeletal muscle of HFrEF when compared to HFpEF. The alterations occurring in the skeletal muscle at the molecular level may contribute to exercise intolerance in HFrEF and HFpEF. Nevertheless, the knowledge of changes in the skeletal muscle of HFpEF is still sparsely available and more studies in this HF cohort are clearly warranted.

Heart Failure and Total Hip Arthroplasty: What Are the Perioperative Outcomes and Complications?

AbstractHeart failure (HF) has been reported to cause morbidity and mortality after surgery. As the prevalence of HF and hip osteoarthritis increase, physicians are likely to observe a rise in the number of HF patients requiring total hip arthroplasty (THA). We asked (1) what perioperative outcomes can be expected for patients with HF after THA, and (2) does HF contribute to an increased risk of short-term complications after THA? The National Surgical Quality Improvement Program database was accessed to find patients with osteoarthritis who underwent THA from 2008 to 2014. The HF cohort included 177 patients, while the control group consisted of 64,619 patients. Demographics, comorbidities, outcomes, and complications were collected. Multivariate regression analysis was performed. HF patients were found to have longer hospital stays (β = 0.87; p = 0.004) and were less likely to be discharged home (OR = 1.77, p = 0.001) following THA. It also increased the risk for any complication (OR = 1.54, p = 0.011), mortality (OR = 3.67, p = 0.042), readmission (OR = 1.68, p = 0.041), cardiac arrest (OR = 8.44, p = 0.006), myocardial infarction (OR = 3.75, p = 0.014), and deep surgical site infection (OR = 3.62, p = 0.035). HF patients had longer hospital stays and were discharged to a facility after THA. Overall, they had an increased risk of any complication, readmission, cardiac arrest, myocardial infarction, and deep surgical site infection. Moreover, the mortality risk after THA was significantly high. Cardiac optimization could play a key role in the prevention of these adverse outcomes. Patients should be counseled prior to surgery.