Resuscitated cardiac arrest is associated with high mortality; however, the ability to estimate risk of adverse outcomes using existing illness severity scores is limited. Using in-hospital data ...available within the first 24 hours of admission, we aimed to develop more accurate models of risk prediction using both logistic regression (LR) and machine learning (ML) techniques, with a combination of demographic, physiologic, and biochemical information.
Patient-level data were extracted from the Australian and New Zealand Intensive Care Society (ANZICS) Adult Patient Database for patients who had experienced a cardiac arrest within 24 hours prior to admission to an intensive care unit (ICU) during the period January 2006 to December 2016. The primary outcome was in-hospital mortality. The models were trained and tested on a dataset (split 90:10) including age, lowest and highest physiologic variables during the first 24 hours, and key past medical history. LR and 5 ML approaches (gradient boosting machine GBM, support vector classifier SVC, random forest RF, artificial neural network ANN, and an ensemble) were compared to the APACHE III and Australian and New Zealand Risk of Death (ANZROD) predictions. In all, 39,566 patients from 186 ICUs were analysed. Mean (±SD) age was 61 ± 17 years; 65% were male. Overall in-hospital mortality was 45.5%. Models were evaluated in the test set. The APACHE III and ANZROD scores demonstrated good discrimination (area under the receiver operating characteristic curve AUROC = 0.80 95% CI 0.79-0.82 and 0.81 95% CI 0.8-0.82, respectively) and modest calibration (Brier score 0.19 for both), which was slightly improved by LR (AUROC = 0.82 95% CI 0.81-0.83, DeLong test, p < 0.001). Discrimination was significantly improved using ML models (ensemble and GBM AUROCs = 0.87 95% CI 0.86-0.88, DeLong test, p < 0.001), with an improvement in performance (Brier score reduction of 22%). Explainability models were created to assist in identifying the physiologic features that most contributed to an individual patient's survival. Key limitations include the absence of pre-hospital data and absence of external validation.
ML approaches significantly enhance predictive discrimination for mortality following cardiac arrest compared to existing illness severity scores and LR, without the use of pre-hospital data. The discriminative ability of these ML models requires validation in external cohorts to establish generalisability.
Abstract Purpose The purpose of this article was to review the clinical management of patients with heart failure with preserved ejection fraction (HFPEF). Methods For this critical review, ...electronic databases (MEDLINE, EMBASE, PubMed) were searched for relevant basic research studies and randomized clinical trials recently published or presented at major meetings. Details of in-progress or planned studies were obtained from the ClinicalTrials.gov website. The range of publication dates was the year 2000 to 2015. Search terms included HFPEF, heart failure with preserved ejection fraction, HFPSF, heart failure with preserved systolic function, diastolic heart failure, diastolic dysfunction, HFNEF, heart failure with normal ejection fraction, treatment, management, therapy. Findings Patients with HFPEF account for up to half of all patients with a clinical diagnosis of HF. Key contributing factors include hypertension, obesity, and atrial fibrillation, and other chronic diseases, including diabetes, chronic obstructive pulmonary disease, and anemia, frequently coexist. To date, large-scale clinical trials, particularly those focused on antagonism of the renin-angiotensin-aldosterone system, have provided limited evidence of clinical benefit. Implications The aggressive management of contributing factors, including hypertension, atrial fibrillation, and myocardial ischemia, is key in the management of HFPEF. New insights into the mechanisms and thus the identification of potential therapeutic strategies are urgently required.
Aims
The impact of atrial fibrillation (AF) ablation in early heart failure with preserved ejection fraction (HFpEF) is unknown. Our aim was to determine the impact of AF ablation on symptoms and ...exercise haemodynamic parameters of early HFpEF.
Methods and results
Symptomatic AF patients referred for index AF ablation with ejection fraction ≥50% underwent baseline quality of life questionnaires, echocardiography, cardiac magnetic resonance imaging, exercise right heart catheterisation (exRHC), and brain natriuretic peptide (BNP) testing. HFpEF was defined by resting pulmonary capillary wedge pressure (PCWP) ≥15 mmHg or peak exercise PCWP ≥25 mmHg. Patients with HFpEF were offered AF ablation and follow‐up exRHC ≥6 months post‐ablation. Of 54 patients undergoing baseline evaluation, 35 (65%) had HFpEF identified by exRHC. HFpEF patients were older (64 ± 10 vs. 54 ± 13 years, P < 0.01), and more frequently female (54% vs. 16%, P < 0.01), hypertensive (63% vs. 16%, P < 0.001), and suffering persistent AF (66% vs. 11%, P < 0.001), compared to those without HFpEF. Twenty HFpEF patients underwent AF ablation and follow‐up exRHC 12 ± 6 months post‐ablation. Nine (45%) patients no longer fulfilled exRHC criteria for HFpEF at follow‐up. Patients remaining arrhythmia free (n = 9, 45%) showed significant improvements in peak exercise PCWP (29 ± 4 to 23 ± 2 mmHg, P < 0.01) and Minnesota Living with Heart Failure (MLHF) score (55 ± 30 to 22 ± 30, P < 0.01) while the remainder did not (PCWP 31 ± 5 to 30.0 ± 4 mmHg, P = NS; MLHF score 55 ± 23 to 25 ± 20, P = NS).
Conclusion
Heart failure with preserved ejection fraction frequently coexists in patients with symptomatic AF and preserved ejection fraction. Restoration and maintenance of sinus rhythm in patients with comorbid AF and HFpEF improves haemodynamic parameters, BNP and symptoms associated with HFpEF.
Overview of the study illustrating the proportion of patients referred for consideration of atrial fibrillation (AF) ablation who met the criteria for heart failure with preserved ejection fraction (HFpEF) in panel A. Three‐dimensional reconstruction of the left atrium with radiofrequency lesions used to achieved pulmonary vein electrical isolation at the time of AF ablation in panel B and results of the follow‐up exercise right heart catheterisation at ≥6 months following AF ablation based on arrhythmia recurrence status in panel C. Panel D illustrates the potential interaction between AF and HFpEF. BNP, brain natriuretic peptide; LA, left atrial; LAPW, left atrial posterior wall; LIPV, left inferior pulmonary vein; LSPV, left superior pulmonary vein; PCWP, pulmonary capillary wedge pressure; QoL, quality of life; RIPV, right inferior pulmonary vein; RSPV, right superior pulmonary vein.
Background Risk factors for heart failure with preserved ejection fraction (HFpEF) include hypertension, age, sex, and obesity. Emerging evidence suggests that the gut microbiota independently ...contributes to each one of these risk factors, potentially mediated via gut microbial‐derived metabolites such as short‐chain fatty acids. In this study, we determined whether the gut microbiota were associated with HFpEF and its risk factors. Methods and Results We recruited 26 patients with HFpEF and 67 control participants from 2 independent communities. Patients with HFpEF were diagnosed by exercise right heart catheterization. We assessed the gut microbiome by bacterial 16S rRNA sequencing and food intake by the food frequency questionnaire. There was a significant difference in α‐diversity (eg, number of microbes) and β‐diversity (eg, type and abundance of microbes) between both cohorts of controls and patients with HFpEF ( P =0.001). We did not find an association between β‐diversity and specific demographic or hemodynamic parameters or risk factors for HFpEF. The Firmicutes to Bacteroidetes ratio, a commonly used marker of gut dysbiosis, was lower, but not significantly so ( P =0.093), in the patients with HFpEF. Compared with controls, the gut microbiome of patients with HFpEF was depleted of bacteria that are short‐chain fatty acid producers. Consistent with this, participants with HFpEF consumed less dietary fiber (17.6±7.7 versus 23.2±8.8 g/day; P =0.016). Conclusions We demonstrate key changes in the gut microbiota in patients with HFpEF, including the depletion of bacteria that generate metabolites known to be important for cardiovascular homeostasis. Further studies are required to validate the role of these gut microbiota and metabolites in the pathophysiology of HFpEF.
Background Heart failure with preserved ejection fraction (HFpEF) is an increasingly prevalent form of heart failure, representing half of the total burden of heart failure. We hypothesised that ...modulation of the phosphodiesterase type 3/cyclic AMP using a novel oral formulation of milrinone might exert favorable effects HFpEF via pulmonary and systemic vasodilation and enhancement of ventricular relaxation. We assessed the safety and efficacy of oral milrinone on quality of life and functional outcomes in patients with HFpEF. Methods and Results The MilHFPEF (Extended Release Oral Milrinone for the Treatment of Heart Failure With Preserved Ejection Fraction) study was a randomized, double-blind, placebo-controlled pilot study in 23 patients with symptomatic HFpEF. Efficacy end points included changes from baseline in Kansas City Cardiomyopathy Questionnaire summary score and 6-minute walk distance. The primary safety end point was the development of clinically significant arrhythmia. The Kansas City Cardiomyopathy Questionnaire score improved significantly in milrinone-treated patients compared with placebo (+10±13 versus -3±15;
=0.046). Six-minute walk distance also tended to improve in the treatment group compared with placebo (+22 -8 to 49 versus -47 -97 to 12;
=0.092). Heart rate (-1±5 versus -2±9 bpm;
=0.9) and systolic blood pressure (-3±18 versus +1±12 mm Hg;
=0.57) were unchanged. Early filling velocity/early mitral annular velocity (-0.3±3.0 versus -1.9±4.8;
=0.38) was unchanged. One patient in the placebo arm was hospitalized for heart failure. Holter monitoring did not demonstrate evidence of a proarrhythmic effect of milrinone. Conclusions In this novel pilot study, extended release oral milrinone was well tolerated and associated with improved quality of life in patients with HFpEF. Further longer-term studies are warranted to establish the role of this therapeutic approach in HFpEF. Registration URL: https://www.anzctr.org.au/; Unique identifier: ACTRN12616000619448.
Background Women have higher vascular stiffness with aging. The aim of this study was to characterize sex differences in vascular and ventricular structure and function, and to investigate the impact ...on the primary outcome in the TOPCAT trial (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist Trial). Methods and Results Data from the Americas cohort of the TOPCAT trial were analyzed. Patients with echocardiography (n=654) were compared according to sex, and achievement of the primary end point (a composite of death from cardiovascular causes and heart failure hospitalization) assessed. Echocardiography revealed higher arterial, systolic, and diastolic ventricular elastance and worse ventricular-vascular coupling in women. Women had better overall survival and heart failure hospitalization outcomes (hazard ratio 0.74, 95% CI 0.57-0.98, P=0.034), however, determinants of achievement of the primary outcome differed between the sexes. Pulse pressure was a key determinant of outcome in women (hazard ratio 1.04, 95% CI 1-1.09, P=0.034) whereas in men heart rate (hazard ratio 1.61, 95% CI 1.02-2.52 per 10 mm Hg increase, P=0.04) and B-type natriuretic peptide (hazard ratio 1.01, 95% CI 1-1.02 per 10 ng/mL increase P=0.02) were associated with poorer outcome. Conclusions Outcomes in patients with heart failure with preserved ejection fraction appear to be differentially influenced by key physiological factors that vary according to sex. In women, ventricular-vascular stiffening was the most significant determinant of outcome, whereas in men overall survival was influenced by heart rate and B-type natriuretic peptide; this highlights key sex differences in the pathophysiology and outcomes of heart failure with preserved ejection fraction and warrants further exploration. Clinical Trial Registration URL: https://clinicaltrials.gov . Unique identifier: NCT00094302.
Heart failure with preserved ejection fraction (HFpEF) accounts for approximately half of the current burden of HF, and the prevalence is continuing to rise. In contrast to HF with reduced ejection ...fraction (HFrEF) there are no clinically effective evidence based therapies for HFpEF. The principal pathophysiologic disorder is an elevation of left atrial pressure, most notable during physical activity, which results from impaired left ventricular diastolic reserve, and increased left atrial stiffness. This review outlines the clinical development of a potential device based therapy for HFpEF, the interatrial shunt device (IASD).
Patients with HFPEF (n = 20; age: 68 ± 2 years; left ventricular ejection fraction 64 ± 2%) underwent right heart catheterization and radial arterial cannulation for measurement of hemodynamics at ...rest and during peak symptom-limited exercise, as described previously (3). Pretreatment exercise hemodynamic responses (presented as delta values for pre-placebo vs. pre-milrinone) were generally not significantly different: heart rate (28 ± 5 vs. 30 ± 3 beats/min), mean arterial pressure (21 ± 4 vs. 22 ± 3 mm Hg), mean pulmonary artery pressure (17 ± 2 vs. 23 ± 2 mm Hg), cardiac index (1.8 ± 0.2 vs. 2.3 ± 0.2 l/min/m2), and stroke volume index (6 ± 1 vs. 4 ± 1 ml/m2).
Ten-year risk equations for incident heart failure (HF) are available for the general population, but not for patients with established atherosclerotic cardiovascular disease (ASCVD), which is highly ...prevalent in HF cohorts. This study aimed to develop and validate 10-year risk equations for incident HF in patients with known ASCVD.
Ten-year risk equations for incident HF were developed using the United Kingdom Biobank cohort (recruitment 2006-2010) including participants with established ASCVD but free from HF at baseline. Model performance was validated using the Australian Baker Heart and Diabetes Institute Biobank cohort (recruitment 2000-2011) and compared with the performance of general population risk models. Incident HF occurred in 13.7% of the development cohort (n=31 446, median 63 years, 35% women, follow-up 10.7±2.7 years) and in 21.3% of the validation cohort (n=1659, median age 65 years, 25% women, follow-up 9.4±3.7 years). Predictors of HF included in the sex-specific models were age, body mass index, systolic blood pressure (treated or untreated), glucose (treated or untreated), cholesterol, smoking status, QRS duration, kidney disease, myocardial infarction, and atrial fibrillation. ASCVD-HF equations had good discrimination and calibration in development and validation cohorts, with superior performance to general population risk equations.
ASCVD-specific 10-year risk equations for HF outperform general population risk models in individuals with established ASCVD. The ASCVD-HF equations can be calculated from readily available clinical data and could facilitate screening and preventative treatment decisions in this high-risk group.
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