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Aims Despite major advances in our understanding of ‘systolic’ heart failure, at present the epidemiology, pathophysiology, and therapy of heart failure with preserved left ventricular ejection fraction (HFpEF) is poorly understood, in large part because of the lack of robust and widely accepted diagnostic criteria. Although there is a good evidence base for the treatment of systolic heart failure, similar data are lacking for the treatment of HFpEF. Methods In our study, we will screen a consecutive series of 5000 subjects aged ≥60 from the community. Following symptom questionnaire and echocardiography, metabolic exercise testing will be used to confirm whether or not patients thought clinically to have HFpEF are in fact exercise limited and that this limitation is cardiac in origin. Blood samples for plasma brain natriuretic peptide (BNP) will be taken at rest and following exercise in symptomatic patients and matching controls. Conclusions At the end of our study we will establish community prevalence and population characteristics of HFpEF, and also evaluate the diagnostic accuracy of current echocardiography parameters and BNP for the diagnosis of the condition. [ABSTRACT FROM AUTHOR]

To analyze the cost efficiency of guidelines proposed by the European Society of Cardiology for investigation of patients in the community with suspected heart failure (HF). The guidelines recommend electrocardiography (ECG) and/or measurement of N-terminal pro B type natriuretic peptide (NTproBNP) prior to referral for echocardiography. Portable echocardiography is a new but validated technique for the evaluation of HF. Accordingly, 137 suspected HF patients (mean age 71±13 years) from the community underwent ECG and NTproBNP estimation prior to portable echocardiography. Cost effective analysis for ECG, NTproBNP, portable echocardiography and a combination of these; to define valvular heart disease, right ventricular dysfunction and left ventricular systolic and diastolic dysfunction were compared. The cost of abnormal NTproBNP followed by portable echocardiography, abnormal ECG followed by portable echocardiography and portable echocardiography alone for the detection per case of left ventricular systolic dysfunction were €313, €310, and €296 respectively and that for detection per case of any of the aforementioned cardiac abnormalities were €198, €223, and €170 respectively. Portable echocardiography alone for the assessment of suspected HF patients resulted in a cost reduction of up to €1083 for the detection per case of cardiac abnormality. While a strategy where initial NTproBNP estimation is cost effective in detecting any causes of heart failure, portable echocardiography remains the most costeffective strategy to assess patients from the community with suspected heart failure. [ABSTRACT FROM AUTHOR]

Heart failure (HF) is the end stage of most cardiovascular diseases and remains a significant health problem globally. We aimed to assess whether patients with left ventricular ejection fraction ≤45% had alterations in both the gut microbiome pro- file and production of associated metabolites when compared with a healthy cohort. We also examined the associated inflammatory, metabolomic, and lipidomic profiles of patients with HF. This single center, observational study, recruited 73 patients with HF and 59 healthy volunteers. Blood and stool samples were collected at baseline and 6-mo follow-up, along with anthropometric and clinical data. When compared with healthy controls, patients with HF had reduced gut bacterial alpha diversity at follow-up (P = 0.004) but not at baseline. The stool microbiota of patients with HF was characterized by a depletion of operational taxonomic units representing commensal Clostridia at both baseline and follow-up. Patients with HF also had significantly elevated baseline plasma acetate (P = 0.007), plasma trimethylamine-N-oxide (TMAO) (P = 0.003), serum soluble CD14 (sCD14; P = 0.005), and soluble CD163 (sCD163; P = 0.004) levels compared with healthy controls. Furthermore, patients with HF had a distinct metabolomic and lipidomic profile at baseline when compared with healthy controls. Differences in the composition of the gut microbiome and the levels of associated metabolites were observed in patients with HF when compared with a healthy cohort. This was also associated with an altered metabolomic and lipidomic profile. Our study identifies microorganisms and metabolites that could represent new therapeutic targets and diagnostic tools in the pathogenesis of HF. [ABSTRACT FROM AUTHOR]

Background: The influence of testosterone on risk for cardiovascular events in men is uncertain. Previous observational studies of sex hormones and incident cardiovascular disease in men have reported inconsistent findings, limited by cohort sizes and different selection criteria.Objective: To analyze associations of serum total testosterone and sex hormone-binding globulin (SHBG) with incident cardiovascular events in men.Design: Cohort study.Setting: UK Biobank prospective cohort.Participants: Community-dwelling men aged 40 to 69 years.Measurements: Testosterone and SHBG were assayed, and free testosterone was calculated. Cox proportional hazards regression was done, with outcomes of incident myocardial infarction (MI), hemorrhagic stroke (HS), ischemic stroke (IS), heart failure (HF), and major adverse cardiovascular events (MACE), adjusted for sociodemographic, lifestyle, and medical factors.Results: Of 210 700 men followed for 9 years, 8790 (4.2%) had an incident cardiovascular event. After adjustment for key variables, lower total testosterone concentrations (quintile 1 vs. quintile 5) were not associated with incident MI (fully adjusted hazard ratio [HR], 0.89 [95% CI, 0.80 to 1.00]), HS (HR, 0.94 [CI, 0.70 to 1.26]), IS (HR, 0.95 [CI, 0.82 to 1.10]), HF (HR, 1.15 [CI, 0.91 to 1.45]), or MACE (HR, 0.92 [CI, 0.84 to 1.00]). Men with lower calculated free testosterone values had a lower incidence of MACE (HR, 0.90 [CI, 0.84 to 0.97]). Lower SHBG concentrations were associated with higher incidence of MI (HR, 1.23 [CI, 1.09 to 1.38]) and lower incidence of IS (HR, 0.79 [CI, 0.67 to 0.94]) and HF (HR, 0.69 [CI, 0.54 to 0.89]), but not with HS (HR, 0.81 [CI, 0.57 to 1.14]) or MACE (HR, 1.01 [CI, 0.92 to 1.11]).Limitation: Observational study; single baseline measurement of testosterone and SHBG.Conclusion: Men with lower total testosterone concentrations were not at increased risk for MI, stroke, HF, or MACE. Calculated free testosterone may be associated with risk for MACE. Men with lower SHBG concentrations have higher risk for MI but lower risk for IS and HF, with causality to be determined.Primary Funding Source: Western Australian Health Translation Network, Medical Research Future Fund, and Lawley Pharmaceuticals. [ABSTRACT FROM AUTHOR]

Objectives: Describe the incidence of cardiac complications in patients admitted to hospital with COVID-19 in Australia.Design: Observational cohort study.Setting: Twenty-one (21) Australian hospitals.Participants: Consecutive patients aged ≥18 years admitted to hospital with laboratory confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.Main Outcome Measures: Incidence of cardiac complications.Results: Six-hundred-and-forty-four (644) hospitalised patients (62.5±20.1 yo, 51.1% male) with COVID-19 were enrolled in the study. Overall in-hospital mortality was 14.3%. Twenty (20) (3.6%) patients developed new atrial fibrillation or flutter during admission and 9 (1.6%) patients were diagnosed with new heart failure or cardiomyopathy. Three (3) (0.5%) patients developed high grade atrioventricular (AV) block. Two (2) (0.3%) patients were clinically diagnosed with pericarditis or myopericarditis. Among the 295 (45.8%) patients with at least one troponin measurement, 99 (33.6%) had a peak troponin above the upper limit of normal (ULN). In-hospital mortality was higher in patients with raised troponin (32.3% vs 6.1%, p<0.001). New onset atrial fibrillation or flutter (6.4% vs 1.0%, p=0.001) and troponin elevation above the ULN (50.3% vs 16.4%, p<0.001) were more common in patients 65 years and older. There was no significant difference in the rate of cardiac complications between males and females.Conclusions: Among patients with COVID-19 requiring hospitalisation in Australia, troponin elevation was common but clinical cardiac sequelae were uncommon. The incidence of atrial arrhythmias and troponin elevation was greatest in patients 65 years and older. [ABSTRACT FROM AUTHOR]

Abstract: Background: Left atrial volume index (LAVI) is increasingly recognised as a relatively load-independent marker of left ventricular (LV) filling pressures. We assessed the capacity of LAVI to predict LV diastolic dysfunction in comparison with N-terminal pro B-type natriuretic peptide (NTproBNP) in patients with suspected heart failure and a normal ejection fraction (EF). Methods: 137 patients with suspected heart failure (HF), referred from the community for echocardiography, prospectively underwent Doppler echocardiography, LAVI and NTproBNP estimation. Raised LAVI and reduced LV systolic function were defined as >26 ml/m2 and LV EF <50% respectively. Results: Of 137 patients, 21 were excluded (2 with significant mitral valve disease and 19 with atrial fibrillation). Of the remaining 116 subjects, 92 showed normal LV systolic function. The univariate predictors of serum log NTproBNP were age (p <0.001), LA dimension (p =0.001), LAVI (p <0.001), A wave (p =0.001), E:A (p =0.07) and septal wall thickness (p =0.004). However on multivariate analysis, LAVI was found to be the most consistent and significant predictor of NTproBNP. The area under the curve of the receiver operating characteristic (ROC) curve for NTproBNP in detecting patients with LVEF ≥50% and LAVI >26ml/m2 was 0.81 (p <0.0001) and for patients with LAVI >26ml/m2 with and without LVEF ≥50% was 0.82 (p <0.0001). Conclusion: This data confirms that LAVI on resting echocardiography, specifically in patients with suspected HF and normal LV systolic function is a powerful independent predictor of LV diastolic dysfunction as predicted by serum NTproBNP. In a population with a high suspicion of diastolic heart failure, LAVI may significantly contribute to diagnostic precision. [Copyright &y& Elsevier]

Background: The prediction of readmission or death after a hospital discharge for heart failure (HF) remains a major challenge. Modern healthcare systems, electronic health records, and machine learning (ML) techniques allow us to mine data to select the most significant variables (allowing for reduction in the number of variables) without compromising the performance of models used for prediction of readmission and death. Moreover, ML methods based on transformation of variables may potentially further improve the performance. Objective: To use ML techniques to determine the most relevant and also transform variables for the prediction of 30-day readmission or death in HF patients. Methods: We identified all Western Australian patients aged 65 years and above admitted for HF between 2003–2008 in linked administrative data. We evaluated variables associated with HF readmission or death using standard statistical and ML based selection techniques. We also tested the new variables produced by transformation of the original variables. We developed multi-layer perceptron prediction models and compared their predictive performance using metrics such as Area Under the receiver operating characteristic Curve (AUC), sensitivity and specificity. Results: Following hospital discharge, the proportion of 30-day readmissions or death was 23.7% in our cohort of 10,757 HF patients. The prediction model developed by us using a smaller set of variables (n = 8) had comparable performance (AUC 0.62) to the traditional model (n = 47, AUC 0.62). Transformation of the original 47 variables further improved (p<0.001) the performance of the predictive model (AUC 0.66). Conclusions: A small set of variables selected using ML matched the performance of the model that used the full set of 47 variables for predicting 30-day readmission or death in HF patients. Model performance can be further significantly improved by transforming the original variables using ML methods. [ABSTRACT FROM AUTHOR]

Aims: This study explored characteristics and outcomes of patients with type 1 diabetes mellitus (T1DM) and acute coronary syndromes (ACS).Methods: A retrospective analysis of patients with T1DM admitted with ACS to an Australian hospital was conducted. Risk factor targets were defined by 2021 European Society of Cardiology Guidelines. Outcomes were defined as an adverse cardiovascular event (ACS, unplanned revascularisation, heart failure, stroke, or cardiovascular death) or all-cause mortality within six-months after discharge.Results: 61 patients were included [age 58.5 ± 12.8 years, 39 % female]. Dyslipidaemia (85 %), hypertension (75 %), smoking (28 %), prior coronary artery disease (CAD) (44 %), and microvascular complications (62 %) were common. HbA1c, low-density lipoprotein cholesterol, and blood pressure targets were attained in 12 %, 36 % and 47 %, respectively. ST-elevation myocardial infarction (65 % versus 7 %, p < 0.001) and revascularisation (77 % versus 41 %, p = 0.008) were more common in those without prior CAD. Peak inpatient blood glucose correlated directly with peak troponin (p = 0.011) and inversely with left ventricular ejection fraction (p = 0.027). Nineteen patients experienced an adverse six-month outcome, with peripheral neuropathy (p = 0.039) and in-hospital hypoglycaemia (p = 0.012) being independent predictors.Conclusions: Patients with T1DM and ACS often do not meet guideline targets for cardiovascular risk factors, and frequently present with transmural infarctions. Dysglycemia and microvascular complications predict poorer outcomes. [ABSTRACT FROM AUTHOR]

Background: New-onset or worsening heart failure is the most common extra-pulmonary complication of community-acquired pneumonia (CAP) during the first 30 days after diagnosis.Methods: We evaluated the changes in the right ventricular function amongst adult CAP survivors from the time of acute infection to its resolution. We performed comprehensive transthoracic echocardiographic examinations to assess right heart function during the acute illness and the convalescent period (4 to 6 weeks after hospital discharge).Results: Twenty-six patients underwent acute measurements, of which convalescent measurements were completed in 19 subjects. There was no significant change in any of the right heart function parameters from the acute to convalescent stage of CAP.Conclusions: Our results suggest that right ventricular function does not meaningfully change in the transition from the acute to convalescent stage of CAP in non-critically ill adult CAP survivors. [ABSTRACT FROM AUTHOR]

Background Imaging has become a routine part of heart failure (HF) investigation. Echocardiography is a first-line test in HF given its availability and it provides valuable diagnostic and prognostic information. Cardiac magnetic resonance (CMR) is an emerging clinical tool in the management of patients with non-ischemic heart failure. Current ACC/AHA/CCS/ESC guidelines advocate its role in the detection of a variety of cardiomyopathies but there is a paucity of high quality evidence to support these recommendations. The primary objective of this study is to compare the diagnostic yield of routine cardiac magnetic resonance versus standard care (that is, echocardiography with only selective use of CMR) in patients with non-ischemic heart failure. The primary hypothesisis that the routine use of CMR will lead to a more specific diagnostic characterization of the underlying etiology of non-ischemic heart failure. This will lead to a reduction in the non-specific diagnoses of idiopathic dilated cardiomyopathy and HF with preserved ejection fraction. Design Tertiary care sites in Canada and Finland, with dedicated HF and CMR programs, will randomize consecutive patients with new or deteriorating HF to routine CMR or selective CMR. All patients will undergo a standard clinical echocardiogram and the interpreter will assign the most likely HF etiology. Those undergoing CMR will also have a standard examination and will be assigned a HF etiology based upon the findings. The treating physician's impression about non-ischemic HF etiology will be collected following all baseline testing (including echo ± CMR). Patients will be followed annually for 4 years to ascertain clinical outcomes, quality of life and cost. The expected outcome is that the routine CMR arm will have a significantly higher rate of infiltrative, inflammatory, hypertrophic, ischemic and 'other' cardiomyopathy than the selective CMR group. Discussion This study will be the first multicenter randomized, controlled trial evaluating the role of CMR in non-ischemic HF. Non-ischemic HF patients will be randomized to routine CMR in order to determine whether there are any gains over management strategies employing selective CMR utilization. The insight gained from this study should improve appropriate CMR use in HF. NCT01281384. [ABSTRACT FROM AUTHOR]

Objectives: We sought to evaluate the role of exercise-related changes in left ventricular (LV) relaxation and of LV contractile function and vasculoventricular coupling (VVC) in the pathophysiology of heart failure with preserved ejection fraction (HFpEF) and to assess myocardial energetic status in these patients. Background: To date, no studies have investigated exercise-related changes in LV relaxation and VVC as well as in vivo myocardial energetic status in patients with HFpEF. Methods: We studied 37 patients with HFpEF and 20 control subjects. The VVC and time to peak LV filling (nTTPF, a measure of LV active relaxation) were assessed while patients were at rest and during exercise by the use of radionuclide ventriculography. Cardiac energetic status (creatine phosphate/adenosine triphosphate ratio) was assessed by the use of 31P magnetic resonance spectroscopy at 3-T. Results: When patients were at rest, nTTPF and VVC were similar in patients with HFpEF and control subjects. The cardiac creatine phosphate/adenosine triphosphate ratio was reduced in patients with HFpEF versus control subjects (1.57 ± 0.52 vs. 2.14 ± 0.63; p = 0.003), indicating reduced energy reserves. Peak maximal oxygen uptake and the increase in heart rate during maximal exercise were lower in patients with HFpEF versus control subjects (19 ± 4 ml/kg/min vs. 36 ± 8 ml/kg/min, p < 0.001, and 52 ± 16 beats/min vs. 81 ± 14 beats/min, p < 0.001). The relative changes in stroke volume and cardiac output during submaximal exercise were lower in patients with HFpEF versus control subjects (ratio exercise/rest: 0.99 ± 0.34 vs. 1.25 ± 0.47, p = 0.04, and 1.36 ± 0.45 vs. 2.13 ± 0.72, p < 0.001). The nTTPF decreased during exercise in control subjects but increased in patients with HFpEF (−0.03 ± 12 s vs. +0.07 ± 0.11 s; p = 0.005). The VVC decreased on exercise in control subjects but was unchanged in patients with HFpEF (−0.01 ± 0.15 vs. −0.25 ± 0.19; p < 0.001). Conclusions: Patients with HFpEF have reduced cardiac energetic reserve that may underlie marked dynamic slowing of LV active relaxation and abnormal VVC during exercise. [Copyright &y& Elsevier]

Cardiovascular diseases (CVDs) have been considered the most predominant cause of death and one of the most critical public health issues worldwide. In the past two decades, cardiovascular (CV) mortality has declined in high-income countries owing to preventive measures that resulted in the reduced burden of coronary artery disease (CAD) and heart failure (HF). In spite of these promising results, CVDs are responsible for ~17 million deaths per year globally with ~25% of these attributable to sudden cardiac death (SCD). Pre-clinical data demonstrated that renal denervation (RDN) decreases sympathetic activation as evaluated by decreased renal catecholamine concentrations. RDN is successful in reducing ventricular arrhythmias (VAs) triggering and its outcome was not found inferior to metoprolol in rat myocardial infarction model. Registry clinical data also suggest an advantageous effect of RDN to prevent VAs in HF patients and electrical storm. An in-depth investigation of how RDN, a minimally invasive and safe method, reduces the burden of HF is urgently needed. Myocardial systolic dysfunction is correlated to neuro-hormonal overactivity as a compensatory mechanism to keep cardiac output in the face of declining cardiac function. Sympathetic nervous system (SNS) overactivity is supported by a rise in plasma noradrenaline (NA) and adrenaline levels, raised central sympathetic outflow, and increased organ-specific spillover of NA into plasma. Cardiac NA spillover in untreated HF individuals can reach ~50-fold higher levels compared to those of healthy individuals under maximal exercise conditions. Increased sympathetic outflow to the renal vascular bed can contribute to the anomalies of renal function commonly associated with HF and feed into a vicious cycle of elevated BP, the progression of renal disease and worsening HF. Increased sympathetic activity, amongst other factors, contribute to the progress of cardiac arrhythmias, which can lead to SCD due to sustained ventricular tachycardia. Targeted therapies to avoid these detrimental consequences comprise antiarrhythmic drugs, surgical resection, endocardial catheter ablation and use of the implantable electronic cardiac devices. Analogous NA agents have been reported for single photon-emission-computed-tomography (SPECT) scans usage, specially the 123I-metaiodobenzylguanidine (123I-MIBG). Currently, HF prognosis assessment has been improved by this tool. Nevertheless, this radiotracer is costly, which makes the use of this diagnostic method limited. Comparatively, positron-emission-tomography (PET) overshadows SPECT imaging, because of its increased spatial definition and broader reckonable methodologies. Numerous ANS radiotracers have been created for cardiac PET imaging. However, so far, [11C]-meta-hydroxyephedrine (HED) has been the most significant PET radiotracer used in the clinical scenario. Growing data has shown the usefulness of [11C]-HED in important clinical situations, such as predicting lethal arrhythmias, SCD, and all-cause of mortality in reduced ejection fraction HF patients. In this article, we discussed the role and relevance of novel tools targeting the SNS, such as the [11C]-HED PET cardiac imaging and RDN to manage patients under of SCD risk. [ABSTRACT FROM AUTHOR]