Baseline Heart Failure Research Articles

Use of sodium-glucose co-transporter-2 inhibitors in patients with and without type 2 diabetes: implications for incident and prevalent heart failure.

Type 2 diabetes (T2D) is associated with an increased risk of heart failure (HF), with recent reports indicating that HF with preserved ejection fraction (HFpEF) may be more common than HF with reduced ejection fraction (HFrEF) in patients with T2D. T2D and HF result in worse outcomes than either disease alone. Sodium-glucose co-transporter-2 inhibitors (SGLT-2is) have significantly improved HF outcomes in patients with T2D and may represent a new therapeutic alternative for patients with T2D at risk for or with HF. Current guidelines recommend prevention of HF through risk factor management. Once developed, treatment of HFrEF should include neurohormonal and haemodynamic modulations; however, there are no specific treatments available for HFpEF. SGLT-2is are the first class of glucose-lowering therapy to prevent HF in clinical trials and real-world studies in patients with T2D (with or without established cardiovascular disease and with or without baseline HF). Mechanistic studies suggest that SGLT-2is have beneficial effects on both systolic and diastolic function and additional systemic effects that could benefit HF outcomes. In patients with HFrEF, SGLT-2i treatment as add-on to standard HF therapy has had beneficial effects on HF outcomes, irrespective of T2D status. These results and those of ongoing outcomes trials with SGLT-2is may help establish this drug class as a treatment for HF in patients with HFrEF and HFpEF, as well as HF in patients without T2D.

Efficacy and Safety of Outpatient Clinic-based Elective External Electrical Cardioversion in Patients with Atrial Fibrillation.

Background and ObjectivesLittle is known about the outcomes of outpatient clinic-based elective external cardioversion (OPC-ECV) for persistent atrial fibrillation (PeAF). We investigated the acute, short-term, and long-term elective external cardioversion (ECV) outcomes.MethodsWe included 1,718 patients who underwent OPC-ECV (74% male, 61.1±11.0 years old, 90.9% long-standing PeAF, 9.1% after atrial fibrillation [AF] ablation) after excluding patients with atrial tachycardia or inappropriate antiarrhythmic drug medication, and in-patient ECV. Biphasic shocks were delivered sequentially until successful cardioversion was achieved (70-100-150-200-250 J). If ECV failed at 150 J, we administered intravenous amiodarone 150 mg and delivered 200 J.ResultsECV failed in 11.4%, and the complication rate was 0.47%. Within 3 months, AF recurred in 55.5% (44.7% as sustaining AF, 10.8% as paroxysmal AF), and the AF duration was independently associated (odds ratio [OR], 1.01 [1.00–1.02]; p=0.006), but amiodarone was independently protective (OR, 0.46 [0.27–0.76]; p=0.002, Log rank p<0.001) against an early recurrence. Regarding the long-term recurrence, pre-ECV heart failure was protective against an AF recurrence (hazard ratio, 0.63 [0.41–0.96], p=0.033) over 32 (9–66) months of follow-up. ECV energy (p<0.001) and early recurrence rate within 3 months (p=0.007, Log rank p=0.006) were significantly lower in post-ablation patients than in those with long-standing persistent AF.ConclusionsThe success rate of OPC-ECV was 88.6%, and the complication rate was low. However, AF recurred in 55.5% within 3 months. Amiodarone was protective against short-term AF recurrences, and long-term AF recurrences were less in patients with baseline heart failure.

118 Home Intravenous Furosemide Therapy in Older Patients With Heart Failure

Heart Failure hospitalisation in older patients is associated with a poor prognosis, with 1-year mortality rates approaching 20%. Hospital admission brings risks of iatrogenic complications including delirium, falls, infections and deconditioning. Hospital in the Home (HITH) treatment with intravenous diuretics is an emerging treatment strategy to facilitate early discharge with many potential benefits for both patients and hospitals. The aim of our study was to examine readmission rates and clinical outcomes in older patients admitted to hospital with decompensated heart failure who were subsequently continued on home-based intravenous diuresis using a HITH program. Data from 45 consecutive patients was examined. Median age was 80 (IQR 71–88) and median index hospital length of stay (LOS) was 3 days (IQR 1–7). Median LOS on HITH was 11 days (IQR 6–16). 17 of 45 patients (38%) required readmission to hospital within 30 days of discharge. Of these, 4 (9%) were readmitted for treatment complications (hypotension, infection or AKI) and 6 (13%) were readmitted for fluid overload. 5 patients (11%) were readmitted for non-cardiac reasons. 2 patients suffered major adverse events within 30 days (one NSTEMI, one death from end-stage heart failure). There were no significant differences in demographics, baseline heart failure therapy or baseline biochemical parameters between patients who required readmission and those who did not. HITH therapy may be a safe and effective option to facilitate early hospital discharge in older patients with heart failure. Further study may identify the optimal target demographic to reduce hospital readmissions and complications.

Series: Cardiovascular outcome trials for diabetes drugs Alogliptin and EXAMINE

EXAMINE was an FDA mandated cardiovascular outcome trial with alogliptin. In contrast to other cardiovascular outcome trials with DPP-4 inhibitors, it was performed in subjects with a recent acute coronary syndrome. EXAMINE compared alogliptin and placebo in 5,380 subjects with type 2 diabetes and demonstrated non-inferiority for major cardiovascular events (cardiovascular death, myocardial infarction, stroke) but not superiority. Data on hospitalisation for heart failure were not included in the principal publication. A subsequent publication showed no overall increase in hospitalisation for heart failure with alogliptin, but when subjects with and without baseline heart failure were separated there was a significant increase in the group without heart failure at baseline. No clear clinical benefit has been established for alogliptin, and there are alternatives such as sitagliptin and linagliptin that are not associated with an increase in hospitalisation for heart failure.

P5003Reduced healthcare utilization in routine care initiators of empagliflozin with and without heart failure: interim analysis from the EMPagliflozin compaRative effectIveness and SafEty (EMPRISE) study

Abstract Background Empagliflozin (EMPA) reduced the risk of hospitalization for heart failure (HHF) (HR 0.65; 95% CI 0.50- 0.85) as demonstrated in the EMPA-REG OUTCOME trial in adults with type 2 diabetes (T2D) and established CV disease. However, the impact of EMPA treatment initiation on healthcare resource utilization (HCRU) in routine care in patients with history of heart failure (HF) or without history of HF remains unexplored. Purpose To compare HCRU among EMPA and dipeptidyl peptidase-4 inhibitor (DPP4i) initiators with and without HF history at time of treatment initiation. Methods We analyzed HCRU in the first two years after marketing of EMPA as part of EMPRISE, a non-interventional study on the comparative effectiveness, safety and HCRU of EMPA for T2D patients in routine care in two US commercial and Medicare claims datasets (08/2014–09/2016). We identified a 1:1 propensity-score-matched cohort of T2D patients ≥18 years initiating either EMPA or a DPP4i with and without baseline HF, and assessed the balance at baseline (period of 365 days) on ≥140 covariates including clinical, HCRU, and cost-related covariates using absolute standardized differences. We compared the risk of first all-cause hospitalization, risk of first HHF, risk of first emergency department (ED) visit, hospital length of stay (LOS), HF-related LOS, number of hospital admissions, HF-related hospital admissions, office visits, and ED visits in EMPA and DDP4i initiators. Results After propensity score matching, we identified 2,050 pairs with HF and 15,428 pairs without HF in the three datasets with mean follow-up of 5.2 and 5.4 months, respectively. All baseline characteristics were well balanced (with aSD&lt;0.1). Compared to patients without HF history, patients with HF were older (65 vs 58), more commonly female (51% vs 46%), and had CV history (64% vs 19%) (Table 1). Compared to DPP4i, the hazard ratio (HR) for first hospitalization was 0.68 (95% CI: 0.56, 0.83) for EMPA initiators with HF, and 0.89 (95% CI: 0.80, 1.00) for initiators without HF. Risk of HF-related hospitalization and ED visit was lower in EMPA initiators with prior HF [HR=0.53 (0.38, 0.74) and HR=0.73 (0.58, 0.93), respectively] and without prior HF [HR=0.45 (0.27, 0.73) and HR=0.82 (0.70, 0.95), respectively]. Compared to DPP4i initiators, EMPA initiators with and without baseline HF had lower number of all hospital admissions [Incidence rate ratio (IRR)= 0.59 (0.50, 0.70) and IRR= 0.78 (0.71, 0.85), respectively] and HF-related hospital admissions [IRR=0.49 (0.37, 0.65) and IRR=0.34 (0.22, 0.53), respectively]. In-hospital days and HF-related in-hospital days per member per year (PMPY) in patients with and without HF history initiating EMPA were lower than DDP4i (Table 1). Conclusions Results observed in this interim analysis of EMPRISE showed reduction in overall HCRU as well as HF-related HCRU in both patients with and without heart failure (HF) initiating EMPA compared to DDP4i initiators. Acknowledgement/Funding This study was supported by a research grant to the Brigham and Women's Hospital from Boehringer-Ingelheim.

P4598Clinical implications and predictors of coronary perforations during chronic total occlusion percutaneous coronary interventions: insights from the multicenterLatin America CTO LATAM registry

Abstract Background Chronic total occlusions are still considered one of the most challenging procedures in the field of interventional cardiology and the most feared complication are the perforations. In past studies and series from Asia, Europe and United States the rate of perforations in percutaneous coronary interventions are described as 0.2% whereas this rate increases to 3% when recanalization of a chronic total occlusion is attempted. Purpose Our study sought to identify the frequency, predictors and clinical implications of coronary perforations in chronic total occlusion percutaneous interventions in a contemporary registry with data from Latin America. Methods We reported the data of a prospective multi center Latin American registry from January to December 2018 in 1066 patients who underwent chronic total occlusion percutaneous interventions in 30 centers in the following countries: Brazil, Argentina, Puerto Rico, Chile, Colombia, Ecuador and Mexico. Coronary perforation was defined as evidence of extravasation dye or blood from the coronary artery during or following the procedure. A stepwise logistic regression was performed to investigate the independent predictors of coronary perforations. Results The mean age was 64.2±10.7 years, 79.8% were male, 35.3% diabetics and 6.7% had heart failure. The most commonly involved CTO vessel was right coronary artery (41.4%), the mean J-CTO score was 2.0±1.3 and the mean CL score was 2.7±1.6. The overall procedural success rate was 81.9%. Coronary perforation occurred in 3.3% of cases: type 1 in 1.8%, Type 2 in 0.9% and Type 3 in 0.6%. In comparison with patients without coronary perforation was observed, those with such complication required more often blood transfusion (8.6% vs. 0.7%; p&lt;0.001), experienced more cardiac tamponade (13.4% vs. 0.4%; p&lt;0.001), but not all-cause in-hospital mortality (0 vs. 1.0%; p=1.0; respectively). At multivariate analysis, the independent predictor of coronary perforation was an activated clotting time (ACT) during PCI &gt;470 seconds (OR 6.5; 95% CI 2.4 - 17.3; p&lt;0.001), baseline heart failure (OR 4.2; 95% CI 1.2 - 14.6) and J-CTO score ≥2 (OR7.5; 95% CI 1.0–59.1). Conclusions Coronary perforation during percutaneous interventions in Latin America occurred in 3.3% of patients, being related with adverse events but not in-hospital all-cause mortality. Pharmacological management, high anatomical complexity and heart failure were identified as independent predictors of this still and so feared complication. Acknowledgement/Funding None

Effect of Once-Weekly Exenatide in Patients With Type 2 Diabetes Mellitus With and Without Heart Failure and Heart Failure-Related Outcomes: Insights From the EXSCEL Trial.

Once-weekly exenatide (EQW) had a neutral effect on hospitalization for heart failure (HHF) in the EXSCEL study (Exenatide Study of Cardiovascular Event Lowering), with no differential treatment effect on major adverse cardiac events by baseline heart failure (HF) status. EQW's effects on secondary end points based on HHF status have not been reported. The objective was to explore the effects of EQW on secondary end points in patients with and without baseline HF and test the effects of EQW on recurrent HHF events. The prespecified analysis of the randomized controlled EXSCEL trial, which enrolled patients with type 2 diabetes mellitus with and without additional cardiovascular disease, analyzed EQW effects on all-cause death, each major adverse cardiac event component, first HHF, and repeat HHF, by baseline HF status (regardless of ejection fraction). A subgroup analysis of the population stratified by preserved or reduced baseline ejection fraction was performed. Of 14 752 EXSCEL participants, 2389 (16.2%) had HF at baseline. Compared with those without HF at baseline, patients with preexisting HF were older, and more likely to be male and white, with a higher burden of other cardiovascular diseases. Overall, those assigned to EQW had a lower incidence of all-cause death (hazard ratio [HR], 0.86 [95% CI, 0.77-0.97]) and the composite outcome of all-cause death or HHF (HR, 0.89 [95% CI, 0.80-0.99]). When stratified by presence or absence of baseline HF, there was no observed reduction in all-cause death with EQW with baseline HF (HR, 1.05 [95% CI, 0.85-1.29]), while the risk of mortality was reduced with EQW in the no-HF group (HR, 0.79 [95% CI, 0.68-0.92]) with an interaction P value of 0.031. The reduction in all-cause death or HHF seen with EQW in patients without baseline HF (HR, 0.81 [95% CI, 0.71-0.93]) was not seen in patients with baseline HF (HR, 1.07 [95% CI, 0.89-1.29]; interaction P=0.015). First, plus recurrent, HHF was reduced in the exenatide group versus placebo (HR, 0.82 [95% CI, 0.68-0.99]; P=0.038). In EXSCEL, the use of EQW in patients with or without HF was well tolerated, but benefits of EQW on reduction in all-cause death and first hospitalization for HF were attenuated in patients with baseline HF. https://www.clinicaltrials.gov. Unique identifier: NCT01144338.

Modifiable Factors Associated with Quality of Life at 3 Months and the Mediator Effect of Functional Status in Patients with Heart Failure

Objectives To examine modifiable factors associated with quality of life (QOL) at 3 months and the mediator effect of functional status at 3 months on the relationship between baseline heart failure (HF) symptoms and QOL at 3 months in patients with HF. Background Good QOL in patients with HF is as value as or more valuable than longer survival. Thus, it is important to know modifiable factors associated with QOL. HF symptoms have been suggested to impact functional status, and, in turn, QOL, but the mediator effect of functional status on the relationship between HF symptoms and QOL has not been frequently examined. Methods and Materials In a descriptive, correlational study, data on QOL (the EQ-VAS) and functional status (the Korean Activity Scale/Index) were collected at 3 months; and HF symptoms (the Symptom Status Questionnaire-Heart Failure), depressive symptoms (the Patient Health Questinnaire-9), and sample characteristics, such as age, comorbidity, and New York Heart Association (NYHA) class (severity of disease), were collected at baseline from 65 patients with HF (Mean age: 75 years, 60% males, and 31% NYHA III). Multiple regression and Process Macro for SPSS were used to analyze the data. Results In multiple regression analysis, among the modifiable factors of HF symptoms, functional status, depressive symptoms, and severity of disease, only functional status at 3 months (p = .024) was significantly associated with QOL at 3 months, controlling for age and comorbidities (F = 2.557, p = .029, R2 = .209). Better functional status was associated with better QOL. In the Process Macro analysis, baseline HF symptoms (p = .012) and age (p Conclusion Functional status was directly and indirectly associated with QOL, while HF symptoms only indirectly predicted QOL through the effects on functional status. Clinicians and researcher need to assess and manage both HF symptoms and functional status to improve QOL in patients with HF. Further studies are needed to examine whether improvements in HF symptoms lead to improvements in functional status, and in turn, improvements in QOL.

Transitioning Patients to Oral Diuretics 24 Hours before Discharge from Heart Failure Hospitalization Does Not Improve 30 Day Outcomes

Background Patients hospitalized with acute heart failure (AHF) are at increased risk for clinical events during the 30-day period following discharge. The 2013 ACC/AHA heart failure (HF) guidelines recommend that such patients should be “transitioned to oral diuretic therapy to verify its effectiveness.” Although evidence that this strategy is effective is limited, many institutions transition patients from intravenous to oral diuretic therapy for at least 24 hours based on the premise that it improves outcomes. We investigated the effectiveness of this strategy on post-discharge outcomes in patients hospitalized for AHF at our institution. Methods In a retrospective chart review study, we evaluated all patients with a primary diagnosis of HF, regardless of left ventricular ejection fraction (LVEF), who were hospitalized from 8/1/2016 - 7/31/2017, discharged on an oral diuretic and followed at our institution. Baseline characteristics of patients who were discharged with at least a 24-hour period on oral diuretics and those who were discharged with less than 24 hours of observation on oral diuretics were compared and the effect of these strategies on a composite of all-cause mortality and all-cause rehospitalization, HF rehospitalization and all-cause rehospitalization were assessed. Results Of the 285 consecutive patients who met study entry criteria, 178 were observed for at least 24 hours on oral diuretics prior to discharge and 104 were not. These groups were similar in baseline characteristics including age, gender, co-morbidities, baseline blood chemistries, hemoglobin, BNPP, HF etiology, LVEF and factors triggering HF exacerbation. The group that was observed for 24 hours or more on oral diuretics had longer hospital stays and experienced greater weight and net volume loss than patients observed on oral diuretics for less than 24 hours. The latter group was more likely to have had changes made in their dose of neurohormonal blocking agents and diuretics within the 24-hour period prior to discharge. In contrast to expectations, all-cause mortality or all-cause hospitalization (27.5% vs 15%; p=0.019), all-cause rehospitalization (27% vs 14%; p=0.009) and AHF rehospitalization (12.9% vs 6.5%; p=0.064) occurred more commonly in patients who were observed for 24 hours on oral diuretics than for patients who were not. Conclusion In a population of patients discharged from an academic medical center after an episode of AHF, the strategy of transitioning patients to oral diuretics for at least 24 hours prior to discharge failed to improve 30-day outcomes. While this study has limitations due to the relatively small patient population followed at a single center, the results do not support the recommendation to observe patients on oral diuretics for at least 24 hours prior to discharge and they raise the question of whether providers should be encouraged to follow this practice without prospective studies demonstrating its effectiveness.

Management of Heart Failure in Left Ventricular Assist Device (LVAD) Patients Utilizing an Outpatient Diuresis Clinic

Background Left ventricular assist device (LVAD) implantation for treatment of heart failure (HF) is on the rise, and with technologic advancements, patients are living longer on device support. This has led to increased LVAD-related hospitalizations and health care expenditures, including management of volume overload. The Johns Hopkins Heart Failure Bridge Clinic (HFBC), a HF-trained Nurse Practitioner (NP) led clinic with ability to administer outpatient intravenous (IV) diuretics, has resulted in significant reductions in HF readmission rates. We developed a protocol for LVAD patient assessment and management via the HFBC, and describe our initial experience regarding the role and efficacy of this unique program in outpatient management of HF in LVAD patients. Methods LVAD patients were evaluated by an LVAD provider and subsequently referred to the diuresis clinic for volume overload thought not to be related to an LVAD issue. If seen in the diuresis clinic, patients then had repeat evaluation with the LVAD/HF team within one week. Baseline characteristics and HF outcomes were assessed. Results Twelve patients were seen in the diuresis clinic a total of 29 times (average 2.41 ± 2.84 visits per patient) (Table). In the clinic, IV furosemide was administered 23 times in 11 patients. Mean IV furosemide dose administered was 116 ± 24 mg. During the visits, 13 (17%) received potassium. The mean urine output during first in clinic void after IV diuretic was 198 ± 144 ml. There were no significant changes in blood pressure, renal function, weight, or electrolytes post-diuresis. At 9 of 29 visits (31%), oral diuretic dose was uptitrated. Prior to establishing care in the HFBC, the 12 patients had 30 total post-LVAD hospitalizations for volume overload. All 29 HFBC clinic visits resulted in successful discharge of patients to home in improved and stable condition, therefore avoiding immediate hospitalization for acute decompensated HF. Conclusions We describe successful implementation of an outpatient IV diuresis protocol for treatment of HF in LVAD patients. This strategy has major implications in reducing LVAD-related HF hospitalizations and healthcare utilization.

Utilizing Cardia Dimensions to Determine Future Heart Failure Events: Analysis from the PASED CRT Study

Background Cardiac resynchronization therapy (CRT) is a well established treatment for patients with systolic dysfunction and QRS >120ms with LBBB. Still about 30% of CRT patients with devices remain as non-responders. Few non-invasive techniques have been developed to predict clinical response to resynchronization before the device implantation to assist with better patient selection. Objective The aim of the study was to assess the relationship between the diameter of the cardiac silhouette and the distance between the pacing poles on chest radiographs with the efficacy of cardiac electrical resynchronization and clinical outcomes in patients receiving CRT devices. Methods Patients from the PASED-CRT randomized controlled trial who received a de novo CRT device were analyzed. Baseline demographic, echocardiographic, EKG, and heart failure hospitalization (HFH) data were obtained at baseline and after 3 months. Measurements of the cardiac width (CW) and the distance between the RV-LV pacing poles were obtained using chest x-rays in AP view by blinded observers. Results Of the 58 analyzed patients (Age 66±12 years, 85% Male, LVEF 27±8%), the rate of HFH in the 3 months post CRT implantation was reduced by 0.36±0.75 events when compared to the same duration before the procedure. Using univariate analysis, CW (P=0.003), LVEDD (P Conclusion In patients receiving CRT, CW is an independent predictor of cardiac electrical resynchronization and clinical outcomes as evidenced by shortening of QRS duration and reduction in HFH. Although patients with smaller hearts have more efficient resynchronization, those with larger hearts experience more reduction in HFH due to their higher baseline event rate.

Would Risk-Stratified Intensive Blood Pressure Lowering Prevent Heart Failure More Effectively?

Objectives Hypertension is the leading risk factor contributing to population burden of heart failure (HF). While the SPRINT trial demonstrated intensive blood pressure (BP) lowering ( Methods We conducted a post-hoc analysis using SPRINT data from the publicly available National Heart Lung and Blood Institute BioLINCC data repository. We included participants with available HF risk factor data. We excluded participants with prevalent cardiovascular disease and those older than 80 years at baseline. We applied a published 10-year incident HF risk prediction model (derived and validated in 7 population-based cohorts) and stratified trial participants into 1) low, 2) intermediate, or 3) high HF risk categories by tertiles of predicted HF risk at baseline. We performed Kaplan-Meier Survival analysis and multivariable Cox proportional hazards models to test the effect of intensive vs. standard BP lowering on incident HF in each baseline HF risk category adjusting for age, sex, and race. Results A total of 6,911 individuals were included in the analysis with a mean follow-up time of 3.3 years, during which 77 incident HF events occurred. Low 10-year predicted HF risk ranged from 0.6-5.4% (N=2303), intermediate 5.4-9.0% (N=2304), and high 9.0-50.3% (N=2304) at baseline. Individuals in the high HF risk group were older, had a higher systolic BP, and higher fasting glucose level at baseline (p Conclusion Benefits of intensive BP lowering for HF prevention may be maximized among individuals at high predicted risk of HF.

The Economic Impact of Mitral Regurgitation on Patients With Medically Managed Heart Failure

The objective of this study was to quantify the financial healthcare burden of mitral regurgitation (MR) on medically managed heart failure (HF) patients. Data from the Truven Health MarketScan Commercial Claims and Medicare Supplemental Databases were analyzed. Included patients had a minimum of 1 inpatient or 2 outpatient claims for HF with a 6-month preperiod (baseline). A 6-month postperiod (landmark) after HF index was used to capture MR diagnosis and severity. Following the landmark period, patients had to have 12 months of continuous medical and prescription drug plan enrollment with at least 2 records of HF medication refills. A therapeutic intensity score was calculated based on HF medication usage. Medically managed HF patients were separated into 3 cohorts: without MR (no MR), insignificant MR (iMR), and significant MR (sMR). Healthcare utilization and all-cause expenditures were modeled to quantify the burden of MR. All models controlled for baseline demographics, co-morbid conditions, and HF therapeutic intensity. Medically managed incident HF patients with sMR had significantly more hospital days (1.91 vs 1.72 days; p = 0.0096) and annual expenditures ($23,988 vs $21,530; p < 0.0001) compared with no MR patients. No differences were identified when comparing iMR and no MR. When evaluating HF admissions, sMR patients had an estimated 50% greater HF admissions rate (0.036 vs 0.024; p < 0.0001) compared with no MR patients. Additionally, HF admits for iMR were 23% more than those with no MR (0.029 vs 0.024; p = 0.0064). In conclusion, evidence of MR in retrospective claims significantly increases the healthcare impact of medically managed HF patients. Both utilization and financial burden is more pronounced when MR is clinically significant.

Impact of serum 25-hydroxyvitamin D on cardiac prognosis in Chinese patients with heart failure.

There is growing evidence that suggests the association of vitamin D status with the development and progression of heart failure (HF). The objective of the present study is to assess the impact of concentration of serum 25-hydroxyvitamin D (25(OH)D) on cardiac prognosis in patients with HF. Between 1 January 2015 and 31 December 2016, we consecutively recruited patients with HF. Patients were followed prospectively for a median duration of 1 year. Serum concentration of 25(OH)D was measured with competitive chemiluminescent immunoassay. The endpoints were cardiac events, including CVD death and rehospitalisation for worsening HF. Univariate and multivariable adjustments were performed with Cox proportional-hazard regression analyses. The 25(OH)D concentration was obtained in 343 patients with a median value of 17·4 (interquartile range 12·6-23·4) ng/ml. There were 102 cardiac events, including forty-three deaths and fifty-nine rehospitalisations. Multivariate Cox hazard analysis found that the serum concentration 25(OH)D was independently associated with cardiac events (hazard ratio 0·93, 95 % CI 0·88, 0·97) and CVD mortality (hazard ratio 0·83; 95 % CI 0·77, 0·89) after adjustment for confounding factors. We divided the HF patients into four groups according to the 25(OH)D quartiles. Kaplan-Meier analysis found that the patients with lower serum 25(OH)D concentration had a higher risk of cardiac events or CVD mortality than those with high serum 25(OH)D concentration (log-rank test P < 0·001 and P = 0·032). Decreased serum concentrations of 25(OH)D were associated with cardiac prognosis and CVD mortality in a Chinese population with HF independent of other baseline HF markers.

Cardiorenal syndrome in incident peritoneal dialysis patients: What is its effect on patients' outcomes?

BackgroundPeritoneal dialysis (PD) is increasingly used for long-term management of Cardiorenal Syndrome (CRS). We compared outcomes in incident PD patients according to their baseline heart failure status.MethodsThis retrospective cohort study evaluated all-cause and cardiovascular mortality in incident PD patients with different heart failure status (non-CRS, acute heart failure [AHF], type II CRS, type IV CRS) who started PD between 2006 and 2016 in the Peking University Third Hospital.ResultsOf 748 patients included in the study, there were 466 (62.3%), 214 (28.6%), 27 (3.6%), and 41 (5.5%) patients in the non-CRS, AHF, type II CRS and type IV CRS groups, respectively. Patients with CRS were older (p<0.001), with more diabetes mellitus (p<0.001), coronary heart history (p<0.001), higher estimated glomerular filtration rate (eGFR) (p<0.001), lower serum creatinine (p<0.001) and phosphorus levels (p = 0.003) compared to non-CRS patients. Respective all-cause survival rates for patients with non-CRS, AHF, type II CRS and type IV CRS were 90.6%, 87.1%, 85.2% and 84.8% at 1 year, and 63.1%, 47.7%, 27.3% and 35.1% at 5 years (p<0.001). The corresponding figures for cardiovascular survival were 93%, 92%, 84% and 81% at 1 year, and 67%, 59%, 55% and 54% at 5 years (p<0.001). However, after adjusting for confounding factors, the presence of CRS was not independently associated with all-cause mortality whereas type IV CRS (HR 2.10, 95% CI 1.03–4.28, p = 0.04) was associated with higher cardiovascular mortality as compared to without CRS.ConclusionIncident PD patients with different types of CRS had higher rates of both all-cause and cardiovascular mortality compared with patients without CRS. However, these observed adverse outcomes may be related to associated older age and higher prevalence of comorbidities, rather than CRS per se, except for type IV CRS, treatment strategies to reduce high cardiovascular CVD mortality may needed.

Empagliflozin Improves Kidney Outcomes in Patients With or Without Heart Failure.

Background In EMPA-REG OUTCOME (Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients) empagliflozin significantly reduced the risk of cardiovascular and kidney outcomes in patients with type 2 diabetes mellitus and established cardiovascular disease. Post hoc, we evaluated empagliflozin on kidney outcomes in patients with or without heart failure (HF). Methods and Results Individuals were randomized to empagliflozin 10 mg, 25 mg, or placebo. Prespecified analyses by baseline HF status included risk of incident or worsening nephropathy and estimated glomerular filtration rate slope analyses. Cox proportional hazards models assessed consistency of treatment effect across subgroups. Safety evaluations included kidney-related adverse events. At baseline, 244 (10.5%) and 462 (9.9%) patients had HF in the placebo and empagliflozin groups, respectively. Overall, the incidence of kidney outcome events was numerically higher in patients with than without HF. In the HF group, empagliflozin reduced risk of incident or worsening nephropathy or cardiovascular death by 43% (hazard ratio, 0.57 [95% CI, 0.42-0.77]) and progression to macroalbuminuria by 50% (hazard ratio, 0.50 [0.33-0.75]). After an initial transient decrease, estimated glomerular filtration rate stabilized over time with empagliflozin but gradually declined with placebo. Kidney effects in patients with HF were consistent with those in the overall study population (all P values for interaction >0.05). Across groups, the incidence rate of kidney-related adverse events/100 patient-years was higher in patients with than without HF; however, overall rates were comparable between groups. Conclusions These findings from EMPA-REG OUTCOME support the hypothesis that empagliflozin could reduce the risk of clinically relevant kidney events and may slow progression of chronic kidney disease in individuals with type 2 diabetes mellitus regardless of HF status. Clinical Trial Registration URL: https://www.clinicaltrials.gov . Unique identifier: NCT01131676.

Association Between Cardiorespiratory Fitness and Risk of Heart Failure: A Meta-Analysis

Evidence emerges that cardiorespiratory fitness (CRF) might be implicated in the development of heart failure (HF). This meta-analysis aimed to quantify the association between CRF exposed at baseline and HF risk with dose-response analysis and to assess whether CRF changes over time are correlated with alterations in HF risk. Cohort studies that assessed the association between CRF and risk of HF in subjects without baseline HF were included. Study-specific multivariate-adjusted relative risks (RRs) with 95% confidence intervals (CIs) were pooled using a random-effects model. Ten studies from 8 articles were included, enrolling 8987 incident HF cases from 154,598 participants. The RR of HF per 1-metabolic equivalent (MET) higher CRF at baseline was 0.82 (95% CI 0.80-0.84) in the overall population. The RRs were similar in men (0.82, 95% CI 0.80-0.85) and women (0.81, 95% CI 0.78-0.84), and remained minorly changed in patients with existing diabetes, hypertension, or cardiovascular disease at entry. No evidence of a nonlinear relationship between CRF at baseline and risk of HF was observed (Pnonlinearity = .18). The RR of HF per 1-MET increase in CRF over time was 0.79 (95% CI 0.67-0.93), and the measurement of CRF provided incremental value to the prediction of HF beyond conventional models. High or increased CRF resulted in reduced risk of HF in a dose-dependent manner, supporting the necessity to increase CRF to prevent HF in clinical practice.

Dietary Patterns and Incident Heart Failure in U.S. Adults Without Known Coronary Disease

BackgroundDietary patterns and associations with incident heart failure (HF) are not well established in the United States. ObjectivesThe purpose of this study was to determine associations of 5 dietary patterns with incident HF hospitalizations among U.S. adults. MethodsThe REGARDS (REasons for Geographic and Racial Differences in Stroke) trial is a prospective cohort of black and white adults followed from 2003 to 2007 through 2014. Inclusion criteria included completion of a food frequency questionnaire and no baseline coronary heart disease or HF. Five dietary patterns (convenience, plant-based, sweets, Southern, and alcohol/salads) were derived from principal component analysis. The primary endpoint was incident HF hospitalization. ResultsThis study included 16,068 participants (mean age 64.0 ± 9.1 years, 58.7% women, 33.6% black participants, 34.0% residents of the stroke belt). After a median of 8.7 years of follow-up, 363 participants had incident HF hospitalizations. Compared with the lowest quartile, the highest quartile of adherence to the plant-based dietary pattern was associated with a 41% lower risk of HF in multivariable-adjusted models (hazard ratio: 0.59; 95% confidence interval: 0.41 to 0.86; p = 0.004). Highest adherence to the Southern dietary pattern was associated with a 72% higher risk of HF after adjusting for age, sex, and race and for other potential confounders (education, income, region of residence, total energy intake, smoking, physical activity, and sodium intake; hazard ratio: 1.72; 95% confidence interval: 1.20 to 2.46; p = 0.005). However, the association was attenuated and no longer statistically significant after further adjusting for body mass index in kg/m2, waist circumference, hypertension, dyslipidemia, diabetes mellitus, atrial fibrillation, and chronic kidney disease. No statistically significant associations were observed with incident HF with reduced or preserved ejection fraction hospitalizations and the dietary patterns. No associations were observed with the other 3 dietary patterns. ConclusionsAdherence to a plant-based dietary pattern was inversely associated with incident HF risk, whereas the Southern dietary pattern was positively associated with incident HF risk.

Effect of Dapagliflozin on Heart Failure and Mortality in Type 2 Diabetes Mellitus.

In DECLARE-TIMI 58 (Dapagliflozin Effect on Cardiovascular Events-Thrombolysis in Myocardial Infarction 58), the sodium-glucose cotransporter 2 inhibitor dapagliflozin reduced the composite end point of cardiovascular death/hospitalization for heart failure (HHF) in a broad population of patients with type 2 diabetes mellitus. However, the impact of baseline left ventricular ejection fraction (EF) on the clinical benefit of sodium-glucose cotransporter 2 inhibition is unknown. In the DECLARE-TIMI 58 trial, baseline heart failure (HF) status was collected from all patients, and EF was collected when available. HF with reduced EF (HFrEF) was defined as EF <45%. Outcomes of interest were the composite of cardiovascular death/HHF, its components, and all-cause mortality. Of 17 160 patients, 671 (3.9%) had HFrEF, 1316 (7.7%) had HF without known reduced EF, and 15 173 (88.4%) had no history of HF at baseline. Dapagliflozin reduced cardiovascular death/HHF more in patients with HFrEF (hazard ratio [HR], 0.62 [95% CI, 0.45-0.86]) than in those without HFrEF (HR, 0.88 [95% CI, 0.76-1.02]; P for interaction=0.046), in whom the treatment effect of dapagliflozin was similar in those with HF without known reduced EF (HR, 0.88 [95% CI, 0.66-1.17]) and those without HF (HR, 0.88 [95% CI, 0.74-1.03]). Whereas dapagliflozin reduced HHF both in those with (HR, 0.64 [95% CI, 0.43-0.95]) and in those without HFrEF (HR, 0.76 [95% CI, 0.62-0.92]), it reduced cardiovascular death only in patients with HFrEF (HR, 0.55 [95% CI, 0.34-0.90]) but not in those without HFrEF (HR, 1.08 [95% CI, 0.89-1.31]; P for interaction=0.012). Likewise, dapagliflozin reduced all-cause mortality in patients with HFrEF (HR, 0.59 [95% CI, 0.40-0.88;) but not in those without HFrEF (HR, 0.97 [95% CI, 0.86-1.10]; P for interaction=0.016). In the first sodium-glucose cotransporter 2 inhibitor cardiovascular outcome trial to evaluate patients with type 2 diabetes mellitus stratified by EF, we found that dapagliflozin reduced HHF in patients with and without HFrEF and reduced cardiovascular death and all-cause mortality in patients with HFrEF. URL: https://www.clinicaltrials.gov . Unique identifier: NCT01730534.

ISOLATED SYSTOLIC HYPERTENSION (ISH) BY NEW ACC/AHA HYPERTENSION (HTN) GUIDELINES AND OUTCOMES IN OLDER ADULTS OVER 23 YEARS IN THE CARDIOVASCULAR HEALTH STUDY (CHS)

The new HTN guideline redefines HTN from systolic/diastolic blood pressure (SBP/DBP) >140/90 to >130/80 mmHg. We examined the association of ISH, defined per the new definition, with outcomes in older adults. In CHS, of 4431 community-dwelling adults age ≥65 yrs without baseline heart failure (HF