Heart failure with preserved ejection fraction management: a systematic review of clinical practice guidelines and recommendations.

Multiple guidelines exist for the diagnosis and management of heart failure with preserved ejection fraction (HFpEF). We systematically reviewed current guidelines and recommendations, developed by national and international medical organizations, on the management of HFpEF in adults to aid clinical decision-making. We searched MEDLINE and EMBASE on 28 February 2024 for publications over the last 10 years as well as websites of organizations relevant to guideline development. Of the ten guidelines and recommendations retrieved, seven showed considerable rigour of development and were subsequently retained for analysis. There was consensus on the definition of HFpEF and the diagnostic role of serum natriuretic peptides and resting transthoracic echocardiography. Discrepancies were identified in the thresholds of serum natriuretic peptides and transthoracic echocardiography parameters used to diagnose HFpEF. There was agreement on the general pharmacological and supportive management of acute and chronic HFpEF. However, differences exist in strategies to identify and address specific phenotypes. Contemporary guidelines for HFpEF management agree on measures to avoid its development and the consideration of cardiac transplantation in advanced disease. There were discrepancies in recommended frequency of surveillance for patients with HFpEF and sparse recommendations on screening for HFpEF in the general population, use of diagnostic scoring systems, and the role of newly emerging therapies.

Global Longitudinal Active Strain Energy Density (GLASED): A Powerful Prognostic Marker in a Community-Based Cohort.

BACKGROUND: Identifying the imaging method that best predicts all-cause mortality, cardiovascular adverse events and heart failure risk is crucial for tailoring optimal management. Potential prognostic markers include left ventricular myocardial mass, ejection fraction, myocardial strain, stroke work, contraction fraction, pressure-strain product and a new measurement called global longitudinal active strain density (GLASED). OBJECTIVES: This study sought to compare the utility of 23 potential left ventricular prognostic markers of structure and contractile function in a community-based cohort. METHODS: The impact of cardiovascular magnetic resonance image-derived markers extracted by machine learning algorithms was compared to the future risk of adverse events in a group of 44,957 UK Biobank participants. RESULTS: Most markers, including the left ventricular ejection fraction, have limited prognostic value. GLASED was significantly associated with all-cause mortality and major adverse cardiovascular events, with the largest hazard ratio, highest ranking and differentiated risk in all three tertiles (P ≤ 0.0003). CONCLUSIONS: GLASED predicted all-cause mortality and major cardiovascular adverse events better than conventional markers of risk and is recommended for assessing patient prognosis.

Sex-specific cardiac magnetic resonance pulmonary capillary wedge pressure.

Aims: Heart failure (HF) with preserved ejection fraction disproportionately affects women. There are no validated sex-specific tools for HF diagnosis despite widely reported differences in cardiac structure. This study investigates whether sex, as assigned at birth, influences cardiac magnetic resonance (CMR) assessment of left ventricular filling pressure (LVFP), a hallmark of HF agnostic to ejection fraction. Methods and results: A derivation cohort of patients with suspected pulmonary hypertension and HF from the Sheffield centre underwent invasive right heart catheterization and CMR within 24 h of each other. A sex-specific CMR model to estimate LVFP, measured as pulmonary capillary wedge pressure (PCWP), was developed using multivariable regression. A validation cohort of patients with confirmed HF from the Leeds centre was used to evaluate for the primary endpoints of HF hospitalization and major adverse cardiovascular events (MACEs). Comparison between generic and sex-specific CMR-derived PCWP was undertaken. A total of 835 (60% female) and 454 (36% female) patients were recruited into the derivation and validation cohorts respectively. A sex-specific model incorporating left atrial volume and left ventricular mass was created. The generic CMR PCWP showed significant differences between males and females (14.7 ± 4 vs. 13 ± 3.0 mmHg, P > 0.001), not present with the sex-specific CMR PCWP (14.1 ± 3 vs. 13.8 mmHg, P = 0.3). The sex-specific, but not the generic, CMR PCWP was associated with HF hospitalization (hazard ratio 3.9, P = 0.0002) and MACE (hazard ratio 2.5, P = 0.001) over a mean follow-up period of 2.4 ± 1.2 years. Conclusion: Accounting for sex improves precision and prognostic performance of CMR biomarkers for HF.

Cardiovascular Magnetic Resonance Reference Ranges From the Healthy Hearts Consortium.

BACKGROUND: The absence of population-stratified cardiovascular magnetic resonance (CMR) reference ranges from large cohorts is a major shortcoming for clinical care. OBJECTIVES: This paper provides age-, sex-, and ethnicity-specific CMR reference ranges for atrial and ventricular metrics from the Healthy Hearts Consortium, an international collaborative comprising 9,088 CMR studies from verified healthy individuals, covering the complete adult age spectrum across both sexes, and with the highest ethnic diversity reported to date. METHODS: CMR studies were analyzed using certified software with batch processing capability (cvi42, version 5.14 prototype, Circle Cardiovascular Imaging) by 2 expert readers. Three segmentation methods (smooth, papillary, anatomic) were used to contour the endocardial and epicardial borders of the ventricles and atria from long- and short-axis cine series. Clinically established ventricular and atrial metrics were extracted and stratified by age, sex, and ethnicity. Variations by segmentation method, scanner vendor, and magnet strength were examined. Reference ranges are reported as 95% prediction intervals. RESULTS: The sample included 4,452 (49.0%) men and 4,636 (51.0%) women with average age of 61.1 ± 12.9 years (range: 18-83 years). Among these, 7,424 (81.7%) were from White, 510 (5.6%) South Asian, 478 (5.3%) mixed/other, 341 (3.7%) Black, and 335 (3.7%) Chinese ethnicities. Images were acquired using 1.5-T (n = 8,779; 96.6%) and 3.0-T (n = 309; 3.4%) scanners from Siemens (n = 8,299; 91.3%), Philips (n = 498; 5.5%), and GE (n = 291, 3.2%). CONCLUSIONS: This work represents a resource with healthy CMR-derived volumetric reference ranges ready for clinical implementation.

Left Ventricular Trabeculations at Cardiac MRI: Reference Ranges and Association with Cardiovascular Risk Factors in UK Biobank.

Background The extent of left ventricular (LV) trabeculation and its relationship with cardiovascular (CV) risk factors is unclear. Purpose To apply automated segmentation to UK Biobank cardiac MRI scans to (a) assess the association between individual characteristics and CV risk factors and trabeculated LV mass (LVM) and (b) establish normal reference ranges in a selected group of healthy UK Biobank participants. Materials and Methods In this cross-sectional secondary analysis, prospectively collected data from the UK Biobank (2006 to 2010) were retrospectively analyzed. Automated segmentation of trabeculations was performed using a deep learning algorithm. After excluding individuals with known CV diseases, White adults without CV risk factors (reference group) and those with preexisting CV risk factors (hypertension, hyperlipidemia, diabetes mellitus, or smoking) (exposed group) were compared. Multivariable regression models, adjusted for potential confounders (age, sex, and height), were fitted to evaluate the associations between individual characteristics and CV risk factors and trabeculated LVM. Results Of 43 038 participants (mean age, 64 years ± 8 [SD]; 22 360 women), 28 672 individuals (mean age, 66 years ± 7; 14 918 men) were included in the exposed group, and 7384 individuals (mean age, 60 years ± 7; 4729 women) were included in the reference group. Higher body mass index (BMI) (ß = 0.66 [95% CI: 0.63, 0.68]; P < .001), hypertension (ß = 0.42 [95% CI: 0.36, 0.48]; P < .001), and higher physical activity level (ß = 0.15 [95% CI: 0.12, 0.17]; P < .001) were associated with higher trabeculated LVM. In the reference group, the median trabeculated LVM was 6.3 g (IQR, 4.7-8.5 g) for men and 4.6 g (IQR, 3.4-6.0 g) for women. Median trabeculated LVM decreased with age for men from 6.5 g (IQR, 4.8-8.7 g) at age 45-50 years to 5.9 g (IQR, 4.3-7.8 g) at age 71-80 years (P = .03). Conclusion Higher trabeculated LVM was observed with hypertension, higher BMI, and higher physical activity level. Age- and sex-specific reference ranges of trabeculated LVM in a healthy middle-aged White population were established. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Kawel-Boehm in this issue.

Validation of 2D flow MRI for helical and vortical flows.

PURPOSE: The main objective of this study was to develop two-dimensional (2D) phase contrast (PC) methods to quantify the helicity and vorticity of blood flow in the aortic root. METHODS: This proof-of-concept study used four-dimensional (4D) flow cardiovascular MR (4D flow CMR) data of five healthy controls, five patients with heart failure with preserved ejection fraction and five patients with aortic stenosis (AS). A PC through-plane generated by 4D flow data was treated as a 2D PC plane and compared with the original 4D flow. Visual assessment of flow vectors was used to assess helicity and vorticity. We quantified flow displacement (FD), systolic flow reversal ratio (sFRR) and rotational angle (RA) using 2D PC. RESULTS: For visual vortex flow presence near the inner curvature of the ascending aortic root on 4D flow CMR, sFRR demonstrated an area under the curve (AUC) of 0.955, p<0.001. A threshold of >8% for sFRR had a sensitivity of 82% and specificity of 100% for visual vortex presence. In addition, the average late systolic FD, a marker of flow eccentricity, also demonstrated an AUC of 0.909, p<0.001 for visual vortex flow. Manual systolic rotational flow angle change (ΔsRA) demonstrated excellent association with semiautomated ΔsRA (r=0.99, 95% CI 0.9907 to 0.999, p<0.001). In reproducibility testing, average systolic FD (FDsavg) showed a minimal bias at 1.28% with a high intraclass correlation coefficient (ICC=0.92). Similarly, sFRR had a minimal bias of 1.14% with an ICC of 0.96. ΔsRA demonstrated an acceptable bias of 5.72°-and an ICC of 0.99. CONCLUSION: 2D PC flow imaging can possibly quantify blood flow helicity (ΔRA) and vorticity (FRR). These imaging biomarkers of flow helicity and vorticity demonstrate high reproducibility for clinical adoption. TRIALS REGISTRATION NUMBER: NCT05114785.

Evaluation of GeneXpert and advanced biological laboratories UltraGene HCV diagnostic detection and performance against Roche real time PCR in Myanmar.

BACKGROUND: Developing countries experience limited access to HCV laboratory tests for different reasons. Providing near to real-time HCV testing and results especially to at-risk populations including those in rural settings for timely initiation to treatment is key. Within a rural Myanmar setting, we compared HCV diagnostic detection and quantification of the GeneXpert, and Advanced Biological Laboratories UltraGene-HCV assays against the gold standard and reference method Roche real-time HCV in Myanmar. METHODS: Blood samples from 158 high-risk individuals were assessed using three different methods at baseline. Results were checked for normality and log transformed. Log differences and bias between methods were calculated and correlated. Pearson's correlation coefficient was used to determine the association of HCV viral loads across all methods. The level of agreement with the standard method (Roche real time HCV) was assessed using Bland-Altman analyses. RESULTS: There was a strong positive correlation coefficient between all three methods with GeneXpert and Roche having the strongest, r = 0.96, (p<0.001). Compared to Roche, ABL (mean difference, 95 % limits of agreement; -0.063 and -1.4 to 1.3 Log10IU/mL) and GeneXpert (mean difference, 95 % limits of agreement; -0.28 and -0.7 to 1.8 Log10IU/mL) showed a good level of agreement with the GeneXpert being slightly superior. CONCLUSION: We demonstrate the excellent performance and no-inferiority, in terms of levels of agreements of both GeneXpert and ABL compared to the Roche platform and supporting the use of the POC assays as alternative a cost-effective methods in HCV detection and diagnosis in developing and low resource settings countries.

Assessing heterogeneity on cardiovascular magnetic resonance imaging: a novel approach to diagnosis and risk stratification in cardiac diseases.

Cardiac disease affects the heart non-uniformly. Examples include focal septal or apical hypertrophy with reduced strain in hypertrophic cardiomyopathy, replacement fibrosis with akinesia in an infarct-related coronary artery territory, and a pattern of scarring in dilated cardiomyopathy. The detail and versatility of cardiovascular magnetic resonance (CMR) imaging mean it contains a wealth of information imperceptible to the naked eye and not captured by standard global measures. CMR-derived heterogeneity biomarkers could facilitate early diagnosis, better risk stratification, and a more comprehensive prediction of treatment response. Small cohort and case-control studies demonstrate the feasibility of proof-of-concept structural and functional heterogeneity measures. Detailed radiomic analyses of different CMR sequences using open-source software delineate unique voxel patterns as hallmarks of histopathological changes. Meanwhile, measures of dispersion applied to emerging CMR strain sequences describe variable longitudinal, circumferential, and radial function across the myocardium. Two of the most promising heterogeneity measures are the mean absolute deviation of regional standard deviations on native T1 and T2 and the standard deviation of time to maximum regional radial wall motion, termed the tissue synchronization index in a 16-segment left ventricle model. Real-world limitations include the non-standardization of CMR imaging protocols across different centres and the testing of large numbers of radiomic features in small, inadequately powered patient samples. We, therefore, propose a three-step roadmap to benchmark novel heterogeneity biomarkers, including defining normal reference ranges, statistical modelling against diagnosis and outcomes in large epidemiological studies, and finally, comprehensive internal and external validations.

Application of Different Wavelengths of LED Lights in Antimicrobial Photodynamic Therapy for the Treatment of Periodontal Disease.

Therapeutic light has been increasingly used in clinical dentistry for surgical ablation, disinfection, bio-stimulation, reduction in inflammation, and promotion of wound healing. Photodynamic therapy (PDT), a type of phototherapy, has been used to selectively destroy tumor cells. Antimicrobial PDT (a-PDT) is used to inactivate causative bacteria in infectious oral diseases, such as periodontitis. Several studies have reported that this minimally invasive technique has favorable therapeutic outcomes with a low probability of adverse effects. PDT is based on the photochemical reaction between light, a photosensitizer, and oxygen, which affects its efficacy. Low-power lasers have been predominantly used in phototherapy for periodontal treatments, while light-emitting diodes (LEDs) have received considerable attention as a novel light source in recent years. LEDs can emit broad wavelengths of light, from infrared to ultraviolet, and the lower directivity of LED light appears to be suitable for plaque control over large and complex surfaces. In addition, LED devices are small, lightweight, and less expensive than lasers. Although limited evidence exists on LED-based a-PDT for periodontitis, a-PDT using red or blue LED light could be effective in attenuating bacteria associated with periodontal diseases. LEDs have the potential to provide a new direction for light therapy in periodontics.

Effects of various light-emitting diode wavelengths on periodontopathic bacteria and gingival fibroblasts: An in vitro study.

BACKGROUND: In recent years, light has been used for bacterial control of periodontal diseases. This in vitro study evaluated the effects of light-emitting diode (LED) irradiation at different wavelengths on both Porphyromonas gingivalis and human gingival fibroblasts (HGF-1). METHODS: P. gingivalis suspension was irradiated with LEDs of 365, 405, 450, 470, 565, and 625 nm at 50, 100, 150, and 200 mW/cm2 for 3 min (radiant exposure: 9, 18, 27, 36 J/cm2, respectively). Treated samples were anaerobically cultured on agar plates, and the number of colony-forming units (CFUs) was determined. Reactive oxygen species (ROS) levels were measured after LED irradiation. The viability and damage of HGF-1 were measured through WST-8 and lactate dehydrogenase assays, respectively. Gene expression in P. gingivalis was evaluated through quantitative polymerase chain reaction. RESULTS: The greatest reduction in P. gingivalis CFUs was observed on irradiation at 365 nm with 150 mW/cm2 for 3 min (27 J/cm2), followed by 450 and 470 nm under the same conditions. While 365-nm irradiation significantly decreased the viability of HGF-1 cells, the cytotoxic effects of 450- and 470-nm irradiation were comparatively low and not significant. Further, 450-nm irradiation indicated increased ROS production and downregulated the genes related to gingipain and fimbriae. The 565- and 625-nm wavelength groups exhibited no antibacterial effects; rather, they significantly activated HGF-1 proliferation. CONCLUSIONS: The 450- and 470-nm blue LEDs showed high antibacterial activity with low cytotoxicity to host cells, suggesting promising bacterial control in periodontal therapy. Additionally, blue LEDs may attenuate the pathogenesis of P. gingivalis.

Association between subclinical atherosclerosis and cardiac structure and function-results from the UK Biobank Study.

Aims: Heart failure (HF) is a major health problem and early diagnosis is important. Atherosclerosis is the main cause of HF and carotid intima-media thickness (IMT) is a recognized early measure of atherosclerosis. This study aimed to investigate whether increased carotid IMT is associated with changes in cardiac structure and function in middle-aged participants of the UK Biobank Study without overt cardiovascular disease. Methods and results: Participants of the UK Biobank who underwent CMR and carotid ultrasound examinations were included in this study. Patients with heart failure, angina, atrial fibrillation, and history of myocardial infarction or stroke were excluded. We used multivariable linear regression models adjusted for age, sex, physical activity, body mass index, body surface area, hypertension, diabetes, smoking, ethnicity, socioeconomic status, alcohol intake, and laboratory parameters. In total, 4301 individuals (61.6 ± 7.5 years, 45.9% male) were included. Multivariable linear regression analyses showed that increasing quartiles of IMT was associated with increased left and right ventricular (LV and RV) and left atrial volumes and greater LV mass. Moreover, increased IMT was related to lower LV end-systolic circumferential strain, torsion, and both left and right atrial ejection fractions (all P < 0.05). Conclusion: Increased IMT showed an independent association over traditional risk factors with enlargement of all four cardiac chambers, decreased function in both atria, greater LV mass, and subclinical LV dysfunction. There may be additional risk stratification that can be derived from the IMT to identify those most likely to have early cardiac structural/functional changes.

Prognostic Significance of Different Ventricular Ectopic Burdens During Submaximal Exercise in Asymptomatic UK Biobank Subjects.

BACKGROUND: The consequences of exercise-induced premature ventricular contractions (PVCs) in asymptomatic individuals remain unclear. This study aimed to assess the association between PVC burdens during submaximal exercise and major adverse cardiovascular events (MI/HF/LTVA: myocardial infarction [MI], heart failure [HF], and life-threatening ventricular arrhythmia [LTVA]), and all-cause mortality. Additional end points were MI, LTVA, HF, and cardiovascular mortality. METHODS: A neural network was developed to count PVCs from ECGs recorded during exercise (6 minutes) and recovery (1 minute) in 48 315 asymptomatic participants from UK Biobank. Associations were estimated using multivariable Cox proportional hazard models. Explorative studies were conducted in subgroups with cardiovascular magnetic resonance imaging data (n=6290) and NT-proBNP (N-terminal Pro-B-type natriuretic peptide) levels (n=4607) to examine whether PVC burden was associated with subclinical cardiomyopathy. RESULTS: Mean age was 56.8±8.2 years; 51.1% of the participants were female; and median follow-up was 12.6 years. Low PVC counts during exercise and recovery were both associated with MI/HF/LTVA risk, independently of clinical factors: adjusted hazard ratio (HR), 1.2 (1-5 exercise PVCs, P<0.001) and HR, 1.3 (1-5 recovery PVCs, P<0.001). Risks were higher with increasing PVC count: HR, 1.8 (>20 exercise PVCs, P<0.001) and HR, 1.6 (>5 recovery PVCs, P<0.001). A similar trend was observed for all-cause mortality, although associations were only significant for high PVC burdens: HRs, 1.6 (>20 exercise PVCs, P<0.001) and 1.5 (>5 recovery PVCs, P<0.001). Complex PVC rhythms were associated with higher risk compared with PVC count alone. PVCs were also associated with incident HF, LTVA, and cardiovascular mortality, but not MI. In the explorative studies, high PVC burden was associated with larger left ventricular volumes, lower ejection fraction, and higher levels of NT-proBNP compared with participants without PVCs. CONCLUSIONS: In this cohort of middle-aged and older adults, PVC count during submaximal exercise and recovery were both associated with MI/HF/LTVA, all-cause mortality, HF, LTVAs, and cardiovascular mortality, independent of clinical and exercise test factors, indicating an incremental increase in risk as PVC count rises. Complex PVC rhythms were associated with higher risk compared with PVC count alone. Underlying mechanisms may include the presence of subclinical cardiomyopathy.

Predicted Deleterious Variants in Cardiomyopathy Genes Prognosticate Mortality and Composite Outcomes in UK Biobank.

BACKGROUND: Inherited cardiomyopathies present with broad variation of phenotype. Data are limited regarding genetic screening strategies and outcomes associated with predicted deleterious variants in cardiomyopathy-associated genes in the general population. OBJECTIVES: The authors aimed to determine the risk of mortality and composite cardiomyopathy-related outcomes associated with predicted deleterious variants in cardiomyopathy-associated genes in the UK Biobank. METHODS: Using whole exome sequencing data, variants in dilated, hypertrophic, and arrhythmogenic right ventricular cardiomyopathy-associated genes with at least moderate evidence of disease causality according to ClinGen Expert Panel curations were annotated using REVEL (≥0.65) and ANNOVAR (predicted loss-of-function) considering gene-disease mechanisms. Genotype-positive and genotype-negative groups were compared using time-to-event analyses for the primary (all-cause mortality) and secondary outcomes (diagnosis of cardiomyopathy; composite outcome of diagnosis of cardiomyopathy, heart failure, arrhythmia, stroke, and death). RESULTS: Among 200,619 participants (age at recruitment 56.46 ± 8.1 years), 5,292 (2.64%) were found to host ≥1 predicted deleterious variants in cardiomyopathy-associated genes (CMP-G+). After adjusting for age and sex, CMP-G+ individuals had higher risk for all-cause mortality (HR: 1.13 [95% CI: 1.01-1.25]; P = 0.027), increased risk for being diagnosed with cardiomyopathy later in life (HR: 5.75 [95% CI: 4.58-7.23]; P < 0.0001), and elevated risk for composite outcome (HR: 1.29 [95% CI: 1.20-1.39]; P < 0.0001) than CMP-G- individuals. The higher risk for being diagnosed with cardiomyopathy and composite outcomes in the genotype-positive subjects remained consistent across all cardiomyopathy subgroups. CONCLUSIONS: Adults with predicted deleterious variants in cardiomyopathy-associated genes exhibited a slightly higher risk of mortality and a significantly increased risk of developing cardiomyopathy, and cardiomyopathy-related composite outcomes, in comparison with genotype-negative controls.

Phenotyping left ventricular systolic dysfunction in asymptomatic individuals for improved risk stratification.

AIMS: Left ventricular systolic dysfunction (LSVD) is a heterogeneous condition with several factors influencing prognosis. Better phenotyping of asymptomatic individuals can inform preventative strategies. This study aims to explore the clinical phenotypes of LVSD in initially asymptomatic subjects and their association with clinical outcomes and cardiovascular abnormalities through multi-dimensional data clustering. METHODS AND RESULTS: Clustering analysis was performed on 60 clinically available variables from 1563 UK Biobank participants without pre-existing heart failure (HF) and with left ventricular ejection fraction (LVEF) < 50% on cardiovascular magnetic resonance (CMR) assessment. Risks of developing HF, other cardiovascular events, death, and a composite of major adverse cardiovascular events (MACE) associated with clusters were investigated. Cardiovascular imaging characteristics, not included in the clustering analysis, were also evaluated. Three distinct clusters were identified, differing considerably in lifestyle habits, cardiovascular risk factors, electrocardiographic parameters, and cardiometabolic profiles. A stepwise increase in risk profile was observed from Cluster 1 to Cluster 3, independent of traditional risk factors and LVEF. Compared with Cluster 1, the lowest risk subset, the risk of MACE ranged from 1.42 [95% confidence interval (CI): 1.03-1.96; P < 0.05] for Cluster 2 to 1.72 (95% CI: 1.36-2.35; P < 0.001) for Cluster 3. Cluster 3, the highest risk profile, had features of adverse cardiovascular imaging with the greatest LV re-modelling, myocardial dysfunction, and decrease in arterial compliance. CONCLUSIONS: Clustering of clinical variables identified three distinct risk profiles and clinical trajectories of LVSD amongst initially asymptomatic subjects. Improved characterization may facilitate tailored interventions based on the LVSD sub-type and improve clinical outcomes.

Predicting left ventricular hypertrophy from the 12-lead electrocardiogram in the UK Biobank imaging study using machine learning.

Aims: Left ventricular hypertrophy (LVH) is an established, independent predictor of cardiovascular disease. Indices derived from the electrocardiogram (ECG) have been used to infer the presence of LVH with limited sensitivity. This study aimed to classify LVH defined by cardiovascular magnetic resonance (CMR) imaging using the 12-lead ECG for cost-effective patient stratification. Methods and results: We extracted ECG biomarkers with a known physiological association with LVH from the 12-lead ECG of 37 534 participants in the UK Biobank imaging study. Classification models integrating ECG biomarkers and clinical variables were built using logistic regression, support vector machine (SVM) and random forest (RF). The dataset was split into 80% training and 20% test sets for performance evaluation. Ten-fold cross validation was applied with further validation testing performed by separating data based on UK Biobank imaging centres. QRS amplitude and blood pressure (P < 0.001) were the features most strongly associated with LVH. Classification with logistic regression had an accuracy of 81% [sensitivity 70%, specificity 81%, Area under the receiver operator curve (AUC) 0.86], SVM 81% accuracy (sensitivity 72%, specificity 81%, AUC 0.85) and RF 72% accuracy (sensitivity 74%, specificity 72%, AUC 0.83). ECG biomarkers enhanced model performance of all classifiers, compared to using clinical variables alone. Validation testing by UK Biobank imaging centres demonstrated robustness of our models. Conclusion: A combination of ECG biomarkers and clinical variables were able to predict LVH defined by CMR. Our findings provide support for the ECG as an inexpensive screening tool to risk stratify patients with LVH as a prelude to advanced imaging.

Cardiac magnetic resonance left ventricular filling pressure is linked to symptoms, signs and prognosis in heart failure.

AIMS: Left ventricular filling pressure (LVFP) can be estimated from cardiovascular magnetic resonance (CMR). We aimed to investigate whether CMR-derived LVFP is associated with signs, symptoms, and prognosis in patients with recently diagnosed heart failure (HF). METHODS AND RESULTS: This study recruited 454 patients diagnosed with HF who underwent same-day CMR and clinical assessment between February 2018 and January 2020. CMR-derived LVFP was calculated, as previously, from long- and short-axis cines. CMR-derived LVFP association with symptoms and signs of HF was investigated. Patients were followed for median 2.9 years (interquartile range 1.5-3.6 years) for major adverse cardiovascular events (MACE), defined as the composite of cardiovascular death, HF hospitalization, non-fatal stroke, and non-fatal myocardial infarction. The mean age was 62 ± 13 years, 36% were female (n = 163), and 30% (n = 135) had raised LVFP. Forty-seven per cent of patients had an ejection fraction < 40% during CMR assessment. Patients with raised LVFP were more likely to have pleural effusions [hazard ratio (HR) 3.2, P = 0.003], orthopnoea (HR 2.0, P = 0.008), lower limb oedema (HR 1.7, P = 0.04), and breathlessness (HR 1.7, P = 0.01). Raised CMR-derived LVFP was associated with a four-fold risk of HF hospitalization (HR 4.0, P < 0.0001) and a three-fold risk of MACE (HR 3.1, P < 0.0001). In the multivariable model, raised CMR-derived LVFP was independently associated with HF hospitalization (adjusted HR 3.8, P = 0.0001) and MACE (adjusted HR 3.0, P = 0.0001). CONCLUSIONS: Raised CMR-derived LVFP is strongly associated with symptoms and signs of HF. In addition, raised CMR-derived LVFP is independently associated with subsequent HF hospitalization and MACE.