Composite Of Heart Failure Hospitalization Research Articles

Association of Renin-Angiotensin-Aldosterone System Inhibitors With Clinical Outcomes, Hemodynamics, and Myocardial Remodeling Among Patients With Advanced Heart Failure on Left Ventricular Assist Device Support.

We evaluated the potential benefits of renin-angiotensin-aldosterone system inhibitors (RAASi) in patients with left ventricular assist device support. A total of 165 consecutive patients undergoing left ventricular assist device implant and alive at 6-month on support were studied. RAASi status after 6-month visit along with clinical reasons for nonprescription/uptitration were retrospectively assessed. The primary outcome was a composite of heart failure hospitalization or cardiovascular death between 6 and 24 months after left ventricular assist device implant. Remodeling and hemodynamic outcomes were explored by studying the association of RAASi new prescription/uptitration versus unmodified therapy at 6-month visit with the change in echocardiographic parameters and hemodynamics between 6 and 18 months. After the 6-month visit, 76% of patients were on RAASi. Patients' characteristics among those receiving and not receiving RAASi were mostly similar. Of 85 (52%) patients without RAASi new prescription/uptitration at 6-month visit, 62% had no apparent clinical reason. RAASi were independently associated with the primary outcome (adjusted hazard ratio, 0.31 [95% CI, 0.16-0.69]). The baseline rates of optimal echocardiographic profile (neutral interventricular septum, mitral regurgitation less than mild, and aortic valve opening) and hemodynamic profile (cardiac index ≥2.2 L/min per m2, wedge pressure <18 mm Hg, and right atrial pressure <12 mm Hg) were similar between groups. At 18 months, patients receiving RAASi new prescription/uptitration at 6 months had higher rates of optimal hemodynamic profile (57.5% versus 37.0%; P=0.032) and trends for higher rates of optimal echocardiographic profile (39.6% versus 22.9%; P=0.055) compared with patients with 6-month unmodified therapy. Optimal 18-month hemodynamic and echocardiographic profiles were associated with the primary outcome (log-rank=0.022 and log-rank=0.035, respectively). RAASi are associated with improved outcomes and improved hemodynamics among mechanically unloaded patients.

Glucagon-like peptide-1 receptor agonists use and associations with outcomes in heart failure and type 2 diabetes. Data from the Swedish Heart Failure and Swedish National Diabetes Registries.

To assess use and associations with outcomes of glucagon-like peptide-1 receptor agonists (GLP-1 RA) in a real-world population with heart failure (HF) and type 2 diabetes (T2DM). The Swedish HF Registry was linked with the National Diabetes Registry and other national registries. Independent predictors of GLP-1 RA use were assessed by multivariable logistic regressions, and associations with outcomes by Cox regressions in a 1:1 propensity score-matched cohort. Of 8188 patients enrolled in 2017-2021, 9% received a GLP-1 RA. Independent predictors of GLP-1 RA use were age<75, worse glycaemic control, impaired renal function, obesity and reduced ejection fraction (EF). GLP-1 RA use was not significantly associated with a composite of HF hospitalization (HHF) or cardiovascular (CV) death regardless of EF, but was associated with lower risk of major adverse CV events (CV death, non-fatal stroke/transient ischemic attack or myocardial infarction), CV and all-cause death. In patients with body mass index≥30 kg/m2, GLP-1 RA use was also associated with lower risk of HHF/CV death and HHF alone. In patients with HF and T2DM, GLP-1 RA use was independently associated with more severe T2DM, reduced EF and obesity, and was not associated with a higher risk of HHF/CV death but with longer survival and less major CV adverse events. An association with lower HHF/CV death and HHF was observed in obese patients. Our findings provide new insights into GLP-1 RA use and its safety in HF and T2DM.

Effect of Empagliflozin on Heart Failure Outcomes After Acute Myocardial Infarction: Insights From the EMPACT-MI Trial.

Empagliflozin reduces the risk of heart failure (HF) events in patients with type 2 diabetes at high cardiovascular risk, chronic kidney disease, or prevalent HF irrespective of ejection fraction. Whereas the EMPACT-MI trial (Effect of Empagliflozin on Hospitalization for Heart Failure and Mortality in Patients With Acute Myocardial Infarction) showed that empagliflozin does not reduce the risk of the composite of hospitalization for HF and all-cause death, the effect of empagliflozin on first and recurrent HF events after myocardial infarction is unknown. EMPACT-MI was a double-blind, randomized, placebo-controlled, event-driven trial that randomized 6522 patients hospitalized for acute myocardial infarction at risk for HF on the basis of newly developed left ventricular ejection fraction of <45% or signs or symptoms of congestion to receive empagliflozin 10 mg daily or placebo within 14 days of admission. In prespecified secondary analyses, treatment groups were analyzed for HF outcomes. Over a median follow-up of 17.9 months, the risk for first HF hospitalization and total HF hospitalizations was significantly lower in the empagliflozin compared with the placebo group (118 [3.6%] versus 153 [4.7%] patients with events; hazard ratio, 0.77 [95% CI, 0.60, 0.98]; P=0.031, for first HF hospitalization; 148 versus 207 events; rate ratio, 0.67 [95% CI, 0.51, 0.89]; P=0.006, for total HF hospitalizations). Subgroup analysis showed consistency of empagliflozin benefit across clinically relevant patient subgroups for first and total HF hospitalizations. The need for new use of diuretics, renin-angiotensin modulators, or mineralocorticoid receptor antagonists after discharge was less in patients randomized to empagliflozin versus placebo (all P<0.05). Empagliflozin reduced the risk of HF in patients with left ventricular dysfunction or congestion after acute myocardial infarction. URL: https://www.clinicaltrials.gov; Unique identifier: NCT04509674.

Cardiorenal effectiveness of empagliflozin vs. glucagon-like peptide-1 receptor agonists: final-year results from the EMPRISE study

BackgroundNo randomized clinical trials have directly compared the cardiorenal effectiveness of empagliflozin and GLP-1RA agents with demonstrated cardioprotective effects in patients with a broad spectrum of cardiovascular risk. We reported the final-year results of the EMPRISE study, a monitoring program designed to evaluate the cardiorenal effectiveness of empagliflozin across broad patient subgroups.MethodsWe identified patients ≥ 18 years old with type 2 diabetes who initiated empagliflozin or GLP-1RA from 2014 to 2019 using US Medicare and commercial claims databases. After 1:1 propensity score matching using 143 baseline characteristics, we evaluated risks of outcomes including myocardial infarction (MI) or stroke, hospitalization for heart failure (HHF), major adverse cardiovascular events (MACE – MI, stroke, or cardiovascular mortality), a composite of HHF or cardiovascular mortality, and progression to end-stage kidney disease (ESKD) (in patients with chronic kidney disease stages 3–4). We estimated hazard ratios (HR) and rate differences (RD) per 1,000 person-years, overall and within subgroups of age, sex, baseline atherosclerotic cardiovascular disease (ASCVD), and heart failure (HF).ResultsWe identified 141,541 matched pairs. Compared with GLP-1RA, empagliflozin was associated with similar risks of MI or stroke [HR: 0.99 (0.92, 1.07); RD: -0.23 (-1.25, 0.79)], and lower risks of HHF [HR: 0.50 (0.44, 0.56); RD: -2.28 (-2.98, -1.59)], MACE [HR: 0.90 (0.82, 0.99); RD: -2.54 (-4.76, -0.32)], cardiovascular mortality or HHF [HR: 0.77 (0.69, 0.86); RD: -4.11 (-5.95, -2.29)], and ESKD [0.75 (0.60, 0.94); RD: -6.77 (-11.97, -1.61)]. Absolute risk reductions were larger in older patients and in those with baseline ASCVD/HF. They did not differ by sex.ConclusionsThe cardiovascular benefits of empagliflozin vs. cardioprotective GLP-1RA agents were larger in older patients and in patients with history of ASCVD or HF, while they did not differ by sex. In patients with advanced CKD, empagliflozin was associated with risk reductions of progression to ESKD.

Early changes in estimated glomerular filtration rate post-initiation of empagliflozin in EMPEROR-Preserved.

Renal function (estimated glomerular filtration rate [eGFR]) changes early after the introduction of empagliflozin have not been described in heart failure with preserved ejection fraction (HFpEF). The aim of this study was to describe early eGFR changes, assess its determinants and its clinical impact on cardiovascular and renal outcomes in patients with HFpEF enrolled in EMPEROR-Preserved. Estimated glomerular filtration rate changes (absolute and relative) from randomization to week 4 were calculated and landmark analyses performed. Initial eGFR change was available in 5836 patients (97.5% of the population). Empagliflozin induced a mean eGFR change of -3.2 ml/min/1.73 m2 versus placebo from baseline to week 4. After week 4, in the empagliflozin group, the risk of the primary outcome (composite of heart failure hospitalization or cardiovascular death), cardiovascular, all-cause mortality and sustained ≥50% eGFR decrease or end-stage renal disease (ESRD) did not differ by eGFR change levels. In contrast, in the placebo group, patients included in the tertile with most profound eGFR decrease (i.e. ≥5.1% from baseline) had a higher risk of the primary outcome (hazard ratio [HR] 1.46, 95% confidence interval [CI] 1.17-1.82), cardiovascular mortality (HR 1.38, 95% CI 1.01-1.89) and sustained ≥50% eGFR decrease or ESRD (HR 2.20, 95% CI 1.20-4.04) versus tertile with eGFR increase. An initial relatively small eGFR decrease may be expected after empagliflozin initiation. Such small eGFR decrease was not associated with adverse cardiovascular outcomes with empagliflozin. In contrast, eGFR decrease was associated with poor cardiovascular outcomes with placebo.

Clinical Impact of the Volumetric Quantification of Ventricular Secondary Mitral Regurgitation by Three-Dimensional Echocardiography

The assessment of ventricular secondary mitral regurgitation (v-SMR) severity through effective regurgitant orifice area (EROA) and regurgitant volume (RegVol) calculations using the proximal isovelocity surface area (PISA) method and the two-dimensional echocardiography volumetric method (2DEVM) is prone to underestimation. Accordingly, we sought to investigate the accuracy of the three-dimensional echocardiography volumetric method (3DEVM) and its association with outcomes in v-SMR patients. We included 229 patients (70±13years, 74% men) with v-SMR. We compared EROA and RegVol calculated by the 3DEVM, 2DEVM, and PISA methods. The end point was a composite of heart failure hospitalization and death for any cause. After a mean follow-up of 20±11months, 98 patients (43%) reached the end point. Regurgitant volume and EROA calculated by 3DEVM were larger than those calculated by 2DEVM and PISA. Using receiver operating characteristic curve analysis, both EROA (area under the curve, 0.75; 95% CI, 0.68-0.81; P=.008) and RegVol (AUC, 0.75; 95% CI, 0.68-0.82; P=.02) measured by 3DEVM showed the highest association with the outcome at 2years compared to PISA and 2DEVM (P<.05 for all). Kaplan-Meier analysis demonstrated a significantly higher rate of events in patients with EROA ≥ 0.3cm2 (cumulative survival at 2years: 28%±7% vs 32%±10% vs 30%±11%) and RegVol ≥ 45mL (cumulative survival at 2years: 21%±7% vs 24%±13% vs 22%±10%) by 3DEVM compared to those by PISA and 2DEVM, respectively. In Cox multivariable analysis, 3DEVM EROA remained independently associated with the end point (hazard ratio, 1.02, 95% CI, 1.00-1.05; P=.02). The model including EROA by 3DEVM provided significant incremental value to predict the combined end point compared to those using 2DEVM (net reclassification index=0.51, P=.003; integrated discrimination index=0.04, P=.014) and PISA (net reclassification index=0.80, P<.001; integrated discrimination index=0.06, P<.001). Effective regurgitant orifice area and RegVol calculated by 3DEVM were independently associated with the end point, improving the risk stratification of patients with v-SMR compared to the 2DEVM and PISA methods.

Effects of empagliflozin on collagen biomarkers in patients with heart failure: Findings from the EMPEROR trials.

Extracellular matrix remodelling is one of the key pathways involved in heart failure (HF) progression. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) may have a role in attenuating myocardial fibrosis. The impact of SGLT2i on blood markers of collagen turnover in humans is not fully elucidated. This study aimed to investigate the effect of empagliflozin on serum markers of collagen turnover in patients enrolled in the EMPEROR-Preserved and EMPEROR-Reduced trials. Overall, 1084 patients (545 in empagliflozin and 539 in placebo) were included in the analysis. Procollagen type I carboxy-terminal propeptide (PICP), a fragment of N-terminal type III collagen (PRO-C3), procollagen type I amino-terminal peptide (PINP), a fragment of C-terminal type VIa3 collagen (PRO-C6), a fragment of type I collagen (C1M), and a fragment of type III collagen (C3M) were measured in serum at baseline, 12 and 52 weeks. A mixed model repeated measurements model was used to evaluate the effect of empagliflozin versus placebo on the analysed biomarkers. Higher baseline PICP, PRO-C6 and PINP levels were associated with older age, a more severe HF presentation, higher levels of natriuretic peptides and high-sensitivity troponin T, and the presence of comorbid conditions such as chronic kidney disease and atrial fibrillation. Higher PICP levels were associated with the occurrence of the study primary endpoint (a composite of HF hospitalization or cardiovascular death), and PRO-C6 and PINP were associated with the occurrence of sustained worsening of kidney function. On the other hand, PRO-C3, C1M, and C3M were not associated with worse HF severity or study outcomes. Compared to placebo, empagliflozin reduced PICP at week 12 by 5% and at week 52 by 8% (week 12: geometric mean ratio = 0.95, 95% confidence interval [CI] 0.91-0.99, p = 0.012; week 52: geometric mean ratio = 0.92, 95% CI 0.88-0.97, p = 0.003). Additionally, empagliflozin reduced PRO-C3 at week 52 by 7% (week 12: geometric mean ratio = 0.98, 95% CI 0.95-1.02, p = 0.42; week 52: geometric mean ratio = 0.93, 95% CI 0.89-0.98, p = 0.003), without impact on other collagen markers. Our observations are consistent with experimental observations that empagliflozin down-regulates profibrotic signalling. The importance of such an effect for the clinical benefits of SGLT2i in HF remains to be elucidated.

Sodium-glucose cotransporter-2 inhibitors improve clinical outcomes in patients with type 2 diabetes mellitus undergoing anthracycline-containing chemotherapy: an emulated target trial using nationwide cohort data in South Korea

Novel hypoglycemic agents, sodium-glucose cotransporter 2 inhibitors (SGLT2i), have shown protective effects against anthracycline (AC)-induced cardiotoxicity and exhibit partial anticancer effects in animal models. However, clinical evidence for this is scarce. This study aimed to evaluate whether SGLT2i improve the clinical outcomes of patients with type 2 diabetes mellitus (T2DM) undergoing AC-containing chemotherapy. A total of 81,572 patients who underwent AC chemotherapy between 2014 and 2021 were recruited from a nationwide Korean cohort. Patients were classified into three groups: patients with T2DM taking SGLT2i (n = 780) and other hypoglycemic agents excluding SGLT2i (non-SGLT2i; n = 3,455) during AC chemotherapy, and the non-DM group (n = 77,337). The clinical outcome was a composite of heart failure hospitalization, acute myocardial infarction, ischemic stroke, and death. After propensity score matching, 779 SGLT2i users were compared with 7800 non-DM patients and 2,337 non-SGLT2i users. The SGLT2i group had better composite outcomes compared with the non-DM group (adjusted hazard ratio [HR] = 0.35, 95% confidence interval [95% CI] = 0.25–0.51) and compared with the non-SGLT2i group (adjusted HR = 0.47, 95% CI = 0.32–0.69). In conclusion, SGLT2i may contribute to improving clinical outcomes in patients with T2DM undergoing AC-containing chemotherapy, through an emulated target trial using Korean nationwide cohort data.

Exercise Capacity and Clinical Outcomes in Chronic Heart Failure Patients with Mild Tricuspid Regurgitation

Aim: The present study aimed to investigate the impact of mild tricuspid regurgitation (TR) on the exercise capacity or clinical outcomes in patients with chronic heart failure (CHF). Methods and Results: The study enrolled 511 patients with CHF who underwent cardiopulmonary exercise testing (CPET) between 2013 and 2018. The primary outcome was a composite of heart failure hospitalization and death. Patients with mild TR (n = 324) or significant TR (moderate or greater; n = 60) displayed worse NHYA class and reduced exercise capacity on CPET than those with non-TR (n = 127), but these were more severely impaired in patients with significant TR. A total of 90 patients experienced events over a median follow-up period of 3.3 (interquartile range 0.8–5.5) years. Patients with significant TR displayed a higher risk of events, while patients with mild TR had a 3.0-fold higher risk of events than patients with non-TR (hazard ratio (HR) 3.01; 95% confidence interval (CI), 1.50–6.07). Multivariate Cox regression analysis showed that, compared with non-TR, mild TR was associated with increased adverse events, even after adjustment for co-variates (HR 2.97; 95% CI, 1.35–6.55). Conclusions: TR severity was associated with worse symptoms, reduced exercise capacity, and poor clinical outcomes. Even patients with mild TR had worse clinical characteristics than those with non-TR.

Validation of a new CPET multivariable score to predict cardiovascular events in heart failure patients

Abstract Introduction Cardiopulmonary exercise testing (CPET) is recommended in patients with heart failure (HF) to optimize exercise prescription and as part of the evaluation for heart transplantation. Recently, a new multivariable score (MVS) was proposed as a powerful method to predict HF events with an optimal cut-off value of 120. Purpose We aimed to evaluate the prognostic value of this tool in patients with HF. Methods We conducted a single-centre study assessing consecutive patients with HF who underwent CPET from 2013 to 2017. Classic and recently proposed variables were collected, including peak O2 uptake (pVO2), minute ventilation–CO2 production (VE/VCO2 slope), partial pressure of end-tidal CO2 at the anaerobic threshold (PETCO2L), circulatory power (CP=pVO2 x peak SBP), and ventilatory power (VP=peak SBP/(VE/VCO2) slope). The score was calculated as follows: (pVO2 × 2.194) + (PETCO2L × 1.545) + (LVEF × 1.134) + (HR × 1.055; 0 if AF, 1 if sinus rhythm). The primary outcome was a composite of HF hospitalization, heart transplant, and all-cause mortality. Results We included 212 patients 76.9% male and with a mean age of 55.4±10.9 years-old. The most frequent aetiology was dilated cardiomyopathy (43.9%) followed by ischaemic heart disease (38.7%). Accordingly, the mean left ventricle ejection fraction was 29±13%. Additionally, 39.8% had atrial fibrillation. The most used exercise protocol was the modified Naughton (76.6%). Mean pVO2 was 16.7±5.9mL O2·kg−1·min−1, median VE/VCO2 slope was 37.5 [32.7-44.3], and PETCO2L 33.5±5.2mmHg. Mean VP was 3.46±1.31mmHg while the median CP was 1927 [1427-2697]mmHg·min/mL/kg. The mean MVS was 116.2±23.1. Despite weak, there were significant positive correlations between the MVS and both VP (r=0.59, p&amp;lt;0.01) and CP (rs=0.64, p&amp;lt;0.01). After a median follow-up of 71 [49-81] months, the primary outcome occurred in 66.0% of patients (rehospitalization, heart transplant, and all-cause death occurred in 56.1%, 25.9%, and 32.5%, respectively). The new CPET MVS was associated with the primary outcome (p&amp;lt;0.01). Additionally, patients with MVS &amp;lt;120 had a higher rate of the primary outcome (83.2% vs. 39.1%, p&amp;lt;0.01). Kaplan-Meier estimates of tthe primary outcome according to the optimal cut-off value of 120 are shown in Figure 1A. Receiver operating characteristic curve revealed that the MVS has higher discriminative power for the primary endpoint (AUC 0.80, p&amp;lt;0.01) compared to pVVO2, VP, and CP (Figure 1B). Conclusion The novel multivariable score is associated with the composite of HF hospitalization, heart transplant, and all-cause mortality in patients with heart failure, enhancing the role of CPET in risk stratification.

Combined therapy with SGLT2i and GLP-1ra improves cardiovascular prognosis in a population with diabetes and overweigh or obesity. A real-world clinical practice study

Abstract Background Prior clinical trials found diabetic patients treated with SGLT2i and/or GLP1ra had lower rates of cardiovascular complications. Purpose This study (CardioCHUS-T2D) sought to determine the association between initiation of SGLT2i, GLP1ra or both, and major cardiovascular complications or death in high risk diabetic patients. Materials and methods The CardioCHUS-T2D study was an observational study in which adults with type 2 diabetes, older than 65 years old and overweight or obesity were identified in a Galician health area. Patients prescribed an SGLT2i, GLP1ra or both over the last 5 years were matched base on antidiabetic treatment, duration of treatment, sex, age, diabetes duration, arterial hypertension, hyperlipidemia, CAD, HF, atrial fibrillation, CVA and peripheral artery disease (PAD) and were included on a regression Cox for determining the main variables associated with outcomes. After score matching, we selected 5132 patients who were taking SGLT2i, GLP-1ra or both. The data records were obtained from shared electronic patient dossier (EPD). Patients were classified in 3 groups according antidiabetic drugs, SGLT2i or/and GLP-1ra. During follow-up, after treatment intake, the main outcomes were recorded (hospitalization for coronary artery disease (CAD), heart failure (HF) or cerebrovascular accident (CVA) events, overall and cardiovascular death. Results The main clinical characteristics of patients regarding antidiabetic treatment are represented on table 1. No clinical relevant differences were observed between the group of patients treated with any of the monotherapies (SGLT2i or GLP-1ra) and the patients treated with the combined therapy. During the period of observation, the group of patients receiving the combined therapy (SGLT2 + GLP-1ra) were associated with a significant reduction in the risk of suffering heart failure (HF) events (composite of HF hospitalization and HF-related death): HR: 0,651 (95%CI: 0,457-0,927; p=0,017), and all-cause mortality (HR: 0,602 (95%CI:0,443-0,817; p=0,001) (Figure 1) without significative differences in cerebrovascular events. Conclusions In a real-world practice observational study (CardioCHUS-T2D) combined therapy with SGLT2i + GLP1ra in patients with T2D older than 65 years with overweight or obesity was associated with a significative reduction in major cardiovascular complications.Clinical characteristics of patientsKaplan-Meier curves

Mechanisms of benefits of sodium-glucose cotransporter 2 inhibitors in heart failure with preserved ejection fraction.

For decades, heart failure with preserved ejection fraction (HFpEF) proved an elusive entity to treat. Sodium-glucose cotransporter 2 (SGLT2) inhibitors have recently been shown to reduce the composite of heart failure hospitalization or cardiovascular death in patients with HFpEF in the landmark DELIVER and EMPEROR-Preserved trials. While improvements in blood sugar, blood pressure, and attenuation of kidney disease progression all may play some role, preclinical and translational research have identified additional mechanisms of these agents. The SGLT2 inhibitors have intriguingly been shown to induce a nutrient-deprivation and hypoxic-like transcriptional paradigm, with increased ketosis, erythropoietin, and autophagic flux in addition to altering iron homeostasis, which may contribute to improved cardiac energetics and function. These agents also reduce epicardial adipose tissue and alter adipokine signalling, which may play a role in the reductions in inflammation and oxidative stress observed with SGLT2 inhibition. Emerging evidence also indicates that these drugs impact cardiomyocyte ionic homeostasis although whether this is through indirect mechanisms or via direct, off-target effects on other ion channels has yet to be clearly characterized. Finally, SGLT2 inhibitors have been shown to reduce myofilament stiffness as well as extracellular matrix remodelling/fibrosis in the heart, improving diastolic function. The SGLT2 inhibitors have established themselves as robust, disease-modifying therapies and as recent trial results are incorporated into clinical guidelines, will likely become foundational in the therapy of HFpEF.

Coronary revascularization for heart failure with coronary artery disease: a systematic review and meta-analysis of randomized trials.

Coronary artery disease (CAD) is a common cause of heart failure (HF). Whether coronary revascularisation improves outcomes in patients with HF receiving guideline-recommended pharmacological therapy (GRPT) remains uncertain; therefore, we conducted a systematic review and meta-analysis of relevant randomized controlled trials (RCTs). We searched in public databases for RCTs published between 1st January 2001 and 22nd November 2022, investigating the effects of coronary revascularisation on morbidity and mortality in patients with chronic HF due to CAD. All-cause mortality was the primary outcome. We included five RCTs that enrolled, altogether, 2,842 patients (most aged <65 years; 85% men; 67% with left ventricular ejection fraction ≤35%). Overall, compared to medical therapy alone, coronary revascularisation was associated with a lower risk of all-cause mortality (HR 0.88 [95% CI, 0.79-0.99]; p=0.0278) and cardiovascular mortality (HR 0.80 [95% CI, 0.70-0.93]; p=0.0024) but not the composite of hospitalisation for HF or all-cause mortality (HR 0.87 [95% CI, 0.74-1.01]; p=0.0728). There were insufficient data to show whether the effect of CABG or PCI were similar or differed. For patients with chronic HF and CAD enrolled in RCTs, the effect of coronary revascularization on all-cause mortality was statistically significant but neither substantial (HR 0.88) nor robust (upper 95% CI close to 1.0). RCTs were not blinded, which may bias reporting of the cause-specific reasons for hospitalization and mortality. Further trials are required to determine which patients with HF and CAD obtain a substantial benefit from coronary revascularization by either CABG or PCI. This article is protected by copyright. All rights reserved.

Prognostic value of left-ventricular hemodynamic forces by echocardiography in patients with left-ventricular non-compaction

Abstract Funding Acknowledgements Type of funding sources: None. Background Left-ventricular (LV) non-compaction (LVNC) is a poorly defined entity characterized by marked LV hypertrabeculation and risk of cardiovascular complications (1). LV ejection fraction (LVEF) by echocardiography (TTE) is the main prognostic factor, but on its own it does not allow for proper risk assessment (2). The evaluation of hemodynamic forces (HDF), a recently-introduced technique for mechanistic description of LV-blood interaction (3), may provide additional information on LVNC mechanics. However, their prognostic value is unknown. Purpose To test whether HDF provide prognostic value in LVNC patients beyond conventional TTE parameters. Methods This is a retrospective longitudinal study including patients diagnosed with LVNC (according to Jenni criteria) (1) who underwent TTE evaluation between 2015 and 2019. Patients were excluded if they had moderate-severe valvular heart disease and if follow-up was &amp;lt;12 months. Major cardiovascular events (MACE) were considered as a composite of heart failure hospitalization, ventricular arrhythmias, systemic embolism, and all-cause death. LV HDF were analyzed on apical 2-, 3-, and 4-chamber view TTE images with a prototype software (Medis Suite Qstrain, The Netherlands). HDF were decomposed into apex-base (HDFab) and lateral-septal (HDFls) components. According to its waveform during the cardiac cycle, HDFab was further decomposed into 3 main components: systolic acceleration, LV suction, and diastolic deceleration (DiastDec) (4). DiastDec was also dichotomized according to its distribution. Results 107 patients were included: 60 (56%) were males, mean age was 45.7±18.5 years, mean LVEF was 50.6±10.0%. During median follow-up of 4.5 [3.4–6.1] years MACE occurred in 19 patients (17.8%). Compared to patients who did not experience MACE, those with MACE had lower DiastDec (2.44±1.62 vs. 3.86±2.24%, p = 0.010), while the other HDF parameters were similar. On Cox univariate analysis age (HR 1.06 [95% CI 1.03–1.09], p&amp;lt;0.001), LVEF (HR 0.93 [95% CI 0.90–0.97], p&amp;lt;0.001), longitudinal strain (GLS) (HR 1.21 [95% CI 1.10–1.33], p&amp;lt;0.001), left atrial volume (LAVi) (HR 1.05 [95% CI 1.02–1.08], p&amp;lt;0.001), and DiaDec (HR 0.69 [95% CI 0.51–0.93], p = 0.015) were significantly associated with MACE. 16 patients (84%) who experienced MACE had low DiastDec (&amp;lt; 3%). Low DiastDec was strongly associated with MACE (HR 7.65 [95% CI 2.23–26.27], p&amp;lt;0.001), and remained independently associated with MACE after adjusting for age, LVEF, GLS, and LAVi on separate multivariate Cox analyses. The best performance for MACE prediction was obtained by the multivariate Cox model including age, GLS, and DiastDec (AUC 71.5%). Conclusions Reduced hemodynamic forces in apex-base direction during diastolic deceleration were significantly associated with MACE in LVNC patients beyond conventional echocardiography parameters. Low DiastDec may be a marker of altered intra-cardiac flow and impaired recoil function of the LV in LVNC.

Specialized heart failure clinics versus primary care: Extended registry-based follow-up of the NorthStar trial.

Whether continued follow-up in specialized heart failure (HF) clinics after optimization of guideline-directed therapy improves long-term outcomes in patients with HF with reduced ejection fraction (HFrEF) is unknown. 921 medically optimized HFrEF patients enrolled in the NorthStar study were randomly assigned to follow up in a specialized HF clinic or primary care and followed for 10 years using Danish nationwide registries. The primary outcome was a composite of HF hospitalization or cardiovascular death. We further assessed the 5-year adherence to prescribed neurohormonal blockade in 5-year survivors. At enrollment, the median age was 69 years, 24,7% were females, and the median NT-proBNP was 1139 pg/ml. During a median follow-up time of 4.1 (Q1-Q3 1.5-10.0) years, the primary outcome occurred in 321 patients (69.8%) randomized to follow-up in specialized HF clinics and 325 patients (70.5%) randomized to follow-up in primary care. The rate of the primary outcome, its individual components, and all-cause death did not differ between groups (primary outcome, hazard ratio 0.96 [95% CI, 0.82-1.12]; cardiovascular death, 1.00 [0.81-1.24]; HF hospitalization, 0.97 [0.82-1.14]; all-cause death, 1.00 [0.83-1.20]). In 5-year survivors (N = 660), the 5-year adherence did not differ between groups for angiotensin-converting enzyme inhibitors (p = 0.78), beta-blockers (p = 0.74), or mineralocorticoid receptor antagonists (p = 0.47). HFrEF patients on optimal medical therapy did not benefit from continued follow-up in a specialized HF clinic after initial optimization. Development and implementation of new monitoring strategies are needed.

Intravenous iron therapy among patients with heart failure and iron deficiency: An updated meta-analysis of randomized controlled trials

BackgroundRandomized clinical trials (RCTs) evaluating the role of intravenous (IV) iron administration in patients with heart failure (HF) and iron deficiency (ID) have yielded inconsistent results. MethodsElectronic search of MEDLINE, EMBASE and OVID databases was performed until November 2022 for RCTs that evaluated the role of IV iron administration in patients with HF and ID. The main study outcomes were the composite of HF hospitalization or cardiovascular mortality, and individual outcome of HF hospitalization. Summary estimates were evaluated using random effects model. ResultsThe final analysis included 12 RCTs with 3,492 patients (1,831 patients in the IV iron group and 1,661 patients in the control group). The mean follow-up was 8.3 months. IV iron was associated with a lower incidence in the composite of HF hospitalization or cardiovascular mortality (31.9% vs. 45.3%; relative risk [RR] 0.72; 95% confidence interval [CI] 0.59–0.88) and individual outcome of HF hospitalization (28.4% vs. 42.2; RR 0.69; 95% CI 0.57–0.85). There was no significant difference between both groups in cardiovascular mortality (RR 0.88; 95% CI 0.75–1.04) and all-cause mortality (RR 0.95; 95% CI 0.83–1.09). IV iron was associated with lower New York Heart Association class and higher left ventricular ejection fraction (LVEF). Meta-regression analyses showed no effect modification for the main outcomes based on age, hemoglobin level, ferritin level or LVEF. ConclusionAmong patients with HF and ID, IV iron administration was associated with reduction in the composite of HF hospitalization or cardiovascular mortality and driven by a reduction in HF hospitalization.

Urinary cGMP (Cyclic Guanosine Monophosphate)/BNP (B-Type Natriuretic Peptide) Ratio, Sacubitril/Valsartan, and Outcomes in Heart Failure With Reduced Ejection Fraction: An Analysis of the PARADIGM-HF Trial.

The ratio of ucGMP (urinary cyclic guanosine monophosphate) to BNP (B-type natriuretic peptide) is thought to reflect the responsiveness of tissues to natriuretic peptides. We examined the relationship between ucGMP/BNP ratio and clinical outcomes, the effect of sacubitril/valsartan, compared with enalapril, on the ucGMP/BNP ratio, and the efficacy of sacubitril/valsartan on clinical outcomes according to baseline ucGMP/BNP ratio in PARADIGM-HF trial (Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure). ucGMP/BNP ratio was available at baseline (N=2031), 1 month (N=1959), and 8 months after randomization (N=1746). The primary outcome was a composite of heart failure hospitalization or cardiovascular death. Compared with the lowest tertile of baseline ucGMP/BNP ratio, patients in the higher tertiles had a lower risk of the primary outcome (tertile 1, reference; tertile 2, hazard ratio 0.57 [95% CI, 0.45-0.71]; tertile 3, hazard ratio, 0.54 [0.43-0.67]). Compared with baseline, the ucGMP/BNP ratio at 1 month and 8 months after randomization was higher with sacubitril/valsartan than with enalapril: ratio of geometric mean ratios at 1 month, 1.38 (95% CI, 1.27-1.51) and 8 months, 1.32 (95% CI, 1.20-1.45), and this difference was consistent across tertiles of ucGMP/BNP ratio at baseline (Pinteraction=0.19 and 0.91, respectively). The effect of sacubitril/valsartan, compared with enalapril, was consistent across tertiles of ucGMP/BNP ratio at baseline for all outcomes (Pinteraction ≥0.31). In patients with heart failure and reduced ejection fraction, higher ucGMP/BNP ratio was associated with better outcomes. Sacubitril/valsartan increased the ucGMP/BNP ratio, compared with enalapril, and the effect of sacubitril/valsartan on clinical outcomes was not modified by baseline ucGMP/BNP ratio. URL: https://www. gov; Unique Identifier: NCT01035255.

Prognostic value of temporal patterns of global longitudinal strain in patients with chronic heart failure.

We investigated whether repeatedly measured global longitudinal strain (GLS) has incremental prognostic value over repeatedly measured left ventricular ejection fraction (LVEF) and N-terminal pro B-type natriuretic peptide (NT-proBNP), and a single "baseline" GLS value, in chronic heart failure (HF) patients. In this prospective observational study, echocardiography was performed in 173 clinically stable chronic HF patients every six months during follow up. During a median follow-up of 2.7 years, a median of 3 (25th-75th percentile:2-4) echocardiograms were obtained per patient. The endpoint was a composite of HF hospitalization, left ventricular assist device, heart transplantation, cardiovascular death. We compared hazard ratios (HRs) for the endpoint from Cox models (used to analyze the first available GLS measurements) with HRs from joint models (which links repeated measurements to the time-to-event data). Mean age was 58 ± 11 years, 76% were men, 81% were in New York Heart Association functional class I/II, and all had LVEF < 50% (mean ± SD: 27 ± 9%). The endpoint was reached by 53 patients. GLS was persistently decreased over time in patients with the endpoint. However, temporal GLS trajectories did not further diverge in patients with versus without the endpoint and remained stable during follow-up. Both single measurements and temporal trajectories of GLS were significantly associated with the endpoint [HR per SD change (95%CI): 2.15(1.34-3.46), 3.54 (2.01-6.20)]. In a multivariable model, repeatedly measured GLS maintained its prognostic value while repeatedly measured LVEF did not [HR per SD change (95%CI): GLS:4.38 (1.49-14.70), LVEF:1.14 (0.41-3.23)]. The association disappeared when correcting for repeatedly measured NT-proBNP. Temporal evolution of GLS was associated with adverse events, independent of LVEF but not independent of NT-proBNP. Since GLS showed decreased but stable values in patients with adverse prognosis, single measurements of GLS provide sufficient information for determining prognosis in clinical practice compared to repeated measurements, and temporal GLS patterns do not add prognostic information to NT-proBNP.

Maximizing QRS duration reduction in contemporary cardiac resynchronization therapy is feasible and shorter QRS duration is associated with better clinical outcome

BackgroundWe aimed to evaluate if optimization by maximizing QRS duration (QRSd) reduction is feasible in an all-comer cardiac resynchronization therapy (CRT) population, and if reduced, QRSd is associated with a better clinical outcome.MethodsPatients with LBBB receiving CRT implants during the period 2015–2020 were retrospectively evaluated. Implants from 2015–2017 were designated as controls. Starting from 2018, an active 12-lead electrogram-based optimization of QRSd reduction was implemented (intervention group). QRSd reduction was evaluated in a structured way at various device AV and VV settings, aiming to maximize the reduction. The primary endpoint was a composite of heart failure hospitalization or death from any cause.ResultsA total of 254 patients were followed for up to 6 years (median 2.9 [1.8–4.1]), during which 82 patients (32%) reached the primary endpoint; 53 deaths (21%) and 58 (23%) heart failure hospitalizations. Median QRS duration pre-implant was 162 ms [150–174] and post-implant 146ms [132–160]. Mean reduction in QRS duration was progressively larger for each year during the intervention period, ranging from − 9.5ms in the control group to − 24 in the year 2020 (p = 0.005). QRS reduction > 14 ms (median value) was associated with a lower risk of death or heart failure hospitalization (adjusted HR 0.54 [0.29–0.98] (p = 0.04).ConclusionsImplementing a general strategy of CRT device optimization by aiming for shorter QRS duration is feasible in a structured clinical setting and results in larger reductions in QRS duration post-implant. In patients with a larger QRS reduction, compared to those with a smaller QRS reduction, there is an association with a better clinical outcome.Graphical

192 GLP1-RA AND HEART FAILURE-RELATED OUTCOMES IN PATIENTS WITH AND WITHOUT HISTORY OF HEART FAILURE: A SYSTEMATIC REVIEW AND METANALYSIS

Abstract Background GLP1-receptor agonists (GLP1-ra) are recently developed anti-diabetic drugs which have shown promising results in phase-3 cardiovascular (CV) outcomes trials in diabetic patients, demonstrating a reduction in major adverse cardiovascular events (MACE) and, possibly, in heart failure (HF) hospitalizations. However, whether these medications improve such outcomes in patients with a history of HF remains unknown. Methods All randomized, placebo-controlled trials of GLP1-ra (and predefined/post-hoc analysis) reporting CV outcomes stratified by HF history were searched in Pubmed from inception to August 31st, 2022. The primary outcome was HF hospitalizations. Secondary outcomes included MACE, CV death and a composite of HF hospitalization and CV death. The analysis was performed after stratifying for HF history. Odds-ratio (OR) and 95% confidence interval (CIs) were used as effect estimated and calculated via a random-effects model. P for interaction between subgroups were calculated via meta-regression analysis and a level of p&amp;lt;0.10 was considered as significant. Results Data from 6 trials and a total of 40300 patients (n=20127 GLP1-ra group, n=20173 placebo group) were included. GLP1-ra reduced HF hospitalizations in patients without HF history (OR 0.71, 95% CI 0.51-0.99) but had neutral effect on those with previous HF (OR 1.04, 95% CI 0.88–1.22, p-interaction=0.089). CV death was also reduced by intervention only in the group without history of HF (OR 0.81, 95% CI 0.71–0.92), as well as the composite of HF hospitalizations and CV death (OR 0.80, 95% CI 0.72–0.90). Indeed, no difference between treatment arms was found in the HF group for CV death (OR 0.99, 95% CI 0.82–1.18, p-interaction=0.18) and the composite of HF hospitalization or CV death (OR 1.02 95%CI 0.89–1.18, p-interaction=0.073). MACE reduction was similar in patients with (OR 0.87 95% CI 0.72–1.06) and without HF history (OR 0.84 95% CI 0.76–0.93, p-interaction = 0.75). Conclusion GLP1-ra do not reduce HF hospitalization and CV death in patients with history of HF, as the benefit on cardiovascular outcomes provided by this anti-diabetic class of drugs seems to be mainly limited to patients without HF history. Future studies focused on HF patients are needed to confirm such findings and clarify the limited efficacy of GLP1-ra in this relevant group of patients.