Temporal Relation Between Myocardial Fibrosis and Heart Failure With Preserved Ejection Fraction

Schelbert, Erik B.; Fridman, Yaron; Wong, Timothy C.; Daya, Hussein Abu; Piehler, Kayla; Kadakkal, Ajay; Miller, Chris; Ugander, Martin; Maanja, Maren; Kellman, Peter; Shah, Dipan J.; Abebe, Kaleab Z.; Simon, Marc A.; Quarta, Giovanni; Senni, Michele; Butler, Javed; Dı́ez, Javier; Redfield, Margaret M.; Gheorghiade, Mihai

doi:10.1001/jamacardio.2017.2511

Cited by 178 publications

(117 citation statements)

References 30 publications

Supporting

Mentioning

112

Contrasting

Order By: Relevance

“…These findings should be considered hypothesis‐generating and tested in more extensive, longitudinal trials evaluating the transition from HT to HFpEF. Alternative techniques should be performed to confirm our results, including the assessment of central aortic pressure, arterial stiffness and myocardial fibrosis . HFpEF represents a complex clinical syndrome to which different cardiovascular risk factors and diseases are related.…”

Section: Discussionmentioning

confidence: 63%

Haemodynamic and metabolic phenotyping of hypertensive patients with and without heart failure by combining cardiopulmonary and echocardiographic stress test

Pugliese

Mazzola

Fabiani

et al. 2020

European J of Heart Fail

View full text Add to dashboard Cite

Aim We combined cardiopulmonary exercise test (CPET) and exercise stress echocardiography (ESE) to identify early haemodynamic and metabolic alterations in patients with hypertension (HT) with and without heart failure with preserved ejection fraction (HFpEF). Methods and results Fifty stable HFpEF‐HT outpatients (mean age 68 ± 14 years) on optimal medical therapy, 63 well‐controlled HT subjects (mean age 63 ± 11 years) and 32 age and sex‐matched healthy controls (mean age 59 ± 15 years) underwent a symptom‐limited graded ramp bicycle CPET‐ESE. The acquisition protocol included left ventricular cardiac output, global longitudinal strain, E/e′, peak oxygen consumption (VO2), non‐invasive arterial–venous oxygen content difference (AVO2diff) and lung ultrasound B‐lines. There was a decline in peak VO2 from controls (24.4 ± 3 mL/min/kg) to HFpEF‐HT (15.2 ± 2 mL/min/kg), passing through HT (18.7 ± 2 mL/min/kg; P < 0.0001). HFpEF‐HT displayed a lower peak cardiac output (9.8 ± 0.9 L/min) compared to HT (12.6 ± 1.0 L/min; P = 0.02) and controls (13.3 ± 1.0 L/min; P = 0.01). Peak AVO2diff was reduced in HFpEF‐HT and HT (13.3 ± 2 and 13.5 ± 2 mL/dL vs. controls: 16.9 ± 2 mL/dL; P < 0.0001). A different left ventricular contractility was observed among groups, expressed as low‐load global longitudinal strain (−16.8 ± 5% in HFpEF‐HT, −18.2 ± 3% in HT, and 20.9 ± 3% in controls; P < 0.0001), and distribution of E/e′ and B‐lines [HFpEF‐HT: 13.7 ± 3 and 16, interquartile range (IQR) 10–22; HT: 9.5 ± 2 and 8, IQR 4–10; controls: 6.2 ± 2 and 0, IQR 0–2; P < 0.0001]. Conclusions Reduced peak VO2 values in HT with and without HFpEF may be the result of decreased AVO2diff. CPET‐ESE can also identify mild signs of left ventricular systo‐diastolic dysfunction and pulmonary congestion, promoting advances in personalized therapy.

show abstract

Section: Discussionmentioning

confidence: 63%

Haemodynamic and metabolic phenotyping of hypertensive patients with and without heart failure by combining cardiopulmonary and echocardiographic stress test

Pugliese

Mazzola

Fabiani

et al. 2020

European J of Heart Fail

View full text Add to dashboard Cite

show abstract

“…This antioxidant effect also contributes to decrease paracrine pro‐fibrotic signalling . This anti‐fibrotic effect is likely to prevent further degradation of LV compliance leading to HFpEF, as fibrosis is a pathogenic component of diastolic dysfunction . In addition, β 3 AR was also shown to attenuate the oxidative inactivation of the Na‐K‐ATPase pump in animal models, thereby reducing Na overload in the failing heart; this may also contribute to correct diastolic dysfunction .…”

Section: Discussionmentioning

confidence: 99%

Rationale and design of a multicentre, randomized, placebo‐controlled trial of mirabegron, a Beta3‐adrenergic receptor agonist on left ventricular mass and diastolic function in patients with structural heart disease Beta3‐left ventricular hypertrophy (Beta3‐LVH)

et al. 2018

Self Cite

View full text Add to dashboard Cite

AimsProgressive left ventricular (LV) remodelling with cardiac myocyte hypertrophy, myocardial fibrosis, and endothelial dysfunction plays a key role in the onset and progression of heart failure with preserved ejection fraction. The Beta3‐LVH trial will test the hypothesis that the β3 adrenergic receptor agonist mirabegron will improve LV hypertrophy and diastolic function in patients with hypertensive structural heart disease at high risk for developing heart failure with preserved ejection fraction.Methods and resultsBeta3‐LVH is a randomized, placebo‐controlled, double‐blind, two‐armed, multicentre, European, parallel group study. A total of 296 patients will be randomly assigned to receive either mirabegron 50 mg daily or placebo over 12 months. The main inclusion criterion is the presence of LV hypertrophy, that is, increased LV mass index (LVMi) or increased wall thickening by echocardiography. The co‐primary endpoints are a change in LVMi by cardiac magnetic resonance imaging and a change in LV diastolic function (assessed by the E/e′ ratio). Secondary endpoints include mirabegron's effects on cardiac fibrosis, left atrial volume index, maximal exercise capacity, and laboratory markers. Two substudies will evaluate mirabegron's effect on endothelial function by pulse amplitude tonometry and brown fat activity by positron emission tomography using 17F‐fluorodeoxyglucose. Morbidity and mortality as well as safety aspects will also be assessed.ConclusionsBeta3‐LVH is the first large‐scale clinical trial to evaluate the effects of mirabegron on LVMi and diastolic function in patients with LVH. Beta3‐LVH will provide important information about the clinical course of this condition and may have significant impact on treatment strategies and future trials in these patients.

show abstract

“…Cardiac magnetic resonance imaging (MRI) reveals meaningful myocardial fibrosis (in the LA and LV) in both patients with HFpEF and those with AF . Fibrosis is indicative of an underlying atrial and ventricular myopathy and may precede the clinical identification of AF or HFpEF …”

Section: Pathophysiological Mechanisms Leading To Hfpefmentioning

confidence: 99%

Do most patients with obesity or type 2 diabetes, and atrial fibrillation, also have undiagnosed heart failure? A critical conceptual framework for understanding mechanisms and improving diagnosis and treatment

Packer

2019

European J of Heart Fail

View full text Add to dashboard Cite

Obesity and diabetes can lead to heart failure with preserved ejection fraction (HFpEF), potentially because they both cause expansion and inflammation of epicardial adipose tissue and thus lead to microvascular dysfunction and fibrosis of the underlying left ventricle. The same process also causes an atrial myopathy, which is clinically evident as atrial fibrillation (AF); thus, AF may be the first manifestation of HFpEF. Many patients with apparently isolated AF have latent HFpEF or subsequently develop HFpEF. Most patients with obesity or diabetes who have AF and exercise intolerance have increased left atrial pressures at rest or during exercise, even in the absence of diagnosed HFpEF. Among patients with AF, those who also have latent HFpEF have increased risk for systemic thromboembolism and death. The identification of HFpEF in patients with obesity or diabetes alters the risk‐to‐benefit relationship of commonly prescribed treatments. Bariatric surgery and statins can ameliorate AF and reduce the risk for HFpEF. Conversely, antihyperglycaemic drugs that promote adipogenesis or cause sodium retention (insulin and thiazolidinediones) may increase the risk for heart failure in patients with an underlying ventricular myopathy. Patients with obesity and diabetes who undergo catheter ablation for AF are at increased risk for AF recurrence and for post‐ablation increases in pulmonary venous pressures and worsening heart failure, especially if HFpEF coexists. Therefore, AF may be the earliest indicator of HFpEF in patients with obesity or type 2 diabetes, and recognition of HFpEF alters the management of these patients.

show abstract

Temporal Relation Between Myocardial Fibrosis and Heart Failure With Preserved Ejection Fraction

Cited by 178 publications

References 30 publications

Haemodynamic and metabolic phenotyping of hypertensive patients with and without heart failure by combining cardiopulmonary and echocardiographic stress test

Haemodynamic and metabolic phenotyping of hypertensive patients with and without heart failure by combining cardiopulmonary and echocardiographic stress test

Rationale and design of a multicentre, randomized, placebo‐controlled trial of mirabegron, a Beta3‐adrenergic receptor agonist on left ventricular mass and diastolic function in patients with structural heart disease Beta3‐left ventricular hypertrophy (Beta3‐LVH)

Do most patients with obesity or type 2 diabetes, and atrial fibrillation, also have undiagnosed heart failure? A critical conceptual framework for understanding mechanisms and improving diagnosis and treatment

Contact Info

Product

Resources

About