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This article discusses the challenges in diagnosing heart failure with preserved ejection fraction (HFpEF) and the potential of artificial intelligence (AI) and natural language processing (NLP) to improve diagnosis. HFpEF is difficult to diagnose and often underdiagnosed, leading to missed opportunities for treatment and management. The study by Wu et al. applied NLP to a database of patients with a clinical diagnosis of heart failure and found a significant disparity in the diagnosis rates of HFpEF. NLP can aid clinicians in identifying high-risk patients and prompt further investigation for accurate diagnosis and personalized treatment. The incorporation of AI and NLP into HFpEF detection shows promise for enhancing diagnosis, monitoring disease progression, and tailoring treatment regimens. However, further research, validation, and ethical considerations are needed for the full integration of AI and NLP into clinical practice. [Extracted from the article]

Background Individuals with diabetes have a high frailty burden and increased risk of heart failure (HF). In this study, we evaluated the association of baseline and longitudinal changes in frailty with risk of HF and its subtypes: HF with preserved ejection fraction (HFpEF), and HF with reduced ejection fraction (HFrEF). Methods Participants (age: 45–76 years) of the Look AHEAD trial without prevalent HF were included. The frailty index (FI) was used to assess frailty burden using a 35-variable deficit model. The association between baseline and longitudinal changes (1- and 4-year follow-up) in FI with risk of overall HF, HFpEF (ejection fraction [EF] ≥ 50%), and HFrEF (EF < 50%) independent of other risk factors and cardiorespiratory fitness was assessed using adjusted Cox models. Results The study included 5 100 participants with type 2 diabetes mellitus, of which 257 developed HF. In adjusted analysis, higher frailty burden was significantly associated with a greater risk of overall HF. Among HF subtypes, higher baseline FI was significantly associated with risk of HFpEF (hazard ratio [HR] [95% CI] per 1- SD higher FI: 1.37 [1.15–1.63]) but not HFrEF (HR [95% CI]: 1.19 [0.96–1.46]) after adjustment for potential confounders, including traditional HF risk factors. Among participants with repeat measures of FI at 1- and 4-year follow-up, an increase in frailty burden was associated with a higher risk of HFpEF (HR [95% CI] per 1- SD increase in FI at 4 years: 1.78 [1.35–2.34]) but not HFrEF after adjustment for other confounders. Conclusions Among individuals with type 2 diabetes mellitus, higher baseline frailty and worsening frailty burden over time were independently associated with higher risk of HF, particularly HFpEF after adjustment for other confounders. [ABSTRACT FROM AUTHOR]

Heart failure with preserved ejection fraction (HFpEF) accounts for nearly half of all heart failure, but its etiology is poorly understood. Clonal hematopoiesis (CH) has been shown to promote atherosclerosis and heart failure with reduced ejection fraction, but whether and how CH may promote HFpEF is less well understood. We screened for CH in 109 HFpEF patients at UTSW and identified CH in 25% of patients, as compared with 19% of age/gender-matched controls. The most frequent mutation was in TET2 (63%), and notably 42% of patients with TET2-mutated CH harbored two TET2 mutations. In contrast, mutations in DNMT3A, classically the most frequent mutation in age-associated CH, were present at a much lower rate (30%). To test if TET2-mutated CH promotes HFpEF, we used a mouse model in which a high-fat diet and nitric oxide synthase inhibition by L-NAME recapitulate the clinical features of HFpEF (Nature 2019;568:351). We transplanted pIpC-treated bone marrow from Mx1-Cre;Tet2fl/fl mice or Cre-negative Tet2fl/fl control mice into wild-type mice, and six weeks later we induced HFpEF for 12 weeks. Consistent with our clinical observations, we discovered that recipients of Tet2-null hematopoietic cells exhibited significantly worse diastolic dysfunction. This effect was dependent on the NLRP3 inflammasome and was specific to loss of Tet2, while mice transplanted with Dnmt3a-null bone marrow did not manifest a worse HFpEF phenotype. Additionally, bulk and single-cell transcriptomic analyses revealed that HFpEF induction led to an expansion in the heart of Spp1+ macrophages, which exhibit both pro-inflammatory and pro-fibrotic features, which was exacerbated in the setting of CH. In sum, TET2-mutated CH is common in patients with HFpEF and drives disease pathogenesis in an allele-specific manner. These findings establish a rationale for targeting CH to treat or prevent HFpEF. [ABSTRACT FROM AUTHOR]

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Background: Supervised aerobic exercise training (ET) is recommended for stable outpatients with heart failure (HF) with reduced ejection fraction (HFrEF). Frailty, a syndrome characterized by increased vulnerability and decreased physiologic reserve, is common in patients with HFrEF and associated with a higher risk of adverse outcomes. The effect modification of baseline frailty on the efficacy of aerobic ET in HFrEF is not known.Methods: Stable outpatients with HFrEF randomized to aerobic ET versus usual care in the HF-ACTION (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training) trial were included. Baseline frailty was estimated using the Rockwood frailty index (FI), a deficit accumulation-based model of frailty assessment; participants with FI scores >0.21 were identified as frail. Multivariable Cox proportional hazard models with multiplicative interaction terms (frailty × treatment arm) were constructed to evaluate whether frailty modified the treatment effect of aerobic ET on the primary composite end point (all-cause hospitalization or mortality), secondary end points (composite of cardiovascular death or cardiovascular hospitalization, and cardiovascular death or HF hospitalization), and Kansas City Cardiomyopathy Questionnaire score. Separate models were constructed for continuous (FI) and categorical (frail versus not frail) measures of frailty.Results: Among 2130 study participants (age, 59±13 years; 28% women), 1266 (59%) were characterized as frail (FI>0.21). Baseline frailty burden significantly modified the treatment effect of aerobic ET (P interaction: FI × treatment arm=0.02; frail status [frail versus nonfrail] × treatment arm=0.04) with a lower risk of primary end point in frail (hazard ratio [HR], 0.83 [95% CI, 0.72-0.95]) but not nonfrail (HR, 1.04 [95% CI, 0.87-1.25]) participants. The favorable effect of aerobic ET among frail participants was driven by a significant reduction in the risk of all-cause hospitalization (HR, 0.84 [95% CI, 0.72-0.99]). The treatment effect of aerobic ET on all-cause mortality and other secondary endpoints was not different between frail and nonfrail patients (P interaction>0.1 for each). Aerobic ET was associated with a nominally greater improvement in Kansas City Cardiomyopathy Questionnaire scores at 3 months among frail versus nonfrail participants without a significant treatment interaction by frailty status (P interaction>0.2).Conclusions: Among patients with chronic stable HFrEF, baseline frailty modified the treatment effect of aerobic ET with a greater reduction in the risk of all-cause hospitalization but not mortality. [ABSTRACT FROM AUTHOR]

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Exercise intolerance (EI) is the primary manifestation of chronic heart failure with preserved ejection fraction (HFpEF), the most common form of heart failure among older individuals. The recent recognition that HFpEF is likely a systemic, multiorgan disorder that shares characteristics with other common, difficult-to-treat, aging-related disorders suggests that novel insights may be gained from combining knowledge and concepts from aging and cardiovascular disease disciplines. This state-of-the-art review is based on the outcomes of a National Institute of Aging-sponsored working group meeting on aging and EI in HFpEF. We discuss aging-related and extracardiac contributors to EI in HFpEF and provide the rationale for a transdisciplinary, "gero-centric" approach to advance our understanding of EI in HFpEF and identify promising new therapeutic targets. We also provide a framework for prioritizing future research, including developing a uniform, comprehensive approach to phenotypic characterization of HFpEF, elucidating key geroscience targets for treatment, and conducting proof-of-concept trials to modify these targets. [ABSTRACT FROM AUTHOR]

This editorial comments on the article "Frailty implications for exercise participation and outcomes in patients with heart failure" by Mudge et al. in the current issue. [ABSTRACT FROM AUTHOR]

This editorial comments on the article by Dasarathy et al. in this issue. [ABSTRACT FROM AUTHOR]

Initiating HF therapies traditionally involves starting 1 to 3 medications (angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, -blocker, mineralocorticoid receptor antagonist) at low doses, followed by methodical uptitration. Furthermore, observations from the SCD-HeFT trial (Sudden Cardiac Death in Heart Failure) demonstrated early improvements in left ventricular ejection fraction recorded within 3 to 7 months of treatment initiation in 67% of patients treated with -blockers and angiotensin-converting enzyme inhibitors/angiotensin receptor blockers. Keywords: evidence-based practice; heart failure; heart failure, systolic; practice guidelines as topic EN evidence-based practice heart failure heart failure, systolic practice guidelines as topic 276 278 3 07/25/22 20220726 NES 220726 Heart failure (HF) is the leading cause of hospitalization among older adults and a major cause of morbidity and mortality. [Extracted from the article]

Background: Studies examining gender-based differences in outcomes of patients experiencing out-of-hospital cardiac arrest have demonstrated that, despite a higher likelihood of return of spontaneous circulation, women do not have higher survival.Methods: Patients successfully resuscitated from out-of-hospital cardiac arrest enrolled in the CCC trial (Trial of Continuous or Interrupted Chest Compressions during CPR) were included. Hierarchical multivariable logistic regression models were constructed to evaluate the association between gender and survival after adjustment for age, gender, cardiac arrest rhythm, witnessed status, bystander cardiopulmonary resuscitation, episode location, epinephrine dose, emergency medical services response time, and duration of resuscitation. Do not resuscitate (DNR) and withdrawal of life-sustaining therapy (WLST) order status were used to assess whether differences in postresuscitation outcomes were modified by baseline prognosis. The analysis was replicated among ALPS trial (Amiodarone, Lidocaine, or Placebo in Out-of-Hospital Cardiac Arrest) participants.Results: Among 4875 successfully resuscitated patients, 1825 (37.4%) were women and 3050 (62.6%) were men. Women were older (67.5 versus 65.3 years), received less bystander cardiopulmonary resuscitation (49.1% versus 54.9%), and had a lower proportion of cardiac arrests that were witnessed (55.1% versus 64.5%) or had shockable rhythm (24.3% versus 44.6%, P<0.001 for all). A significantly higher proportion of women received DNR orders (35.7% versus 32.1%, P=0.009) and had WLST (32.8% versus 29.8%, P=0.03). Discharge survival was significantly lower in women (22.5% versus 36.3%, P<0.001; adjusted odds ratio, 0.78 [95% CI, 0.66-0.93]; P=0.005). The association between gender and survival to discharge was modified by DNR and WLST order status such that women had significantly reduced survival to discharge among patients who were not designated DNR (31.3% versus 49.9%, P=0.005; adjusted odds ratio, 0.74 [95% CI, 0.60-0.91]) or did not have WLST (32.3% versus 50.7%, P=0.002; adjusted odds ratio, 0.73 [95% CI, 0.60-0.89]). In contrast, no gender difference in survival was noted among patients receiving a DNR order (6.7% versus 7.4%, P=0.90) or had WLST (2.8% versus 2.4%, P=0.93). Consistent patterns of association between gender and postresuscitation outcomes were observed in the secondary cohort.Conclusions: Among patients resuscitated after experiencing out-of-hospital cardiac arrest, discharge survival was significantly lower in women than in men, especially among patients considered to have a favorable prognosis. [ABSTRACT FROM AUTHOR]

Background: Patients with heart failure (HF) have multiple coexisting comorbidities. The temporal trends in the burden of comorbidities and associated risk of mortality among patients with HF with preserved ejection fraction (HFpEF) and HF with reduced ejection fraction (HFrEF) are not well established.Methods: HF-related hospitalizations were sampled by stratified design from 4 US areas in 2005 to 2014 by the community surveillance component of the ARIC study (Atherosclerosis Risk in Communities). Acute decompensated HF was classified by standardized physician review and a previously validated algorithm. An ejection fraction <50% was considered HFrEF. A total of 15 comorbidities were abstracted from the medical record. Mortality outcomes were ascertained for up to 1-year postadmission by linking hospital records with death files.Results: A total of 5460 hospitalizations (24 937 weighted hospitalizations) classified as acute decompensated HF had available ejection fraction data (53% female, 68% white, 53% HFrEF, 47% HFpEF). The average number of comorbidities was higher for patients with HFpEF versus HFrEF, both for women (5.53 versus 4.94; P<0.0001) and men (5.20 versus 4.82; P<0.0001). There was a significant temporal increase in the overall burden of comorbidities, both for patients with HFpEF (women: 5.17 in 2005-2009 to 5.87 in 2010-2013; men: 4.94 in 2005-2009 and 5.45 in 2010-2013) and HFrEF (women: 4.78 in 2005-2009 to 5.14 in 2010-2013; men: 4.62 in 2005-2009 and 5.06 in 2010-2013; P-trend<0.0001 for all). Higher comorbidity burden was significantly associated with higher adjusted risk of 1-year mortality, with a stronger association noted for HFpEF (hazard ratio [HR] per 1 higher comorbidity, 1.19 [95% CI, 1.14-1.25] versus HFrEF (HR, 1.10 [95% CI, 1.05-1.14]; P for interaction by HF type=0.02). The associated mortality risk per 1 higher comorbidity also increased significantly over time for patients with HFpEF and HFrEF, as well (P for interaction with time=0.002 and 0.02, respectively) Conclusions: The burden of comorbidities among hospitalized patients with acute decompensated HFpEF and HFrEF has increased over time, as has its associated mortality risk. Higher burden of comorbidities is associated with higher risk of mortality, with a stronger association noted among patients with HFpEF versus HFrEF. [ABSTRACT FROM AUTHOR]

Background: The utility of 30-day risk-standardized readmission rate (RSRR) as a hospital performance metric has been a matter of debate. Home time is a patient-centered outcome measure that accounts for rehospitalization, mortality, and postdischarge care. We aim to characterize risk-adjusted 30-day home time in patients with acute myocardial infarction (AMI) as a hospital-level performance metric and to evaluate associations with 30-day RSRR, 30-day risk-standardized mortality rate (RSMR), and 1-year RSMR.Methods: The study included 984 612 patients with AMI hospitalization across 2379 hospitals between 2009 and 2015 derived from 100% Medicare claims data. Home time was defined as the number of days alive and spent outside of a hospital, skilled nursing facility, or intermediate-/long-term acute care facility 30 days after discharge. Correlations between hospital-level risk-adjusted 30-day home time and 30-day RSRR, 30-day RSMR, and 1-year RSMR were estimated with the Pearson correlation. Reclassification in hospital performance using 30-day home time versus 30-day RSRR and 30-day RSMR was also evaluated.Results: Median hospital-level risk-adjusted 30-day home time was 24.0 days (range, 15.3-29.0 days). Hospitals with higher home time were more commonly academic centers, had available cardiac surgery and rehabilitation services, and had higher AMI volume and percutaneous coronary intervention use during the AMI hospitalization. Of the mean 30-day home time days lost, 58% were to intermediate-/long-term care or skilled nursing facility stays (4.7 days), 30% to death (2.5 days), and 12% to readmission (1.0 days). Hospital-level risk-adjusted 30-day home time was inversely correlated with 30-day RSMR (r=-0.22, P<0.0001) and 30-day RSRR (r=-0.25, P<0.0001). Patients admitted to hospitals with higher risk-adjusted 30-day home time had lower 30-day readmission (quartile 1 versus 4, 21% versus 17%), 30-day mortality rate (5% versus 3%), and 1-year mortality rate (18% versus 12%). Furthermore, 30-day home time reclassified hospital performance status in ≈30% of hospitals versus 30-day RSRR and 30-day RSMR.Conclusions: Thirty-day home time for patients with AMI can be assessed as a hospital-level performance metric with the use of Medicare claims data. It varies across hospitals, is associated with postdischarge readmission and mortality outcomes, and meaningfully reclassifies hospital performance compared with the 30-day RSRR and 30-day RSMR metrics. [ABSTRACT FROM AUTHOR]

Background: Type 2 diabetes mellitus (T2DM) is associated with a higher risk for heart failure (HF). The impact of a lifestyle intervention and changes in cardiorespiratory fitness (CRF) and body mass index on risk for HF is not well established.Methods: Participants from the Look AHEAD trial (Action for Health in Diabetes) without prevalent HF were included. Time-to-event analyses were used to compare the risk of incident HF between the intensive lifestyle intervention and diabetes support and education groups. The associations of baseline measures of CRF estimated from a maximal treadmill test, body mass index, and longitudinal changes in these parameters with risk of HF were evaluated with multivariable adjusted Cox models.Results: Among the 5109 trial participants, there was no significant difference in the risk of incident HF (n=257) between the intensive lifestyle intervention and the diabetes support and education groups (hazard ratio, 0.96 [95% CI, 0.75-1.23]) over a median follow-up of 12.4 years. In the most adjusted Cox models, the risk of HF was 39% and 62% lower among moderate fit (tertile 2: hazard ratio, 0.61 [95% CI, 0.44-0.83]) and high fit (tertile 3: hazard ratio, 0.38 [95% CI, 0.24-0.59]) groups, respectively (referent group: low fit, tertile 1). Among HF subtypes, after adjustment for traditional cardiovascular risk factors and interval incidence of myocardial infarction, baseline CRF was not significantly associated with risk of incident HF with reduced ejection fraction. In contrast, the risk of incident HF with preserved ejection fraction was 40% lower in the moderate fit group and 77% lower in the high fit group. Baseline body mass index also was not associated with risk of incident HF, HF with preserved ejection fraction, or HF with reduced ejection fraction after adjustment for CRF and traditional cardiovascular risk factors. Among participants with repeat CRF assessments (n=3902), improvements in CRF and weight loss over a 4-year follow-up were significantly associated with lower risk of HF (hazard ratio per 10% increase in CRF, 0.90 [95% CI, 0.82-0.99]; per 10% decrease in body mass index, 0.80 [95% CI, 0.69-0.94]).Conclusions: Among participants with type 2 diabetes mellitus in the Look AHEAD trial, the intensive lifestyle intervention did not appear to modify the risk of HF. Higher baseline CRF and sustained improvements in CRF and weight loss were associated with lower risk of HF. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00017953. [ABSTRACT FROM AUTHOR]

Background: Risk for atherosclerotic cardiovascular disease was a novel consideration for antihypertensive medication initiation in the 2017 American College of Cardiology/American Heart Association Blood Pressure (BP) guideline. Whether biomarkers of chronic myocardial injury (high-sensitivity cardiac troponin T ≥6 ng/L] and stress (N-terminal pro-B-type natriuretic peptide [NT-proBNP] ≥100 pg/mL) can inform cardiovascular (CV) risk stratification and treatment decisions among adults with elevated BP and hypertension is unclear.Methods: Participant-level data from 3 cohort studies (Atherosclerosis Risk in Communities Study, Dallas Heart Study, and Multiethnic Study of Atherosclerosis) were pooled, excluding individuals with prevalent CV disease and those taking antihypertensive medication at baseline. Participants were analyzed according to BP treatment group from the 2017 American College of Cardiology/American Heart Association BP guideline and those with high BP (120 to 159/<100 mm Hg) were further stratified by biomarker status. Cumulative incidence rates for CV event (atherosclerotic cardiovascular disease or heart failure), and the corresponding 10-year number needed to treat to prevent 1 event with intensive BP lowering (to target systolic BP <120 mm Hg), were estimated for BP and biomarker-based subgroups.Results: The study included 12 987 participants (mean age, 55 years; 55% women; 21.5% with elevated high-sensitivity cardiac troponin T; 17.7% with elevated NT-proBNP) with 825 incident CV events over 10-year follow-up. Participants with elevated BP or hypertension not recommended for antihypertensive medication with versus without either elevated high-sensitivity cardiac troponin T or NT-proBNP had a 10-year CV incidence rate of 11.0% and 4.6%, with a 10-year number needed to treat to prevent 1 event for intensive BP lowering of 36 and 85, respectively. Among participants with stage 1 or stage 2 hypertension recommended for antihypertensive medication with BP <160/100 mm Hg, those with versus without an elevated biomarker had a 10-year CV incidence rate of 15.1% and 7.9%, with a 10-year number needed to treat to prevent 1 event of 26 and 49, respectively.Conclusions: Elevations in high-sensitivity cardiac troponin T or NT-proBNP identify individuals with elevated BP or hypertension not currently recommended for antihypertensive medication who are at high risk for CV events. The presence of nonelevated biomarkers, even in the setting of stage 1 or stage 2 hypertension, was associated with lower risk. Incorporation of biomarkers into risk assessment algorithms may lead to more appropriate matching of intensive BP control with patient risk. [ABSTRACT FROM AUTHOR]

Aims Methods Conclusions Compared with those without obesity, patients with obesity‐related heart failure with preserved ejection fraction (HFpEF) have worse symptoms, haemodynamics, and outcomes. Current weight loss strategies (diet, drug, and surgical) work through decreased energy intake rather than increased expenditure and cause significant loss of skeletal muscle mass in addition to adipose tissue. This may have adverse implications for patients with HFpEF, who already have reduced skeletal muscle mass and function and high rates of physical frailty. Mitochondrial uncoupling agents may have unique beneficial effects by producing weight loss via increased catabolism rather than reduced caloric intake, thereby causing loss of adipose tissue while sparing skeletal muscle. HU6 is a controlled metabolic accelerator that is metabolized to the mitochondrial uncoupling agent 2,4‐dinotrophenol. HU6 selectively increases carbon oxidation from fat and glucose while also decreasing toxic reactive oxygen species (ROS) production. In addition to sparing skeletal muscle loss, HU6 may have other benefits relevant to obesity‐related HFpEF, including reduced specific tissue depots contributing to HFpEF; improved glucose utilization; and reduction in systemic inflammation via both decreased ROS production from mitochondria and decreased cytokine elaboration from excess, dysfunctional adipose.We describe the rationale and design of HuMAIN‐HFpEF, a Phase 2a randomized, double‐blind, placebo‐controlled, dose‐titration, parallel‐group trial in patients with obesity‐related HFpEF to evaluate the effects of HU6 on weight loss, body composition, exercise capacity, cardiac structure and function, metabolism, and inflammation, and identify optimal dosage for future Phase 3 trials.HuMAIN will test a promising novel agent for obesity‐related HFpEF. [ABSTRACT FROM AUTHOR]

B This article refers to 'Baseline characteristics of patients in the PARALLAX trial: insights into quality of life and exercise capacity in heart failure with preserved ejection fraction' by S.J. Shah I et al i ., published in this issue on pages 1541-1551. b Heart failure with preserved ejection fraction (HFpEF) is growing in prevalence and associated with a high burden of morbidity, mortality, and poor quality of life.1,2 HFpEF is common in older adults and particularly among women, with more than 80% of new-onset heart failure among octogenarian women being due to HFpEF.3 Development of HFpEF involves a complex interplay of multiple pathophysiologic impairments, including adverse physiologic consequences of adiposity, increased comorbidity burden, accelerated decline in exercise capacity with aging, up-regulation of inflammatory pathways, and sarcopenia, that culminates in decreased aerobic physiologic reserve and symptoms of clinical heart failure.2,4-7 Patients with HFpEF have a similar high burden of functional impairment, frailty, and poor quality of life as patients with heart failure with reduced ejection fraction.7-9 Exercise intolerance, characterized by reduced exercise capacity and symptoms of fatigue and dyspnoea with usual daily activities, is one the most common manifestations of HFpEF. Patients with HFpEF have 30-40% lower exercise capacity than healthy age- and sex-matched controls and often perform activities of daily living using near maximal aerobic effort.10-12 Exercise intolerance is associated with higher risk of hospitalization, death, and poor quality of life in HFpEF.12,13 Thus, exercise intolerance and low aerobic capacity are meaningful endpoints that should be targeted for developing effective therapies to improve this patient-centred outcome. Improving exercise tolerance and quality of life in heart failure with preserved ejection fraction - time to think outside the heart. [Extracted from the article]

Objective: Lifestyle intervention remains the cornerstone of management of type 2 diabetes mellitus (T2DM). However, adherence to physical activity (PA) recommendations and the impact of that adherence on cardiorespiratory fitness in this population have been poorly described. We sought to investigate adherence to PA recommendations and its association with cardiorespiratory fitness in a population of patients with T2DM.Research Design and Methods: A cross-sectional analysis of baseline data from a randomized clinical trial (NCT00424762) was performed. A total of 150 individuals with medically treated T2DM and atherosclerotic cardiovascular disease (ASCVD) or risk factors for ASCVD were recruited from outpatient clinics at a single academic medical center. All individuals underwent a graded maximal exercise treadmill test to exhaustion with breath-by-breath gas exchange analysis to determine VO2peak. PA was estimated using a structured 7-Day Physical Activity Recall interview.Results: Participants had a mean ± SD age of 54.9 ± 9.0 years; 41% were women, 40% were black, and 21% were Hispanic. The mean HbA1c was 7.7 ± 1.8% and the mean BMI, 34.5 ± 7.2 kg/m2. A total of 72% had hypertension, 73% had hyperlipidemia, and 35% had prevalent ASCVD. The mean ± SD reported daily PA was 34.3 ± 4 kcal/kg, only 7% above a sedentary state; 47% of the cohort failed to achieve the minimum recommended PA. Mean ± SD VO2peak was 27.4 ± 6.5 mL/kg fat-free mass/min (18.8 ± 5.0 mL/kg/min).Conclusions: On average, patients with T2DM who have or are at risk for ASCVD report low levels of PA and have low measured cardiopulmonary fitness. This underscores the importance of continued efforts to close this therapeutic gap. [ABSTRACT FROM AUTHOR]

The author comments on the results of the OptimEx-Clin study, published in the issue, which examined the role of exercise training in patients with heart failure with preserved ejection fraction. Topics covered include the lessons provided by the clinical trial, the factors attributed to the lack of greater efficacy of high-intensity interval training versus moderate continuous training and the approaches that could be considered to improve long-term adherence to exercise training.

Source Citation: Gupta K, Spertus JA, Birmingham M, et al. Racial differences in quality of life in patients with heart failure treated with sodium–glucose cotransporter 2 inhibitors: a patient-level meta-analysis of the CHIEF-HF, DEFINE-HF, and PRESERVED-HF trials. Circulation. 2023;148:220-228. 37191040 Clinical Impact Ratings: GIM/FP/GP: Cardiology: [ABSTRACT FROM AUTHOR]

Background: Lifetime risk of heart failure has been estimated to range from 20% to 46% in diverse sex and race groups. However, lifetime risk estimates for the 2 HF phenotypes, HF with preserved ejection fraction (HFpEF) and HF with reduced ejection fraction (HFrEF), are not known.Methods: Participant-level data from 2 large prospective cohort studies, the CHS (Cardiovascular Health Study) and MESA (Multiethnic Study of Atherosclerosis), were pooled, excluding individuals with prevalent HF at baseline. Remaining lifetime risk estimates for HFpEF (EF ≥45%) and HFrEF (EF <45%) were determined at different index ages with the use of a modified Kaplan-Meier method with mortality and the other HF subtype as competing risks.Results: We included 12 417 participants >45 years of age (22.2% blacks, 44.8% men) who were followed up for median duration of 11.6 years with 2178 overall incident HF events with 561 HFrEF events and 726 HFpEF events. At the index age of 45 years, the lifetime risk for any HF through 90 years of age was higher in men than women (27.4% versus 23.8%). Among HF subtypes, the lifetime risk for HFrEF was higher in men than women (10.6% versus 5.8%). In contrast, the lifetime risk for HFpEF was similar in men and women. In race-stratified analyses, lifetime risk for overall HF was higher in nonblacks than blacks (25.9% versus 22.4%). Among HF subtypes, the lifetime risk for HFpEF was higher in nonblacks than blacks (11.2% versus 7.7%), whereas that for HFrEF was similar across the 2 groups. Among participants with antecedent myocardial infarction before HF diagnosis, the remaining lifetime risks for HFpEF and HFrEF were up to 2.5-fold and 4-fold higher, respectively, compared with those without antecedent myocardial infarction.Conclusions: Lifetime risks for HFpEF and HFrEF vary by sex, race, and history of antecedent myocardial infarction. These insights into the distribution of HF risk and its subtypes could inform the development of targeted strategies to improve population-level HF prevention and control. [ABSTRACT FROM AUTHOR]

Both obesity and atrial fibrillation (AF) are increasing in epidemic proportions, and both increase the prevalence of cardiovascular disease events. Obesity has adverse effects on cardiovascular hemodynamics and cardiac structure and function, and increases the prevalence of AF, partly related to electroanatomic remodeling in obese patients. However, numerous studies, including in AF, have demonstrated an obesity paradox, where overweight and obese patients with these disorders have a better prognosis than do leaner patients with the same degree of severity of cardiovascular disease/AF. In this paper, the authors discuss special issues regarding AF in obesity, as well as the evidence that despite the presence of an obesity paradox, there are benefits of weight loss, physical activity/exercise training, and increases in cardiorespiratory fitness on the prognosis of obese patients with AF. [ABSTRACT FROM AUTHOR]

Objectives To systematically examine the relative magnitude and predictors of responses to exercise training in older adult with heart failure ( HF) with reduced ejection fraction ( HFr EF), and preserved EF ( HFp EF). Design Secondary analysis of a randomized controlled trial. Setting Outpatient cardiac rehabilitation program. Participants Individuals with HF (24 HFrEF, 24 HFpEF) who underwent supervised exercise training. Measurements The study included individual-level data from the exercise training arms of a randomized controlled trial that evaluated the effect of 16 weeks of supervised moderate-intensity endurance exercise training in older adults with chronic, stable HFp EF and HFr EF. Changes in peak oxygen uptake ( VO2peak) in response to supervised training in individuals with HFp EF were compared with that of individuals with HFr EF. The significant clinical predictors of changes in VO2peak with exercise training were assessed using univariate and multivariate regression models. Results Training-related improvement in VO2peak was higher in participants with HFp EF than in those with HFr EF (change: 18.7 ± 17.6% vs −0.3 ± 15.4%, P < .001). In univariate analysis, echocardiographic abnormalities in left ventricular structure and function and lower body mass index were associated with blunted response of VO2peak with exercise training. In multivariate regression analysis using stepwise selection, submaximal exercise systolic blood pressure, and resting early deceleration time were independent predictors of change in VO2peak. Conclusion The change in VO2peak in response to endurance exercise training in older adults with HF differs significantly according to HF subtype, with greater VO2peak improvement in HFp EF than HFr EF. These results suggest that the current Centers for Medicare and Medicaid Services policy excluding individuals with HFp EF from reimbursement from cardiac rehabilitation may need to be revisited. [ABSTRACT FROM AUTHOR]

Background: Lower leisure-time physical activity (LTPA) and higher body mass index (BMI) are independently associated with risk of heart failure (HF). However, it is unclear if this relationship is consistent for both heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF).Objectives: This study sought to quantify dose-response associations between LTPA, BMI, and the risk of different HF subtypes.Methods: Individual-level data from 3 cohort studies (WHI [Women's Health Initiative], MESA [Multi-Ethnic Study of Atherosclerosis], and CHS [Cardiovascular Health Study]) were pooled and participants were stratified into guideline-recommended categories of LTPA and BMI. Associations between LTPA, BMI, and risk of overall HF, HFpEF (ejection fraction ≥45%), and HFrEF (ejection fraction <45%) were assessed by using multivariable adjusted Cox models and restricted cubic splines.Results: The study included 51,451 participants with 3,180 HF events (1,252 HFpEF, 914 HFrEF, and 1,014 unclassified HF). In the adjusted analysis, there was a dose-dependent association between higher LTPA levels, lower BMI, and overall HF risk. Among HF subtypes, LTPA in any dose range was not associated with HFrEF risk. In contrast, lower levels of LTPA (<500 MET-min/week) were not associated with HFpEF risk, and dose-dependent associations with lower HFpEF risk were observed at higher levels. Compared with no LTPA, higher than twice the guideline-recommended minimum LTPA levels (>1,000 MET-min/week) were associated with an 19% lower risk of HFpEF (hazard ratio: 0.81; 95% confidence interval: 0.68 to 0.97). The dose-response relationship for BMI with HFpEF risk was also more consistent than with HFrEF risk, such that increasing BMI above the normal range (≥25 kg/m2) was associated with a greater increase in risk of HFpEF than HFrEF.Conclusions: Our study findings show strong, dose-dependent associations between LTPA levels, BMI, and risk of overall HF. Among HF subtypes, higher LTPA levels and lower BMI were more consistently associated with lower risk of HFpEF compared with HFrEF. [ABSTRACT FROM AUTHOR]

This article discusses the complexity of exercise intolerance in heart failure with preserved ejection fraction (HFpEF). Exercise intolerance is a common symptom of HFpEF and is associated with a poor quality of life and increased risk of adverse outcomes. The article highlights a study that characterizes the haemodynamic profiles of HFpEF patients and identifies four clinically defined phenogroups: cardiometabolic, left atrial myopathy, pulmonary vascular disease, and vascular stiffening. The study findings reveal distinct exercise haemodynamic impairments across these phenogroups and provide insights into the physiologic basis of disease progression. The article suggests that personalized treatment approaches based on these phenogroups may improve exercise capacity and quality of life for HFpEF patients. [Extracted from the article]

Background and Objectives: Epidemiologic data on hospitalizations for acute pericarditis are scarce. We sought to study the trends in these hospitalizations and outcomes in the USA over a 10-year period. Methods: We used the 2003- 2012 Nationwide Inpatient Sample database to identify admissions with a primary diagnosis of acute pericarditis. Outcomes included hospitalization rate, case fatality rate (CFR), length of stay (LOS), hospital charges, complications and diagnostic and therapeutic procedures. Results: We observed an estimated 135,710 hospitalizations for acute pericarditis among patients ≥ 16 years during the study period (mean age 53.5 ± 18.5 years; 40.5% women). The incidence of acute pericarditis hospitalizations was significantly higher for men than for women [incidence rate ratio (IRR) 1.56; 95% confidence interval (CI) 1.54-1.58; p < 0.001]; it decreased from 66 to 54 per million person-years (p < 0.001). CFR and LOS declined significantly during the study period (CFR: 2.2% in 2003 to 1.4% in 2012; LOS: 4.8 days in 2003 to 4.1 days in 2012; p < 0.001 for both). The average inflation-adjusted health-care charge increased from USD 31,242 to 38,947 (p < 0.001). Conclusion: The hospitalization rate, CFR and LOS associated with acute pericarditis have declined significantly in the US population. Average charges for acute pericarditis hospitalization have increased. [ABSTRACT FROM AUTHOR]

Background: Prior studies have reported an inverse association between physical activity (PA) and risk of heart failure (HF). However, a comprehensive assessment of the quantitative dose-response association between PA and HF risk has not been reported previously.Methods and Results: Prospective cohort studies with participants >18 years of age that reported association of baseline PA levels and incident HF were included. Categorical dose-response relationships between PA and HF risk were assessed with random-effects models. Generalized least-squares regression models were used to assess the quantitative relationship between PA (metabolic equivalent [MET]-min/wk) and HF risk across studies reporting quantitative PA estimates. Twelve prospective cohort studies with 20 203 HF events among 370 460 participants (53.5% women; median follow-up, 13 years) were included. The highest levels of PA were associated with significantly reduced risk of HF (pooled hazard ratio for highest versus lowest PA, 0.70; 95% confidence interval, 0.67-0.73). Compared with participants reporting no leisure-time PA, those who engaged in guideline-recommended minimum levels of PA (500 MET-min/wk; 2008 US federal guidelines) had modest reductions in HF risk (pooled hazard ratio, 0.90; 95% confidence interval, 0.87-0.92). In contrast, a substantial risk reduction was observed among individuals who engaged in PA at twice (hazard ratio for 1000 MET-min/wk, 0.81; 95% confidence interval, 0.77-0.86) and 4 times (hazard ratio for 2000 MET-min/wk, 0.65; 95% confidence interval, 0.58-0.73) the minimum guideline-recommended levels.Conclusions: There is an inverse dose-response relationship between PA and HF risk. Doses of PA in excess of the guideline-recommended minimum PA levels may be required for more substantial reductions in HF risk. [ABSTRACT FROM AUTHOR]

Until recently, therapies to mitigate atherosclerotic cardiovascular disease (ASCVD) risk have been limited to lifestyle interventions, blood pressure lowering medications, high intensity statin therapy, antiplatelet agents, and in select patients, coronary artery revascularization. Despite administration of these evidence-based therapies, substantial residual risk for cardiovascular events persists, particularly among individuals with known ASCVD. Moreover, the current guideline-based approach does not adequately account for patient-specific, causal pathways that lead to ASCVD progression and complications. In the past few years, multiple new pharmacological agents, targeting conceptually distinct pathophysiological targets, have been shown in large and well-conducted clinical trials to lower cardiovascular risk among patients with established ASCVD receiving guideline directed medical care. These evidenced-based therapies reduce event rates, and in some cases all-cause and cardiovascular mortality; these benefits confirm important new disease targets and challenge the adequacy of the current "standard of care" for secondary prevention. [ABSTRACT FROM AUTHOR]

Background Current guidelines recommend cardiac rehabilitation (CR) in medically stable outpatients with heart failure (HF); however, temporal trends and factors associated with CR referral among these patients in real-world practice are not entirely known. Objectives The purpose of this study was to assess proportional use, temporal trends, and factors associated with CR referral at discharge among patients admitted with decompensated HF. Methods Using data from a national Get With the Guidelines–Heart Failure registry, we assessed the temporal trends in CR referral among eligible patients with HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF) at discharge after HF hospitalization between 2005 and 2014. On multivariable analysis, we also assessed patient- and hospital-level characteristics that are associated with CR referral. Results Among 105,619 HF patients (48% with HFrEF, 52% with HFpEF), 10.4% (12.2% with HFrEF, 8.8% with HFpEF) received CR referral at discharge. A significant increase in CR referral rates was observed among both HFpEF and HFrEF patients over the study period (p trend <0.0001 for HFrEF, HFpEF, and overall). Compared with patients discharged without CR referral, patients referred for CR were younger, predominantly men, and more likely to receive evidence-based HF therapies at discharge. On multivariable analysis, younger age, fewer comorbid conditions, and in-hospital procedures such as coronary artery bypass grafting, percutaneous coronary intervention, and cardiac valve surgery were most strongly associated with CR referral. Conclusions Only one-tenth of eligible HF patients received CR referral at discharge after hospitalization for HF. The proportional use of CR referral is increasing over time among both HFrEF and HFpEF patients. Further strategies to improve physician and patient awareness in regard to the benefit of CR should be used to increase CR referral among patients with HF. [ABSTRACT FROM AUTHOR]

OBJECTIVE To evaluate the impact of exercise training (ET) on metabolic parameters among participants with type 2 diabetes mellitus (T2DM) who do not improve their cardiorespiratory fitness (CRF) with training. RESEARCH DESIGN AND METHODS We studied participants with T2DMparticipating in the Health Benefits of Aerobic and Resistance Training in Individuals With Type 2 Diabetes (HART-D) trial who were randomized to a control group or one of three supervised ET groups for 9 months. Fitness response to ET was defined as a change in measured peak absolute oxygen uptake (ΔVO2peak, in liters perminute) from baseline to follow-up. ET participants were classified based on ΔVO2peak into fitness responders (ΔVO2peak ≥5%) and nonresponders (ΔVO2peak <5%), and changes in metabolic pro les were compared across control, fitness responder, and fitness nonresponder groups. RESULTS A total of 202 participants (mean age 57.1 ± 7.9 years, 63% women) were included. Among the exercise groups (n = 161), there was substantial heterogeneity in ΔVO2peak; 57% had some improvement in CRF (ΔVO2peak >0), with only 36.6% having a ≥5% increase in VO2peak. Both fitness responders and nonresponders (respectively) had significant improvements in hemoglobin A1c and measures of adiposity (ΔHbA1c: -0.26% [95%CI - 0.5 to -0.01] and -0.26% [-0.45 to -0.08]; Δwaist circumference: -2.6 cm [-3.7 to -1.5] and -1.8 cm [-2.6 to -1.0]; Δbody fat: -1.07% [-1.5 to -0.62] and -0.75% [-1.09 to -0.41]). No significant differences were observed in the degree of change of these metabolic parameters between fitness responders and nonresponders. Control group participants had no significant changes in any of these metabolic parameters. CONCLUSIONS ET is associated with significant improvements in metabolic parameters irrespective of improvement in cardiorespiratory fitness. [ABSTRACT FROM AUTHOR]

The impact of preoperative stable angina pectoris on postoperative cardiovascular outcomes in patients with previous myocardial infarction (MI) who underwent major noncardiac surgery is not well studied. We studied patients with previous MI who underwent elective major noncardiac surgeries within the American College of Surgeons-National Surgical Quality Improvement Program (2005 to 2011). Primary outcome was occurrence of an adverse cardiac event (MI and/or cardiac arrest). Multivariable logistic regression models evaluated the impact of stable angina on outcomes. Of 1,568 patients (median age 70 years; 35% women) with previous MI who underwent major noncardiac surgery, 5.5% had postoperative MI and/or cardiac arrest. Patients with history of preoperative angina had significantly greater incidence of primary outcome compared to those without anginal symptoms (8.4% vs 5%, p = 0.035). In secondary outcomes, reintervention rates (22.5% vs 11%, p <0.001) and length of stay (median 6-days vs 5-days; p <0.001) were also higher in patients with preoperative angina. In multivariable analyses, preoperative angina was a significant predictor for postoperative MI (odds ratio 2.49 [1.20 to 5.58]) and reintervention (odds ratio 2.40 [1.44 to 3.82]). In conclusion, our study indicates that preoperative angina is an independent predictor for adverse outcomes in patients with previous MI who underwent major noncardiac surgery, and cautions against overreliance on predictive tools, for example, the Revised Cardiac Risk Index, in these patients, which does not treat stable angina and previous MI as independent risk factors during risk prognostication. [ABSTRACT FROM AUTHOR]

Background: Behçet's disease (BD) is a multisystem vasculitis of unknown etiology. We aimed to determine the prevalence and predictors of coronary artery disease (CAD) in patients with BD. Methods: All adult patients diagnosed with BD from the National Inpatient Sample database using the International Classification of Diseases 9th revision (ICD-9 code 136.1) during 2009-2010 were included in the analysis. We analyzed the demographics, traditional risk factors, prevalence, and predictors of CAD in patients with BD using ICD-9 codes. Results: The prevalence of BD among adults was 0.006% (n = 2,540) of all in-hospital admissions in the USA. The mean age was 43.9 years, with women (45 years) being older than men (40 years) (p < 0.001). Traditional risk factors prevalent in our study were hypertension (35%), hyperlipidemia (17.4%), diabetes mellitus (13.8%), smoking (13.1%), and obesity (7.2%). The prevalence of CAD was 12.1%. Hypertension (OR = 2.20, p = 0.03) and hyperlipidemia (OR = 2.34, p = 0.02) were found to be independent predictors of CAD in a multimodel regression analysis. Conclusion: In patients with BD, traditional risk factors associated with CAD were similar to what is expected in the overall population. However, the young age of patients with CAD in this population suggests an accelerated course of atherosclerosis in BD. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

B This article refers to 'Peripheral and pulmonary effects of inorganic nitrite during exercise in heart failure with preserved ejection fraction' by Y.N.V. Reddy I et al i ., published in this issue on pages 814-823. b The burden of heart failure with preserved ejection fraction (HFpEF) continues to grow, and it remains refractory to available pharmacotherapies.1 Exercise intolerance is one of the key clinical manifestations of HFpEF, particularly in older adults.2 Reduced peak exercise oxygen (O SB 2 sb ) uptake, an objective measure of exercise intolerance, is a significant predictor of morbidity, mortality, and poor quality of life among patients with HFpEF.3,4 Accordingly, improvement in exercise capacity has been the target of many recent therapies in patients with HFpEF.5-10 Exercise training and intentional weight loss are two such therapeutic approaches that have been shown to improve exercise capacity in patients with HFpEF.11,12 In contrast, therapies targeting neurohormonal and vasodilatory pathways have failed to improve exercise capacity and quality of life in patients with HFpEF consistently.5,8-10 This highlights the need to better identify and target potentially modifiable pathophysiologic impairments in the O SB 2 sb pathway to deliver atmospheric O SB 2 sb to the exercising muscles. Targeting the nitrate-nitrite-nitric oxide pathway in heart failure with preserved ejection fraction: too soon to say no to nitric oxide? To this end, the study by Reddy I et al i .15 provides important insights into how inorganic nitrites, one of the emerging therapies for HFpEF, may improve peak exercise capacity through its effects on skeletal muscle O SB 2 sb conductance. [Extracted from the article]

An introduction is presented in which the editor discusses the level of physical activity and its association with the risk of adverse clinical results in patients suffering from heart failure with preserved ejection fraction (HEpEF).

Heart failure with preserved ejection fraction (HFpEF) is common, recalcitrant to treatment, and associated with poor outcomes. Diastolic dysfunction (DD) is an independent predictor of HFpEF risk, associated clinical manifestations, and long-term outcomes. However, the usefulness of diastolic function assessment is limited by the heterogeneity in the existing definitions of DD. In this issue of the Journal, Rasmussen-Torvik et al. (Am J Epidemiol. 2017;185(12):1221-1227) have highlighted this problem by evaluating the prevalence and concordance of 4 established definitions of DD in the Coronary Artery Risk Development in Young Adults (CARDIA) cohort. The authors demonstrate significant variability in prevalence of DD and its association with established risk factors across the different definitions. These findings suggest that the current 1-dimensional approach to HFpEF risk prediction based on noninvasive measures of diastolic function may not be optimal. Perhaps the future of HFpEF risk assessment lies in a multimodality approach that combines the relevant echocardiographic measures of diastolic function with blood-based biomarkers (such as N-terminal prohormone of brain natriuretic peptide (NT-proBNP)) and a measure of functional status (such as exercise capacity). [ABSTRACT FROM AUTHOR]

Nanomedicines that preferentially deploy cytotoxic agents to tumors and molecular targeted therapeutics that inhibit specific aberrant oncogenic drivers are emerging as the new paradigm for the management of cancer. While combination therapies are a mainstay of cancer chemotherapy, few studies have addressed the combination of nanomedicines and molecular targeted therapeutics. Furthermore, limited knowledge exists on the impact of sequencing of such therapeutics and nanomedicines on the antitumor outcome. Here, we engineered a supramolecular cis-platinum nanoparticle, which induced apoptosis in breast cancer cells but also elicited prosurvival signaling via an EGF receptor/phosphoinositide 3-kinase (PI3K) pathway. A combination of mathematical modeling and in vitro and in vivo validation using a pharmacologic inhibitor of PI3K, PI828, demonstrate that administration of PI828 following treatment with the supramolecular cis-platinum nanoparticle results in enhanced antitumor efficacy in breast cancer as compared with when the sequence is reversed or when the two treatments are administered simultaneously. This study addresses, for the first time, the impact of drug sequencing in the case of a combination of a nanomedicine and a targeted therapeutic. Furthermore, our results indicate that a rational combination of cis-platinum nanoparticles and a PI3K-targeted therapeutic can emerge as a potential therapy for breast cancer. [ABSTRACT FROM AUTHOR]

The ability of embryonic stem cells to differentiate into endothelium and form functional blood vessels has been well established and can potentially be harnessed for therapeutic angiogenesis. However, after almost two decades of investigation in this field, limited knowledge exists for directing endothelial differentiation. A better understanding of the cellular mechanisms regulating vasculogenesis is required for the development of embryonic stem cell-based models and therapies. In this study, we elucidated the mechanistic role of insulin-like growth factors (IGF1 and 2) and IGF receptors (IGFR1 and 2) in endothelial differentiation using an embryonic stem cell embryoid body model. Both IGF1 or IGF2 predisposed embryonic stem to differentiate towards a mesodermal lineage, the endothelial precursor germ layer, as well as increased the generation of significantly more endothelial cells at later stages. Inhibition of IGFR1 signaling using neutralizing antibody or a pharmacological inhibitor, picropodophyllin, significantly reduced IGF-induced mesoderm and endothelial precursor cell formation. We confirmed that IGF-IGFR1 signaling stabilizes HIF1a and leads to up-regulation of VEGF during vasculogenesis in embryoid bodies. Understanding the mechanisms that are critical for vasculogenesis in various models will bring us one step closer to enabling cell based therapies for neovascularization. [ABSTRACT FROM AUTHOR]

Abstract: Although lactosylceramide (LacCer) plays a pivotal role in the biosynthesis of nearly all the major glycosphingolipids, its function in regulating cellular function has begun to emerge only recently. Our current opinion is that several physiologically critical molecules such as modified/oxidized LDL, growth factors, pro-inflammatory cytokines and fluid shear stress converge upon and activate lactosylceramide synthase to generate LacCer. In turn, LacCer activates an “oxygen-sensitive” signaling pathway involving superoxides, nitric oxide, p21 Ras GTP loading, kinase cascade, PI3kinase/Akt activation, nuclear factor up-regulation ultimately contributing to phenotypic changes such as cell proliferation, adhesion, migration and angiogenesis. Since dys-regulation of such phenotypic changes constitute a hallmark in several diseases of the cardiovascular system, proliferative disorders such as cancer, polycystic kidney disease and inflammatory diseases, LacCer synthase and LacCer provide novel targets for the development of therapeutics aimed at these health conditions. [Copyright &y& Elsevier]

Their findings illuminate the potential of these models to improve the early identification of patients at risk of developing HF, particularly stage B HF, which could lead to early intervention strategies and, ultimately, improved patient outcomes. B This article refers to 'Prediction models for heart failure in the community: A systematic review and meta-analysis' by R Nadarajah I et al i ., published in this issue on pages 1724-1738. b Heart failure (HF) is a complex clinical syndrome that represents a significant and growing public health concern worldwide.[1] With an aging population and increasing prevalence of risk factors such as hypertension, diabetes, and obesity, the incidence of HF is only expected to increase. [Extracted from the article]

Aims Methods and results Conclusion Abnormalities in specific echocardiographic parameters and cardiac biomarkers have been reported among individuals with diabetes. However, a comprehensive characterization of diabetic cardiomyopathy (DbCM), a subclinical stage of myocardial abnormalities that precede the development of clinical heart failure (HF), is lacking. In this study, we developed and validated a machine learning‐based clustering approach to identify the high‐risk DbCM phenotype based on echocardiographic and cardiac biomarker parameters.Among individuals with diabetes from the Atherosclerosis Risk in Communities (ARIC) cohort who were free of cardiovascular disease and other potential aetiologies of cardiomyopathy (training, n = 1199), unsupervised hierarchical clustering was performed using echocardiographic parameters and cardiac biomarkers of neurohormonal stress and chronic myocardial injury (total 25 variables). The high‐risk DbCM phenotype was identified based on the incidence of HF on follow‐up. A deep neural network (DeepNN) classifier was developed to predict DbCM in the ARIC training cohort and validated in an external community‐based cohort (Cardiovascular Health Study [CHS]; n = 802) and an electronic health record (EHR) cohort (n = 5071). Clustering identified three phenogroups in the derivation cohort. Phenogroup‐3 (n = 324, 27% of the cohort) had significantly higher 5‐year HF incidence than other phenogroups (12.1% vs. 4.6% [phenogroup 2] vs. 3.1% [phenogroup 1]) and was identified as the high‐risk DbCM phenotype. The key echocardiographic predictors of high‐risk DbCM phenotype were higher NT‐proBNP levels, increased left ventricular mass and left atrial size, and worse diastolic function. In the CHS and University of Texas (UT) Southwestern EHR validation cohorts, the DeepNN classifier identified 16% and 29% of participants with DbCM, respectively. Participants with (vs. without) high‐risk DbCM phenotype in the external validation cohorts had a significantly higher incidence of HF (hazard ratio [95% confidence interval] 1.61 [1.18–2.19] in CHS and 1.34 [1.08–1.65] in the UT Southwestern EHR cohort).Machine learning‐based techniques may identify 16% to 29% of individuals with diabetes as having a high‐risk DbCM phenotype who may benefit from more aggressive implementation of HF preventive strategies. [ABSTRACT FROM AUTHOR]