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      Coronary microvascular dysfunction and future risk of heart failure with preserved ejection fraction

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          Abstract

          <div class="section"> <a class="named-anchor" id="s1"> <!-- named anchor --> </a> <h5 class="section-title" id="d7565161e232">Aims</h5> <p id="d7565161e234">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. </p> </div><div class="section"> <a class="named-anchor" id="s2"> <!-- named anchor --> </a> <h5 class="section-title" id="d7565161e237">Methods and results</h5> <p id="d7565161e239">Consecutive patients ( <i>n</i> = 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 ( <i>E</i>) and relaxation ( <i>e</i>′) velocities were obtained via transmitral and tissue Doppler, respectively. Patients with impaired CFR (&lt;2, <i>n</i> = 108) demonstrated linearly decreasing <i>e</i>′ and increasing <i>E</i>/ <i>e</i>′ consistent with worsening diastolic function ( <i>P</i> for trend &lt;0.0001). A detectable troponin was associated with diastolic dysfunction only in the presence of impaired CFR (interaction <i>P</i> = 0.002). In adjusted analyses, impaired CFR was independently associated with diastolic dysfunction ( <i>E</i>/ <i>e</i>′ <sub>septal</sub> &gt; 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 &gt;five-fold increased risk of HFpEF hospitalization ( <i>P</i> &lt; 0.001). </p> </div><div class="section"> <a class="named-anchor" id="s3"> <!-- named anchor --> </a> <h5 class="section-title" id="d7565161e283">Conclusion</h5> <p id="d7565161e285">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. </p> <p id="d7565161e287"> <div class="fig panel" id="ehx721-F5a"> <a class="named-anchor" id="ehx721-F5a"> <!-- named anchor --> </a> <div class="figure-container so-text-align-c"> <img alt="" class="figure" src="/document_file/e5d743ab-fe20-4d6d-874a-d489c36ab8e8/PubMedCentral/image/ehx721f5"/> </div> <div class="panel-content"/> </div> </p> </div>

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          Most cited references17

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          Coronary microvascular rarefaction and myocardial fibrosis in heart failure with preserved ejection fraction.

          Characterization of myocardial structural changes in heart failure with preserved ejection fraction (HFpEF) has been hindered by the limited availability of human cardiac tissue. Cardiac hypertrophy, coronary artery disease (CAD), coronary microvascular rarefaction, and myocardial fibrosis may contribute to HFpEF pathophysiology.
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            Ischemia and No Obstructive Coronary Artery Disease (INOCA): Developing Evidence-Based Therapies and Research Agenda for the Next Decade.

            The Cardiovascular Disease in Women Committee of the American College of Cardiology, in conjunction with interested parties (from the National Heart, Lung, and Blood Institute, American Heart Association, and European Society of Cardiology), convened a working group to develop a consensus on the syndrome of myocardial ischemia with no obstructive coronary arteries. In general, these patients have elevated risk for a cardiovascular event (including acute coronary syndrome, heart failure hospitalization, stroke, and repeat cardiovascular procedures) compared with reference subjects and appear to be at higher risk for development of heart failure with preserved ejection fraction. A subgroup of these patients also has coronary microvascular dysfunction and evidence of inflammation. This document provides a summary of findings and recommendations for the development of an integrated approach for identifying and managing patients with ischemia with no obstructive coronary arteries and outlines knowledge gaps in the area. Working group members critically reviewed available literature and current practices for risk assessment and state-of-the-science techniques in multiple areas, with a focus on next steps needed to develop evidence-based therapies. This report presents highlights of this working group review and a summary of suggested research directions to advance this field in the next decade.
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              Stable angina pectoris with no obstructive coronary artery disease is associated with increased risks of major adverse cardiovascular events.

              Patients with chest pain and no obstructive coronary artery disease (CAD) are considered at low risk for cardiovascular events but evidence supporting this is scarce. We investigated the prognostic implications of stable angina pectoris in relation to the presence and degree of CAD with no obstructive CAD in focus. We identified 11 223 patients referred for coronary angiography (CAG) in 1998-2009 with stable angina pectoris as indication and 5705 participants from the Copenhagen City Heart Study for comparison. Main outcome measures were major adverse cardiovascular events (MACE), defined as cardiovascular death, myocardial infarction, stroke or heart failure, and all-cause mortality. Significantly more women (65%) than men (32%) had no obstructive CAD (P< 0.001). In Cox's models adjusted for age, body mass index, diabetes, smoking, and use of lipid-lowering or antihypertensive medication, hazard ratios (HRs) associated with no obstructive CAD were similar in men and women. In the pooled analysis, the risk of MACE increased with increasing degrees of CAD with multivariable-adjusted HRs of 1.52 (95% confidence interval, 1.27-1.83) for patients with normal coronary arteries and 1.85 (1.51-2.28) for patients with diffuse non-obstructive CAD compared with the reference population. For all-cause mortality, normal coronary arteries and diffuse non-obstructive CAD were associated with HRs of 1.29 (1.07-1.56) and 1.52 (1.24-1.88), respectively. Patients with stable angina and normal coronary arteries or diffuse non-obstructive CAD have elevated risks of MACE and all-cause mortality compared with a reference population without ischaemic heart disease.
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                Author and article information

                Journal
                European Heart Journal
                Oxford University Press (OUP)
                0195-668X
                1522-9645
                March 07 2018
                March 07 2018
                : 39
                : 10
                : 840-849
                Article
                10.1093/eurheartj/ehx721
                48284ffb-ffd1-4598-86f0-77a146610e8b
                © 2018
                History

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