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.

18F-FDG PET/CT improves diagnostic certainty in native and prosthetic valve Infective Endocarditis over the modified Duke Criteria.

BACKGROUND: International guidance recognizes the shortcomings of the modified Duke Criteria (mDC) in diagnosing infective endocarditis (IE) when transoesophageal echocardiography (TOE) is equivocal. 18F-FDG PET/CT (PET) has proven benefit in prosthetic valve endocarditis (PVE), but is restricted to extracardiac manifestations in native disease (NVE). We investigated the incremental benefit of PET over the mDC in NVE. METHODS: Dual-center retrospective study (2010-2018) of patients undergoing myocardial suppression PET for NVE and PVE. Cases were classified by mDC pre- and post-PET, and evaluated against discharge diagnosis. Receiver Operating Characteristic (ROC) analysis and net reclassification index (NRI) assessed diagnostic performance. Valve standardized uptake value (SUV) was recorded. RESULTS: 69/88 PET studies were evaluated across 668 patients. At discharge, 20/32 had confirmed NVE, 22/37 PVE, and 19/69 patients required surgery. PET accurately re-classified patients from possible, to definite or rejected (NRI: NVE 0.89; PVE 0.90), with significant incremental benefit in both NVE (AUC 0.883 vs 0.750) and PVE (0.877 vs 0.633). Sensitivity and specificity were 75% and 92% in NVE; 87% and 86% in PVE. Duration of antibiotics and C-reactive Protein level did not impact performance. No diagnostic SUV cut-off was identified. CONCLUSION: PET improves diagnostic certainty when combined with mDC in NVE and PVE.

20-hydroxyeicosatetraenoic acid (20-HETE) is a pivotal endogenous ligand for TRPV1-mediated neurogenic inflammation in the skin.

BACKGROUND AND PURPOSE: Transient receptor potential cation channel subfamily V member 1 (TRPV1) is localized to sensory C-fibres and its opening leads to membrane depolarization, resulting in neuropeptide release and neurogenic inflammation. However, the identity of the endogenous activator of TRPV1 in this setting is unknown. The arachidonic acid metabolites 12-hydroperoxyeicosatetraenoyl acid (12-HpETE) and 20-hydroxyeicosatetraenoic acid (20-HETE) have emerged as potential endogenous activators of TRPV1. However, whether these lipids underlie TRPV1-mediated neurogenic inflammation remains unknown. EXPERIMENTAL APPROACH: We analysed human cantharidin-induced blister samples and inflammatory responses in TRPV1 transgenic mice. KEY RESULTS: In a human cantharidin-blister model, the potent TRPV1 activators 20-HETE but not 12-HETE (stable metabolite of 12-HpETE) correlated with arachidonic acid levels. Similarly, in mice, levels of 20-HETE (but not 12-HETE) and arachidonic acid were strongly positively correlated within the inflammatory milieu. Furthermore, LPS-induced oedema formation and neutrophil recruitment were substantially and significantly attenuated by pharmacological block or genetic deletion of TRPV1 channels, inhibition of 20-HETE formation or SP receptor neurokinin 1 (NK1 ) blockade. LPS treatment also increased cytochrome P450 ω-hydroxylase gene expression, the enzyme responsible for 20-HETE production. CONCLUSION AND IMPLICATIONS: Taken together, our findings suggest that endogenously generated 20-HETE activates TRPV1 causing C-fibre activation and consequent oedema formation. These findings identify a novel pathway that may be useful in the therapeutics of diseases/conditions characterized by a prominent neurogenic inflammation, as in several skin diseases.

Recurrent strokes in an occult case of recurrent Cutibacterium acnes prosthetic valve infective endocarditis: a case report.

BACKGROUND: Infective endocarditis (IE) is a known but uncommon cause of cardioembolic stroke and there are rare but recognized cases of IE without an inflammatory response. Cutibacterium acnes is an increasingly recognized source of invasive infections, including IE, but diagnosis is challenging due to its low virulence and fastidious nature. CASE SUMMARY: A 47-year-old man presented with a multi-focal stroke suggestive of a cardioembolic source. Outpatient transoesophageal echocardiography (TOE) was concerning for vegetation or thrombus associated with his previous mitral valve repair. He remained clinically well, with no evidence of an inflammatory response and sterile blood cultures. Computed tomography-positron emission tomography (CT-PET) corroborated the TOE findings, however, given the atypical presentation, he was treated for valvular thrombus. Following discharge, he quickly re-presented with further embolic phenomena and underwent emergency mitral valve replacement. Intraoperative findings were consistent with prosthetic valve IE (PVE) and a 6-week course of antibiotics commenced. C. acnes was identified on molecular testing. Eighteen months later, he re-presented with further neurological symptoms. Early TOE and CT-PET were consistent with IE. Blood cultures grew C. acnes after prolonged incubation. Given the absence of surgical indications, he was managed medically, and the vegetation resolved without valvular dysfunction. He continues to be followed up in an outpatient setting. DISCUSSION: In patients presenting with multi-territory stroke, IE should be considered despite sterile blood cultures and absent inflammatory response. C. acnes is an increasingly recognized cause of PVE in this context, often requiring surgical intervention. A high index of suspicion and collaboration with an Endocarditis Team is therefore essential to diagnose and treat.