BACKGROUND AND AIMS:Type 2 diabetes mellitus (T2DM) and obesity are the archetypal components of cardiometabolic syndromes associated with heart failure (HF) with preserved or mildly reduced ejection fraction (HFpEF/HFmrEF). The specific contribution of T2DM, independent of obesity, to myocardial adaptations and outcomes remains uncertain. We aimed to explore the obesity-independent contribution of T2DM to cardiac structure, function, central haemodynamics, and outcomes. METHODS:We leveraged the sham-control arm of the REDUCE LAP-HF II trial (n = 312), a prospectively phenotyped cohort of patients with HFpEF/HFmrEF undergoing invasive haemodynamic assessment. Multivariable models were used to adjust for body mass index (BMI) and clinical covariates. Outcomes included cardiovascular (CV) death and total HF events. RESULTS:T2DM was present in 37% of patients and was associated with higher BMI, chronic kidney disease, and prior HF hospitalization. Obesity was present in 62% of patients and was more prevalent in those with T2DM (70% vs 57%, P = .032). After adjustment for BMI, T2DM remained independently associated with greater left ventricular mass, lower EF, impaired left ventricular global longitudinal strain, reduced right ventricular free-wall strain, and higher resting filling pressures. Over a median of 4.0-year (2.5-5.0) follow-up, T2DM was independently associated with increased risk of HF events or CV death (adjusted hazard ratio: 1.96, 95% confidence interval: 1.28-3.00), driven by HF events, whereas BMI was not independently prognostic. CONCLUSIONS:HFpEF/HFmrEF patients with T2DM experience adverse myocardial remodelling, impaired biventricular function, adverse central haemodynamics, and worse clinical outcomes independent of obesity. These findings indicate that T2DM confers additional metabolic burden to the myocardium, beyond that attributable to obesity alone.

Pulmonary hypertension (PH) is common in heart failure with preserved ejection fraction (HFpEF), driven in many patients by a combination of elevated left atrial pressure and pulmonary vascular remodelling. Whether local biomarker release contributes to pulmonary remodelling in HFpEF is unknown. We, therefore, aimed to compare the transpulmonary inflammatory biomarker release profile in healthy control subjects and HFpEF patients and to investigate the contribution of biomarkers to adverse pulmonary vascular remodelling as reflected via invasive haemodynamics. Thirty-four participants (20 HFpEF, 14 healthy controls) underwent exercise hemodynamic testing and concurrent target organ blood sampling (pulmonary artery & systemic arterial). A panel of 157 inflammatory biomarkers were analysed via OLink proteomics using proximity extension assay technology and subsequent polymerase chain reaction. Transpulmonary gradient (TPG) was calculated as [pulmonary artery]-[systemic arterial]. HFpEF patients were older (70±9 vs 53±8 years, p<0.001) with higher BMI (34±9 vs 26±9 kg/m², p=0.004). While no healthy controls had PH, 55% of HFpEF patients did. Pulmonary vascular resistance was higher (1.95±0.83 vs 0.93±0.50WU, p<0.001), and pulmonary artery compliance (PAC) lower (4.2±1.7 vs 7.1±2.4ml/mmHg, p<0.001) in HFpEF at rest as well as at peak exercise. From 157 biomarkers, 22 demonstrated significantly different TPGs between groups, with 12 demonstrating association with invasive haemodynamics, Figure 1. Principal coordinate analysis revealed significantly different transpulmonary biomarker release profiles between HFpEF and controls (p=0.002), Figure 2. Correlations between PAC and the TPG of follistatin, agouti-related protein, lipoprotein lipase, and thrombomodulin were significantly different (p<0.05) between groups, as were correlations for exercise mean pulmonary artery pressure and TPG of thrombomodulin, leptin, ADAMTS13, adrenomedullin, CCL11, decorin, GDF-2, and PD-L2 (all p<0.05). TPGs for lipoprotein lipase, adrenomedullin, leptin, agouti-related protein, thrombomodulin, ADAMTS13, decorin and PD-L2 were also associated with differences in exercise pulmonary vasodilatory capacity between HFpEF and controls, as assessed by ΔPVR or ΔPAC (all p<0.05). We identified a significantly altered transpulmonary flux profile of inflammatory biomarkers in HFpEF compared to healthy controls. These locally generated biomarkers demonstrated association with adverse pulmonary remodelling in HFpEF and may thereby be targets for therapeutic intervention.Figure 1 Figure 2

Objective: To evaluate the incidence of hypertension and blood pressure (BP) phenotypes using 24-hour ambulatory BP (24hr-ABP) in women with past pregnancy complications who were recruited into a Women's Heart Clinic (WHC). Study design: We recruited 156 women aged 30-55 years with past hypertensive disorders of pregnancy (HDP) and/or gestational diabetes (GDM) to a multidisciplinary six-month WHC that provided cardiovascular risk management in Melbourne, Australia. Women were referred for 24 hr-ABP monitoring if clinic BP was >= 130/80 mmHg. Main outcome measures: Primary outcome was incident hypertension, defined by 24 hr-ABP monitoring as daytime hypertension >= 135/85 mmHg, nocturnal hypertension >= 120/70 mmHg, and/or 24hr-average hypertension >= 130/80 mmHg. Results: From 156 women, 54 women underwent 24hr-ABP monitoring (mean age 41.3 f 4.5 years; 3.9 f 2.6 years post-partum), with 64.8 % HDP and 45.2 % GDM. Incidence of hypertension was 61.1 % [95 % CI 48.2 %- 74.0 %]. Higher proportion of women with past HDP had daytime hypertension compared to those with GDM only (57.1 % vs. 26.3 %; p = 0.05) and higher nocturnal mean systolic-BP [116.0 f 11.2 mmHg vs. 109.6 f 8.7 mmHg; p = 0.04]. Women with HDP had increased odds of hypertension [adjusted-OR 5.26 95 % CI (1.07-32.76); p = 0.05]. Following management at the WHC, women diagnosed with hypertension had significantly improved BP control (6.1 % at baseline vs. 75.8 % at six-month follow-up; p < 0.001). Conclusion: Women with past HDP had five-fold increased incidence of hypertension, with higher daytime hypertension and nocturnal systolic-BP, compared to women with GDM. After attending WHC, BP control significantly improved. Our findings suggest routine postpartum follow-up with 24hr-ABP monitoring, through a WHC, may be useful in early detection and management of hypertension in these women.

The gut microbiota is a crucial link between diet and cardiovascular disease (CVD). Using fecal metaproteomics, a method that concurrently captures human gut and microbiome proteins, we determined the crosstalk between gut microbiome, diet, gut health, and CVD. Traditional CVD risk factors (age, BMI, sex, blood pressure) explained < 10% of the proteome variance. However, unsupervised human protein-based clustering analysis revealed two distinct CVD risk clusters (low-risk and high-risk) with different blood pressure (by 9 mmHg) and sex-dependent dietary potassium and fiber intake. In the human proteome, the low-risk group had lower angiotensin-converting enzymes, inflammatory proteins associated with neutrophil extracellular trap formation and auto-immune diseases. In the microbial proteome, the low-risk group had higher expression of phosphate acetyltransferase that produces SCFAs, particularly in fiber-fermenting bacteria. This model identified severity across phenotypes in heart failure patients and long-term risk of cardiovascular events in a large population-based cohort. These findings underscore multifactorial gut-to-host mechanisms that may underlie risk factors for CVD.

: Pulmonary hypertension is associated with worse outcomes across systemic and cardiopulmonary conditions. Right ventricular (RV) dysfunction often leads to poor outcomes due to a progressive increase in RV afterload. Recognition and management of RV dysfunction are important to circumvent hospitalization and improve patient outcomes. Early recognition of patients at risk for RV failure is important to ensure that medical therapy is optimized and, where appropriate, referral for lung transplant assessment is undertaken. Patients initiated on parenteral prostanoids and those with persistent intermediate to high risk for poor outcomes should be referred. For patients with RV failure, identifying reversible causes should be a priority in conjunction with efforts to optimize RV preload and strategies to reduce RV afterload. Admission to a monitored environment where vasoactive medications can treat RV failure and its sequelae, such as renal dysfunction, is essential in patients with severe RV failure. Exit strategies need to be identified early on, with consideration and implementation of extracorporeal support for those in whom recovery or transplantation are viable options. Enlisting the skills and support of a palliative care team may improve the quality of life for patients with limited options and those with ongoing symptoms from heart failure in the face of medical treatments.

Case Presentation: A 56yo woman with a 12-year history of idiopathic pHTN and severe RV dysfunction presented with worsening exertional angina (CCS III). Perfusion imaging demonstrated a large apical-septal defect, corresponding to an 80% eccentric stenosis of the LMCA on angiography ( Fig 1AB ) due to compression on ostium and shaft by a severely dilated pulmonary trunk ( Fig 1C ). Right heart catheterization revealed pulmonary artery pressures (PAPs) of 90/40/68mmHg. Operative risk for CABG was deemed prohibitive, thus the patient underwent high-risk PCI of the LMCA under IV conscious sedation. Initial angiography confirmed a patent LMCA with minimal longitudinal compression. Opening PAPs (102/37/64mmHg) with supplemental oxygen (FiO 2 /PaO 2 0.76/168mmHg) were similar to preop findings ( Fig 1D ). To replicate her symptomatology, supplemental oxygen was discontinued, resulting in rapid worsening of LMCA compression with severe reduction in LMCA cross-sectional area at room air conditions (FiO 2 /PaO 2 0.21/70mmHg), with corresponding suprasystemic PAP (122/44/73mmHg) ( Fig 1E) . Under IVUS guidance, a preselected stent was deployed producing complete LMCA patency without evidence of dynamic compression; minimal stent areas were unchanged at supraphysiologic and physiologic conditions: 19 vs 20mm 2 , FiO 2 0.73 vs 0.21 ( Fig 1F ). Discussion: LMCA stenosis from extrinsic compression of the vessel by an enlarged pulmonary artery is a rare etiology of acute coronary syndromes. Treatment options include PCI, CABG, reimplantation, or PA reduction plasty. While preop imaging clearly demonstrated LMCA compression by a dilated PA, during PCI true and dynamic severity of LMCA compression was revealed only under “normoxic conditions” (FiO 2 0.21). This paroxysmal “nut-cracker” phenomenon from inadvertent reversal of dynamic LMCA compression highlights the importance of normoxia in making the diagnosis of such anomalies in susceptible individuals with pHTN.

ABSTRACTAimsElevated left atrial (LA) pressure is a pathophysiologic hallmark of heart failure with preserved ejection fraction (HFpEF). Chronically elevated LA pressure leads to LA enlargement, which may impair LA function and increase pulmonary pressures. We sought to evaluate the relationship between LA volume and pulmonary arterial haemodynamics in patients with HFpEF.Methods and resultsData from 85 patients (aged 69 ± 8 years) who underwent exercise right heart catheterization and echocardiography were retrospectively analysed. All had symptoms of heart failure, left ventricular ejection fraction ≥50% and haemodynamic features of HFpEF. Patients were divided into LA volume index‐based tertiles (≤34 ml/m2, >34 to ≤45 ml/m2, >45 ml/m2). A subgroup analysis was performed in patients with recorded LA global reservoir strain (n = 60), with reduced strain defined as ≤24%. Age, sex, body surface area and left ventricular ejection fraction were similar between volume groups. LA volume was associated with blunted increases in cardiac output with exercise (padjusted <0.001), higher resting mean pulmonary artery pressure (padjusted = 0.003), with similar wedge pressure (padjusted = 1). Pulmonary vascular resistance (PVR) increased with increasing LA volume (padjusted <0.001). Larger LA volumes featured reduced LA strain (padjusted <0.001), with reduced strain associated with reduced PVR–compliance time (0.34 [0.28–0.40] vs. 0.38 [0.33–0.43], p = 0.03).ConclusionIncreasing LA volume may be associated with more advanced pulmonary vascular disease in HFpEF, featuring higher PVR and pulmonary pressures. Reduced LA function, worse at increasing LA volumes, is associated with a disrupted PVR–compliance relationship, further augmenting impaired pulmonary haemodynamics.

Background Hypertensive disorders of pregnancy, gestational diabetes, and having a small‐for‐gestational‐age baby are known to substantially increase a woman's risk of cardiovascular disease. Despite this, evidence for models of care that mitigate cardiovascular disease risk in women with these pregnancy‐related conditions is lacking. Methods and Results A 6‐month prospective cohort study assessed the effectiveness of a multidisciplinary Women's Heart Clinic on blood pressure and lipid control in women aged 30 to 55 years with a past pregnancy diagnosis of hypertensive disorders of pregnancy, gestational diabetes, or a small‐for‐gestational age baby in Melbourne, Australia. The co‐primary end points were (1) blood pressure <140/90 mm Hg or <130/80 mm Hg if diabetes and (2) total cholesterol to high‐density lipoprotein cholesterol ratio <4.5. The study recruited 156 women with a mean age of 41.0±4.2 years, 3.9±2.9 years from last delivery, 68.6% White, 20.5% South/East Asian, and 80.5% university‐educated. The proportion meeting blood pressure target increased (69.2% to 80.5%, P=0.004), with no significant change in lipid targets (80.6% to 83.7%, P=0.182). Systolic blood pressure (−6.9 mm Hg [95% CI, −9.1 to −4.7], P<0.001), body mass index (−0.6 kg/m2 [95% CI, −0.8 to −0.3], P<0.001), low‐density lipoprotein cholesterol (−4.2 mg/dL [95% CI, −8.2 to −0.2], P=0.042), and total cholesterol (−4.6 mg/dL [95% CI, −9.1 to −0.2] P=0.042) reduced. Heart‐healthy lifestyle significantly improved with increased fish/olive oil (36.5% to 51.0%, P=0.012), decreased fast food consumption (33.8% to 11.0%, P<0.001), and increased physical activity (84.0% to 92.9%, P=0.025). Conclusions Women at high risk for cardiovascular disease due to past pregnancy‐related conditions experienced significant improvements in multiple cardiovascular risk factors after attending a Women's Heart Clinic, potentially improving long‐term cardiovascular disease outcomes. Registration URL: https://www.anzctr.org.au; Unique identifier: ACTRN12622000646741.

"When You Cannot Rest Assured That Hemodynamics Are Normal in Chronic Thromboembolic Disease: Beyond the European Society of Cardiology/European Respiratory Society Guideline Definition." Annals of the American Thoracic Society, 20(5), pp. 749–755

Background Worldwide, the cardiology profession has an under-representation of women. We assessed medical students' perceptions of cardiology as a career choice with the aim of identifying barriers to gender diversity.Method An anonymous survey was distributed to medical students studying at three Australian medical universities. Questions pertained to demographics, year and stage of medical training, desire to pursue cardiology, and perceived barriers to a cardiology career.Results were analysed according to identified gender and desire to pursue or not pursue a cardiology career. Multivariable logistic regression evaluated for independent associations. The primary outcome were barriers identified to pursuing a career in cardiology.Results From 127 medical student respondents (86.6% female, mean age 25.964.8 years), 37.0% stated they wanted to pursue a career in cardiology (39.1% of women versus 23.5% of men, p=0.54). The top four perceived barriers to a cardiology career included: poor work-life balance (92/127, 72.4%), physician training process (63/127, 49.6%), on-call requirements (50/127, 39.4%) and lack of flexibility (49/127, 38.6%), with no gender differences. Women were more likely to report gender-related barriers (37.3% versus 5.9%, p=0.01) and less likely to identify procedural aspects as a barrier (5.5% women versus 29.4% men, p=0.001). Stu-dents in their pre-clinical years were more likely to want a career in cardiology (odds ratio 3.0, 95% con-fidence interval 1.2-7.7, p=0.02).Conclusions A high proportion of female and male medical students want to pursue a career in cardiology with both genders identifying major barriers of poor work-life balance, lack of flexibility, on-call requirements and the training process.

Cardiogenic shock is associated with a high risk for morbidity and mortality. The impact of gender on treatment and outcomes is poorly defined. This study aimed to evaluate whether gender influences the clinical management and outcomes of patients with prehospital cardiogenic shock. Consecutive adult patients with cardiogenic shock who were transferred to hospital by emergency medical services (EMS) between January 1, 2015 and June 30, 2019 in Victoria, Australia were included. Data were obtained from individually linked ambulance, hospital, and state death index datasets. The primary outcome assessed was 30-day mortality, stratified by patient gender. Propensity score matching was performed for risk adjustment. Over the study period a total of 3,465 patients were identified and 1,389 patients (40.1%) were women. Propensity score matching yielded 1,330 matched pairs with no differences observed in baseline characteristics, including age, initial vital signs, pre-existing co-morbidities, etiology of shock, and prehospital interventions. In the matched cohort, women had higher rates of 30-day mortality (44.7% vs 39.2%, p = 0.009), underwent less coronary angiography (18.3% vs 27.2%, p <0.001), and revascularization with percutaneous coronary intervention (8.9% vs 14.2%, p <0.001), compared with men. In conclusion, in this large population-based study, women with cardiogenic shock who were transferred by EMS to hospital had significantly worse survival outcomes and reduced rates of invasive cardiac interventions compared to men. These data underscore the urgent need for targeted public health measures to redress gender differences in outcomes and variation with clinical care for patients with cardiogenic shock.

Arrhythmias are the most common cardiac complications occurring in pregnancy. Although the majority of palpitations in pregnancy may be explained by atrial or ventricular premature complexes, the full spectrum of arrhythmias can occur. In this article, we establish a systematic approach to the evaluation and management of arrhythmias in pregnancy. Haemodynamically unstable arrhythmias warrant urgent cardioversion. For mild cases of benign arrhythmia, treatment is usually not needed. Symptomatic but haemodynamically stable arrhythmic patients should first undergo a thorough evaluation to establish the type of arrhythmia and the presence or absence of structural heart disease. This will ultimately determine the necessity for treatment given the potential risks of anti-arrhythmic pharmacotherapy in pregnancy. We will discuss the main catalogue of anti-arrhythmic medications, which have some established evidence of safety in pregnancy. Based on our appraisal, we provide a treatment algorithm for the tachyarrhythmic pregnant patient.

Heart failure affects over 2.6 million women and 3.4 million men in the United States with known sex differences in epidemiology, management, response to treatment, and outcomes across a wide spectrum of cardiomyopathies that include peripartum cardiomyopathy, hypertrophic cardiomyopathy, stress cardiomyopathy, cardiac amyloidosis, and sarcoidosis. Some of these sex-specific considerations are driven by the cellular effects of sex hormones on the renin-angiotensin-aldosterone system, endothelial response to injury, vascular aging, and left ventricular remodeling. Other sex differences are perpetuated by implicit bias leading to undertreatment and underrepresentation in clinical trials. The goal of this narrative review is to comprehensively examine the existing literature over the last decade regarding sex differences in various heart failure syndromes from pathophysiological insights to clinical practice.

Paradoxical cerebral embolism, although rare, can be secondary to acquired causes such as superior vena cava (SVC) occlusion and development of a mediastinal right-to-left shunt. Such shunts allow undisturbed passage of thromboemboli to bypass the pulmonary circulation and enter the systemic circulation. This report presents a case of paradoxical cerebral embolism due to a right-to-left shunt originating from occlusion of the SVC. The etiology of the SVC occlusion stems from a prior central venous access line used for treatment of lymphoma. The patient underwent endovascular treatment with successful coil embolization of the mediastinal shunt.

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.

Objective Significant gender disparities exist in some medical specialties, particularly cardiology. We assessed work, personal life and work-life balance in women in cardiology in Australia and New Zealand (NZ), compared with other specialties, to determine factors that may contribute to the lack of women in the specialty. Methods This study is a prospective survey-based cohort study comparing cardiology and non-cardiology specialties. An online survey was completed by female doctors in Australia and NZ, recruited via email lists and relevant social media groups. The survey included demographics, specialty, stage of training, work hours/setting, children and relationships, career satisfaction, income and perceptions of specialty. Results 452 participants completed the survey (median age 36 years), of which 57 (13%) worked in cardiology. Of all respondents, 84% were partnered and 75% had children, with no difference between cardiology and non-cardiology specialties. Compared with non-cardiology specialties, women in cardiology worked more hours per week (median 50 hours vs 40 hours, p<0.001), were more likely to be on call more than once per week (33% vs 12%, p<0.001) and were more likely to earn an annual income >$3 00 000 (35% vs 10%, p<0.001). Women in cardiology were less likely to agree that they led a balanced life (33% vs 51%, p=0.03) or that their specialty was female friendly (19% vs 75%, p<0.001) or family friendly (20% vs 63%, p<0.001). Conclusions Compared with other specialties, women in cardiology reported poorer work-life balance, greater hours worked and on-call commitments and were less likely to perceive their specialty as female friendly or family friendly. Addressing work-life balance may attract and retain more women in cardiology.

Abstract Aims Women are overrepresented amongst patients with heart failure with preserved ejection fraction (HFpEF); however, the underpinning mechanism for this asymmetric distribution is unclear. Pregnancy represents a potential gender‐specific risk factor for HFpEF. It leads to significant physiological adaption, and increasing parity has been associated with some cardiovascular risk. We sought to examine the relationship between prior parity with the rest and exercise haemodynamic and echocardiographic profile of women with HFpEF. Methods and results Patients referred for assessment of exertional dyspnoea and confirmed to have a haemodynamic and clinical profile consistent with HFpEF were included. Detailed evaluation consisted of rest and exercise right heart catheterization and echocardiography. A socio‐economic and obstetric history was also documented. Fifty‐eight women were assessed and categorized as having either 0–2 births or ≥3 births, dividing the cohort equally. Women with ≥3 births achieved a lower symptom‐limited workload than those with 0–2 births [38 (24–51) vs. 46 (31–68) W, P = 0.04]. Women with ≥3 births had a greater rise in pulmonary capillary wedge pressure indexed to workload with exercise [0.5 (0.3–0.8) vs. 0.3 (0.2–0.5) mmHg/W, P = 0.03], paralleled by a greater rise in right atrial pressure [10 (8–12) vs. 7 (3–11), P = 0.01]. Pulmonary vascular resistance was also higher in women with ≥3 births [1.9 (1.6–2.4) vs. 1.6 (1.4–1.9) mmHg/L/min rest, P = 0.046, and 1.9 (2.4–2.4) vs. 1.4 (1–1.8) mmHg/L/min exercise, P = 0.024]. Left ventricular ejection fraction was lower at rest [60 (57–61) vs. 63 (60–66), P = 0.008] and during exercise [65 (62–67) vs. 68 (66–70), P = 0.038] in women with higher parity. Conclusions Higher parity is associated with greater impairments in multiple physiologic parameters of HFpEF severity in women, including diastolic reserve, pulmonary vascular resistance, and systolic dysfunction.

Heart failure (HF) with a preserved ejection fraction (HFpEF) is now the predominant HF subtype in Europe. It manifests as reduced cardiac output and/or increased left ventricular filling pressures at rest and/or during exercise, caused by left ventricular diastolic dysfunction. HFpEF is proposed to occur as a result of systemic microvascular endothelial inflammation associated with various comorbidities such as hypertension, obesity, and diabetes. However, nearly two-thirds of those with HFpEF are females, which points to sex-specific driving factors such as differences in cardiac structure and physiology, and in systemic and pulmonary circulation; oestrogenic influence on physiology and molecular mechanisms; and pregnancy-related hypertensive disorders. Pharmacotherapy for HFpEF is lagging behind that for HF with reduced ejection fraction, and no treatment has yet been convincingly shown to reduce morbidity or mortality. Current treatment strategies target symptom alleviation and comorbidities. No trials have specifically examined the difference between sexes in response to HFpEF treatment; however, post hoc analyses have revealed differing effects of some treatments according to sex, such as spironolactone or sacubitril/ valsartan, which may be of more use in females with HFpEF than in males. Further studies are needed to confirm if better outcomes were because of specific female physiology and HFpEF pathophysiology, and whether the outcome measures can be more tailored to address the goals Authors: *Philippe Meyer,1 Anna L. Beale2,3 1. Heart Failure and Cardiac Rehabilitation Unit, Cardiology Service, Geneva University Hospitals, Geneva, Switzerland 2. Cardiology Unit, Alfred Hospital, Melbourne, Australia 3. Heart Failure Research Group, Baker Heart and Diabetes Institute, Melbourne, Australia *Correspondence to philippe.meyer@hcuge.ch Disclosure: Dr Meyer has served on advisory boards for and participated in seminars organised by Novartis, Vifor Pharma, Servier, Abbott, Boehringer Ingelheim, and Bayer, whose honoraria have been entirely paid to a private research foundation of the Cardiology Service of the University Hospitals of Geneva (GEcor foundation). Dr Beale has declared no conflicts of interest. Acknowledgements: All authors participated in writing and approved the final manuscript. Writing assistance was provided by Dr Eleanor Roberts of Beeline Science Communications Ltd, London, UK, funded by the EMJ. The authors would like to thank Prof John McMurray who provided supplementary data of the PARAGON-HF trial used in

Hypertensive response to exercise (HTR - peak systolic blood pressure (BP) ≥190 mmHg in women; ≥220 mmHg in men during exercise) contributes to the development of HFpEF and subsequent exercise intolerance. This study assesses the reliability of non-invasive (NI) BP monitoring for the diagnosis of HTR in suspected HFpEF patients undergoing exercise right heart catheterisation (ExRHC). Methods: Data from 12 patients with suspected HFpEF undergoing ExRHC were retrospectively analysed. BP was recorded simultaneously from invasive radial arterial monitoring (IBP) and NI cuff measurements. 6 patients met HTR criteria from IBP monitoring, and 6 did not (non-HTR). BP at rest and peak exercise in the HTR and non-HTR subgroups were correlated and also analysed for agreement using the Bland-Altman method and plotted graphically as shown. Results: NIBP monitoring detected HTR in only 2 of 6 (33%) cases. Poor correlation between IBP and NIBP at exercise in HTR is demonstrated from Pearson correlation coefficient analysis: Non-HTR – rest r = 0.88; exercise r = 0.87 – HTR: rest r = 0.81; exercise r = 0.44. Agreement between measurement techniques diverges at peak exercise; with this discrepancy exaggerated in patients with HTR. Conclusion: Invasive BP monitoring may be required to accurately diagnose HTR in this patient cohort, and its use could be considered during ExRHC.

Over the past decade, the immune system has emerged as an important component in the aetiology of hypertension. There has been a blooming interest in the contribution of the gut microbiota, the microbes that inhabit our small and large intestine, to blood pressure (BP) regulation. The gastrointestinal tract houses the largest number of immune cells in our body, thus, it is no surprise that its microbiota plays an important functional role in the appropriate development of the immune system through a co-ordinated sequence of events leading to immune tolerance of commensal bacteria. Importantly, recent evidence supports that the gut microbiota can protect or promote the development of experimental hypertension and is likely to have a role in human hypertension. One of the major modulators of the gut microbiota is diet: diets that emphasize high intake of fermentable fibre, such as the Mediterranean diet and the Dietary Approaches to Stop Hypertension, promote expansion of protective microbes that release gut metabolites such as short-chain fatty acids, which are immune-, BP-, and cardio-protective, likely acting through G-coupled protein receptors. In contrast, diets lacking fibre or high in salt and fat, such as the Western diet, reduce prevalence of commensal microbial species and support a pathogenic and pro-inflammatory environment, including the release of the pro-atherosclerotic trimethylamine N-oxide. Here, we review the current understanding of the gut microbiota-driven immune dysfunction in both experimental and clinical hypertension, and how these changes may be addressed through dietary interventions.