Mihai Gheorghiade, MD-Life and Concepts

How do you capture an idea, shape it, and then bring it into the world? Of his many talents, this ability was a fundamental characteristic of Mihai Gheorghiade. A quick glance through PubMed confirms his prodigious output, likely to overwhelm any novice or even expert scholar. His contribution to heart failure, especially acute heart failure (AHF), is profound, He authored several major concepts in acute heart failure, disseminated further by his students. Most concepts remained indelibly linked to his name: Digoxin trials research(1–3), AHFS (acute heart failure syndromes) definition(4), hemodynamic congestion(5), hospitalized heart failure (HHF) (6), the vulnerable phase(7,8), neutral hemodynamic agents(9), registries(10–12) and pre-trial registries(13), the “6-axis model”(14) and then the “8-axis model”(15). His work shaped the field of AHF

Revisiting hyperkalaemia guidelines: rebuttal

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146358/1/ejhf1249_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146358/2/ejhf1249.pd

Need to revisit heart failure treatment guidelines for hyperkalaemia management during the use of mineralocorticoid receptor antagonists

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146426/1/ejhf1217.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146426/2/ejhf1217_am.pd

Emerging therapies in transthyretin amyloidosis – a new wave of hope after years of stagnancy?

Transthyretin amyloidosis (ATTR) is a rare, yet underdiagnosed disease characterized by progressive impairment of neurologic and cardiac function due to deposition of misfolded transthyretin. Despite great efforts, such as the introduction of orthotopic liver transplant, the devastating prognosis for both variant and wild-type ATTR patients remained unchanged over the last decades, mainly due to a lack of specific therapies. Fortunately, recent years saw the introduction of promising targeted therapies, which aim to interfere with the deposition of misfolded transthyretin (TTR) at various stages of the cascade underlying ATTR progression. These include TTR tetramer stabilizers (tafamidis, diflunisal, epigallocatechin-3-gallate), TTR silencers (inotersen, patisiran) and fibril disruptors (monoclonal antibodies, doxycycline and tauroursodeoxycholic acid). In the context of this review we explain their mechanisms of action, analyse their efficacy on neurologic and cardiac function based on all clinical trials conducted to date and discuss their clinical applicability. Eventually suggestions for future clinical research into the field are provided

Effects of canagliflozin on cardiovascular biomarkers in older adults with type 2 diabetes

Background: Sodium glucose co-transporter 2 (SGLT2) inhibitors may reduce cardiovascular and heart failure risk in patients with type 2 diabetes mellitus (T2DM). Objectives: To examine the effects of canagliflozin on cardiovascular biomarkers in older patients with T2DM. Methods: In 666 T2DM patients randomized to receive canagliflozin 100 or 300 mg or placebo, we assessed median percent change in serum N-terminal pro-B type natriuretic peptide (NT-proBNP), high-sensitivity troponin I (hsTnI) , soluble (s)ST2, and galectin-3 from baseline to 26, 52, and 104 weeks. Results: Both serum NT-proBNP and serum hsTnI levels increased in placebo recipients but remained largely unchanged in those randomized to canagliflozin. Hodges-Lehmann estimates of the difference in median percent change between pooled canagliflozin and placebo were –15.0%, –16.1%, and –26.8% for NT-proBNP, and –8.3%, –11.9%, and –10.0% for hsTnI at weeks 26, 52, and 104, respectively (all P <0.05). Serum sST2 was unchanged with canagliflozin and placebo over 104 weeks. Serum galectin-3 modestly increased from baseline with canagliflozin versus placebo, with significant differences observed at 26 and 52 weeks but not at 104 weeks. These results remained unchanged when only patients with complete samples were assessed. Conclusions: Compared to placebo, treatment with canagliflozin delayed rise in serum NT-proBNP and hsTnI over 2 years in older T2DM patients. These cardiac biomarker data provide support for beneficial cardiovascular effect of SGLT2 inhibitors in T2DM

Acute Dyspnea and Decompensated Heart Failure

The majority of patients hospitalized with acute heart failure (AHF) initially present to the emergency department (ED). Correct diagnosis followed by prompt treatment ensures optimal outcomes. Paradoxically, identification of high risk is not the unmet need, given nearly all ED AHF patients are hospitalized; rather, it is identification of low-risk. Currently, no risk-stratification instrument can be universally recommended to safely discharge ED patients. With the exception of diagnosis, management recommendations are largely expert opinion, informed by existing evidence and tradition. In the absence of robust evidence, we propose a framework for management to guide the busy clinician