Rates Of Heart Failure Events Research Articles

Outcomes in patients treated with loop diuretics without a diagnosis of heart failure: a retrospective cohort study

BackgroundLoop diuretics are commonly prescribed in the community, not always to patients with a recorded diagnosis of heart failure (HF). The rate of HF events in patients prescribed loop diuretics...

The Characteristics and Outcomes of Nonhospitalized Patients With Heart Failure in Saudi Arabia: A Contemporary Single-Center Study.

Background Contemporary data on patients with heart failure (HF) in Saudi Arabia is limited. Methods This was a retrospective study of patients who were followed in the HF Clinic at our center after January 1, 2022. The study end date was August 31, 2023. Patients who were alive and followed for <6 months were excluded. We reported the clinical characteristics, utilization of established therapies for HF, proportion of potential candidates for ancillary HF treatments, and rates of HF events and mortality. Results A total of 202 patients met the study criteria. The mean age was 56.0 ± 15.2 years. The median follow-up from the initial visit to the study end date was 47 months (interquartile range {IQR}: 29-58 months). Coronary artery disease (CAD) was the cause of HF in 85 (42%) patients. At their latest visit, 103 (51%) patients had diabetes, 82 (41%) were obese, and 134 (66%) received quadruple therapy. Iron deficiency was present in 143 (71%) patients during follow-up. At their latest visit, moderate-to-severe or severe functional mitral regurgitation (MR) and hyperkalemia were present in 15 (7%) and 20 (10%) patients, respectively. The combined annual rate of HF hospitalization and emergency visits for HF was 20%. At least one hospitalization for HF within a year before the study end date occurred in 19 (9%) patients. The annual all-cause mortality was 1.8%. Conclusion This contemporary cohort of outpatients with HF was relatively young and had a high prevalence of diabetes, obesity, and iron deficiency. An estimate of potential candidates for iron replacement, transcatheter repair of the mitral valve, novel potassium binders, and the implantation of the pulmonary artery pressure monitorwas among the first reported regionally. All-cause mortality was low, yet the burden of HF-related events was significant.

Abstract 13820: Association of Cardiothoracic Ratio With Heart Failure Events in Atrial Fibrillation Without Heart Failure: The Fushimi AF Registry

Background: The cardiothoracic ratio (CTR) is a readily available and non-invasive tool with which to assess cardiac volume status. We previously reported that N-terminal pro-B-type natriuretic peptide (NT-proBNP) level was associated with higher incidence of clinical events in patients with atrial fibrillation (AF) without pre-existing heart failure (HF). However, it remains unknown whether CTR on chest radiography is associated with the incidence of HF events in AF patients without HF. Methods: The Fushimi AF Registry is a community-based prospective survey of AF patients in Fushimi-ku, Kyoto, Japan. After excluding patients with pre-existing HF (defined as having one of the following; prior HF hospitalization, New York Heart Association class ≥2, or left ventricular ejection fraction &lt;40%), we divided 1,049 patients into four groups according to their CTR and NT-proBNP level (median value: 495 ng/L) at baseline, and compared the incidence of HF events (composite of cardiac death or HF hospitalization) among the groups; G1 (Lower CTR&lt;50% and Lower NT-proBNP&lt;495, n=256), G2 (Higher CTR≥50% and Lower NT-proBNP&lt;495, n=268), G3 (Lower CTR&lt;50% and Higher NT-proBNP≥495, n=117) and G4 (Higher CTR≥50% and Higher NT-proBNP≥495, n=408). Results: During the median follow-up of 5.4 years, the incidence rates of HF events in the groups either having higher NT-pro BNP group or higher CTR group were higher, as compared with patients with lower CTR and lower NT-proBNP (G1: 0.5% per person-year, G2: 1.3%, G3: 1.6% and G4: 2.5%; p&lt;0.01) (Figure). Multivariate Cox regression analysis revealed that higher CTR (≥50%) was independently associated with the incidence of HF events in AF patients without prior HF hospitalization (hazard ratio: 1.47, 95% confidence interval: 1.09-2.00). Conclusion: In Japanese AF patients without pre-existing HF, higher CTR was associated with higher incidence of HF events irrespective of NT-proBNP level.

Does cardiac imaging surveillance strategy influence outcomes in patients with early breast cancer?

Many patients with breast cancer receive therapies with the potential to cause cardiotoxicity. Echocardiography and multiple-gated acquisition (MUGA) scans are the most used modalities to assess cardiac function during treatment in high-risk patients; however, the optimal imaging strategy and the impact on outcome are unknown. Consecutive patients with stage 0-3 breast cancer undergoing pre-treatment echocardiography or MUGA were identified from a tertiary care cancer center from 2010-2019. Demographics, medical history, imaging data and clinical events were collected from hospital charts and administrative databases. The primary outcome is a composite of all-cause death or heart failure event. Clinical and imaging predictors of outcome were evaluated on univariable and multivariable analyses. 1028 patients underwent pre-treatment MUGA and 1032 underwent echocardiography. The groups were well matched for most clinical characteristics except patients undergoing MUGA were younger, had more stage 3 breast cancer and more HER2 over-expressing and triple negative cases. Routine follow-up cardiac imaging scan was obtained in 39.3% of patients with MUGA and 38.0% with echocardiography. During a median follow-up of 2448 (1489, 3160) days, there were 194 deaths, including 7 cardiovascular deaths, and 28 heart failure events with no difference in events between the MUGA and echocardiography groups. There were no imaging predictors of the primary composite outcome or cardiac events. Patients without follow-up imaging had similar adjusted risk for the composite outcome compared to those with imaging follow-up, hazard ratio 0.8 (95% confidence interval 0.5,1.3), p=0.457. The selection of pretreatment echocardiography or MUGA did not influence the risk of death or heart failure in patients with early breast cancer. Many patients did not have any follow-up cardiac imaging and did not suffer worse outcomes. Cardiovascular deaths and heart failure event rates were low and the value of long-term cardiac imaging surveillance should be further evaluated.

Levosimendan in outpatients with advanced heart failure: Single-center experience of 200 intermittent perfusions

IntroductionPatients with advanced heart failure (HF) have high morbidity and mortality, with only a small proportion being eligible for advanced therapies. Intermittent outpatient levosimendan infusion has been shown to provide symptomatic relief and reduce the rate of HF events. Our aim was to assess the safety and efficacy of outpatient levosimendan administration in an advanced HF population. MethodsThis is a report of a single-center experience of consecutive advanced HF patients referred for intermittent intravenous outpatient administration of levosimendan, between January 2018 and March 2021. Baseline and follow-up evaluation included clinical assessment, laboratory tests, transthoracic echocardiography and cardiopulmonary exercise testing. Baseline and clinical follow-up data were compared using the Wilcoxon signed-rank test. ResultsA total of 24 patients (60.8 years, 83% male, mean left ventricular ejection fraction [LVEF] 24%), with a median of 1.5 HF hospitalizations in the previous six months, were referred for outpatient levosimendan pulses, the majority as a bridge to transplantation or due to clinical deterioration. At six-month follow-up there was a significant reduction in HF hospitalizations to 0.4±0.7 (p<0.001). NYHA class IV (52.2% to 12.5%, p=0.025) and NT-proBNP (8812.5 to 3807.4 pg/ml, p=0.038) were also significantly reduced. Exercise capacity was significantly improved, including peak oxygen uptake (p=0.043) and VE/VCO2 slope (p=0.040). LVEF improved from 24.0% to 29.7% (p=0.008). No serious adverse events were reported. ConclusionRepeated levosimendan administration in advanced HF patients is a safe procedure and was associated with a reduction in HF hospitalizations, functional and LVEF improvement, and reduction in NT-proBNP levels during follow-up.

Proteinuria is independently associated with heart failure events in patients with atrial fibrillation: the Fushimi AF registry.

Previous studies have shown that proteinuria is independently associated with the incidence of atrial fibrillation (AF), and is also associated with the incidence of cardiovascular events such as stroke and thromboembolism in patients with AF. However, the association of proteinuria with heart failure (HF) events in patients with AF remains unclear. The Fushimi AF Registry is a community-based prospective study of patients with AF. Of the entire cohort of 4489 patients, 2164 patients had available data of proteinuria. We compared the clinical background and outcomes between patients with proteinuria (n=606, 28.0%) and those without (n=1558, 72.0%). Patients with proteinuria were older and had a higher prevalence of major co-morbidities. During the median follow-up of 5.0 years, the incidence rates of HF events (composite of cardiac death or HF hospitalization) were higher in patients with proteinuria than those without (4.1% vs. 2.1% person-year, P<0.01). Multivariate analyses revealed that proteinuria was an independent risk factor of the incidence of HF events [adjusted hazard ratio (HR): 1.40, 95% confidence interval (CI): 1.13-1.74]. This association was consistent among the various subgroups, except for the age subgroup in which there was a significant interaction (P<0.01) between younger (<75 years) (unadjusted HR: 3.03, 95% CI: 2.12-4.34) and older (≥75 years) patients (unadjusted HR: 1.59, 95% CI: 1.23-2.05). Our community-based large prospective cohort suggests that proteinuria is independently associated with the incidence of HF events in Japanese patients with AF.

Type III procollagen peptide level can indicate liver dysfunction associated with volume overload in acute heart failure.

AimThe role of serum type III procollagen peptide (P3P) level in the acute phase of acute heart failure (AHF) requires clarification. We hypothesized that serum P3P level is temporarily higher during the acute phase, reflecting liver dysfunction due to congestion.Methods and resultsA total of 800 AHF patients were screened, and data from 643 patients were analysed. Heart failure was diagnosed by the treating physician according to the European Society of Cardiology (ESC) guidelines, and included patients being treated with high‐concentration oxygen inhalation (including mechanical support) for orthopnea, inotrope administration, or mechanical support for low blood pressure, and various types of diuretics for peripheral or pulmonary oedema. In all cases, diuretics or vasodilators were administered to treat AHF. The patients were divided into three groups according to their quartile (Q) serum P3P level: low‐P3P (Q1, P3P ≤ 0.6 U/mL), mid‐P3P (Q2/Q3, 0.6 < P3P <1.2 U/mL), and high‐P3P (Q4, P3P ≥ 1.2 U/mL). The plasma volume status (PVS) was calculated using the following formula: ([actual PV − ideal PV]/ideal PV) × 100 (%). The primary endpoint was 365 day mortality. A Kaplan–Meier curve analysis showed that prognoses, including all‐cause mortality and heart failure events within 365 days, were significantly (P < 0.001) worse in the high‐P3P group when compared with the mid‐P3P and low‐P3P groups. A multivariate logistic regression analysis showed that high PVS (Q4, odds ratio [OR]: 4.702, 95% CI: 2.012–20.989, P < 0.001), high fibrosis‐4 index (Q4, OR: 2.627, 95% CI: 1.311–5.261, P = 0.006), and low estimated glomerular filtration rate per 10 mL/min/1.73 m2 decrease (OR: 1.996, 95% CI: 1.718–2.326, P < 0.001) were associated with high P3P values. The Kaplan–Meier curve analysis demonstrated a significantly lower survival rate, as well as a higher rate of heart failure events, in the high‐P3P and high‐PVS groups when compared with the other groups. A multivariate Cox regression model identified high P3P level and high PVS as an independent predictor of 365 day all‐cause mortality (hazard ratio [HR]: 2.249; 95% CI: 1.081–3.356; P = 0.026) and heart failure events (HR: 1.586, 95% CI: 1.005–2.503, P = 0.048).ConclusionA high P3P level during the acute phase of AHF served as a comprehensive biomarker of liver dysfunction with volume overload (i.e. liver congestion) and renal dysfunction. A high P3P level at admission may be able to predict adverse outcomes in AHF patients.

Atrial shunt device for heart failure with preserved and mildly reduced ejection fraction (REDUCE LAP-HF II): a randomised, multicentre, blinded, sham-controlled trial

Placement of an interatrial shunt device reduces pulmonary capillary wedge pressure during exercise in patients with heart failure and preserved or mildly reduced ejection fraction. We aimed to investigate whether an interatrial shunt can reduce heart failure events or improve health status in these patients. In this randomised, international, blinded, sham-controlled trial performed at 89 health-care centres, we included patients (aged ≥40 years) with symptomatic heart failure, an ejection fraction of at least 40%, and pulmonary capillary wedge pressure during exercise of at least 25 mm Hg while exceeding right atrial pressure by at least 5 mm Hg. Patients were randomly assigned (1:1) to receive either a shunt device or sham procedure. Patients and outcome assessors were masked to randomisation. The primary endpoint was a hierarchical composite of cardiovascular death or non-fatal ischemic stroke at 12 months, rate of total heart failure events up to 24 months, and change in Kansas City Cardiomyopathy Questionnaire overall summary score at 12 months. Pre-specified subgroup analyses were conducted for the heart failure event endpoint. Analysis of the primary endpoint, all other efficacy endpoints, and safety endpoints was conducted in the modified intention-to-treat population, defined as all patients randomly allocated to receive treatment, excluding those found to be ineligible after randomisation and therefore not treated. This study is registered with ClinicalTrials.gov, NCT03088033. Between May 25, 2017, and July 24, 2020, 1072 participants were enrolled, of whom 626 were randomly assigned to either the atrial shunt device (n=314) or sham procedure (n=312). There were no differences between groups in the primary composite endpoint (win ratio 1·0 [95% CI 0·8-1·2]; p=0·85) or in the individual components of the primary endpoint. The prespecified subgroups demonstrating a differential effect of atrial shunt device treatment on heart failure events were pulmonary artery systolic pressure at 20W of exercise (pinteraction=0·002 [>70 mm Hg associated with worse outcomes]), right atrial volume index (pinteraction=0·012 [≥29·7 mL/m2, worse outcomes]), and sex (pinteraction=0·02 [men, worse outcomes]). There were no differences in the composite safety endpoint between the two groups (n=116 [38%] for shunt device vs n=97 [31%] for sham procedure; p=0·11). Placement of an atrial shunt device did not reduce the total rate of heart failure events or improve health status in the overall population of patients with heart failure and ejection fraction of greater than or equal to 40%. Corvia Medical.

Abstract 9958: Calcium-Phosphorus Product is Associated with Adverse Prognosis in Hospitalized Patients with Heart Failure and Chronic Kidney Disease

Introduction: It has been reported that calcium-phosphorus (Ca-P) product &amp;gt 55 mg 2 /dl 2 is an independent predictor for coronary calcifications, and Ca-P product &amp;gt 80 or &amp;lt 40 is a mortality risk in patients undergoing chronic hemodialysis. However, the association between Ca-P product and prognosis in patients with heart failure (HF) and chronic kidney disease (CKD) remains unclear. We aimed to evaluate the significance of the Ca-P product to predict prognosis of patients with HF and CKD. Methods: We conducted a prospective observational study of 793 patients with decompensated HF and CKD, who had been discharged from our hospital. According to the receiver operating characteristic curve analysis, the accurate cut-off value of Ca-P product in predicting post-discharge all-cause mortality and/or worsening HF was 28 mg 2 /dl 2 . These patients were divided into two groups: the high group (Ca-P product &amp;gt 28, n=594) and the low group (Ca-P product &amp;lt 28, n=199). We compared the patient baseline characteristics and their post-discharge prognosis between the two groups. Results: Age was significantly higher, and the prevalence of male, ischemic etiology and anemia was significantly higher in the low group than in the high group. In contrast, there was no difference in echocardiographic parameters between two groups. Ca-P product was correlated with cardio-ankle vascular index (a marker of arterial stiffness), but not with left ventricular ejection fraction. In the Kaplan-Meier analysis (mean follow-up 1089 days), all-cause mortality and/or worsening HF event rates were higher in the low group than in the high group (Figure, log-rank P=0.001). In the multivariable Cox proportional hazard analysis, the low group was found to be an independent predictor of all-cause mortality and/or worsening HF (hazard ratio 1.218, P=0.048). Conclusions: Lower Ca-P product is associated with arterial stiffness, and predicts adverse prognosis in patients with HF and CKD.

Incident Heart Failure Within the First and Fifth Year after Delivery Among Women With Hypertensive Disorders of Pregnancy and Prepregnancy Hypertension in a Diverse Population.

BackgroundHypertensive disorders of pregnancy (HDP) and pre‐pregnancy hypertension are associated with increased morbidity and mortality for the mother. Our aim was to investigate the relationships between HDP and pre‐pregnancy hypertension with maternal heart failure (HF) within 1 and 5 years of delivery and to examine racial/ethnic differences.Methods and ResultsWe conducted a retrospective cohort study in South Carolina (2004–2016) involving 425 649 women aged 12 to 49 years (58.9% non‐Hispanic White [NHW], 31.5% non‐Hispanic Black [NHB], 9.6% Hispanic) with a live, singleton birth. Incident HF was defined by hospital/emergency department visit and death certificate data. Pre‐pregnancy hypertension and HDP (preeclampsia, eclampsia, or gestational hypertension) were based on hospitalization/emergency department visit and birth certificate data (i.e., gestational hypertension for HDP). The 425 649 women had pre‐pregnancy hypertension without superimposed HDP (pre‐pregnancy hypertension alone; 0.4%), HDP alone (15.7%), pre‐pregnancy hypertension with superimposed HDP (both conditions; 2.2%), or neither condition in any pregnancy (81.7%). Incident HF event rates per 1000 person‐years were higher in NHB than NHW women with HDP (HDP: 2.28 versus 0.96; both conditions: 4.30 versus 1.22, respectively). After adjustment, compared with women with neither condition, incident HF risk within 5 years of delivery was increased for women with pre‐pregnancy hypertension (HR,2.55, 95% CI: 1.31–4.95), HDP (HR,4.20, 95% CI: 3.66–4.81), and both conditions (HR,5.25, 95% CI: 4.24–6.50).ConclusionsWomen with HDP and pre‐pregnancy hypertension were at higher HF risk (highest for superimposed preeclampsia) within 5 years of delivery. NHB women with HDP had higher HF risk than NHW women, regardless of pre‐pregnancy hypertension.

The cost of non-response to cardiac resynchronization therapy: characterizing heart failure events following cardiac resynchronization therapy.

The aim of this study is to quantify healthcare resource utilization among non-responders to cardiac resynchronization therapy (CRT-NR) by heart failure (HF) events and influence of comorbidities. The ADVANCE CRT registry (2013-2015) prospectively identified responders/CRT-NRs 6 months post-implant using the clinical composite score. Heart failure event rates and associated cost, both overall and separated for inpatient hospitalizations, office visits, emergency room visits, and observational stays, were quantified. Costs of events were imputed from payments for similar real-world encounters in subjects with CRT-D/P devices in the MarketScan™ commercial and Medicare Supplemental insurance claims databases. Effects of patient demographics and comorbidities on event rates and cost were evaluated. Of 879 US patients (age 69 ± 11 years, 29% female, ischaemic disease 52%), 310 (35%) were CRT-NR. Among CRT-NRs vs. responders, more patients developed HF (41% vs. 11%, P < 0.001), HF event rate was higher (67.0 ± 21.7 vs. 11.4 ± 3.7/100 pt-year, P < 0.001), and HF readmission within 30 days was more common [hazard ratio 7.06, 95% confidence interval (2.1-43.7)]. Inpatient hospitalization was the most common and most expensive event type in CRT-NR. Comorbid HF was increased by diabetes, hypertension, and pulmonary disorders. Over 2 years, compared to CRT responders, each CRT-NR resulted in excess cost of $6388 ($3859-$10 483) to Medicare (P = 0.015) or $10 197 ($6161-$17 394) to private insurances (P = 0.014). Healthcare expenditures associated with contemporary CRT non-response management are among the highest for any HF patient group. This illustrates an unmet need for interventions to improve HF outcomes and reduce costs among some CRT recipients.

Multiparametric Implantable Cardioverter-Defibrillator Algorithm for Heart Failure Risk Stratification and Management: An Analysis in Clinical Practice.

The HeartLogic algorithm combines multiple implantable cardioverter-defibrillator sensors to identify patients at risk of heart failure (HF) events. We sought to evaluate the risk stratification ability of this algorithm in clinical practice. We also analyzed the alert management strategies adopted in the study group and their association with the occurrence of HF events. The HeartLogic feature was activated in 366 implantable cardioverter-defibrillator and cardiac resynchronization therapy implantable cardioverter-defibrillator patients at 22 centers. The median follow-up was 11 months [25th-75th percentile: 6-16]. The HeartLogic algorithm calculates a daily HF index and identifies periods IN alert state on the basis of a configurable threshold. The HeartLogic index crossed the threshold value 273 times (0.76 alerts/patient-year) in 150 patients. The time IN alert state was 11% of the total observation period. Patients experienced 36 HF hospitalizations, and 8 patients died of HF during the observation period. Thirty-five events were associated with the IN alert state (0.92 events/patient-year versus 0.03 events/patient-year in the OUT of alert state). The hazard ratio in the IN/OUT of alert state comparison was (hazard ratio, 24.53 [95% CI, 8.55-70.38], P<0.001), after adjustment for baseline clinical confounders. Alerts followed by clinical actions were associated with less HF events (hazard ratio, 0.37 [95% CI, 0.14-0.99], P=0.047). No differences in event rates were observed between in-office and remote alert management. This multiparametric algorithm identifies patients during periods of significantly increased risk of HF events. The rate of HF events seemed lower when clinical actions were undertaken in response to alerts. Extra in-office visits did not seem to be required to effectively manage HeartLogic alerts. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02275637.

A multiparametric ICD algorithm for heart failure risk stratification and management: an analysis in clinical practice

Abstract Funding Acknowledgements Type of funding sources: None. Introduction The HeartLogic algorithm combines multiple implantable cardioverter defibrillator (ICD) sensors to identify patients at risk of heart failure (HF) events. Purpose We sought to evaluate the risk stratification ability of this algorithm in clinical practice. We also analyzed the alert management strategies adopted in the study group and their association with the occurrence of HF events. Methods The HeartLogic feature was activated in 366 ICD and cardiac resynchronization therapy ICD patients at 22 centers. The HeartLogic algorithm automatically calculates a daily HF index and identifies periods IN or OUT of an alert state on the basis of a configurable threshold (in this analysis set to 16). Results The HeartLogic index crossed the threshold value 273 times (0.76 alerts/patient-year) in 150 patients over a median follow-up of 11 months [25-75 percentile: 6-16]. Overall, the time IN the alert state was 11% of the total observation period. Patients experienced 36 HF hospitalizations and 8 patients died of HF (rate: 0.12 events/patient-year) during the observation period. Thirty-five events were associated with the IN alert state (0.92 events/patient-year versus 0.03 events/patient-year in the OUT of alert state). The hazard ratio in the IN/OUT of alert state comparison was (HR: 24.53, 95% CI: 8.55-70.38, p &amp;lt; 0.001), after adjustment for baseline clinical confounders. Alerts followed by clinical actions were associated with a lower rate of HF events (HR: 0.37, 95% CI: 0.14-0.99, p = 0.047). No differences in event rates were observed between in-office and remote alert management. By contrast, verification of HF symptoms during post-alert examination was associated with a higher risk of HF events (HR: 5.23, 95% CI: 1.98-13.83, p &amp;lt; 0.001). Conclusions This multiparametric ICD algorithm identifies patients during periods of significantly increased risk of HF events. The rate of HF events seemed lower when clinical actions were undertaken in response to alerts. Extra in-office visits did not seem to be required in order to effectively manage HeartLogic alerts, while post-alert verification of symptoms seemed useful in order to better stratify patients at risk of HF events.

Abstract 16910: High-Frequency In-Person Visits During Clinical Trial Enrollment is Associated With Relative Reduction in Event Rates in Heart Failure Patients Followed Longitudinally

Introduction: The COVID-19 Pandemic has mandated limiting routine visit frequency for patients with chronic cardiovascular (CV) diseases. In patients with heart failure (HF) followed longitudinally, the period of clinical trial participation provides an opportunity to evaluate the influence of high-frequency per-protocol in-person visits compared to less frequent routine visits during longitudinal clinical care. Hypothesis: Patients enrolled in clinical trials will have a lower CV and HF event rates during periods of trial enrollment than during non-trial periods. Methods: We examined clinical characteristics, CV and HF hospitalization rates, and outcomes in patients with HF receiving longitudinal HF care at a single center. We evaluated hospitalization rates during the 1-year preceding trial enrollment and hospitalization and death rates during enrollment in clinical trials and for up to 1 year following trial completion. Results: Among the 121 patients enrolled in HF clinical trials, 72% were HFrEF (age 62±11, 19% females, BMI 30.4±6.0, LVEF 25±7, NYHA 2.7±0.6, NT-proBNP 2336±2671) and 28% were HFpEF (age 69±9, BMI 32.1±5.5, 29% females, LVEF 60±10, NYHA 2.4±0.5, NT-proBNP 957±997). Average clinical trial exposure was 8±6.6 months. Per-protocol visit frequency was 16±7 per year during clinical trial enrollment. In the one-year pre-trial period, compared to the within-trial period, CV hospitalizations were 0.88/patient-year vs. 0.32/patient-year (p&lt;0.001) and HF hospitalizations were 0.63/patient-year and 0.24/patient-year (p&lt;0.001), with a mortality rate of 0.04/patient-year during trial participation. In the period of up-to 1 year following the end of trial enrollment CV and HF hospitalizations were intermediate at 0.51/patient-year and 0.27/patient-year with an annualized incremental mortality rate of 0.03/patient-year. Conclusion: In HF patients followed longitudinally at a single center, periods of clinical trial enrollment were associated with high visit frequency and lower CV and HF hospitalization rates. These findings highlight the potential benefits of trial enrollment and high-frequency visits for HF patients at a time when routine visit frequency is being carefully considered during the COVID-19 Pandemic.

The HeartLogic multi-sensor algorithm significantly augments the prognosis of a baseline NT-proBNP assessment for heart failure events

Purpose To determine whether HeartLogic, a device based multi-sensor algorithm, augments the prognosis of a single baseline NT-proBNP assessment for HF events over the course of a year. Background Guidelines carry a class IA recommendation for the use of natriuretic peptides (BNP or NT-proBNP) to establish prognosis or disease severity in chronic Heart Failure (HF). However, these reflect a snapshot assessment at the time of blood draw, which lose relevance over time with changes in the patient's condition. We recently reported on a multi-sensor HF Index and alert algorithm (HeartLogic) using hardware already present in an implantable defibrillator that detected HF events with 70% sensitivity and 34 day advance warning, and identified patients with 10-fold increased risk of worsening HF. In this analysis, our objective was to evaluate whether HeartLogic augments the prognosis of a single baseline NT-proBNP assessment for HF events over the course of a year. Methods The MultiSENSE trial enrolled patients in North America, Europe, and Asia implanted with CRT-Ds that enabled multi-sensor data collection for up to one year. Patient demographics, clinical history, and baseline measurements including NT-proBNP were obtained at enrollment. HF events were defined as either HF admissions or unscheduled visits with augmented intravenous HF treatment, and were independently adjudicated. The HeartLogic algorithm continuously measured sensor data including heart sounds, respiration rate and tidal volume, thoracic impedance, heart rate, and activity; sensor changes from the patient's own baseline were aggregated and weighted on the basis of an individual daily risk to calculate the daily HeartLogic HF index and compared against a user-configurable alert threshold. Clinicians were blinded to the sensor data and HeartLogic index and alert. HF event rates (expressed as events/pt-yr) were calculated for patients with baseline NT-proBNP above and below 1000 pg/mL and periods with HeartLogic in or out of alert relative to the nominal threshold of 16. Conclusions HeartLogic alerts significantly augment the ability of baseline NT-proBNP to identify periods with an elevated risk of HF event over up to a year. B-type natriuretic peptides are the current gold standard marker of adverse heart failure risk, but the prognostic ability decreases over time. Dynamic assessment using HeartLogic alerts in conjunction with intermittent/sparse NT-proBNP could automatically identify periods of time in which patients are at significantly increased risk of worsening HF and help better triage resources to this vulnerable patient population. Results Total of 900 patients were followed for up to one year (72.7% male; age 66.6 ± 10.5 years; NYHA Class II/III: 67.2%/26.8%; LVEF 30.0 ± 11.4%) resulting in a total of 192 HF events (average event rate: 0.23 events/pt-yr). The HF event rates are shown in figure (right), with the proportion of patient follow-up for each risk stratification listed below the figure. About half of follow-up time (53%) was within the lowest risk group (0.02 events/pt-yr): out of alert and NT-proBNP

HeartLogic Multisensor Algorithm Identifies Patients During Periods of Significantly Increased Risk of Heart Failure Events: Results From the MultiSENSE Study.

Care of heart failure (HF) patients results in a high burden on healthcare resources, and estimating prognosis is becoming increasingly important to triage resources wisely. Natriuretic peptides are recommended prognosticators in chronic HF. Our objective was to evaluate whether a multisensor HF index and alert algorithm (HeartLogic) replaces or augments current HF risk stratification. MultiSENSE (Multisensor Chronic Evaluation in Ambulatory Heart Failure Patients) enrolled 900 patients with cardiac resynchronization therapy defibrillators enabled for collection of heart sounds, respiration, thoracic impedance, heart rate, and activity data. The HeartLogic algorithm automatically calculated a daily HF index and identified periods IN or OUT of an active alert state relative to a configurable threshold. Patients experienced 192 independently adjudicated HF events (average rate, 0.20/patient-year [pt-yr]) during 1 year of follow-up. HF event rates while IN alert was 10-fold higher than OUT of alert (0.80 versus 0.08 events/pt-yr). Combined with NT-proBNP (N-terminal pro-B-type natriuretic peptide) at enrollment (relative to 1000 pg/mL threshold, event rate was 0.42 [HIGH] versus 0.07 [LOW] events/pt-yr), substratification found the lowest risk group (LOW NT-proBNP and OUT of alert) experienced 0.02 events/pt-yr, whereas the highest risk group (HIGH NT-proBNP and IN alert) was associated with a 50-fold increased risk of an HF event (1.00 events/pt-yr) relative to the lowest risk group. Dynamic assessment using implantable device sensors within HeartLogic by itself or in conjunction with NT-proBNP measurements can identify time-intervals when patients are at significantly increased risk of worsening HF and potentially better triage resources to this vulnerable patient population. https://www.clinicaltrials.gov. Unique identifier: NCT01128166.

Association Between Use of Sodium-Glucose Cotransporter 2 Inhibitors, Glucagon-like Peptide 1 Agonists, and Dipeptidyl Peptidase 4 Inhibitors With All-Cause Mortality in Patients With Type 2 Diabetes

The comparative clinical efficacy of sodium-glucose cotransporter 2 (SGLT-2) inhibitors, glucagon-like peptide 1 (GLP-1) agonists, and dipeptidyl peptidase 4 (DPP-4) inhibitors for treatment of type 2 diabetes is unknown. To compare the efficacies of SGLT-2 inhibitors, GLP-1 agonists, and DPP-4 inhibitors on mortality and cardiovascular end points using network meta-analysis. MEDLINE, Embase, Cochrane Library Central Register of Controlled Trials, and published meta-analyses from inception through October 11, 2017. Randomized clinical trials enrolling participants with type 2 diabetes and a follow-up of at least 12 weeks were included, for which SGLT-2 inhibitors, GLP-1 agonists, and DPP-4 inhibitors were compared with either each other or placebo or no treatment. Data were screened by 1 investigator and extracted in duplicate by 2 investigators. A Bayesian hierarchical network meta-analysis was performed. The primary outcome: all-cause mortality; secondary outcomes: cardiovascular (CV) mortality, heart failure (HF) events, myocardial infarction (MI), unstable angina, and stroke; safety end points: adverse events and hypoglycemia. This network meta-analysis of 236 trials randomizing 176 310 participants found SGLT-2 inhibitors (absolute risk difference [RD], -1.0%; hazard ratio [HR], 0.80 [95% credible interval {CrI}, 0.71 to 0.89]) and GLP-1 agonists (absolute RD, -0.6%; HR, 0.88 [95% CrI, 0.81 to 0.94]) were associated with significantly lower all-cause mortality than the control groups. SGLT-2 inhibitors (absolute RD, -0.9%; HR, 0.78 [95% CrI, 0.68 to 0.90]) and GLP-1 agonists (absolute RD, -0.5%; HR, 0.86 [95% CrI, 0.77 to 0.96]) were associated with lower mortality than were DPP-4 inhibitors. DPP-4 inhibitors were not significantly associated with lower all-cause mortality (absolute RD, 0.1%; HR, 1.02 [95% CrI, 0.94 to 1.11]) than were the control groups. SGLT-2 inhibitors (absolute RD, -0.8%; HR, 0.79 [95% CrI, 0.69 to 0.91]) and GLP-1 agonists (absolute RD, -0.5%; HR, 0.85 [95% CrI, 0.77 to 0.94]) were significantly associated with lower CV mortality than were the control groups. SGLT-2 inhibitors were significantly associated with lower rates of HF events (absolute RD, -1.1%; HR, 0.62 [95% CrI, 0.54 to 0.72]) and MI (absolute RD, -0.6%; HR, 0.86 [95% CrI, 0.77 to 0.97]) than were the control groups. GLP-1 agonists were associated with a higher risk of adverse events leading to trial withdrawal than were SGLT-2 inhibitors (absolute RD, 5.8%; HR, 1.80 [95% CrI, 1.44 to 2.25]) and DPP-4 inhibitors (absolute RD, 3.1%; HR, 1.93 [95% CrI, 1.59 to 2.35]). In this network meta-analysis, the use of SGLT-2 inhibitors or GLP-1 agonists was associated with lower mortality than DPP-4 inhibitors or placebo or no treatment. Use of DPP-4 inhibitors was not associated with lower mortality than placebo or no treatment.

Bardoxolone Methyl Improves Kidney Function in Patients with Chronic Kidney Disease Stage 4 and Type 2 Diabetes: Post-Hoc Analyses from Bardoxolone Methyl Evaluation in Patients with Chronic Kidney Disease and Type 2 Diabetes Study

Background: Increases in measured inulin clearance, measured creatinine clearance, and estimated glomerular filtration rate (eGFR) have been observed with bardoxolone methyl in 7 studies enrolling approximately 2,600 patients with type 2 diabetes (T2D) and chronic kidney disease (CKD). The largest of these studies was Bardoxolone Methyl Evaluation in Patients with Chronic Kidney Disease and Type 2 Diabetes (BEACON), a multinational, randomized, double-blind, placebo-controlled phase 3 trial which enrolled patients with T2D and CKD stage 4. The BEACON trial was terminated after preliminary analyses showed that patients randomized to bardoxolone methyl experienced significantly higher rates of heart failure events. We performed post-hoc analyses to characterize changes in kidney function induced by bardoxolone methyl. Methods: Patients in ­BEACON (n = 2,185) were randomized 1: 1 to receive once-daily bardoxolone methyl (20 mg) or placebo. We compared the effects of bardoxolone methyl and placebo on a post-hoc composite renal endpoint consisting of ≥30% decline from baseline in eGFR, eGFR <15 mL/min/1.73 m², and end-stage renal disease (ESRD) events (provision of dialysis or kidney transplantation). Results: Consistent with prior studies, patients randomized to bardoxolone methyl experienced mean increases in eGFR that were sustained through study week 48. Moreover, increases in eGFR from baseline were sustained 4 weeks after cessation of treatment. Patients randomized to bardoxolone methyl were significantly less likely to experience the composite renal endpoint (hazards ratio 0.48 [95% CI 0.36–0.64]; p < 0.0001). Conclusions: Bardoxolone methyl preserves kidney function and may delay the onset of ESRD in patients with T2D and stage 4 CKD.

Use of Electronic Health Data to Estimate Heart Failure Events in a Population-Based Cohort with CKD.

Studies that use electronic health data typically identify heart failure (HF) events from hospitalizations with a principal diagnosis of HF. This approach may underestimate the total burden of HF among persons with CKD. We assessed the accuracy of algorithms for identifying validated HF events from hospitalizations and outpatient encounters, and we used this validation information to estimate the rate of HF events in a large CKD population. We identified a cohort of 15,141 adults age 18-89 years with an eGFR<60 ml/min per 1.73 m2 from 2008 to 2011. Potential HF events during follow-up were randomly sampled for validation with medical record review. Positive predictive values from the validation study were used to estimate the rate of validated HF events in the full cohort. A total of 1864 participants had at least one health care encounter that qualified as a potential HF event during 2.7 years of mean follow-up. Among 313 potential events that were randomly sampled for validation, positive predictive values were 92% for hospitalizations with a principal diagnosis of HF, 32% for hospitalizations with a secondary diagnosis of HF, and 70% for qualifying outpatient HF encounters. Through use of this validation information in the full cohort, the rate of validated HF events estimated from the most comprehensive algorithm that included principal and secondary diagnosis hospitalizations and outpatient encounters was 35.2 events/1000 person-years (95% confidence interval, 33.1 to 37.4), compared with 9.5 events/1000 person-years (95% confidence interval, 8.7 to 10.5) from the algorithm that included only principal diagnosis hospitalizations. Outpatient encounters accounted for 20% of the total number of validated HF events. In studies that rely on electronic health data, algorithms that include hospitalizations with a secondary diagnosis of HF and outpatient HF encounters more fully capture the burden of HF, although validation of HF events may be necessary with this approach.

Abstract 250: Real-world Rates and Costs of Heart Failure Events Among Patients with Hyperlipidemia

Background: This real-world retrospective cohort study estimated the rate of heart failure events and total healthcare costs among patients with hyperlipidemia. Methods: Patients (aged 18-64 years) with hyperlipidemia diagnosis and/or lipid-lowering medications were identified from the HealthCore Integrated Research Database SM from 1/1/2007 to 12/31/2008 and followed until 2/28/2013. Patients were stratified by cardiovascular (CV) risk level as (1) secondary prevention with a history of myocardial infarction, stroke, unstable angina, or revascularization, (2) modified coronary heart disease (CHD) risk equivalent (RE) without a history of CV events but with peripheral artery disease, type 2 diabetes, abdominal aortic aneurysm, ischemic heart disease, stable angina, or TIA, and (3) primary prevention without a history of CV events or CHD RE. Patients with new CV event hospitalization during follow-up were propensity score-matched to patients without new CV events within each cohort. Proportion of patients with heart failure events and incremental total costs during 2 years of follow-up were evaluated. Results: Before matching, 62,427 patients had ≥1 CV event (13.2% secondary prevention, 38.4% CHD RE, 48.5% primary prevention). For patients with ≥1 CV event during follow-up, 38.8% of secondary prevention, 42.6% of CHD RE, and 30.0% of primary prevention had heart failure as their index event. Of patients with heart failure index event, 58.3% of secondary prevention, 47.3% of CHD RE, and 30.5% of primary prevention patients had 1 or more heart failure events over 2 years. Among patients with ≥1 heart failure events, 36.2% of secondary prevention, 30.0% of CHD RE, and 17.7% of primary prevention patients had ≥3 heart failure events over 2 years. Among matched patients (85-87% of patients), incremental total cost over 2 years for patients with heart failure as their index event compared with patients without CV events was $56,078 for secondary prevention, $53,247 for CV RE, and $49,637 for primary prevention cohorts. Conclusions: The rate and recurrence of heart failure among hyperlipidemic patients is very high and the long term healthcare costs substantial in this real-world 2-year study.