Endomyocardial Biopsy Characterization of Heart Failure With Preserved Ejection Fraction and Prevalence of Cardiac Amyloidosis

Hahn, Virginia S.; Yanek, Lisa R.; Vaishnav, Joban; Ying, Wendy; Vaidya, Dhananjay; Lee, Yi Zhen Joan; Riley, Sarah; Subramanya, Vinita; Brown, Emily; Hopkins, C. Danielle; Ononogbu, Sandra; Mandell, Kira A. Perzel; Halushka, Marc K.; Steenbergen, Charles; Rosenberg, Avi Z.; Tedford, Ryan J.; Judge, Daniel P.; Shah, Sanjiv J.; Russell, Stuart D.; Kass, David A.; Sharma, Kavita

doi:10.1016/j.jchf.2020.04.007

Cited by 152 publications

(143 citation statements)

References 30 publications

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“…In 2015 Gonzalez-Lopez et al 3 suggested that ATTRwt is an underdiagnosed disease accounting for up to 13% of HFpEF cases. Although this percentage appeared very high and might have been related to a possible referral bias in a specialized centre in Madrid, a similar figure was reported in a retrospective analysis of endomyocardial biopsies by Hahn et al 4 Given the high prevalence of HFpEF in the general population (that has been reported between 1% and 5%), this suggests that a very high number of patients in whom wild-type transthyretin deposit is contributing to heart failure are still without a diagnosis. This clearly represents an unmet need asking for a proactive approach.…”

Section: This Article Refers To 'Efficacy and Safety Of Tafamidis Dossupporting

confidence: 70%

“…The availability of several treatment options is forcing the clinician to strive for a much earlier diagnosis, that implies a raised awareness of the disease in the general 'real-world' patient population. 16 Given the potential prevalence of ATTR cardiomyopathy in heart failure that has been suggested by Gonzalez-Lopez et al 3 and Hahn et al, 4 the number of still undiagnosed patients is unacceptably high. A 'call-to-action' is clearly needed, with the further advantage of a general consensus on the diagnostic workup 17,18 and the possibilities offered by bone tracer scintigraphy in recognizing cardiac deposits.…”

Section: This Article Refers To 'Efficacy and Safety Of Tafamidis Dosmentioning

confidence: 99%

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New effective treatment options reinforce disease awareness: the case of transthyretin cardiac amyloidosis

Perlini

Mussinelli

Salinaro

2021

European J of Heart Fail

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Section: This Article Refers To 'Efficacy and Safety Of Tafamidis Dossupporting

confidence: 70%

Section: This Article Refers To 'Efficacy and Safety Of Tafamidis Dosmentioning

confidence: 99%

New effective treatment options reinforce disease awareness: the case of transthyretin cardiac amyloidosis

Perlini

Mussinelli

Salinaro

2021

European J of Heart Fail

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“…Due to these significant therapeutic effects of Sac/Val in patients with HFrEF, several important international medical institutions, such as European Medicines Agency (EMA), Food and Drug Administration (FDA), American Heart Association (AHA), and New York Heart Association (NYHA), have approved Sac/Val as a replacement of ACE inhibitors for treating HFrEF patients ( Fala, 2015 ; Yancy et al, 2017 ). HFpEF and HFrEF are known to share some pathophysiological characteristics, such as cardiac fibrosis ( Hahn et al, 2020 ). Thus, we conducted this study to investigate whether Sac/Val could relieve symptoms of HFpEF.…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies have shown that HFpEF and HFrEF share some pathophysiological characteristics, such as fibrosis ( Hahn et al, 2020 ). Thus, Sac/Val could serve as a novel therapeutic agent for the treatment of HFpEF as well.…”

Section: Introductionmentioning

confidence: 99%

Sacubitril/Valsartan Reduces Fibrosis and Alleviates High-Salt Diet-Induced HFpEF in Rats

Zhang

Liu

et al. 2021

Front. Pharmacol.

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Previous studies have confirmed the clinical efficacy of sacubitril/valsartan (Sac/Val) for the treatment of heart failure with reduced ejection fraction (HFrEF). However, the role of Sac/Val in heart failure with preserved ejection fraction (HFpEF) remains unclear. Sac/Val is a combination therapeutic medicine comprising sacubitril and valsartan that acts as a first angiotensin receptor blocker and neprilysin inhibitor (angiotensin-receptor neprilysin inhibitor (ARNI)). Here, we investigated the role of Sac/Val in high-salt diet-induced HFpEF coupled with vascular injury as well as the underlying mechanism. Rats were fed with high-salt feed, followed by intragastric administration of Sac/Val (68 mg/kg; i.g.). The results of functional tests revealed that a high-salt diet caused pathological injuries in the heart and vascular endothelium, which were significantly reversed by treatment with Sac/Val. Moreover, Sac/Val significantly decreased the levels of fibrotic factors, including type I collagen and type Ⅲ collagen, thus, reducing the ratio of MMP2/TIMP2 while increasing Smad7 levels. Further investigation suggested that Sac/Val probably reversed the effects of high-salt diet-induced HFpEF by inhibiting the activation of the TGF-β1/Smad3 signaling pathway. Thus, treatment with Sac/Val effectively alleviated the symptoms of high-salt diet-induced HFpEF, probably by inhibiting fibrosis via the TGF-β1/Smad3 signaling pathway, supporting the therapeutic potential of Sac/Val for the treatment of HFpEF.

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“…Higher competing risks of non‐cardiovascular death among patients with HFpEF may be less modifiable with ARNI. Amyloid deposition and sarcomeric myocardial abnormalities (including hypertrophic cardiomyopathy) may be important to disease progression in some patients with HFpEF (especially with normal or supra‐normal LVEF), 31 which would not be expected to be modified with ARNI.…”

Section: Therapeutic Heterogeneity To Angiotensin Receptor–neprilysinmentioning

confidence: 99%

Angiotensin receptor–neprilysin inhibition in heart failure with preserved ejection fraction: lessons from PARAGON‐HF

Vaduganathan

McMurray

Solomon

2020

European J of Heart Fail

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Identifying effective therapies for patients living with heart failure (HF) with preserved ejection fraction (HFpEF) has remained challenging. The recently completed PARAGON-HF (Prospective Comparison of ARNI with ARB Global Outcomes in HF With Preserved Ejection Fraction), 1 the largest HFpEF trial conducted to date, examined a first-in-class angiotensin receptor-neprilysin inhibitor (ARNI), sacubitril/valsartan, compared with valsartan among 4822 patients with signs and symptoms of HF, left ventricular ejection fraction (LVEF) ≥45%, elevated natriuretic peptides, and evidence of structural heart disease. Patients allocated to sacubitril/valsartan experienced modestly lower rates of composite cardiovascular death and total HF hospitalizations compared with patients randomized to valsartan after a median follow-up of 35 months, but this treatment effect did not meet pre-specified statistical significance thresholds (Figure 1). We contextualize these trial findings, including learnings from subsequent secondary analyses, and reflect on key trial elements that may inform the next phase of therapeutic development in HFpEF. Were the intended biological pathways affected and anticipated haemodynamic responses achieved in PARAGON-HF? Irrespective

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Endomyocardial Biopsy Characterization of Heart Failure With Preserved Ejection Fraction and Prevalence of Cardiac Amyloidosis

Cited by 152 publications

References 30 publications

New effective treatment options reinforce disease awareness: the case of transthyretin cardiac amyloidosis

New effective treatment options reinforce disease awareness: the case of transthyretin cardiac amyloidosis

Sacubitril/Valsartan Reduces Fibrosis and Alleviates High-Salt Diet-Induced HFpEF in Rats

Angiotensin receptor–neprilysin inhibition in heart failure with preserved ejection fraction: lessons from PARAGON‐HF

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