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Microvascular Dysfunction in Heart Failure with Preserved Ejection Fraction: Pathophysiology, Assessment, Prevalence and Prognosis.

ABSTRACT: Heart failure with preserved ejection fraction (HFpEF) currently accounts for approximately half of all new heart failure cases in the community. HFpEF is closely associated with chronic lifestyle-related diseases, such as obesity and type 2 diabetes, and clinical outcomes are worse in those with than without comorbidities. HFpEF is pathophysiologically distinct from heart failure with reduced ejection fraction, which may explain, in part, the disparity of treatment options available between the two heart failure phenotypes. The mechanisms underlying HFpEF are complex, with coronary microvascular dysfunction (MVD) being proposed as a potential key driver in its pathophysiology. In this review, the authors highlight the evidence implicating MVD in HFpEF pathophysiology, the diagnostic approaches for identifying MVD (both invasive and non-invasive) and the prevalence and prognostic significance of MVD.

SUBMITTER: Bilak JM

PROVIDER: S-EPMC9274364 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature

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Microvascular Dysfunction in Heart Failure with Preserved Ejection Fraction: Pathophysiology, Assessment, Prevalence and Prognosis.

Bilak Joanna M JM Alam Uazman U Miller Christopher A CA McCann Gerry P GP Arnold Jayanth R JR Kanagala Prathap P

Cardiac failure review 20220101

Heart failure with preserved ejection fraction (HFpEF) currently accounts for approximately half of all new heart failure cases in the community. HFpEF is closely associated with chronic lifestyle-related diseases, such as obesity and type 2 diabetes, and clinical outcomes are worse in those with than without comorbidities. HFpEF is pathophysiologically distinct from heart failure with reduced ejection fraction, which may explain, in part, the disparity of treatment options available between the ...[more]

PMID: 35846985

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Project description:Heart failure with preserved ejection fraction (HFpEF) is an increasingly studied entity accounting for 50% of all diagnosed heart failure and that has claimed its own dignity being markedly different from heart failure with reduced EF in terms of etiology and natural history (Graziani et al., 2018). Recently, a growing body of evidence points the finger toward microvascular dysfunction as the major determinant of the pathological cascade that justifies clinical manifestations (Crea et al., 2017). The high burden of comorbidities such as metabolic syndrome, hypertension, atrial fibrillation, chronic kidney disease, obstructive sleep apnea, and similar, could lead to a systemic inflammatory state that impacts the physiology of the endothelium and the perivascular environment, engaging complex molecular pathways that ultimately converge to myocardial fibrosis, stiffening, and dysfunction (Paulus and Tschope, 2013). These changes could even self-perpetrate with a positive feedback where hypoxia and locally released inflammatory cytokines trigger interstitial fibrosis and hypertrophy (Ohanyan et al., 2018). Identifying microvascular dysfunction both as the cause and the maintenance mechanism of this condition has opened the field to explore specific pharmacological targets like nitric oxide (NO) pathway, sarcomeric titin, transforming growth factor beta (TGF-β) pathway, immunomodulators or adenosine receptors, trying to tackle the endothelial impairment that lies in the background of this syndrome (Graziani et al., 2018;Lam et al., 2018). Yet, many questions remain, and the new data collected still lack a translation to improved treatment strategies. To further elaborate on this tangled and exponentially growing topic, we will review the evidence favoring a microvasculature-driven etiology of this condition, its clinical correlations, the proposed diagnostic workup, and the available/hypothesized therapeutic options to address microvascular dysfunction in the failing heart.

Project description:Aims:Coronary microvascular ischaemia, cardiomyocyte injury and stiffness may play an important role in the pathophysiology of heart failure with preserved ejection fraction (HFpEF). To date, the relationship between coronary flow reserve (CFR), myocardial injury, diastolic dysfunction, and future HFpEF risk is unknown. Methods and results:Consecutive patients (n = 201) undergoing evaluation for suspected coronary artery disease (CAD) with stress myocardial perfusion positron emission tomography, serum troponin, and transthoracic echocardiography who did not have flow-limiting CAD or reduced left ventricular ejection fraction were identified. Patients were followed up (median 4.1 years) for cardiovascular death and hospitalization for non-fatal myocardial infarction or heart failure. Coronary flow reserve was quantified as stress/rest myocardial blood flow. Early diastolic flow (E) and relaxation (e') velocities were obtained via transmitral and tissue Doppler, respectively. Patients with impaired CFR (<2, n = 108) demonstrated linearly decreasing e' and increasing E/e' consistent with worsening diastolic function (P for trend <0.0001). A detectable troponin was associated with diastolic dysfunction only in the presence of impaired CFR (interaction P = 0.002). In adjusted analyses, impaired CFR was independently associated with diastolic dysfunction (E/e'septal > 15, adjusted OR 2.58, 95%CI 1.22-5.48) and composite cardiovascular outcomes or HFpEF hospitalization alone (adjusted HR 2.47, 95%CI 1.09-5.62). Patients with both impaired CFR and diastolic dysfunction demonstrated >five-fold increased risk of HFpEF hospitalization (P < 0.001). Conclusion:In symptomatic patients without overt CAD, impaired CFR was independently associated with diastolic dysfunction and adverse events, especially HFpEF hospitalization. The presence of both coronary microvascular and diastolic dysfunctions was associated with a markedly increased risk of HFpEF events.

Project description:ImportanceCoronary artery disease (CAD) and coronary microvascular dysfunction (CMD) may contribute to the pathophysiologic characteristics of heart failure with preserved ejection fraction (HFpEF). However, the prevalence of CAD and CMD have not been systematically studied.ObjectiveTo examine the prevalence of CAD and CMD in hospitalized patients with HFpEF.Design, setting, and participantsA total of 106 consecutive patients hospitalized with HFpEF were evaluated in this prospective, multicenter, cohort study conducted between January 2, 2017, and August 1, 2018; data analysis was performed from March 4 to September 6, 2019. Participants underwent coronary angiography with guidewire-based assessment of coronary flow reserve, index of microvascular resistance, and fractional flow reserve, followed by coronary vasoreactivity testing. Cardiac magnetic resonance imaging was performed with late gadolinium enhancement and assessment of extracellular volume. Myocardial perfusion was assessed qualitatively and semiquantitatively using the myocardial-perfusion reserve index.Main outcomes and measuresThe prevalence of obstructive epicardial CAD, CMD, and myocardial ischemia, infarction, and fibrosis.ResultsOf 106 participants enrolled (53 [50%] women; mean [SD] age, 72 [9] years), 75 had coronary angiography, 62 had assessment of coronary microvascular function, 41 underwent coronary vasoreactivity testing, and 52 received cardiac magnetic resonance imaging. Obstructive epicardial CAD was present in 38 of 75 participants (51%, 95% CI, 39%-62%); 19 of 38 (50%; 95% CI, 34%-66%) had no history of CAD. Endothelium-independent CMD (ie, coronary flow reserve <2.0 and/or index of microvascular resistance ≥25) was identified in 41 of 62 participants (66%; 95% CI, 53%-77%). Endothelium-dependent CMD (ie, abnormal coronary vasoreactivity) was identified in 10 of 41 participants (24%; 95% CI, 13%-40%). Overall, 45 of 53 participants (85%; 95% CI, 72%-92%) had evidence of CMD and 29 of 36 (81%; 95% CI, 64%-91%) of those without obstructive epicardial CAD had CMD. Cardiac magnetic resonance imaging findings included myocardial-perfusion reserve index less than or equal to 1.84 (ie, impaired global myocardial perfusion) in 29 of 41 patients (71%; 95% CI, 54%-83%), visual perfusion defect in 14 of 46 patients (30%; 95% CI, 19%-46%), ischemic late gadolinium enhancement (ie, myocardial infarction) in 14 of 52 patients (27%; 95% CI, 16%-41%), and extracellular volume greater than 30% (ie, diffuse myocardial fibrosis) in 20 of 48 patients (42%; 95% CI, 28%-56%). Patients with obstructive CAD had more adverse events during follow-up (28 [74%]) than those without obstructive CAD (17 [46%]).Conclusions and relevanceIn this cohort study, 91% of patients with HFpEF had evidence of epicardial CAD, CMD, or both. Of those without obstructive CAD, 81% had CMD. Obstructive epicardial CAD and CMD appear to be common and often unrecognized in hospitalized patients with HFpEF and may be therapeutic targets.

Dataset Information

Microvascular Dysfunction in Heart Failure with Preserved Ejection Fraction: Pathophysiology, Assessment, Prevalence and Prognosis.

Publications

Microvascular Dysfunction in Heart Failure with Preserved Ejection Fraction: Pathophysiology, Assessment, Prevalence and Prognosis.

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