Response by Taqueti and Di Carli to Letter Regarding Article, “Excess Cardiovascular Risk in Women Relative to Men Referred for Coronary Angiography Is Associated With Severely Impaired Coronary Flow Reserve, Not Obstructive Disease”
We thank Drs Zimmermann, Zelis, and van’t Veer for their interest in our article,1 in which we found that excess cardiovascular risk in women relative to men was independently associated with and mediated by impaired coronary flow reserve.
In response to their first inquiry regarding whether we examined the contribution of absolute stress flow in addition to coronary flow reserve, the answer is yes, and it was concordantly reduced (from Table 1, median [Q1–Q3] stress myocardial blood flow in mL·g–1·min–1 was 1.7 [1.2–2.3] in women and 1.5 [1.0–1.9] in men). As such, these patients have ischemic heart disease; in fact, many of them demonstrated a severe ischemic burden as measured semi-quantitatively by positron emission tomography myocardial perfusion imaging (also from Table 1, median [Q1–Q3] % left ventricular ischemia was 10.3 [5.1–17.7] in women and 10.3 [5.9–16.2] in men). An important finding of this study was that the ischemic burden in women, although similar to that in men, occurred independently of severely obstructive coronary artery disease, with diverging implications for management in regard to options for revascularization and impact on outcomes.
To the second inquiry regarding the prognostic value of regional versus global stress flow and coronary flow reserve, we agree that global measures averaged over the left ventricle may not reflect variations in regional perfusion, but recognize that this may serve as a strength for a marker of clinical prognosis. As the authors note, a broad literature supports the prognostic value of global coronary flow reserve; this parallels an evidence base supporting the prognostic value of global percent left ventricular ischemia. Although small regional areas of inducible ischemia, ie, from single-vessel disease, may be present, focally intervening on such lesions in the absence of global disease may not lead to improved survival in stable patients. Rather, the collective health of the whole ventricle may be most important.
To the third inquiry about current standards of care for diagnosis of obstructive coronary artery disease (which occurs primarily through angiography, and is separate from that of flow-limiting coronary artery disease, which occurs through functional assessments such as invasive fractional flow reserve or myocardial perfusion imaging), we are strong advocates for the use of complementary functional and anatomical evaluations, which we believe are critical for accurate diagnosis across the phenotypic continuum of ischemic heart disease. This is evident in the design of our study, the findings of which validate the importance of functional assessments added to angiographic ones. We congratulate the authors on their work using fractional flow reserve. Although invasive fractional flow reserve measurements were not available in this cohort, the majority of patients demonstrated functional evidence of significant ischemia by positron emission tomography myocardial perfusion imaging, as highlighted above.
Last, to the inquiry about whether preexisting heart failure might have served as an unrecognized confounder for events, we note in the Methods that patients with a clinical diagnosis of heart failure were excluded. Indeed, hospitalization for heart failure, whether incident or not, is increasingly recognized as an important, morbid end point. We wholeheartedly agree that additional investigations of coronary flow reserve, diastolic dysfunction, and heart failure with a preserved ejection fraction outcomes are warranted, and that this pathophysiology may be particularly relevant in women.
Viviany R. Taqueti, MD, MPH
Marcelo F. Di Carli, MD
Circulation is available at http://circ.ahajournals.org.
- © 2017 American Heart Association, Inc.
- Taqueti VR,
- Shaw LJ,
- Cook NR,
- Murthy VL,
- Shah NR,
- Foster CR,
- Hainer J,
- Blankstein R,
- Dorbala S,
- Di Carli MF