scholarly journals Prevalence and correlates of coronary microvascular dysfunction in heart failure with preserved ejection fraction: PROMIS-HFpEF

2018 ◽  
Vol 39 (37) ◽  
pp. 3439-3450 ◽  
Author(s):  
Sanjiv J Shah ◽  
Carolyn S P Lam ◽  
Sara Svedlund ◽  
Antti Saraste ◽  
Camilla Hage ◽  
...  
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
Endothelial Dysfunction ◽  
Ejection Fraction ◽  
Microvascular Dysfunction ◽  
Left Ventricular ◽  
Coronary Microvascular Dysfunction ◽  
Preserved Ejection Fraction ◽  
Transthoracic Doppler Echocardiography ◽  
Flow Reserve

Abstract Aims To date, clinical evidence of microvascular dysfunction in patients with heart failure (HF) with preserved ejection fraction (HFpEF) has been limited. We aimed to investigate the prevalence of coronary microvascular dysfunction (CMD) and its association with systemic endothelial dysfunction, HF severity, and myocardial dysfunction in a well defined, multi-centre HFpEF population. Methods and results This prospective multinational multi-centre observational study enrolled patients fulfilling strict criteria for HFpEF according to current guidelines. Those with known unrevascularized macrovascular coronary artery disease (CAD) were excluded. Coronary flow reserve (CFR) was measured with adenosine stress transthoracic Doppler echocardiography. Systemic endothelial function [reactive hyperaemia index (RHI)] was measured by peripheral arterial tonometry. Among 202 patients with HFpEF, 151 [75% (95% confidence interval 69–81%)] had CMD (defined as CFR <2.5). Patients with CMD had a higher prevalence of current or prior smoking (70% vs. 43%; P = 0.0006) and atrial fibrillation (58% vs. 25%; P = 0.004) compared with those without CMD. Worse CFR was associated with higher urinary albumin-to-creatinine ratio (UACR) and NTproBNP, and lower RHI, tricuspid annular plane systolic excursion, and right ventricular (RV) free wall strain after adjustment for age, sex, body mass index, atrial fibrillation, diabetes, revascularized CAD, smoking, left ventricular mass, and study site (P < 0.05 for all associations). Conclusions PROMIS-HFpEF is the first prospective multi-centre, multinational study to demonstrate a high prevalence of CMD in HFpEF in the absence of unrevascularized macrovascular CAD, and to show its association with systemic endothelial dysfunction (RHI, UACR) as well as markers of HF severity (NTproBNP and RV dysfunction). Microvascular dysfunction may be a promising therapeutic target in HFpEF.

Coronary Microcirculation in Heart Failure with Preserved Systolic Function

2018 ◽  
Vol 24 (25) ◽  
pp. 2960-2966
Author(s):  
Zorana Vasiljevic ◽  
Gordana Krljanac ◽  
Marija Zdravkovic ◽  
Ratko Lasica ◽  
Danijela Trifunovic ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Diastolic Dysfunction ◽  
Microvascular Dysfunction ◽  
Left Ventricular ◽  
Coronary Microcirculation ◽  
Left Ventricular Ejection ◽  
Coronary Microvascular Dysfunction ◽  
Fractional Flow ◽  
Flow Reserve

Background: The Heart Failure with Preserved Ejection Fraction (HFpEF) is defined as the preserved left ventricular ejection fraction (LVEF) with the signs of heart failure, elevated natriuretic peptides, and either the evidence of the structural heart disease or diastolic dysfunction. The importance of this form of heart failure was increased after studies where the mortality rates and readmission to the hospital were founded similar as in patients with HF and reduced EF (HFrEF). Coronary microvascular ischemia, cardiomyocyte injury and stiffness could be important factors in the pathophysiology of HFpEF. Methods: The goal of this work is to analyse the relationship of HFpEF and coronary microcirculation in previous studies. Results: The useful diagnostic marker of coronary microcirculation in HFpEF may be the parameters measured by transthoracic echocardiography (TTE), the coronary flow reserve (CFR), as well as fractional flow reserve (FFR) and quantitative myocardial contrast echocardiography (MCE). Cardiac magnetic resonance (CMR) imaging represents the diagnostic gold standard in HFpEF. Coronary microvascular dysfunction in the absence of obstructive coronary artery disease (CAD) is poorly understood and may be more prevalent amongst women than men. Troponin level may be important in risk stratification of HEpEF patients. Conclusion: There are no precise answers with respect to the pathophysiological mechanism, nor are there any precise practical clinical assessment of and diagnostic method for coronary microvascular dysfunction and diastolic dysfunction. In accordance with that, there is no well-established treatment for HFpEF.

scholarly journals Untangling the pathophysiologic link between coronary microvascular dysfunction and heart failure with preserved ejection fraction

2021 ◽  
Author(s):  
Aish Sinha ◽  
Haseeb Rahman ◽  
Andrew Webb ◽  
Ajay M Shah ◽  
Divaka Perera
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Obstructive Coronary Artery Disease ◽  
Microvascular Disease ◽  
Microvascular Dysfunction ◽  
Common Finding ◽  
Coronary Microvascular Dysfunction ◽  
Preserved Ejection Fraction ◽  
Flow Reserve ◽  
Artery Disease

Abstract Coronary microvascular disease (CMD), characterized by impaired coronary flow reserve (CFR), is a common finding in patients with stable angina. Impaired CFR, in the absence of obstructive coronary artery disease, is also present in up to 75% of patients with heart failure with preserved ejection fraction (HFpEF). Heart failure with preserved ejection fraction is a heterogeneous syndrome comprising distinct endotypes and it has been hypothesized that CMD lies at the centre of the pathogenesis of one such entity: the CMD–HFpEF endotype. This article provides a contemporary review of the pathophysiology underlying CMD, with a focus on the mechanistic link between CMD and HFpEF. We discuss the central role played by subendocardial ischaemia and impaired lusitropy in the development of CMD–HFpEF, as well as the clinical and research implications of the CMD–HFpEF mechanistic link. Future prospective follow-up studies detailing outcomes in patients with CMD and HFpEF are much needed to enhance our understanding of the pathological processes driving these conditions, which may lead to the development of physiology-stratified therapy to improve the quality of life and prognosis in these patients.

scholarly journals 127Prevalence of coronary artery disease and coronary microvascular dysfunction in heart failure with preserved ejection fraction

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
C Rush ◽  
C Berry ◽  
K Oldroyd ◽  
P Rocchiccioli ◽  
M Lindsay ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Heart Failure ◽  
Ejection Fraction ◽  
Invasive Coronary Angiography ◽  
Microvascular Dysfunction ◽  
Coronary Microvascular Dysfunction ◽  
P Value ◽  
Preserved Ejection Fraction ◽  
Flow Reserve ◽  
Artery Disease

Abstract Background/Introduction The prevalence of epicardial coronary artery disease (CAD) and coronary microvascular dysfunction (CMD) have not been studied systematically in an unselected cohort of patients with heart failure and preserved ejection fraction (HFpEF). Both types of coronary disease may play an important role in the pathophysiology and prognosis of HFpEF. Methods This prospective multi-centre observational study enrolled near-consecutive patients hospitalized with HFpEF. Patients underwent invasive coronary angiography. Where possible, patients also had guidewire-based assessment of fractional flow reserve, coronary flow reserve (CFR) and index of microcirculatory resistance (IMR) performed, followed by vasoreactivity testing with intracoronary acetylcholine. Results A total of 75 patients underwent invasive coronary angiography. Guidewire-based assessment of FFR/CFR/IMR was performed in 62 patients, and vasoreactivity testing was possible in 41 patients. Obstructive epicardial CAD was identified in 38 patients (51%). CMD (defined as a CFR <2.0 and/or IMR ≥25) was present in 66% of patients assessed and was similarly prevalent in those with and without obstructive epicardial disease (62% vs. 69%, p 0.52). During vasoreactivity testing, 24% of those assessed had evidence of coronary microvascular endothelial dysfunction. Patients with obstructive CAD were more often male (63% vs. 38%, p 0.028), and had a history of CAD (50% vs. 19%, p 0.005), diabetes mellitus (63% vs. 41%, p 0.05), and a higher E/e' on echocardiography (median 14.4 vs. 12.3, p 0.044) than those without obstructive coronary disease. Patients with CMD had higher B-type natriuretic peptide levels (median 569 vs. 197 pg/ml, p 0.036) than those without microvascular dysfunction. Selected baseline characteristics No obstructive CAD (n=37) Obstructive CAD (n=38) p-value No CMD (n=21) CMD (n=41) p-value Age (mean, years) 72 73 0.4 74 72 0.41 Female, n (%) 23 (62%) 14 (37%) 0.028 11 (52%) 22 (54%) 0.92 CAD history, n (%) 7 (19%) 19 (50%) 0.005 7 (33%) 12 (29%) 0.74 Diabetes mellitus, n (%) 15 (41%) 24 (63%) 0.05 11 (52%) 22 (54%) 0.92 BNP (median, pg/ml) 323 315 0.9 197 569 0.036 Ejection fraction (median, %) 59 58 0.35 60 56 0.064 E/e' (median) 12.3 14.4 0.044 14.2 12.4 0.74 Study flow diagram Conclusion Both epicardial CAD and CMD are common in HFpEF and each may be a therapeutic target in this condition. Although it has been hypothesized that CMD may be due to endothelial dysfunction, our findings suggest that CMD is predominantly due to structural abnormalities in HFpEF. Acknowledgement/Funding Chief Scientist Office

Using A 21-Year Real-World Database from a Private Cardiologist's Practice to Test the Hypothesis that Combining Pharmacological Therapies (Carvedilol, Spironolactone and Statins) with Weight Loss May Benefit Patients with HFpEF

2020 ◽  
pp. 1-9
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
Weight Loss ◽  
Clinical Trials ◽  
Endothelial Dysfunction ◽  
Combination Therapy ◽  
Ejection Fraction ◽  
Diastolic Dysfunction ◽  
Left Ventricular ◽  
Lv Diastolic Dysfunction

Heart Failure with preserved Ejection Fraction (HFpEF) is a clinical syndrome in which patients have symptoms of Heart Failure (HF), such as dyspnea and fatigue, a Left Ventricular Ejection Fraction (LVEF) ≥ 50% and evidence of cardiac dysfunction as a cause of symptoms, such as abnormal Left Ventricular (LV) diastolic dysfunction with elevated filling pressures. Besides LV diastolic dysfunction, recent investigations suggest a more complex and heterogeneous pathophysiology, including systolic reserve abnormalities, chronotropic incompetence, stiffening of ventricular tissue, atrial dysfunction, secondary Pulmonary Arterial Hypertension (PAH), impaired vasodilatation and endothelial dysfunction. Unlike Heart Failure with Reduced Ejection Fraction (HFrEF), clinical trials over the years have not yet identified effective treatments that reduce mortality in patients with HFpEF. A database on use of carvedilol in a private cardiologist's practice was begun in 1997 and concluded at the end of 2018. We used this database to test the hypothesis that combining pharmacological interventions to address diastolic dysfunction (carvedilol), volume overload (spironolactone/eplerenone) and endothelial dysfunction (statins) with weight loss may benefit patients with HFpEF. We report analysis of 335 patients with HFpEF comprised of 61% female (mean age 74 ± 8) and 39% males (mean age 72 ± 7). Initial EF ranged between 50 and 77% with mean EF of 57 ± 6%. Only 15 patients were changed to metoprolol succinate, verapamil or diltiazem because of adverse side effects. Two hundred and twenty of the patients were in normal sinus rhythm when started on carvedilol, spironolactone/eplerenone and statin therapy with weight loss counseling. After 5 years, 191 patients were still on combination therapy, and only 31 (17%) had developed Atrial Fibrillation (AF). Compared to previous HFpEF trials reporting a 32% risk of developing atrial fibrillation after 4 years, our combination therapy significantly (p < 0.05) reduced the risk of developing AF over 5 years. Thus, irrespective of age and sex with comorbidities of type 2 Diabetes Mellitus (DM) and Chronic Kidney Disease (CKD), patients with HFpEF can be managed successfully with carvedilol, spironolactone/eplerenone and statins with a clinical benefit being a reduced risk of developing AF. We consider these data hypothesis-generating and hope these results will be tested further in database analyses and clinical trials.

scholarly journals Application of the current HFA-ESC consensus guidelines on diagnosis of heart failure with preserved ejection fraction to a population referred for echocardiography

2021 ◽  
Vol 22 (Supplement_1) ◽  
Author(s):  
K Liang ◽  
R Hearse-Morgan ◽  
S Fairbairn ◽  
Y Ismail ◽  
AK Nightingale
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
Ejection Fraction ◽  
Diastolic Function ◽  
Global Longitudinal Strain ◽  
Diagnostic Algorithm ◽  
Left Ventricular ◽  
Lv Function ◽  
Preserved Ejection Fraction ◽  
Consensus Guidelines

Abstract Funding Acknowledgements Type of funding sources: None. BACKGROUND The recent Heart Failure Association (HFA) of the European Society of Cardiology (ESC) consensus guidelines on diagnosis of heart failure with preserved ejection fraction (HFpEF) have developed a simple diagnostic algorithm for clinical use. PURPOSE To assess whether echocardiogram (echo) parameters needed to assess diastolic function are routinely collected in patients referred for assessment of heart failure symptoms. METHODS Retrospective analysis of echo referrals in January 2020 were assessed for parameters of diastolic function as per step 2 of the HF-PEFF diagnostic algorithm.  Echo images and clinical reports were reviewed. Electronic records were utilised to obtain clinical history, blood results (NT-proBNP) and demographic data. RESULTS 1330 patients underwent an echo in our department during January 2020. 83 patients were referred with symptoms of heart failure without prior history of cardiac disease; 20 patients found to have impaired left ventricular (LV) function were excluded from analysis. Of the 63 patients with possible HFpEF, HF-PEFF score was low in 18, intermediate in 33 and high in 12. Median age was 68 years (range 32 to 97 years); 25% had a BMI &gt;30. There was a high prevalence of hypertension (52%), diabetes (19%) and atrial fibrillation (40%) (cf. Table 1). Body surface area (BSA) was documented in 65% of echo reports. Most echo parameters were recorded with the exception of global longitudinal strain (GLS) and indexed LV mass (cf. image 1). NT-proBNP was recorded in only 20 patients (31.7%). 12 patients with an intermediate HF-PEFF score could have been re-categorised to a high score depending on GLS and NT-proBNP (which were not recorded). CONCLUSION More than three quarters of echoes acquired in our department obtained the relevant parameters to assess diastolic function. The addition of BSA, and inclusion of NT-proBNP, and GLS would have been additive to a third of ‘intermediate’ patients to determine definite HFpEF. Our study demonstrates that the current HFA-ESC diagnostic algorithm and HF-PEFF scoring system are easy to use, highly relevant and applicable to current clinical practice. Age &gt;70 years 29 (46.0%) Obesity (BMI &gt;30) 16 (25.4%) Diabetes 12 (19%) Hypertension 33 (52.4%) Atrial Fibrillation 25 (39.7%) ECG abnormalities 18 (28.5%) Table 1. Prevalence of Clinical Risk Factors Abstract Figure. Image 1. HFPEFF score & echo parameters

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