Composite Of Heart Failure Hospitalization Research Articles

Cardiovascular outcomes with sodium\u2013glucose cotransporter-2 inhibitors vs other glucose-lowering drugs in 13 countries across three continents: analysis of CVD-REAL data

BackgroundRandomized, controlled cardiovascular outcome trials may not be fully representative of the management of patients with type 2 diabetes across different geographic regions. We conducted analyses of data from the multinational CVD-REAL consortium to determine the association between initiation of sodium–glucose cotransporter-2 inhibitors (SGLT-2i) and cardiovascular outcomes, including subgroup analyses based on patient characteristics.MethodsDe-identified health records from 13 countries across three continents were used to identify patients newly-initiated on SGLT-2i or other glucose-lowering drugs (oGLDs). Propensity scores for SGLT-2i initiation were developed in each country, with 1:1 matching for oGLD initiation. In the matched groups hazard ratios (HRs) for hospitalization for heart failure (HHF), all-cause death (ACD), the composite of HHF or ACD, myocardial infarction (MI) and stroke were estimated by country, and pooled using a weighted meta-analysis. Multiple subgroup analyses were conducted across patient demographic and clinical characteristics to examine any heterogeneity in treatment effects.ResultsFollowing matching, 440,599 new users of SGLT-2i and oGLDs were included in each group. Mean follow-up time was 396 days for SGLT-2i initiation and 406 days for oGLDs initiation. SGLT-2i initiation was associated with a lower risk of HHF (HR: 0.66, 95%CI 0.58–0.75; p < 0.001), ACD (HR: 0.52, 95%CI 0.45–0.60; p < 0.001), the composite of HHF or ACD (HR: 0.60, 95%CI 0.53–0.68; p < 0.001), MI (HR: 0.85, 95%CI 0.78–0.92; p < 0.001), and stroke (HR: 0.78, 95%CI 0.72–0.85; p < 0.001); regardless of patient characteristics, including established cardiovascular disease, or geographic region.ConclusionsThis CVD-REAL study extends the findings from the SGLT-2i clinical trials to the broader setting of an ethnically and geographically diverse population, and across multiple subgroups.Trial registration NCT02993614

Impact of Insulin Treatment on the Effect of Eplerenone: Insights From the EMPHASIS-HF Trial.

Patients with heart failure with reduced ejection fraction (HFrEF) and insulin-treated diabetes have a high risk of cardiovascular complications. Mineralocorticoid receptor antagonists may mitigate this risk. We aim to explore the effect of eplerenone on cardiovascular outcomes and all-cause mortality in HFrEF patients with diabetes, including those treated with insulin in the EMPHASIS-HF trial (Eplerenone in Patients with Systolic Heart Failure and Mild Symptoms). The primary outcome was the composite of heart failure hospitalization or cardiovascular death. Cox models with treatment-by-diabetes subgroup interaction terms were used. The median follow-up was 21 (10-33) months. Of the 2737 patients included, 623 (23%) had non-insulin-treated diabetes, 236 (9%) had insulin-treated diabetes and 1878 did not have diabetes. Patients with insulin-treated diabetes were younger, more often women, with higher body mass index, waist circumference, more frequent ischemic heart failure cause, impaired kidney function, and longer diabetes duration. Compared with patients without diabetes, those with insulin-treated diabetes had a 2-fold higher risk of having a primary outcome event. The hazard ratio (95% CI) for the effect of eplerenone, compared with placebo, on the primary outcome was 0.31 (0.19-0.50) in insulin-treated diabetes, 0.69 (0.50-0.93) in non-insulin-treated diabetes, and 0.72 (0.58-0.88) in patients without diabetes; interaction P=0.007. The annualized number needed-to-treat-to-benefit with regards to the primary outcome was 3 (95% CI, 3-4) in patients with insulin-treated diabetes, 16 (13-19) in patients with diabetes not receiving insulin, and 26 (24-28) in patients without diabetes. Patients with insulin-treated diabetes experienced a greater benefit from eplerenone than those with diabetes not treated with insulin and people without diabetes. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00232180.

Layer-specific global longitudinal strain obtained by speckle tracking echocardiography for predicting heart failure and cardiovascular death following STEMI treated with primary PCI

The aim of this study was to evaluate layer-specific global longitudinal strain (GLS), obtained by speckle tracking, in predicting outcomes following ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (pPCI). Echocardiography, including layer-specific GLS, was performed at median two days after the STEMI in a prospective study of STEMI patients treated with pPCI between September 2006 and December 2008. The outcome was the composite of heart failure hospitalization and/or cardiovascular death (HF/CVD). A total of 349 patients were included. Mean age was 62.2 ± 11.5years, 76% were male, and mean ejection fraction(LVEF) was 46 ± 9. Seventy-seven (22%) patients developed HF/CVD during median follow-up 5.4years. Patients with HF/CVD had lower absolute values for all GLS-layers: endocardial (GLSEndo) 11.4%vs 14.5% (p < 0.001), midmyocardial (GLSMid) 9.8% vs 12.5% (p < 0.001) and epicardial (GLSEpi) 8.5% vs 10.9% (p < 0.001). In unadjusted analysis, all layers were significant predictors of HF/CVD; hazard ratio (HR) per 1% decrease for GLSEndo: HR 1.18 (95%CI 1.11-1.25), GLSMid: HR 1.22 (95%CI 1.14-1.30) and GLSEpi: HR 1.26 (95%CI 1.16-1.36), p < 0.0001 for all. The risk of HF/CVD increased incrementally with increasing tertiles for all layers, being more than three times higher in 3rd tertile compared to 1st tertile. In multivariable models, including baseline clinical and echocardiographic parameters, only GLSMid and GLSEpi remained independent predictors of HF/CVD. Global longitudinal strain obtained from all myocardial layers were significant predictors of incident HF and CVD following STEMI, however, only GLSMid and GLSEpi remained independent predictors after multivariable adjustment.

Right ventricular function and outcome in patients undergoing transcatheter aortic valve implantation

Abstract Funding Acknowledgements Type of funding sources: None. Background. Right ventricular dysfunction (RVD) on echocardiography has been shown to predict outcomes in patients undergoing transcatheter aortic valve implantation (TAVI). However, a comparison with the gold standard, RV ejection fraction (EF) on cardiovascular magnetic resonance (CMR), has never been performed. Objectives. To compare RV function parameters on echocardiography and CMR for prognostication in TAVI patients. Methods. Consecutive patients scheduled for TAVI underwent echocardiography and CMR. RV fractional area change (FAC), TAPSE, RV free-lateral-wall tissue Doppler (S’) and strain were assessed on echocardiography, and RVEF on CMR. Patients were prospectively followed. Adjusted regression analyses were used to report the strength of association per 1-SD decline for each RV function parameter with 1) NT-proBNP levels, 2) prolonged in-hospital stay (&amp;gt;14 days), and 3) a composite of heart failure hospitalization and death. Results. 204 patients (80.9 ± 6.6y/o; 51% female; EuroSCORE-II: 6.5 ± 5.5%) were included. At a cross-sectional level, all RV function parameters were associated with NT-proBNP levels, but only FAC and RVEF were significantly associated with a prolonged in-hospital stay (adj. OR 1.98 [95%CI: 1.15-3.41], p = 0.013 and 2.29 [95%CI: 1.43-3.67], p = 0.001, respectively). A total of 56 events occurred during follow-up (mean 13.7 ± 9.5months). After adjustment for the EuroSCORE-II and NT-proBNP levels, only RVEF was significantly associated with the composite endpoint (adj. HR 1.69 [95%CI: 1.24-2.30], p &amp;lt; 0.001, Figure 1). Conclusions. RVD as defined by echocardiography is associated with an advanced disease state, but fails to predict outcomes after adjustment for pre-existing clinical risk factors in TAVI patients. In contrast, RVEF on CMR is independently associated with heart failure hospitalization and death. Abstract Figure 1. Outcome analysis

Progression of Myocardial Fibrosis in Nonischemic DCM and Association With Mortality and Heart Failure Outcomes

ObjectivesThe purpose of this study was to assess whether the presence and extent of fibrosis changes over time in patients with nonischemic, dilated cardiomyopathy (DCM) receiving optimal medical therapy and the implications of any such changes on left ventricular ejection fraction (LVEF) and clinical outcomes. BackgroundMyocardial fibrosis on cardiovascular magnetic resonance (CMR) imaging has emerged as important risk marker in patients with DCM. MethodsIn total, 85 patients (age 56 ± 15 years, 45% women) with DCM underwent serial CMR (median interval 1.5 years) for assessment of LVEF and fibrosis. The primary outcome was all-cause mortality; the secondary outcome was a composite of heart failure hospitalization, aborted sudden cardiac death, left ventricular (LV) assist device implantation, or heart transplant. ResultsOn CMR-1, fibrosis (median 0.0 [interquartile range: 0% to 2.6%]) of LV mass was noted in 34 (40%) patients. On CMR-2, regression of fibrosis was not seen in any patient. Fibrosis findings were stable in 70 (82%) patients. Fibrosis progression (increase >1.8% of LV mass or new fibrosis) was seen in 15 patients (18%); 46% of these patients had no fibrosis on CMR-1. Although fibrosis progression was on aggregate associated with adverse LV remodeling and decreasing LVEF (40 ± 7% to 34 ± 10%; p < 0.01), in 60% of these cases the change in LVEF was minimal (<5%). Fibrosis progression was associated with increased hazards for all-cause mortality (hazard ratio: 3.4 [95% confidence interval: 1.5 to 7.9]; p < 0.01) and heart failure–related complications (hazard ratio: 3.5 [95% confidence interval: 1.5 to 8.1]; p < 0.01) after adjustment for clinical covariates including LVEF. ConclusionsOnce myocardial replacement fibrosis in DCM is present on CMR, it does not regress in size or resolve over time. Progressive fibrosis is often associated with minimal change in LVEF and identifies a high-risk cohort.

Sodium-glucose co-transporter-2 inhibitors versus dipeptidyl peptidase-4 inhibitors and the risk of heart failure: A nationwide cohort study of older adults with diabetes mellitus.

To analyse the rate of heart failure hospitalization for older adults prescribed a sodium-glucose co-transporter-2 (SGLT2) inhibitor. The study cohort included adults aged 66 years and older diagnosed with diabetes mellitus in Ontario, Canada, between July 2015 and March 2019, who received either an SGLT2 inhibitor or a dipeptidyl peptidase-4 (DPP-4) inhibitor. The primary outcome was a composite of heart failure hospitalization and all-cause mortality. Secondary outcomes included diabetic ketoacidosis and hypoglycaemia. A total of 29 916 adults prescribed an SGLT2 inhibitor were compared with 29 916 adults prescribed a DPP-4 inhibitor. The mean age was 72 years, 60% were men, the baseline glycated haemoglobin concentration was 8.2% and the baseline creatinine was 89 μmol/L. The incidence rate of the primary outcome was 19/1000 person-years for adults prescribed an SGLT2 inhibitor compared to 38/1000 person-years in those prescribed a DPP-4 inhibitor. This resulted in a hazard ratio (HR) of 0.49 (95% confidence interval [CI] 0.45, 0.54) and a rate difference (RD) of 19 fewer events per 1000 person-years (RD -19 [95% CI -22, -17]). Patients prescribed an SGLT2 inhibitor also had a lower rate of hypoglycaemia (HR 0.61 [95% CI 0.46, 0.81); RD -1.6 [95% CI -2.4, -0.8]), but a higher rate of diabetic ketoacidosis (HR 1.84 [95% CI 1.26, 2.70]; RD 1.0 [95% CI 0.4, 1.6]). Older adults prescribed an SGLT2 inhibitor had a lower rate of heart failure hospitalization or death, and a lower rate of hypoglycaemia, but an increased rate of diabetic ketoacidosis compared to older adults prescribed a DPP-4 inhibitor.

Right ventricular function and outcome in patients undergoing transcatheter aortic valve replacement.

Right ventricular dysfunction (RVD) on echocardiography has been shown to predict outcomes in patients undergoing transcatheter aortic valve replacement (TAVR). However, a comparison with the gold standard, RV ejection fraction (EF) on cardiovascular magnetic resonance (CMR), has never been performed. Consecutive patients scheduled for TAVR underwent echocardiography and CMR. RV fractional area change (FAC), tricuspid annular plane systolic excursion, RV free-lateral-wall tissue Doppler (S'), and strain were assessed on echocardiography, and RVEF on CMR. Patients were prospectively followed. Adjusted regression analyses were used to report the strength of association per 1-SD decline for each RV function parameter with (i) N-terminal prohormone of brain natriuretic peptide (NT-proBNP) levels, (ii) prolonged in-hospital stay (>14 days), and (iii) a composite of heart failure hospitalization and death. Two hundred and four patients (80.9 ± 6.6 y/o; 51% female; EuroSCORE-II: 6.3 ± 5.1%) were included. At a cross-sectional level, all RV function parameters were associated with NT-proBNP levels, but only FAC and RVEF were significantly associated with a prolonged in-hospital stay [adjusted odds ratio 1.86, 95% confidence interval (CI) 1.07-3.21; P = 0.027 and 2.29, 95% CI 1.43-3.67; P = 0.001, respectively]. A total of 56 events occurred during follow-up (mean 13.7 ± 9.5 months). After adjustment for the EuroSCORE-II, only RVEF was significantly associated with the composite endpoint (adjusted hazard ratio 1.70, 95% CI 1.32-2.20; P < 0.001). RVD as defined by echocardiography is associated with an advanced disease state but fails to predict outcomes after adjustment for pre-existing clinical risk factors in TAVR patients. In contrast, RVEF on CMR is independently associated with heart failure hospitalization and death.

Sex Differences in Left Ventricular Remodeling and Outcomes in Chronic Aortic Regurgitation.

Background: Left ventricular (LV) dilatation is a key compensatory feature in patients with chronic aortic regurgitation (AR). However, sex-differences in LV remodeling and outcomes in chronic AR have been poorly investigated so far. Methods: We performed cardiovascular magnetic resonance imaging (CMR) including phase-contrast velocity-encoded imaging for the measurement of regurgitant fraction (RegF) at the sinotubular junction, in consecutive patients with at least mild AR on echocardiography. We assessed LV size (end-diastolic volume indexed to body surface area, LVEDV/BSA) and investigated sex differences between LV remodeling and increasing degrees of AR severity. Cox-regression models were used to test differences in outcomes between men and women using a composite of heart failure hospitalization, unscheduled AR intervention, and cardiovascular death. Results: 270 consecutive patients (59.6% male, 59.8 ± 20.8 y/o, 59.6% with at least moderate AR on echocardiography) were included. On CMR, mean RegF was 18.1 ± 17.9% and a total of 65 (24.1%) had a RegF ≥ 30%. LVEDV/BSA was markedly closer related with AR severity (RegF) in men compared to women. Each 1-SD increase in LVEDV/BSA (mL/m2) was associated with a 9.7% increase in RegF in men and 5.9% in women, respectively (p-value for sex-interaction < 0.001). Based on previously published reference values, women—in contrast to men—frequently had a normal LV size despite severe AR (e.g., for LVEDV/BSA on CMR: 35.3% versus 8.7%, p < 0.001). In a Cox-regression model adjusted for age, LVEDV/BSA and RegF, women were at significantly higher risk for the composite endpoint when compared to men (adj. HR 1.81 (95%CI 1.09–3.03), p = 0.022). Conclusion: In patients with chronic AR, LV remodeling is a hallmark feature in men but not in women. Severity of AR may be underdiagnosed in female patients in the absence of LV dilatation. Future studies need to address the dismal prognosis in female patients with chronic AR.

Effect of Dapagliflozin on Clinical Outcomes in Patients With Chronic Kidney Disease, With and Without Cardiovascular Disease.

Dapagliflozin reduces the risk of end-stage renal disease in patients with chronic kidney disease. We examined the relative risk of cardiovascular and renal events in these patients and the effect of dapagliflozin on either type of event, taking account of history of cardiovascular disease. In the DAPA-CKD trial (Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease), 4304 participants with chronic kidney disease were randomly assigned to dapagliflozin 10 mg once daily or placebo. The primary end point was a composite of sustained decline in estimated glomerular filtration rate ≥50%, end-stage kidney disease, or kidney or cardiovascular death. The secondary end points were a kidney composite outcome (primary end point, minus cardiovascular death), the composite of hospitalization for heart failure or cardiovascular death, and all-cause death. In a prespecified subgroup analysis, we divided patients into primary and secondary prevention subgroups according to history of cardiovascular disease. Secondary prevention patients (n=1610; 37.4%) were older, were more often male, had a higher blood pressure and body mass index, and were more likely to have diabetes. Mean estimated glomerular filtration rate and median urinary albumin-to-creatinine ratio were similar in the primary and secondary prevention groups. The rates of adverse cardiovascular outcomes were higher in the secondary prevention group, but kidney failure occurred at the same rate in the primary and secondary prevention groups. Dapagliflozin reduced the risk of the primary composite outcome to a similar extent in both the primary (hazard ratio, 0.61 [95% CI, 0.48-0.78]) and secondary (0.61 [0.47-0.79]) prevention groups (P-interaction=0.90). This was also true for the composite of heart failure hospitalization or cardiovascular death (0.67 [0.40-1.13] versus 0.70 [0.52-0.94], respectively; P-interaction=0.88), and all-cause mortality (0.63 [0.41-0.98] versus 0.70 [0.51-0.95], respectively; P-interaction=0.71). Rates of adverse events were low overall and did not differ between patients with and without cardiovascular disease. Dapagliflozin reduced the risk of kidney failure, death from cardiovascular causes or hospitalization for heart failure, and prolonged survival in people with chronic kidney disease, with or without type 2 diabetes, independently of the presence of concomitant cardiovascular disease. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03036150.

Right ventricular rather than left ventricular systolic dysfunction predicts outcome in patients undergoing transcatheter aortic valve implantation: insights from cardiac magnetic resonance imaging

Abstract Background Right ventricular (RV) function is strongly associated with outcome in heart failure. Whether it also adds important prognostic information in patients undergoing transcatheter aortic valve implantation (TAVI) is unknown. Methods We consecutively enrolled patients with severe aortic stenosis (AS) scheduled for TAVI and preprocedural cardiac magnetic resonance (CMR) imaging. Kaplan-Meier estimates and multivariate Cox regression analyses were used to identify factors associated with outcome. A composite of heart failure hospitalization and/or cardiovascular death was selected as primary study endpoint. Results 423 consecutive patients (80.7±7.3 years; 48% female) were prospectively included, 201 (48%) underwent CMR imaging. 55 (27%) patients presented with RV systolic dysfunction (RVSD) defined by RV ejection fraction (RVEF) &amp;lt;45%. RVSD was associated with male sex (69 vs. 40%; p&amp;lt;0.001), New York Heart Association (NYHA) functional status (NYHA ≥ III: 89 vs. 57%; p&amp;lt;0.001), NT-proBNP serum levels (9365 vs. 2715 pg/mL; p&amp;lt;0.001), and history of atrial fibrillation (AF: 51 vs. 30%; p=0.005). On CMR, RVSD was associated with left ventricular (LV) volumes (end-diastolic: 187 vs. 137 mL, end-systolic: 119 vs. 53 mL; p&amp;lt;0.001) and EF (39 vs. 64%; p&amp;lt;0.001). A total of 51 events (37 deaths, 14 hospitalizations for heart failure) occurred during follow-up (9.8±9 months). While LVSD (LVEF &amp;lt;50%) was not significantly associated with outcome (HR 0.83, 95% CI: 0.33 – 2.11; p=0.694), RVSD showed a strong and independent association with event-free survival by multivariate Cox regression analysis (HR 2.47, 95% CI: 1.07–5.73; p=0.035), which was adjusted for all relevant CMR parameters (LV volumes and EF), cardiovascular risk factors (sex, NYHA, AF, diabetes mellitus type II, use of diuretics), and routine biomarkers (NT-proBNP, creatinine). Conclusions RVSD rather than LVSD, as determined on CMR, is an important predictor of outcome in patients undergoing TAVI. RV function might thus add useful prognostic information on top of established risk factors. Figure 1. Kaplan-Meier survival curves Funding Acknowledgement Type of funding source: None

Relationship between duration of heart failure, patient characteristics, outcomes, and effect of therapy in PARADIGM-HF.

AimsLittle is known about patient characteristics, outcomes, and the effect of treatment in relation to duration of heart failure (HF). We have investigated these questions in PARADIGM‐HF. The aim of the study was to compare patient characteristics, outcomes, and the effect of sacubitril/valsartan, compared with enalapril, in relation to time from HF diagnosis in PARADIGM‐HF.Methods and resultsHF duration was categorized as 0–1, >1–2, >2–5, and >5 years. Outcomes were adjusted for prognostic variables, including N‐terminal pro‐brain natriuretic peptide (NT‐proBNP). The primary endpoint was the composite of HF hospitalization or cardiovascular death. The number of patients in each group was as follows: 0–1 year, 2523 (30%); >1–2 years, 1178 (14%); >2–5 years, 2054 (24.5%); and >5 years, 2644 (31.5%). Patients with longer‐duration HF were older, more often male, and had worse New York Heart Association class and quality of life, more co‐morbidity, and higher troponin‐T but similar NT‐proBNP levels. The primary outcome rate (per 100 person‐years) increased with HF duration: 0–1 year, 8.4 [95% confidence interval (CI) 7.6–9.2]; >1–2 years, 11.2 (10.0–12.7); >2–5 years, 13.4 (12.4–14.6); and >5 years, 14.2 (13.2–15.2); P < 0.001. The hazard ratio was 1.26 (95% CI 1.07–1.48), 1.52 (1.33–1.74), and 1.53 (1.33–1.75), respectively, for >1–2, >2–5, and >5 years, compared with 0–1 year. The benefit of sacubitril/valsartan was consistent across HF duration for all outcomes, with the primary endpoint hazard ratio 0.80 (95% CI 0.67–0.97) for 0–1 year and 0.73 (0.63–0.84) in the >5 year group. For the primary outcome, the number needed to treat for >5 years was 18, compared with 29 for 0–1 year.ConclusionsPatients with longer‐duration HF had more co‐morbidity, worse quality of life, and higher rates of HF hospitalization and death. The benefit of a neprilysin inhibitor was consistent, irrespective of HF duration. Switching to sacubitril/valsartan had substantial benefits, even in patients with long‐standing HF.

Quality of Life and its Determinants in Heart Failure Patients at a Major Tertiary Academic Center in Ontario, Canada

Background Heart failure (HF) greatly impacts quality of life (QoL). Objectives We evaluated QoL, its determinants and associations with major outcomes in HF patients at our institution, Hamilton Health Sciences (HHS), a tertiary academic centre in Ontario. Methods We enrolled 270 patients in a HF registry with standardized recording of data on demographics, social and educational status, living conditions, HF etiology, symptoms, comorbidities, physical exam, medication use, ECG, echocardiographic and biochemical measurements. QoL was measured using the KCCQ-12 questionnaire. Patients are followed prospectively and at the time of this analysis all patients had completed 6 months follow-up. Results Patients' mean age was 70.6±11.2 yrs, 32% were women, 55.6% were married, 25.6% lived alone, 74.4% were enrolled from the outpatient HF clinic and 25.6% during a HF hospitalization. Mean LVEF was 40.1%, 53.2% had HFrEF, 30.3% HFpEF and 16.5% HFmEF. The most common HF etiology was IHD, 48.1% had NYHA class III or IV functional status and 64.4% had 2 or more comorbidities. Average KCCQ-12 summary score was 57.5±27.7, consistent with fair disability level and overall good QoL. 14.1% had severe disability (KCCQ-12 score between 0 and 25) and 33.3% had little or no disability and excellent QoL (KCCQ-12 score between 76 and 100). HFpEF patients had on average a lower KCCQ-12 summary score than HFrEF patients (53.2±28.6 vs. 58.1±27.1, p=0.027) and a higher proportion had a score of 25 or lower consistent with severe disability (21.4% vs. 11.4%). In bivariate analysis lower KCCQ-12 summary score was associated with older age, inpatient status, living alone, NYHA class, time from diagnosis of HF, history of diabetes, COPD, total number of comorbidities, LVEF, heart rate and BMI. However, in multivariate analysis only NYHA class III or IV, inpatient status and COPD emerged as independent predictors of a lower KCCQ-12 summary score. Patients in the upper third of KCCQ-12 scores had the lowest rates of HF hospitalizations, all-cause hospitalizations, CV death, all-cause death and the composite of HF hospitalization and all-cause death. Conclusions Inspite of living with HF, many patients in our registry have fair disability level and good QoL. Patients with HFpEF had worse QoL than those with HFrEF. Advanced NYHA class, inpatient status and COPD were independent predictors of poorer QoL. We observed a strong association between the KCCQ-12 summary score and major CV outcomes.

Statin intensity and risk for cardiovascular events after heart transplantation.

AimsStatins improve survival and reduce rejection and cardiac allograft vasculopathy after heart transplantation (HT). The impact of different statin intensities on clinical outcomes has never been assessed. We set out to determine the impact of statin exposure on cardiovascular outcomes after HT.Methods and resultsWe performed a retrospective study of 346 adult patients who underwent HT from 2006 to 2018. Statin intensity was determined longitudinally after HT based on American College of Cardiology/American Heart Association (ACC/AHA) guidelines. The primary outcome was the time to the first primary event defined as the composite of heart failure hospitalization, myocardial infarction, revascularization, and all‐cause mortality. Secondary outcomes included time to significant rejection and time to moderate–severe cardiac allograft vasculopathy. Adverse events were evaluated for subjects on high‐intensity statin therapy. A Cox proportional hazards model was used to evaluate the relationship between clinical variables, statin intensity, and outcomes. Most subjects were treated with low‐intensity statin therapy although this declined from 89.9% of the population at 1month after HT to 42.8% at 5years after HT. History of ischaemic cardiomyopathy, significant acute rejection, older donor age, and lesser statin intensity (p ≤ 0.001) were associated with reduced time to the primary outcome in a multivariable Cox model. Greater intensity of statin therapy was most beneficial early after HT. There were no statin‐related adverse events for the 14 subjects on high‐intensity statin therapy.ConclusionsGreater statin intensity was associated with a reduction in adverse cardiovascular outcomes after HT.

Liver function and prognosis, and influence of sacubitril/valsartan in patients with heart failure with reduced ejection fraction.

The prevalence of liver function abnormalities is common in patients with heart failure (HF) with reduced ejection fraction (HFrEF). We assessed the impact of liver function on prognosis and the effect of sacubitril/valsartan on measures of liver function in patients with HFrEF. The PARADIGM-HF trial was a randomized, double-blind, active treatment-controlled trial. We included 8232 HFrEF patients with available measures of liver function, including transaminases, alkaline phosphatase (ALP) and bilirubin; the primary endpoint was a composite of HF hospitalization and cardiovascular (CV) death. At screening, 11.6% of study patients had total bilirubin above the upper limit of normal (20.5 μmol/L) and 9.2% had ALP above the upper limit of normal (123 IU/L). Although ALP and albumin were associated with an increased risk of outcomes, among conventional test of liver function, total bilirubin was the strongest predictor for the primary endpoint [hazard ratio (HR) 1.10; 95% confidence interval (CI) 1.04-1.15; P < 0.001], HF hospitalization (HR 1.14; 95% CI 1.07-1.22; P < 0.001); CV death (HR 1.07; 95% CI 1.00-1.14; P=0.040), and all-cause death (HR 1.08; 95% CI 1.02-1.14; P=0.009). All conventional measures of liver function were significantly improved in the sacubitril/valsartan group compared with the enalapril group after randomization (between-group reduction: total bilirubin 2.4%, 95% CI 0.7-4.2%, P=0.007; aspartate aminotransferase 7.9%, 95% CI 6.7-9.0%, P < 0.001; alanine aminotransferase 7.7%; 95% CI 6.2-9.3%, P < 0.001; ALP 5.4%, 95% CI 4.4-6.4%, P < 0.001). Total bilirubin was a significant and independent predictor of CV death or HF hospitalization and all-cause mortality in patients with HFrEF enrolled in PARADIGM-HF. Sacubitril/valsartan improved measures of liver function compared with enalapril.

Increases in repolarization heterogeneity predict left ventricular systolic dysfunction and response to cardiac resynchronization therapy in patients with left bundle branch block.

This study aimed to investigate the association between T-wave morphology and impaired left ventricular ejection fraction (LVEF) in patients with complete left bundle branch block (cLBBB), and the predictive value of T-wave morphology for response to cardiac resynchronization therapy (CRT). We enrolled 189 patients with cLBBB on electrocardiogram performed between January 2007 and December 2011 who underwent standard echocardiography. Repolarization parameters, including the QRS-to-T angle (TCRT), T-wave morphology dispersion (TMD), T-wave loop area (PL), and T-wave residuum (TWR), were reconstructed from digital standard 12-lead electrocardiograms by T-wave morphology analysis. CRT response was defined as ≥15% reduction in left ventricular end-systolic volume at 12 months after CRT implantation. The clinical outcome endpoint was a composite of heart failure hospitalization, heart transplantation, or death during follow up (mean, 5.8 years). On logistic regression, a higher heart rate, longer QRS duration, increased TMD, and larger TWR were all independently associated with LVEF < 40%. Among 40 patients who underwent CRT, those with a larger TMD (P = .007), larger PL (P = .025), and more negative TCRT (P = .015) had better response to CRT. A large TMD (P = .018) and large PL (P = .003) were also independent predictors of the clinical outcome endpoint. Increases in repolarization heterogeneity in patients with cLBBB are associated with impaired LVEF. A large TMD and large PL may be useful as additional predictors of response to CRT, improving patient selection for CRT.

Effects of Liraglutide on Cardiovascular Outcomes in Patients With Diabetes With or Without Heart Failure

BackgroundMore data regarding effects of glucagon-like peptide-1 receptor agonists in patients with type 2 diabetes (T2D) and heart failure (HF) are required. ObjectivesThe purpose of this study was to investigate the effects of liraglutide on cardiovascular events and mortality in LEADER (Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results) participants, by HF history. MethodsIn the multinational, double-blind, randomized LEADER trial, 9,340 patients with T2D and high cardiovascular risk were assigned 1:1 to liraglutide (1.8 mg daily or maximum tolerated dose up to 1.8 mg daily) or placebo plus standard care, and followed for 3.5 to 5 years. New York Heart Association (NYHA) functional class IV HF was an exclusion criterion. The primary composite major adverse cardiovascular events outcome was time to first occurrence of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. Post hoc Cox regression analyses of outcomes by baseline HF history were conducted. ResultsAt baseline, 18% of patients had a history of NYHA functional class I to III HF (liraglutide: n = 835 of 4,668; placebo: n = 832 of 4,672). Effects of liraglutide versus placebo on major adverse cardiovascular events were consistent in patients with (hazard ratio [HR]: 0.81 [95% confidence interval (CI): 0.65 to 1.02]) and without (HR: 0.88 [95% CI: 0.78 to 1.00]) a history of HF (p interaction = 0.53). In both subgroups, fewer deaths were observed with liraglutide (HR: 0.89 [95% CI: 0.70 to 1.14] with HF; HR: 0.83 [95% CI: 0.70 to 0.97] without HF; p interaction = 0.63) versus placebo. No increased risk of HF hospitalization was observed with liraglutide, regardless of HF history (HR: 0.98 [95% CI: 0.75 to 1.28] with HF; HR: 0.78 [95% CI: 0.61 to 1.00] without HF; p interaction = 0.22). Effects of liraglutide on the composite of HF hospitalization or cardiovascular death were consistent in patients with (HR: 0.92 [95% CI: 0.74 to 1.15]) and without (HR: 0.77 [95% CI: 0.65 to 0.91]) a history of HF (p interaction = 0.19). ConclusionsBased on these findings, liraglutide should be considered suitable for patients with T2D with or without a history of NYHA functional class I to III HF. (Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results [LEADER]; NCT01179048)

P4128The right heart in patients undergoing transcatheter aortic valve replacement: insights from cardiac magnetic resonance imaging

Abstract Background Cardiac magnetic resonance (CMR) provides the gold standard for the assessment of ventricular volumes and mass. However, data on right ventricular systolic dysfunction (RVSD) and its prognostic significance on outcome in patients undergoing transcatheter aortic valve replacement (TAVR) are lacking. Methods We consecutively enrolled patients with severe aortic stenosis scheduled for TAVR who underwent preprocedural CMR. Kaplan-Meier estimates and multivariate Cox-regression analysis were used to identify factors associated with outcome, including RVSD. A composite of heart failure hospitalization and/or cardiovascular death was selected as primary study endpoint. Results 145 consecutive patients (80.5±7.6 years; 51.7% female) were prospectively included, 25 (17.2%) of which had RVSD defined as RV ejection fraction (RVEF) &lt;40%. RVSD was significantly associated with male sex, atrial fibrillation, reduced left ventricular (LV) EF (&lt;50%) and RV endsystolic volume on CMR (all p&lt;0.05). Serum NT-proBNP (14065±12042 vs. 3203±4615 ng/ml; p&lt;0.001) and creatinine levels (1.59±0.96 vs. 1.29±1.03 mg/dl; p=0.201) were elevated in patients with RVSD. A total of 27 events occurred during follow-up (29±13 weeks). While LVSD was not significantly associated with outcome (p=0.654), RVSD showed a strong and independent association with event-free survival in the multivariate Cox-regression analysis [hazard ratio 3.836 (95% confidence interval 1.670–8.810); p=0.002], which included all relevant CMR parameters, cardiovascular risk factors and routine biomarkers. Conclusions RVSD rather than LVSD, as determined by CMR, is an important predictor of outcome in patients undergoing TAVR. RV function might thus add useful prognostic information on top of established risk factors.

Relation of Increasing QRS Duration Over Time and Cardiovascular Events in Outpatients With Heart Failure

An increase in the duration of the QRS complex over time has been shown to be associated with poor clinical outcomes in specific subgroups of heart failure (HF) patients. There is a paucity of data on the clinical impact of increasing QRS duration on outcomes in HF with narrow QRS duration. This was a retrospective study of consecutive adult referrals to a tertiary outpatient HF clinic over a 2-year period. All patients with a narrow QRS, (<130 ms) were included. The primary outcome was mortality. Secondary outcomes were HF hospitalization and a composite of HF hospitalization, implantation of cardiac resynchronization therapy or left ventricular assist device and cardiac transplant. A total of 253 patients with 2 or more QRS measurments were included. Death occurred in 41 patients (16%), 258 HF hospitalizations occurred in 116 patients (46%) and the composite occurred in 127 patients (50%). Multivariable analyses found that a rate of QRS duration change of ≥1 ms/month was independently associated with increased mortality (odds ratio [OR] 2.26, 95% confidence interval [CI] 1.04 to 4.91), HF hospitalization (relative risk [RR] 2.01, 95% CI 1.37 to 2.94), and the composite (OR 2.40, 95%CI 1.44 to 4.02). A new QRS >130 ms was also independently associated with mortality (OR 3.27, 95%CI 1.29-8.32), HF hospitalization (RR 2.75, 95% CI 1.72 to 4.4) and the composite (OR 2.52, 95%CI 1.27 to 4.99). In conclusion, in patients with HF and a narrow baseline QRS, an increase in QRS duration of ≥1 ms per month is associated with increased mortality and HF hospitalization. HF patients may benefit from serial monitoring of QRS duration.

19-LB: Consistent Cardiovascular (CV) Benefits from Empagliflozin across the Spectrum of CV Risk Factor Control: Post Hoc Analysis from EMPA-REG OUTCOME

In the EMPA-REG OUTCOME trial of 7020 patients with T2DM and CV disease, empagliflozin (EMPA) significantly reduced risk for 3P-MACE, CV death, hospitalization for heart failure (HHF) and the composite of HHF or CV death, compared to placebo (PBO). We explored these outcomes in subgroups based on achievement of 7 CV risk factor goals at baseline, defined as: HbA1c &amp;lt;7.5%; LDL-C &amp;lt;100 mg/dL or statin use; systolic BP &amp;lt;140 or diastolic BP &amp;lt;90 mmHg; ACE inhibitor/ARB use; normoalbuminuria; aspirin use; and non-smoking status. Within the PBO group alone, the hazard ratio (HR) for 3P-MACE was 2.21 (95% CI 1.53, 3.19) and 1.42 (1.06, 1.89) for patients achieving 0-3 or 4-5 risk factor goals at baseline, respectively, compared to those reaching 6-7. Similarly, patients achieving only 0-3 or 4-5 goals had increased risk for CV death (HR 4.00 [2.26, 7.11] and 2.48 [1.52, 4.06], respectively), HHF or CV death (HR 2.89 [1.82, 4.57] and 1.90 [1.31, 2.78]) and an increased point estimate for HHF (HR 1.91 [0.96, 3.79] and 1.67 [1.00, 2.80]) versus those achieving 6-7 goals at baseline. EMPA consistently reduced the risk for these CV events versus PBO across all subgroups (p for interaction=NS for all; Figure). In conclusion, CV risk increases with fewer CV risk factors controlled, but the cardioprotective effect of EMPA was consistent regardless of the number of risk factors controlled. Disclosure S.E. Inzucchi: Consultant; Self; vTv Therapeutics, Zafgen, Inc. Other Relationship; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Lexicon Pharmaceuticals, Inc., Novo Nordisk A/S, Sanofi. K. Khunti: Advisory Panel; Self; Amgen Inc., AstraZeneca, Eli Lilly and Company, Merck Sharp &amp; Dohme Corp., Novo Nordisk A/S, Sanofi. Consultant; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Merck Sharp &amp; Dohme Corp., Novartis AG, Novo Nordisk A/S, Pfizer Inc., Sanofi-Aventis, Servier, Takeda Pharmaceutical Company Limited. Research Support; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck Sharp &amp; Dohme Corp., Novartis AG, Novo Nordisk A/S, Pfizer Inc., Sanofi-Aventis. Speaker’s Bureau; Self; AstraZeneca, Berlin-Chemie AG, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Menarini Group, Merck Sharp &amp; Dohme Corp., Novartis AG, Novo Nordisk A/S, Roche Pharma, Sanofi, Servier, Takeda Pharmaceutical Company Limited. D.H. Fitchett: Speaker’s Bureau; Self; Boehringer Ingelheim International GmbH, Lilly Diabetes. Other Relationship; Self; Boehringer Ingelheim International GmbH, Novo Nordisk A/S. C. Wanner: Advisory Panel; Self; Bayer AG, Boehringer Ingelheim International GmbH, Merck Sharp &amp; Dohme Corp. Board Member; Self; Boehringer Ingelheim International GmbH. Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Lilly Diabetes, Mitsubishi Tanabe Pharma Corporation. M. Mattheus: Employee; Self; Boehringer Ingelheim Pharma GmbH&amp;Co.KG. J. George: Employee; Self; Boehringer Ingelheim International GmbH. A. Ofstad: Employee; Self; Boehringer Ingelheim International GmbH. B. Zinman: Advisory Panel; Self; Abbott, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Merck &amp; Co., Inc., Novo Nordisk Inc. Consultant; Self; Abbott, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Merck &amp; Co., Inc., Novo Nordisk Inc. Funding Boehringer Ingelheim; Eli Lilly and Company

Circulating Long Noncoding RNA LIPCAR Predicts Heart Failure Outcomes in Patients Without Chronic Kidney Disease.

The plasma levels of long noncoding RNA LIPCAR are elevated in heart failure (HF) patients with reduced ejection fraction and associated with left ventricular remodeling and poor outcomes. We studied whether the presence of chronic kidney disease (CKD), as defined by an estimated glomerular filtration rate value <60mL/(min·1.73m2) modified the associations of plasma LIPCAR with left ventricular remodeling and outcomes in HF patients. Two hundred and thirty-four patients (mean age 74 [9.14] years, 50% male) were enrolled and followed for 4.73 (0.24-7.25) years. Plasma LIPCAR was detected by real-time quantitative polymerase chain reaction. LIPCAR was increased ( P=0.005) in patients compared with 17 age- and sex-matched controls, directly correlated with age ( P=0.001) and with the maximal early transmitral flow velocity to the mean peak early diastolic velocity of the mitral annulus displacement ratio ( P=0.001) and inversely correlated with estimated glomerular filtration rate ( P<0.001). LIPCAR was associated with hospitalization for HF, cardiovascular death, and a composite of hospitalization for HF or cardiovascular death ( P≤0.010), these associations being dependent of estimated glomerular filtration rate. The interactions between estimated glomerular filtration rate and LIPCAR with respect to these outcomes were statistically significant or of borderline significance ( P≤0.060). LIPCAR was increased in CKD patients compared with non-CKD patients ( P=0.021). LIPCAR was independently associated with hospitalization for HF ( P≤0.039) only in non-CKD patients, but its addition to traditional risk factors did not improve risk prediction in these patients. In conclusion, plasma LIPCAR prognosticates outcomes in elderly HF patients without CKD. Thus, there is an effect modification of CKD on the association of circulating LIPCAR with outcomes in HF patients.