Coronary Microvascular Dysfunction and Clinical Outcomes in Patients With Heart Failure With Preserved Ejection Fraction

Allan, T.M.; Dryer, Kathryn; Fearon, William F.; Shah, Sanjiv J.; Blair, John E.

doi:10.1016/j.cardfail.2019.08.010

Cited by 16 publications

(17 citation statements)

References 10 publications

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“…In addition to the different techniques used to measure CFR, other variations in study design may have contributed to different prevalence estimates, including the clinical status of the HFpEF population studied (ambulatory vs hospitalized) and the lower LV ejection fraction inclusion criterion (≥40%) in PROMIS-HFpEF. Earlier studies, including PROMIS-HFpEF, have found that CMD is associated with adverse outcomes in patients with HFpEF …”

Section: Discussioncontrasting

confidence: 77%

Prevalence of Coronary Artery Disease and Coronary Microvascular Dysfunction in Patients With Heart Failure With Preserved Ejection Fraction

et al. 2021

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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.OBJECTIVE To 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 Ն25) 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.

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Section: Discussioncontrasting

confidence: 77%

Prevalence of Coronary Artery Disease and Coronary Microvascular Dysfunction in Patients With Heart Failure With Preserved Ejection Fraction

et al. 2021

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“…Although with few events, these preliminary findings lend support to previous reports in patients with suspected CAD 7 and in HFpEF, correlating CMD with death and/or HF hospitalizations. 8,9 In HFpEF, upregulated inflammation initiating CMD and subclinical atherosclerosis may act as disease drivers impairing outcome. 13À15 Additive information on CMD status may also be more accessible evaluated noninvasively through circulating biomarkers.…”

Section: Discussionmentioning

confidence: 99%

“…2,3 CMD is a strong independent predictor of CV events in patients with clinical indication for cardiac catheterization regardless of macrovascular coronary artery disease (CAD) 4À7 and in HFpEF. 8,9…”

Section: Association Of Coronary Microvascular Dysfunction With Heartmentioning

confidence: 99%

Association of Coronary Microvascular Dysfunction With Heart Failure Hospitalizations and Mortality in Heart Failure With Preserved Ejection Fraction: A Follow-up in the PROMIS-HFpEF Study

Hage

Svedlund

Saraste

et al. 2020

Journal of Cardiac Failure

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Background: Coronary microvascular dysfunction (CMD) is common in heart failure with preserved ejection fraction (HFpEF). We assessed the association of CMD with hospitalization and mortality in HFpEF. Methods and Results: We assessed the 1-year outcomes in patients from the PROMIS-HFpEF study, a prospective observational study of patients with chronic stable HFpEF undergoing coronary flow reserve measurements. Outcomes were (1) time to cardiovascular (CV) death/first HF hospitalization, (2) CV death/recurrent HF hospitalizations, (3) all-cause death/first HF hospitalization, and (4) first and ( 5) recurrent all-cause hospitalizations. CMD was defined as coronary flow reserve of <2.5. Time to CV death/first hospitalization was compared by log-rank test and recurrent HF and all-cause hospitalizations by Poisson test. Of 263 patients enrolled, 257 were evaluable at 1 year. Where the coronary flow reserve was interpretable (n = 201), CMD was present in 150 (75%). The median follow-up was 388 days (Q1, Q3 365, 418). The outcome of CV death/first HF hospitalization occurred in 15 patients (4 CV deaths). The incidence rate was in CMD 96 per 1000 person-years, 95% confidence interval 54À159, vs non-CMD 0 per1000 person-years, 95% confidence interval 0À68, P = .023, and remained significant after accounting for selected clinical variables. In patients with CMD, the incidence rates were significantly higher also for CV death/ recurrent HF hospitalizations, all-cause death/first HF, and recurrent but not first all-cause hospitalization. Conclusions: In this exploratory assessment of the prognostic role of CMD in HFpEF, CMD was independently associated with primarily CV-and HF-specific events. The high prevalence of CMD and its CV and HF specific prognostic role suggest CMD may be a potential treatment target in HFpEF.

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“…Women are more likely to have CMD than men, and studies have demonstrated that women with ischemic symptoms without obstructive coronary disease and preserved EF have higher mortality and HF hospitalization [6,7]. Observational studies using invasive or non-invasive functional testing support the premise that CMD is common in patients with HFpEF and that the presence of both CMD and diastolic dysfunction is associated with a markedly increased risk of future HFpEF hospitalization [8,9]. Current diagnostic pathways to diagnose CMD require the assessment of epicardial coronary anatomy and invasive physiological assessment of the microvasculature's response to both vasodilator (e.g.…”

Section: Introductionmentioning

confidence: 99%

Abnormal left ventricular subendocardial perfusion and diastolic function in women with obesity and heart failure and preserved ejection fraction

Markley

Buono

Mihalick

et al. 2023

Int J Cardiovasc Imaging

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Purpose – Coronary microvascular dysfunction (CMD) is common in patients with heart failure with preserved ejection fraction (HFpEF) and obesity. Stress cardiovascular magnetic resonance (CMR) has been proposed as a non-invasive tool for detection of CMD. The aim of this study was to determine relationship between CMD and diastolic function in patients with HFpEF using a novel CMR technique. Methods – Patients with obesity and HFpEF without epicardial coronary artery disease (CAD) underwent Doppler echocardiography to measure diastolic function, followed by vasodilator stress CMR, using a single bolus, dual sequence, quantitative myocardial perfusion mapping to measure myocardial blood flow (MBF) at rest and at peak hyperemia. With this, myocardial perfusion reserve (MPR), global stress endocardial-to-epicardial (endo:epi) perfusion ratio, and total ischemic burden (IB, defined as myocardial segments with MBF < 1.94 mL/min/g) were calculated. Results are reported as median and interquartile range. Results – Nineteen subjects were enrolled (100% female, 42% Black). Median age was 64 [56–72] years. Global stress MBF was 2.43 ml/min/g [2.16–2.78] and global myocardial perfusion reserve (MPR) was 2.34 [2.07–2.88]. All had an abnormal subendocardial perfusion with an endo:epi of less than 1 (0.87 [0.81–0.90]). Regional myocardial hypoperfusion was detected in 14 (74%) patients with an IB of 6% [0-34.4]. Endo:epi ratio significantly correlated with IB (R=-0.510, p = 0.026) and measures of diastolic function (R = 0.531, p = 0.019 and R=-0.544, p = 0.014 for e’ and E/e’ respectively). Conclusion – Using a novel quantitative stress CMR myocardial perfusion mapping technique, women with obesity and HFpEF were found to have patterns of abnormal subendocardial perfusion which significantly correlated with measures of diastolic dysfunction.

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Coronary Microvascular Dysfunction and Clinical Outcomes in Patients With Heart Failure With Preserved Ejection Fraction

Cited by 16 publications

References 10 publications

Prevalence of Coronary Artery Disease and Coronary Microvascular Dysfunction in Patients With Heart Failure With Preserved Ejection Fraction

Prevalence of Coronary Artery Disease and Coronary Microvascular Dysfunction in Patients With Heart Failure With Preserved Ejection Fraction

Association of Coronary Microvascular Dysfunction With Heart Failure Hospitalizations and Mortality in Heart Failure With Preserved Ejection Fraction: A Follow-up in the PROMIS-HFpEF Study

Abnormal left ventricular subendocardial perfusion and diastolic function in women with obesity and heart failure and preserved ejection fraction

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