Endpoint Of Heart Failure Research Articles

Interleukin-1 Blockade in Patients With ST-Segment Elevation Myocardial Infarction Across the Spectrum of Coronary Artery Disease Complexity.

Patients with ST-segment elevation myocardial infarction (STEMI) and complex coronary artery disease (CAD) face a poor prognosis, including increased heart failure (HF) risk. Phase 2 clinical trials of anakinra have shown inhibition of the acute inflammatory response and prevention of HF after STEMI, but data on its effects based on CAD complexity are lacking. We performed a pooled secondary analysis of 139 patients with STEMI. The SYNTAX (Synergy Between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery), SYNTAX II and Gensini scores were calculated, and patients were divided into two groups below and above the median. We evaluated the effect of anakinra on the area-under-the-curve of high-sensitivity C-reactive protein (hsCRP-AUC) at 14 days, and the composite endpoint of new-onset HF, HF hospitalization, or all-cause death at 1-year follow-up using Kaplan-Meier survival curves, Cox regression analysis for Hazard Ratios (HR), and tested interactions between subgroups. All three CAD complexity scores (SYNTAX, SYNTAX II and Gensini) were associated with an increased risk of adverse events (HR 1.02 to 1.06, all p-values ≤0.025). We found no statistically significant interactions between CAD extent, measured as single-vessel or multi-vessel CAD, SYNTAX score ≤9 or >9, SYNTAX II score ≤24 or >24, Gensini score ≤32 or >32, and treatment effect of anakinra on hsCRP-AUC or the composite clinical endpoint (all p-values for interaction >0.05). In conclusion, among patients with STEMI, IL-1 blockade with anakinra significantly attenuated the acute inflammatory response and reduced the risk of HF-related events regardless of the spectrum of CAD complexity.

Abstract 4117731: Interleukin-1 Blockade in Patients With ST-Segment Elevation Myocardial Infarction Across the Spectrum of Coronary Artery Disease Complexity.

Background: Patients with ST-segment elevation myocardial infarction (STEMI) and complex coronary artery disease (CAD) face a poor prognosis, including increased heart failure (HF) risk. Interleukin-1 (IL-1) blockade with Anakinra inhibits the acute inflammatory response and prevent HF after STEMI, but data on its effects based on CAD complexity are lacking. Aims: To assess the effects of Anakinra in patients with STEMI, across the spectrum of CAD complexity. Methods: We performed a pooled secondary analysis of 139 patients with STEMI from three randomized clinical trials (VCUART studies) comparing Anakinra (N=84) versus placebo (N=55). Multivessel CAD was defined as the presence of at least one ≥70% stenosis in a non-culprit vessel of >2.5 mm diameter, not stented during index coronary intervention. The SYNTAX (Synergy Between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery), SYNTAX II and Gensini scores were calculated, and patients were divided by the median. We evaluated a composite endpoint of new-onset HF, HF hospitalization, or all-cause death at 1-year follow-up using Kaplan-Meier survival curves, Cox regression analysis for Hazard Ratios, and calculated interactions between groups. Results: We included 139 patients with STEMI, 85 (61%) with single vessel CAD and 54 (39%) with multivessel CAD. According to the spectrum of CAD complexity, 60 (43%) presented a SYNTAX score >9, 59 (42%) a SYNTAX II score >24 and 65 (47%) a Gensini score >32. New-onset HF, HF hospitalization, or all-cause death occurred in a total of 23 patients: 7 among the 84 subjects in the Anakinra group and 16 within the 55 patients in the placebo group. We found no statistically significant interactions between CAD complexity and allocation to Anakinra or placebo for the composite endpoint (Figure). Conclusions: Among patients with STEMI, IL-1 blockade with Anakinra significantly reduced the risk of new-onset HF, HF hospitalization, or all-cause death compared to placebo, regardless of the number of vessels affected and the spectrum of CAD complexity.

Centrally adjudicated vs. investigator-reported outcomes in randomized heart failure trials.

Heart failure endpoints in cardiovascular outcome trials are commonly identified through centralized adjudication of investigator-reported events. It remains unclear whether central adjudication improves the accuracy of treatment effect estimates in terms of log[hazard ratios (HR)]. Data from seven cardiovascular outcome trials with >1000 patients that included centrally adjudicated heart failure outcomes were utilized to assess (i) the concordance between investigator-reported and centrally adjudicated heart failure and cardiovascular death events; (ii) rates of subsequent all-cause mortality following positively vs. negatively adjudicated heart failure events; and (iii) the correlation of log(HR) based on centrally adjudicated vs. investigator-reported events. Positive adjudication rates for investigator-reported events varied widely across trials, but were generally higher for cardiovascular death (range: 87.9%-99.2%) than for heart failure hospitalization (range: 61.6%-88.0%). The risk for subsequent all-cause death was similar for positively and negatively adjudicated heart failure hospitalizations. Log(HR) correlated well for cardiovascular death [R2 = .80, 95% credible interval (CrI): 0.53-0.93] and the composite of cardiovascular death or heart failure hospitalization (R2 = .79, 95% CrI: 0.46-0.93), but less for heart failure hospitalization (R2 = .57, 95% CrI: 0.10-0.83). Positive adjudication rates were lower for heart failure events than cardiovascular death, but even negatively adjudicated heart failure events are prognostically important. Central adjudication of events did not alter the results (precision or estimated log(HR)), though some variation was observed, depending on the indication. The results suggest that the decision to pursue centralized adjudication of heart failure events in a specific trial may need to be individualized.

Clinical Features and Outcomes of Pediatric MYH7-Related Dilated Cardiomyopathy.

Although genetic variants in MYH7 are the most frequent cause of pediatric genetic dilated cardiomyopathy (DCM), there are no studies available describing this entity. We sought to describe clinical features, analyze variant location, and explore predictors of bad prognosis in pediatric MYH7-related DCM. We evaluated clinical records from 44 patients (24 men; median age at diagnosis, 0.54 [interquartile range, 0.01-10.8] years) with pathogenic/likely pathogenic variants in MYH7 diagnosed with DCM at pediatric age (<18 years) followed at 13 international centers. We also explored risk factors associated with a composite end point of end-stage heart failure defined as heart transplantation or heart failure-related death. Twenty-two patients (50%) were diagnosed at age <6 months, including 7 (16%) at birth. Left ventricular (LV) hypertrabeculation features were present in 15 (38%), particularly among patients with genetic variants in the head domain. After a median follow-up of 6.1 years (interquartile range, 1.9-13.4), 15 patients (36%) required a heart transplant (n=14) or died due to end-stage heart failure (n=1), 15 patients (36%) persisted with systolic dysfunction despite treatment, 12 (29%) had a significant increase in LV ejection fraction, and 2 were lost to follow-up. Overall, end-stage heart failure event rate was 25% at 5 years. New York Heart Association class III to IV (hazard ratio [HR], 7.67 [95% CI, 2.16-27.2]; P=0.002) and LV ejection fraction ≤35% (HR, 4.00 [95% CI, 1.11-14.4]; P=0.03) were the best predictors of bad prognosis. Pediatric MYH7-related DCM is characterized by early onset, frequent LV hypertrabeculation, and poor prognosis. Advanced New York Heart Association class and low LV ejection fraction emerged as predictors of end-stage heart failure.

Genotype predicts heart failure independent of left ventricular ejection fraction and NT-proBNP levels in hypertrophic cardiomyopathy

Abstract Background/Introduction Hypertrophic cardiomyopathy (HCM) is a myocardial disease associated with progression to heart failure. In around 40% of cases, the disease is caused by variants in genes encoding sarcomere proteins. Purpose To evaluate the role of genotype in predicting heart failure (HF) outcomes. Methods In this observational single-centre cohort study, consecutive patients with HCM were assessed for heart failure clinically stratified by genetic status into genotype-elusive which included those with no significant variants (G-) or variants of unknown significance (VUS) and genotype-positive (G+) with pathogenic/likely pathogenic (LP/P) variants. Heart failure endpoint was defined as left ventricular assist device implantation, heart transplantation or heart-failure-related death. The incidence of HF endpoint was compared between genotypes during follow-up using a time-to-event analysis. Results 474 patients (50.9 ±14.5 years, 67.3 males) with HCM (25% with left ventricular (LV) outflow obstruction) were followed for 10.9 years (IQR 5.1-13.5). G+ LP/P patients (201/474 (42.4%)) were younger (45.8. ±14.0 years) compared to G- (225/474 (47.5%), 55.2 ±13.4 years) and VUS (48/474 (10.1%), 52.0 ± 15 years); 29/474 (6.1%) reached the heart failure endpoint. The incidence of heart failure endpoints was 12.4% (25/201) in the G+ LP/P group compared to 1.5% (4/273) in the gene elusive group. A multivariate Cox proportional hazards model including NT-proBNP and LV ejection fraction (LVEF) and genetic status showed that G+ LP/P was associated with increased risk of heart failure outcomes (HR: 5.11, 95% CI: 1.43–18.25, p=0.012). Every 100-unit rise in NT-proBNP was associated with a 41% increase in risk (HR: 1.41, 95% CI: 1.20–1.66, p&amp;lt;0.0001). A one-unit (1%) reduction in LVEF correlated with a 10% increase in heart failure risk (HR: -0.90, 95% CI: 0.87–0.93, p&amp;lt;0.0001). Conclusion(s) Genetic status is a predictor of heart failure outcomes independent of LVEF and NT-proBNP levels in HCM. This underscores the importance of genetic testing in the clinical management of HCM.

Associations between heart rate, deformational echocardiographic parameters and clinical outcomes in patients with atrial fibrillation

Abstract Background The relationship between baseline heart rates and cardiac function in patients with atrial fibrillation (AF) remains unknown, as does its impact on long-term outcomes. Methods Patients with newly diagnosed AF and available echocardiography images were included. Conventional echocardiography measurement and myocardial deformation analyses using two-dimensional speckle-tracking echocardiography were performed during AF. Clinical endpoints included first-time hospitalization for ischemic stroke, heart failure (HF), all-cause mortality, and composite endpoint. Results Patients were categorized into groups according to baseline heart rates: 40-59, 60-69, 70-79, 80-89, 90-99, 100-109, 110-119, and ≥120 beats per minutes (bpm). As heart rates increased, there was a stepwise decrease of peak atrial longitudinal systolic strain (PALS: 14.6 ± 5.3%, 14.7 ± 5.5%, 14.1 ± 4.6%, 13.4 ± 4.7%,12.6 ± 4.9%, 12.1 ± 4.5%, 11.2 ± 5.2% and 10.8±4.1% in 40-59, 60-69, 70-79, 80-89, 90-99, 100-109, 110-119, and ≥120 bpm groups, respectively; P &amp;lt; 0.001)) and LV strain (-13.8 ± 3.9%, -14.5 ± 4.0%, -13.4 ± 3.4%, -13.4 ± 3.6%, -12.5 ± 3.6%, -11.9 ± 3.8%, -10.3 ± 3.8%, and -10.2 ± 3.8%, in 40-59, 60-69, 70-79, 80-89, 90-99, 100-109, 110-119, and ≥120 bpm groups, respectively; P &amp;lt; 0.001)(Figure). The lowest risk of composite endpoint was observed for patients whose heart rate between 60 to 69 bpm (Figure). Compared to the 60-69 heart rate group, faster heart rates were associated with increased risk of ischemic stroke (adjusted hazard ratios [aHR] 4.448 in the ≥120 bpm group), HF (aHR 1.909 in the ≥120 bpm group), mortality (aHRs 2.487, 2.810, 4.569, 4.760 in the 90-99, 100-109, 110-119, and ≥120 bpm groups, respectively), and composite endpoint (aHRs 2.034, 2.349, 3.492 in the 100-109, 110-119, and ≥120 bpm groups, respectively) (all P &amp;lt; 0.05). Conclusion In patients with AF, heart rate is closely linked to cardiac function and plays a pivotal role in long-term prognosis. Faster heart rates were associated with worse LA/LV functions and increased risk of clinical events. Favorable outcomes were found at heart rates below 100 bpm, with even better LA/LV function noted at heart rates below 80 bpm.

Echocardiographic predictors of cardiovascular outcome in heart failure with preserved ejection fraction

Abstract Background The optimal echocardiographic predictors of cardiovascular outcome in heart failure with presereved ejection fraction (HFpEF) are unknown. Purpose We aimed to identify independent echocardiographic predictors of cardiovascular outcome in patients with HFpEF. Methods Systematic literature search of three electronic databases was conducted from date of inception until November 2022. Hazard ratios (HRs) and their 95% confidence intervals (CIs) for echocardiographic variables from multivariate prediction models for the composite primary endpoint of cardiovascular death and heart failure (HF) hospitalization were pooled using a random effects meta-analysis. Specific subgroup analyses were conducted for studies that enrolled patients with acute versus chronic HF, and for those studies that included E/e’, pulmonary artery systolic pressure (PASP), renal function, natriuretic peptides and diuretic use in multivariate models. Results Forty-six studies totalling 20,056 patients with HFpEF were included. Three echocardiographic parameters emerged as independent predictors in all subgroup analyses: Decreased left ventricular (LV) global longitudinal strain (HR 1.24, 95% CI 1.10-1.39 per 5% decrease), decreased left atrial (LA) reservoir strain (HR 1.30, 95% CI 1.13-1.1.50 per 5% decrease) and lower tricuspid annular plane systolic excursion (TAPSE) to PASP ratio (HR 1.17, 95% CI 1.07-1.25) per 0.1 unit decrease). Other independent echocardiographic predictors of the primary endpoint were a higher E/e’, moderate to severe tricuspid regurgitation, LV mass index and LA ejection fraction, although these variables were less robust. Conclusion Impaired LV global longitudinal strain, lower LA reservoir strain and lower TAPSE/PASP ratio predict cardiovascular death and HF hospitalization in HFpEF and are independent of filling pressures, clinical characteristics and natriuretic peptides. These echocardiographic parameters reflect key functional changes in HFpEF, and should be incorporated in future prospective risk prediction models.

Prognostic prediction of cardiovascular adverse events in patients after percutaneous coronary intervention using machine learning

Abstract Introduction While prevention of major cardiovascular adverse events (MACE) is important in the management of patients after percutaneous coronary intervention (PCI), risk stratification of MACE remains a significant challenge with increasingly diverse and complex patient backgrounds. In response to that, this retrospective observational study aimed to explore whether machine learning (ML) methods can predict future MACE after PCI using a variety of features extracted from electronic medical records (EMRs). Methods In 3,016 patients with coronary artery disease who performed PCI, 3 machine learning (ML) algorithms (gentle boost, random forest, and neural network) and statistical model were retrospectively applied to predict the occurrence of MACE within two years after PCI (564 patients, 18.7%). MACE was defined as composite endpoint of cardiac death, myocardial infarction (MI), any revascularization, and congestive heart failure (CHF). Basic patient information (e.g., age, sex, coronary risk factors) and laboratory test results were used for the analysis. Feature importance was calculated to identify key factors for MACE. Hold-out method with an 8:2 split between training and test was used to calculate sensitivity, specificity, positive predictive value, negative predictive value, and F-value for each model. Results As shown in Figure 1, ML models showed excellent diagnostic accuracies in the prediction of MACE after PCI, demonstrating higher F-values compared with statistical model (logistic regression analysis). Similar results were seen in the subgroup analyses for estimating cardiac death, MI, revascularization, or CHF. Although the weighting of feature importance for MACE recurrence varied among ML models, infarct size (peak CK levels), increased inflammatory status, and traditional coronary risk factors were identified as important features for predicting MACE within two years after PCI (Figure 2). Conclusions It is suggested that ML using EMRs is promising for inferring future MACE within two years after PCI. Further studies are warranted to address whether ML-based risk stratification could lead to improved clinical decision-making after PCI.

Implementation of sodium-glucose co-transporter 2 inhibitors in patients with heart failure through a new digital strategy (EMAIL-HF): a randomised clinical trial study design

Abstract Introduction Delayed implementation of new medical discoveries remains a global healthcare challenge and is mainly due to the complexity of cross-institutional patient care. Sodium-glucose co-transporter-2 (SGLT-2) inhibitors is the latest medical discovery in heart failure (HF) and have recently been added to clinical guidelines as they have proven to reduce the risk of adverse cardiovascular outcomes in patients with HF across the ejection fraction spectrum. Whether a new digital strategy can optimise and accelerate the implementation of SGLT2 inhibitors in patients living with HF is of great importance for public health. Purpose To evaluate whether a new and streamlined digital strategy can optimise and accelerate the implementation of SGLT2 inhibitors in patients with HF. Design and methods: The trial is a multicentre, parallel group, register-based randomised clinical study, evaluating the effect and potential of a new digital strategy to implement new guideline therapies to patients living with a chronic disease, specifically SGLT2 inhibitors to patients with HF (figure 1). The setup employs data from nationwide health registers and official digital letters to inform patients about the new therapy option and invite them to have their eligibility evaluated by a HF specialist and start therapy. A total of ~10,000 patients with HF across the ejection fraction spectrum (with and without diabetes), who have not yet been started on SGLT2 inhibitors, are identified through Danish nationwide health registers, and randomised 1:1 to receive the digital letter (figure 2). The primary outcome is the proportion of patients redeeming a prescription of a SGLT2 inhibitor within six months. Secondary outcome is a composite HF endpoint consisting of all-cause death or HF hospitalisation. Other outcome measures are renal failure, stroke and myocardial infarction, safety outcomes, adherence to therapy and proportion of vulnerable patient groups initiating therapy including immigrants, elderly, frail patients, patients with lower socioeconomic level and lower educational level. A total of 4689 patients have been randomised (February 2024) and data will be presented in 2025. Conclusions The trial will determine the efficacy and safety of a new and streamlined digital strategy to implement SGLT2 inhibitors to patients with chronic HF. The setup has the potential to be used in a broad spectrum of patients living with chronic diseases and is expected to be highly cost-effective.Figure 1.Study hypothesisFigure 2.Study design

A systematic review and meta-analysis of frailty in patients with heart failure.

To systematically evaluate the effect of frailty on the prognosis of patients with heart failure. Computer searches were conducted on PubMed, Embase, The Cochrane Library, Web of Science, CNKI, Wanfang Data Knowledge Service platform, Weipu full-text database of Chinese scientific and technological journals, and Chinese biomedical literature database from August 12, 2022. After literature screening was completed by two researchers, the data extraction (such as study type, sample size, age of included patients, New York Heart Association (NYHA) Functional Classification, frailty assessment tool, frailty positive rate, outcome indicators, etc.) was performed and the risk of bias in the included studies was assessed. Meta-analysis was performed using Revman 5.4 and Stata 14.0 software. A total of 32 studies were included, including 406,269 patients with heart failure. All included studies were rated high overall quality. The results of meta-analysis showed: Frailty increases the risk of all-cause death in patients with heart failure (hazard ratio [HR] = 1.73, 95% confidence interval [CI]: 1.50 - 2.00, p < 0.001), unplanned readmission (HR = 1.96, 95% CI: 1.21 - 3.17, p = 0.006), and joint endpoint risk (HR = 1.66, 95% CI: 1.48 - 1.86, p < 0.001). Current evidence suggests that frailty increases the risk of all-cause death, unplanned readmission, and joint endpoints in patients with heart failure.

Glucagon-like peptide-1 receptor agonists improve outcomes in individuals with type 2 diabetes with and without heart failure

BackgroundThe effectiveness of glucagon-like peptide-1 receptor agonists (GLP1Ras) for prevention of heart failure (HF) in patients with type 2 diabetes (T2DM) without HF and for risk of death in patients with T2DM with HF has not been fully elucidated in routine clinical practice. MethodsUsing the real-world global electronic medical record TriNetX database, individuals with T2DM and with or without HF who initiated either GLP1Ras or sitagliptin from 2017 to 2020 were retrospectively analyzed. In individuals with T2DM without HF, the primary outcome was a composite of all-cause mortality and a new diagnosis of HF within three years. In individuals with T2DM with HF, the primary outcome was all-cause mortality within three years. Propensity-score (PS) matching was used to adjust for over 100 baseline characteristics. ResultsA total of 65,598 individuals with T2DM without HF starting a GLP1Ras were PS matched with 65,598 starting sitagliptin. GLP1Ras were associated with a lower incidence of the composite endpoint (10.5 % versus 11.8 %, hazard ratio [HR] 0.82, [0.80–0.85], p < 0.001), mortality (HR 0.66 [0.63–0.69]) and new diagnosis of HF (HR 0.92 [0.88–0.96]). There were 6002 individuals in each group matched for T2DM and HF. Mortality was lower in the GLP1Ras group (17.6 % versus 22.8 %, HR 0.70 [0.65–0.76], p < 0.001). Results were consistent across subgroups. ConclusionsIn this global real-world data analysis, GLP1Ra use was associated with a lower risk of death and HF in individuals with T2DM without HF, and lower risk of death in those with HF.

Abnormal left atrial strain and left atrial stiffness index are associated with adverse outcomes in children with cardiomyopathies: a pilot study

Conventional diastolic dysfunction parameters seem to be imperfect when applied to the pediatric cardiomyopathy population. The aim of this pilot study was to search for novel echocardiographic parameters associated with adverse outcomes in children with the most common cardiomyopathies. Fifty-six patients with pediatric cardiomyopathies (28 with dilated, 21 with hypertrophic, 7 with left ventricular non-compaction cardiomyopathy) and 28 healthy subjects were included in the study. Left atrial reservoir (LASr), conduit (LAScd) and contraction (LASct) strain, left atrial stiffness index (LASI), as well as conventional diastolic dysfunction parameters were measured using echocardiography. Adverse outcomes were defined as heart failure (including heart transplant) and arrhythmic endpoints. Patients with adverse outcomes presented with significantly lower LASr (16.68% ± 8.64% vs. 33.97% ± 9.99%, p-value < 0.001), lower LAScd (− 10.37% ± 5.83% vs. − 25.50% ± 9.24%, p-value < 0.001) and higher values of LASI (0.69 [IQR 0.34; 1.11] vs. 0.21 [IQR 0.16; 0.31], p-value < 0.001). LASr < 20%, LAScd ≥ − 12%, and LASI ≥ 0.26 were all associated with reduced survival. LASr, LAScd and LASI seem to be promising parameters in predicting adverse outcomes in the most common pediatric cardiomyopathies. Left atrial strain parameters and LASI are helpful in differentiating healthy control subjects from children with hypertrophic and dilated cardiomyopathies.

Therapeutic Effects of Heart Failure Medical Therapies on Standardized Kidney Outcomes: Comprehensive Individual Participant-Level Analysis of 6 Randomized Clinical Trials.

Background: Kidney outcomes have been variably defined using non-standardized composite endpoints in key heart failure (HF) trials, thus introducing complexity in their interpretation and cross-trial comparability. We examined the effects of steroidal mineralocorticoid receptor antagonists (MRAs), the angiotensin receptor-neprilysin inhibitor (ARNI) sacubitril/valsartan, and sodium-glucose cotransporter-2 (SGLT2) inhibitors on composite kidney endpoints using uniform definitions in 6 contemporary HF trials. Methods: Individual participant-level data from trials of steroidal MRAs (EMPHASIS-HF, TOPCAT Americas), ARNI (PARADIGM-HF, PARAGON-HF), and SGLT2 inhibitors (DAPA-HF, DELIVER) were included. The standardized composite kidney endpoint was defined as a sustained decline (a reduction in estimated glomerular filtration rate (eGFR) confirmed by a subsequent measurement at least 30 days later) in eGFR by 40%, 50%, or 57%, end-stage kidney disease, or renal death. eGFR was recalculated in a standardized manner using the 2009 Chronic Kidney Disease Epidemiology Collaboration creatinine equation. Results: Among 28,690 participants across the 6 trials (median age 69 years [IQR, 62-76]; 9,656 [33.7% ] women), the proportion experiencing the composite kidney endpoint with a more stringent definition of a sustained decline in kidney function (eGFR threshold of 57%) ranged from 0.3% to 3.3%. The proportion of patients experiencing this endpoint with a less stringent definition (eGFR threshold of 40%) ranged from 1.0% and 10.0%. The steroidal MRAs doubled the risk of the composite kidney endpoint when applying the least stringent definition compared with placebo, but these effects were less apparent and no longer significant with application of more stringent definitions. ARNI appeared to consistently reduce the occurrence of the composite kidney endpoints irrespective of specific eGFR threshold applied. The potential benefits of SGLT2-inhibitors on the composite kidney endpoints appeared more apparent when defined by more stringent eGFR thresholds, although none of these effects individually were statistically significant. Conclusions: When applying standardized stringent kidney endpoint definitions, steroidal MRAs, ARNI, and SGLT2-inhibitors have either neutral or beneficial effects on kidney outcomes in HF. Applying less stringent definitions increased event rates but included acute declines in eGFR that might not ultimately reflect long-term effects on kidney disease progression.

Accelerometer-measured physical activity in patients with heart failure and reduced ejection fraction: Determinants and relationship with patient-reported health status

Background: Accelerometer-measured physical activity is an increasingly used endpoint in heart failure (HF) trials. We investigated the determinants of accelerometer-measured physical activity and the relationship with patient-reported health status. Methods: Post-hoc analysis of the Empire HF trial, including outpatients with HF with reduced ejection fraction (HFrEF). Physical activity was quantified as average accelerometer counts per minute (CPM) with higher values representing higher activity. We investigated associations between activity level and clinical variables, including age, sex, and body mass index, as well as patient-reported health status assessed by Kansas City Cardiomyopathy Questionnaire (KCCQ). Results: Complete data were available in 180 (95%) patients (86% male, mean age 65 year). Baseline median physical activity level was 1318 CPM (Q1-Q3 1111–1585). Age and anemia were independently associated with activity level (β-coefficients: -10 CPM per year age increase [95% CI -16 to -5.1], p=0.00015, and -126 CPM for anemia [95% CI -9.1 to -244], p=0.035). Significant independent associations were observed between activity level and all KCCQ summary scores (β-coefficient point estimates of 3.7, 4.6, and 4.9 CPM, all p<0.02). For 12-week changes in KCCQ-summary scores, only the KCCQ-CSS was associated with activity level; mean increase of 17.5 CPM [95% CI 1.5 to 34.0], p=0.032, per 5-point increase in KCCQ-CSS. Associations were not modified by treatment allocation (interaction p-values>0.05). Conclusions: In patients with HFrEF, older age and anemia were independently associated with lower activity. Moreover, physical activity only weakly increased with better health status, suggesting that changes in physical activity reflect improvements in patients’ health status to a limited degree. This highlights the need to better understand the endpoint with regards to all other health parameters to ease interpretation in future HF trials.

The value of phenylalanine in predicting atrial fibrillation risk in chronic heart failure.

Atrial fibrillation (AF) is a common complication of chronic heart failure (HF). Serum phenylalanine (Phe) levels are related to inflammation disorder. It is meaningful to study the circulating Phe with AF occurrence in HF. The cross-sectional study recruited 300 patients (78.0% male; mean age, 65 ± 13 years) with HF (left ventricular ejection fraction of ≤50%, containing 70 AF patients) and 100 normal controls. Serum Phe value was measured by liquid chromatography-tandem mass spectrometry. Logistic regression analysis was conducted to measure the association between Phe and AF risk in HF. The association between Phe and high-sensitivity C-reactive protein (hsCRP) was assessed by simple correlation analysis. In the prospective study, the 274 HF subjects (76.6% male; mean age, 65 ± 13 years) were followed up for a mean year (10.99 ± 3.00 months). Serum Phe levels increased across the control, the HF without AF, and the HF with AF groups (77.60 ± 8.67 umol/L vs. 95.24 ± 28.58 umol/L vs. 102.90 ± 30.43 umol/L, ANOVA P < 0.001). Serum Phe value was the independent risk factor for predicting AF in HF [odds ratio (OR), 1.640; 95% CI: 1.150-2.339; P = 0.006]. Phe levels were correlated positively with hsCRP value in HF patients with AF (r = 0.577, P < 0.001). The elevated Phe levels were associated with a higher risk of HF endpoint events in HF patients with AF (log-rank P = 0.005). In HF with AF subjects, elevated Phe value confers an increased risk for prediction AF and was more related to poor HF endpoint events. Phe can be a valuable index of AF in HF.

Diagnosing Myocardial Injury in an Acute Chest Pain Cohort; Long-Term Prognostic Implications of Cardiac Troponin T and I.

There are limited data regarding the utility of follow-up cardiac troponin (cTn) measurements after admission for acute chest pain and how long-term stability of myocardial injury and prognostic value differ when using cardiac troponin T (cTnT) or I (cTnI). We measured high-sensitivity (hs)-cTnT (Roche Diagnostics) and hs-cTnI (Siemens Healthineers) during hospitalization for acute chest pain and after 3 months. Acute myocardial injury was defined as concentrations > sex-specific upper reference limit (URL) during hospitalization and ≤URL at 3-months. Chronic myocardial injury (CMI) was defined as concentrations > URL at both time points. Patients were followed from the 3-month sampling point for a median of 1586 (IQR 1161-1786) days for a primary composite endpoint of all-cause mortality, myocardial infarction (MI), revascularization, and heart failure, and a secondary endpoint of all-cause mortality. Among 754 patients, 33.8% (hs-cTnT) and 19.2% (hs-cTnI) had myocardial injury during hospitalization. The rate of CMI was 5 times higher by hs-cTnT (20%) assay than hs-cTnI (4%), while acute myocardial injury was equally common; 14% (hs-cTnT) and 15% (hs-cTnI), respectively (6% and 5% when excluding index non-ST-elevation MI (NSTEMI). For hs-cTnT, peak index concentration, 3-month concentration and classification of CMI predicted the primary endpoint; hazard ratios (HRs) 1.38 (95% CI 1.20-1.58), 2.34 (1.70-3.20), and 2.31 (1.30-4.12), respectively. For hs-cTnI, peak index concentration predicted the primary endpoint; HR 1.14 (1.03-1.25). This association was nonsignificant after excluding index NSTEMI. Acute myocardial injury is equally frequent, whereas CMI is more prevalent using hs-cTnT assay than hs-cTnI. Measuring hs-cTnT 3 months after an acute chest pain episode could assist in further long-term risk assessment. ClinicalTrials.gov Registration Number: NCT02620202.

Heart Failure Events After Long-term Continuous Screening for Atrial Fibrillation: Results From the Randomized LOOP Study.

Mounting evidence indicates that even device-detected subclinical atrial fibrillation is associated with a higher risk of heart failure (HF). However, the potential impact of atrial fibrillation screening on HF remains unknown. The LOOP Study (Atrial Fibrillation detected by Continuous ECG Monitoring using Implantable Loop Recorder to prevent Stroke in High-risk Individuals) evaluated the effects of atrial fibrillation screening on stroke prevention using an implantable loop recorder (ILR) versus usual care in older individuals with additional stroke risk factors. In this secondary analysis, we explored the following HF end points: (1) HF event or cardiovascular death; (2) HF event; (3) event with HF with reduced ejection fraction (HFrEF); and (4) HFrEF event or cardiovascular death. Outcomes were assessed in a Cox model both as time-to-first events and as total (first and recurrent) events analyzed using the Andersen-and-Gill method. Of 6004 participants (mean age 74.7 and 52.7% men), 1501 were randomized to ILR screening and 4503 to the control group. In total, 77 (5.1%) in the ILR group versus 295 (6.6%) in the control group experienced the primary outcome of an HF event or cardiovascular death. Compared with usual care, ILR screening was associated with a nonsignificant reduction in the primary outcome for the time-to-first event analysis (hazard ratio, 0.78 [95% CI, 0.61-1.01]) and the total event analysis (hazard ratio, 0.77 [95% CI, 0.59-1.01]). Similar results were obtained for the HF event. A significant risk reduction in total events was observed in the ILR group for the composite of HFrEF event or cardiovascular death and for HFrEF event (hazard ratio, 0.74 [95% CI, 0.56-0.98] and 0.65 [95% CI, 0.44-0.97], respectively). In an older population with additional stroke risk factors, ILR screening for atrial fibrillation tended to be associated with a lower rate of total HF events and cardiovascular death, particularly those related to HFrEF. These findings should be considered hypothesis-generating and warrant further investigation. URL: https://www.clinicaltrials.gov; Unique identifier: NCT02036450.

Semaglutide and cardiovascular outcomes in patients with obesity and prevalent heart failure: a prespecified analysis of the SELECT trial

Semaglutide, a GLP-1 receptor agonist, reduces the risk of major adverse cardiovascular events (MACE) in people with overweight or obesity, but the effects of this drug on outcomes in patients with atherosclerotic cardiovascular disease and heart failure are unknown. We report a prespecified analysis of the effect of once-weekly subcutaneous semaglutide 2·4 mg on ischaemic and heart failure cardiovascular outcomes. We aimed to investigate if semaglutide was beneficial in patients with atherosclerotic cardiovascular disease with a history of heart failure compared with placebo; if there was a difference in outcome in patients designated as having heart failure with preserved ejection fraction compared with heart failure with reduced ejection fraction; and if the efficacy and safety of semaglutide in patients with heart failure was related to baseline characteristics or subtype of heart failure. The SELECT trial was a randomised, double-blind, multicentre, placebo-controlled, event-driven phase 3 trial in 41 countries. Adults aged 45 years and older, with a BMI of 27 kg/m2 or greater and established cardiovascular disease were eligible for the study. Patients were randomly assigned (1:1) with a block size of four using an interactive web response system in a double-blind manner to escalating doses of once-weekly subcutaneous semaglutide over 16 weeks to a target dose of 2·4 mg, or placebo. In a prespecified analysis, we examined the effect of semaglutide compared with placebo in patients with and without a history of heart failure at enrolment, subclassified as heart failure with preserved ejection fraction, heart failure with reduced ejection fraction, or unclassified heart failure. Endpoints comprised MACE (a composite of non-fatal myocardial infarction, non-fatal stroke, and cardiovascular death); a composite heart failure outcome (cardiovascular death or hospitalisation or urgent hospital visit for heart failure); cardiovascular death; and all-cause death. The study is registered with ClinicalTrials.gov, NCT03574597. Between Oct 31, 2018, and March 31, 2021, 17 604 patients with a mean age of 61·6 years (SD 8·9) and a mean BMI of 33·4 kg/m2 (5·0) were randomly assigned to receive semaglutide (8803 [50·0%] patients) or placebo (8801 [50·0%] patients). 4286 (24·3%) of 17 604 patients had a history of investigator-defined heart failure at enrolment: 2273 (53·0%) of 4286 patients had heart failure with preserved ejection fraction, 1347 (31·4%) had heart failure with reduced ejection fraction, and 666 (15·5%) had unclassified heart failure. Baseline characteristics were similar between patients with and without heart failure. Patients with heart failure had a higher incidence of clinical events. Semaglutide improved all outcome measures in patients with heart failure at random assignment compared with those without heart failure (hazard ratio [HR] 0·72, 95% CI 0·60-0·87 for MACE; 0·79, 0·64-0·98 for the heart failure composite endpoint; 0·76, 0·59-0·97 for cardiovascular death; and 0·81, 0·66-1·00 for all-cause death; all pinteraction>0·19). Treatment with semaglutide resulted in improved outcomes in both the heart failure with reduced ejection fraction (HR 0·65, 95% CI 0·49-0·87 for MACE; 0·79, 0·58-1·08 for the composite heart failure endpoint) and heart failure with preserved ejection fraction groups (0·69, 0·51-0·91 for MACE; 0·75, 0·52-1·07 for the composite heart failure endpoint), although patients with heart failure with reduced ejection fraction had higher absolute event rates than those with heart failure with preserved ejection fraction. For MACE and the heart failure composite, there were no significant differences in benefits across baseline age, sex, BMI, New York Heart Association status, and diuretic use. Serious adverse events were less frequent with semaglutide versus placebo, regardless of heart failure subtype. In patients with atherosclerotic cardiovascular diease and overweight or obesity, treatment with semaglutide 2·4 mg reduced MACE and composite heart failure endpoints compared with placebo in those with and without clinical heart failure, regardless of heart failure subtype. Our findings could facilitate prescribing and result in improved clinical outcomes for this patient group. Novo Nordisk.

Diabetes and Heart Failure: A Literature Review, Reflection and Outlook.

Heart failure (HF) is a complex clinical syndrome caused by structural or functional dysfunction of the ventricular filling or blood supply. Diabetes mellitus (DM) is an independent predictor of mortality for HF. The increase in prevalence, co-morbidity and hospitalization rates of both DM and HF has further fueled the possibility of overlapping disease pathology between the two. For decades, antidiabetic drugs that are known to definitively increase the risk of HF are the thiazolidinediones (TZDs) and saxagliptin in the dipeptidyl peptidase-4 (DPP-4) inhibitor, and insulin, which causes sodium and water retention, and whether metformin is effective or safe for HF is not clear. Notably, sodium-glucose transporter 2 (SGLT2) inhibitors and partial glucagon-like peptide-1 receptor agonists (GLP-1 RA) all achieved positive results for HF endpoints, with SGLT2 inhibitors in particular significantly reducing the composite endpoint of cardiovascular mortality and hospitalization for heart failure (HHF). Further understanding of the mutual pathophysiological mechanisms between HF and DM may facilitate the detection of novel therapeutic targets to improve the clinical outcome. This review focuses on the association between HF and DM, emphasizing the efficacy and safety of antidiabetic drugs and HF treatment. In addition, recent therapeutic advances in HF and the important mechanisms by which SGLT2 inhibitors/mineralocorticoid receptor antagonist (MRA)/vericiguat contribute to the benefits of HF are summarized.

Left Ventricular Remodeling in Patients with Low Flow Aortic Stenosis Undergoing Transcatheter Aortic Valve Replacement

Low-flow (LF) aortic stenosis (AS) is common among the elderly and associated with worse outcomes than AS with normal stroke volume. It is unknown whether left ventricular (LV) remodeling identifies patients with LF AS at higher risk of complications.LV remodeling was evaluated in 463 patients with severe LF AS referred for transcatheter aortic valve replacement (TAVR) and classified as adaptive (normal geometry and concentric remodeling) or maladaptive (concentric and eccentric hypertrophy) using American Society of Echocardiography sex-specific criteria. Of these, the 390 who underwent TAVR were followed for the endpoints of heart failure (HF) hospitalization and all-cause mortality.The mean patients age was 79 (74.5-84) years. LV remodeling was adaptive in 57.4% (62 normal geometry, 162 concentric remodeling) and maladaptive in 42.6% (127 concentric hypertrophy, 39 eccentric hypertrophy). During a median follow-up of 3 years, 45 patients (11.5%) were hospitalized for HF and 73 (18.7%) died. After adjustment for widely used echocardiographic parameters, maladaptive remodeling was independently associated with HF hospitalization and death (adjusted HR 1.75, CI 1.03-3.00). There was no significant difference between men and women in the association of maladaptive LV remodeling with the composite outcome (p=0.40 for men and p=0.06 for women).In conclusion, in patients with LF AS, maladaptive LV remodeling prior to TAVR is independently associated with higher incidences of post-procedural HF rehospitalization and death in both men and women. Assessment of LV remodeling has prognostic value over and above LVEF and may improve risk stratification for patients with LF AS.