Hemodynamics in Primary Mitral Regurgitation

HomeCirculation: Cardiovascular ImagingVol. 11, No. 2Hemodynamics in Primary Mitral Regurgitation Free AccessEditorialPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessEditorialPDF/EPUBHemodynamics in Primary Mitral RegurgitationSupport for and Challenges to the Conventional Wisdom Linda D. Gillam, MD, MPH and Leo Marcoff, MD Linda D. GillamLinda D. Gillam From the Department of Cardiovascular Medicine, Morristown Medical Center, Atlantic Health System, NJ. and Leo MarcoffLeo Marcoff From the Department of Cardiovascular Medicine, Morristown Medical Center, Atlantic Health System, NJ. Originally published15 Feb 2018https://doi.org/10.1161/CIRCIMAGING.118.007471Circulation: Cardiovascular Imaging. 2018;11:e007471The presence of symptoms in patients with severe primary mitral regurgitation (mitral prolapse/flail) carries a class I indication for intervention in current professional guidelines.1,2 However, symptoms may be underappreciated because of subconscious curtailment of physical activity, and it may be challenging to differentiate class I (no symptoms) from class II (mild symptoms), particularly when the symptoms are as nonspecific as dyspnea and fatigue—the hallmarks of symptomatic mitral regurgitation (MR). Moreover, it may be impossible to be confident that symptoms are attributable to MR when there are cardiac or pulmonary comorbidities. For these reasons, stress testing, typically with echocardiography, has become an increasingly important component of the evaluation and management of patients with MR.See Article by Bakkestrøm et alThere is a substantial literature that speaks to the diagnostic and prognostic importance of stress echocardiography in patients with primary MR. Indeed, such testing provides information as to the patient's functional and symptomatic status,3 inducibility,4 or worsening5 of MR, left ventricular contractile reserve,6,7 and right ventricular function.8 Noninvasively determined hemodynamics, notably pulmonary artery systolic pressure (PASP),9–11 have proven to be particularly important, in part, because resting PASP >50 mm Hg carries a class IIA indication for intervention (IIA) in American and European guidelines1,2 and exercise PASP ≥60 mm Hg carries a IIB indication for intervention in the European guidelines.2The conventional wisdom has been that dyspnea is attributable to increased pulmonary capillary wedge pressure (PCWP), and indirect support for this has come from prior studies in which resting or exertional pulmonary hypertension (PASP >50 mm Hg or exertional PASP ≥60 mm Hg, respectively) has been linked to symptom onset in initially asymptomatic patients.9,11 Fatigue, which is less common, has been attributed to reduced forward flow.In this issue of Circulation: Cardiovascular Imaging, Bakkestrøm et al12 report invasively derived hemodynamics at rest and with exercise in patients with asymptomatic or symptomatic primary MR. Their results demonstrate directly what we have inferred from echocardiographic estimates of PASP in such patients, but also challenge the conventional wisdom of an invariable link between symptoms and pulmonary pressures.Their study group is well characterized and meticulously studied, consisting of 57 patients (28 symptomatic and 29 asymptomatic) with significant primary MR (proximal isovelocity surface area-derived effective regurgitant orifice area, ≥0.30 cm2) and left ventricular ejection fraction >60%. The authors obtained both echocardiographic and magnetic resonance imaging (MRI) measures of cardiac anatomy/function, as well as mitral regurgitant severity, using American Society of Echocardiography/European Association of Cardiovascular Imaging-recommended approaches.13,14 The MRI information is important particularly since the echocardiographic grading of primary MR can be challenging with a tendency to overestimate severity relative to an MRI reference standard15. All patients had transesophageal echocardiograms to characterize the anatomic substrate for the regurgitation. With some exceptions, the patients were largely free of comorbidities and relatively young (mean age, 64–65 years.). Right heart catheterization done at rest and during semirecumbent bicycle stress provided measures of pulmonary artery systolic, diastolic, and mean pressures (PASP, PADP, and mPAP, respectively), PCWP, stroke volume, and cardiac index. To the hemodynamic data, they added pulmonary artery lactate, pH, and mixed venous O2 saturation, as well as speckle tracking echo measurements of global longitudinal strain. A separate cardiopulmonary stress test provided additional information concerning functional capacity with peak Vo2 measurements.The major findings provide confirmation for what most would intuit is the basis of the most common symptom in patients in primary MR—an elevated PCWP resulting in dyspnea. However while PCWP, PASP, pulmonary artery diastolic pressure, and mPAP were, on average, higher in those with symptoms than in asymptomatic patients and tended to increase with exercise, this was not a uniform finding. Indeed, one of the most interesting observations of this study is that the link between invasively measured pulmonary pressures and symptom status was inconsistent. Eight of 28 symptomatic patients had normal PCWPs at rest, and in 3, it remained normal with exercise. Of the 20 symptomatic patients who had elevated PCWPs at rest (>12 mm Hg), 7 had normal PCWPs (≤28 mm Hg) with exercise. The same inconsistency was noted in the asymptomatic group where 8 of 10 with elevated PCWP at rest had normal values with exercise, whereas 7 of those with normal rest values had elevated values with exercise. The exercise normal reference value for PCWP (≤28 mm Hg) may be taken with some reservation because the exercise format used in deriving it was different than the current protocol taking subjects to only 75% MVo2 max.16 However, if one assumes that a higher value would have been obtained at a higher workload comparable with the >100% predicted MVo2 achieved in this study, this would have resulted in a higher normal exercise value and thus even more subjects deemed to have normal rather than elevated exercise PCWPs. Although, as discussed below, there have been several studies assessing PASP noninvasively, none has provided individual data points, and thus the concepts that symptomatic patients might have normal exertional pulmonary pressures and that exercise may be associated with a fall in pulmonary pressures have not been suggested previously.9 Moreover, if fatigue, hypothesized to be because of reduced forward flow, accounted for some of the patients' symptoms, it is notable that cardiac index in the symptomatic patients in this study was normal and similar to that of asymptomatic patients. Additional information concerning the severity and nature of the patients' symptoms would, of course, be helpful in further interpreting these findings.Another interesting observation is that all subjects exercised well enough that, from a clinical perspective, it appears that even the symptomatic patients would be viewed as having normal exercise tolerance. Based on their exercise performance and hemodynamics, one might indeed question the diagnosis of symptomatic MR. This begs the question of the accuracy of attributing symptoms to MR in these patients and emphasizes the real-world clinical challenge of distinguishing the asymptomatic (class I) from the mildly symptomatic (class II) state. In this regard, it would be interesting to know how many patients were class II versus class III (more definitively abnormal). Another confounder is that echocardiography tends to overestimate the severity of MR relative to MRI as a reference standard as has been reported previously15 and as the authors acknowledge here. Thus, it is possible that not all patients deemed to have significant MR by echo did so by MRI.15 It is interesting that MR severity as graded by echocardiographic proximal isovelocity surface area effective regurgitant orifice area was greater in symptomatic versus asymptomatic patients but MRI-derived regurgitant volume was not.Comparison With Prior StudiesPeak Vo2Of the prior studies exploring stress response in patients with primary MR, several offer the opportunity to compare results. In the report of Messika-Zeitoun et al3 in which cardiopulmonary stress testing was performed in 134 asymptomatic patients with primary MR, the mean peak Vo2 was 96% predicted. However, 19% had markedly reduced peak Vo2—a finding that was prognostically important. In the current study, symptomatic and asymptomatic groups achieved Vo2 max values that were on average 106% and 108% of predicted respectively, similar to the findings of Messika-Zeitoun et al. Although there are no comments as to individual peak Vo2 values in the current study, it is noted that all subjects reached a respiratory exchange ratio >1.12 consistent with high-intensity exercise. This suggests that the current group might be biased toward a healthier, well-compensated population perhaps, as the authors suggest, because of the rigor of the investigational protocol.Pulmonary Artery PressuresAnother interesting observation for which we have comparative studies is that exertional PASP was >60 mm Hg in 61% of symptomatic and 34% of asymptomatic subjects (P=0.047).The latter is slightly less than reported by Magne et al9 who noted that 46% of asymptomatic patients reached these levels with semisupine bicycle stress—a protocol similar to that used here. However, in a larger study of 884 consecutive patients with at least 3+ MRs, Naji et al11 reported that only 15% had poststress PASP of ≥60 mm Hg. However, they used a treadmill stress protocol with poststress imaging. It is possible that PASP normalized in the interval between test termination and imaging or that the upright treadmill stress protocol, which was used, may have been associated with relatively reduced venous return mitigating the impact of exercise on pulmonary pressures. In the study by Magne et al,9 exercise PHTN was related to resting PASP, as well as resting and exercise echocardiographic indices of MR severity, which is consistent with the association of abnormal resting PCWP with echo and MRI indices of regurgitant severity in the current study. In a separate report, Magne et al9 reported that 58% of 78 asymptomatic patients with at least moderate primary MR developed exercise PHTN and that, when subsequently operated on for other indications, these patients were more likely to have complications, including atrial fibrillation, stroke, cardiovascular hospitalization, or death. A caveat is that the exercise PHTN patients were older. In aggregate, all these studies indicate that pulmonary pressures increase in a significant number of asymptomatic patients and, in some, to a degree that would provide an indication for surgery. Collectively, these provide support for the utility of stress echocardiography.LimitationsThere are several limitations to the current study beyond those acknowledged by the authors. First, the majority of subjects were men (76% and 82% of those in the symptomatic and asymptomatic groups, respectively), and it is possible that there is some sex specificity to the findings. However, the sex split is similar to that reported in some prior studies.3,9,17 Second, the numbers are too small to permit drilling down in ways that might shed light on some of the findings that are not intuitive. For example, it is not obvious why resting PCWP but not resting or exercise mPAP or exercise PCWP would be higher in the posterior leaflet prolapse group or why there is a trend for more posterior versus anterior leaflet prolapse patients to be symptomatic. Most likely, if this is a true finding, it is related to the degree of MR, but this is an untestable hypothesis in this small study group. It is notable that in the study by Magne et al,9 the presence of exertional pulmonary hypertension was not linked to the site of prolapse.Second, although the authors are to be commended on a study with 2 stress tests, it would have been interesting to have conventional stress echo results to address the issue of whether stress worsened the degree of regurgitation as has been reported previously.4,5 This would be interesting information because Magne et al9 reported that in asymptomatic patients, those who had exercise PHTN had more exertional MR (as assessed by effective regurgitant orifice area and regurgitant volume) than those who did not although MR was comparable at baseline.ConclusionsThe article by Bakkestrøm et al12 is an important contribution to our understanding of the pathophysiology of symptomatic and asymptomatic primary MR. By providing direct measurements of right-sided pressures at rest and with exercise, it has confirmed an overall link between pulmonary pressures and dyspnea, supporting prior studies that have had to rely on echocardiographically estimated PASP to draw similar conclusions. Importantly, their study has also demonstrated that there is not a perfect correspondence between symptoms and exertional pulmonary hypertension—a concept that deserves further study. Although the detailed characterization of the subjects allows the reader to evaluate many potential explanations for the paradoxical response of some subjects, it would be informative to know whether exertional worsening of the degree of MR is contributory. Perhaps individual specific data from prior reports would help resolve these questions.DisclosuresNone.FootnotesThe opinions expressed in this article are not necessarily those of the editors or of the American Heart Association.Correspondence to Linda D. 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Morningstar J, Nieman A, Wang C, Beck T, Harvey A and Norris R (2021) Mitral Valve Prolapse and Its Motley Crew‐Syndromic Prevalence, Pathophysiology, and Progression of a Common Heart Condition, Journal of the American Heart Association, 10:13, Online publication date: 6-Jul-2021. Zhang B, Li M, Kang Y, Xing L and Zhang Y (2020) Comparison of different transcatheter interventions for treatment of mitral regurgitation, Medicine, 10.1097/MD.0000000000023623, 99:50, (e23623) February 2018Vol 11, Issue 2 Advertisement Article InformationMetrics © 2018 American Heart Association, Inc.https://doi.org/10.1161/CIRCIMAGING.118.007471PMID: 29449413 Originally publishedFebruary 15, 2018 Keywordsmagnetic resonance imagingmitral valve insufficiencyhemodynamicsexercise physiologyechocardiographyEditorialsPDF download Advertisement SubjectsEchocardiographyImagingMagnetic Resonance Imaging (MRI)