No abstract

No abstract

Aims The HFA‐PEFF and H2FPEF scores have been developed to diagnose heart failure with preserved ejection fraction (HFpEF), and hold prognostic value. Their value in patients with HFpEF caused by cardiac amyloidosis (CA) has never been investigated. Methods and results We evaluated the diagnostic and prognostic value of the HFA‐PEFF and H2FPEF scores in 304 patients from three cohorts with HFpEF caused by transthyretin CA (n = 160, 53%) or immunoglobulin light‐chain CA (n = 144, 47%). A diagnosis of HFpEF was more likely using the HFA‐PEFF score with 2 (1%), 71 (23%), and 231 (76%) patients ranked as having a low (0–1), intermediate (2–4), or high (5, 6) probability of HFpEF, respectively. Conversely, 36 (12%), 179 (59%) and 89 (29%) of patients ranked as having a low (0–1), intermediate (2–5), or high (6–9) probability of HFpEF using the H2FPEF score. During a median follow‐up of 19 months (interquartile range 8–40), 132 (43%) patients died. The HFA‐PEFF score, but not the H2FPEF score, predicted a high risk of all‐cause death which remained significant after adjustment for age, AL‐CA diagnosis, high‐sensitivity troponin T, N‐terminal pro‐B‐type natriuretic peptide, and echocardiographic parameters, including left ventricular global longitudinal strain, left ventricular diastolic function and right ventricular function (hazard ratio 1.51, 95% confidence interval 1.16–1.95, p = 0.002 for every 1‐point increase in HFA‐PEFF). Conclusions The HFA‐PEFF score has a higher diagnostic utility in HFpEF caused by CA and holds independent prognostic value for all‐cause mortality, while the H2FPEF score does not.

Aims The HFA-PEFF and H2FPEF scores have been developed to diagnose heart failure with preserved ejection fraction (HFpEF), and hold prognostic value. Their use in patients with HFpEF caused by cardiac amyloidosis (CA) has never been investigated. Methods and results We evaluated the diagnostic and prognostic value of the HFA-PEFF and H2FPEF scores in 304 patients from 3 cohorts with HFpEF caused by transthyretin (ATTR)-CA (n=160, 53%) or immunoglobulin light-chain (AL)-CA (n=144, 47%). A diagnosis of HFpEF was more likely using the HFA-PEFF score with 2 (1%), 71 (23%), and 231 (76%) patients ranked as having a low (0–1), intermediate (2–4) or high (5–6) probability of HFpEF, respectively. Conversely, 36 (12%), 179 (59%) and 89 (29%) of patients ranked as having a low (0–1), intermediate (2–5) or high (6–9) probability of HFpEF using the H2FPEF score. During a median follow-up of 19 months (interquartile range 8–40), 132 (43%) patients died. The HFA-PEFF score, but not the H2FPEF, predicted a high risk of all-cause death which remained significant after adjustment for age, AL-CA diagnosis, high-sensitivity troponin T, N-terminal pro-B-type natriuretic peptide, and echocardiographic parameters, including left ventricular (LV) global longitudinal strain, LV diastolic function and right ventricular function (hazard ratio 1.51, 95% confidence interval 1.16–1.95, p=0.002 for every 1-point increase in HFA-PEFF). Conclusions The HFA-PEFF score has a high sensitivity to diagnose HFpEF caused by CA and holds independent prognostic value for all-cause mortality, while the H2FPEF score does not. Funding Acknowledgement Type of funding sources: None.

Aims Cardiac amyloidosis (CA) affects the four heart chambers, which can all be evaluated through speckle-tracking echocardiography (STE). Methods and results We evaluated 423 consecutive patients screened for CA over 5 years at two referral centres. CA was diagnosed in 261 patients (62%) with either amyloid transthyretin (ATTR; n = 144, 34%) or amyloid light-chain (AL; n = 117, 28%) CA. Strain parameters of all chambers were altered in CA patients, particularly those with ATTR-CA. Nonetheless, only peak left atrial longitudinal strain (LA-PALS) displayed an independent association with the diagnosis of CA or ATTR-CA beyond standard echocardiographic variables and cardiac biomarkers (Model 1), or with the diagnosis of ATTR-CA beyond the validated IWT score in patients with unexplained left ventricular (LV) hypertrophy. Patients with the most severe impairment of LA strain were those most likely to have CA or ATTR-CA. Specifically, LA-PALS and/or LA-peak atrial contraction strain (PACS) in the first quartile (i.e. LA-PALS <6.65% and/or LA-PACS <3.62%) had a 3.60-fold higher risk of CA, and a 3.68-fold higher risk of ATTR-CA beyond Model 1. Among patients with unexplained LV hypertrophy, those with LA-PALS or LA-PACS in the first quartile had an 8.76-fold higher risk for CA beyond Model 1, and a 2.04-fold higher risk of ATTR-CA beyond the IWT score. Conclusions Among STE measures of the four chambers, PALS and PACS are the most informative ones to diagnose CA and ATTR-CA. Patients screened for CA and having LA-PALS and/or LA-PACS in the first quartile have a high likelihood of CA and ATTR-CA.

The significant morbidity and mortality associated with heart failure with reduced (HFrEF) or preserved ejection fraction (HFpEF) justify the search for novel therapeutic agents. The nitric oxide (NO)–soluble guanylate cyclase (sGC)-cyclic guanosine monophosphate (cGMP) pathway plays an important role in the regulation of cardiovascular function. This pathway is disrupted in HF resulting in decreased protection against myocardial injury. The sGC activator cinaciguat increases cGMP levels by direct, NO-independent activation of sGC, and may be particularly effective in conditions of increased oxidative stress and endothelial dysfunction, and then reduced NO levels, but this comes at the expense of a greater risk of hypotension. Conversely, sGC stimulators (riociguat and vericiguat) enhance sGC sensitivity to endogenous NO, and then exert a more physiological action. The phase 3 VICTORIA trial found that vericiguat is safe and effective in patients with HFrEF and recent HF decompensation. Therefore, adding vericiguat may be considered in individual patients with HFrEF, particularly those at higher risk of HF hospitalization; the efficacy of the sacubitril/valsartan-vericiguat combination in HFrEF is currently unknown.

Pirfenidone (PFD) slows the progression of idiopathic pulmonary fibrosis (IPF) by inhibiting the exaggerated fibrotic response and possibly through additional mechanisms, such as anti-inflammatory effects. PFD has also been evaluated in other fibrosing lung diseases. Myocardial fibrosis is a common feature of several heart diseases and the progressive deposition of extracellular matrix due to a persistent injury to cardiomyocytes may trigger a vicious cycle that leads to persistent structural and functional alterations of the myocardium. No primarily antifibrotic medications are used to treat patients with heart failure. There is some evidence that PFD has antifibrotic actions in various animal models of cardiac disease and a phase II trial on patients with heart failure and preserved ejection fraction has yielded positive results. This review summarises the evidence about the possible mechanisms of IPF and modulation by PFD, the main results about IPF or non-IPF interstitial pneumonias and also data about PFD as a potential protective cardiac drug.

No abstract