Hearing the Right Heart's Sotto Voce
2012; Lippincott Williams & Wilkins; Volume: 126; Issue: 14 Linguagem: Inglês
10.1161/circulationaha.112.136598
ISSN1524-4539
Autores Tópico(s)Cardiac electrophysiology and arrhythmias
ResumoHomeCirculationVol. 126, No. 14Hearing the Right Heart's Sotto Voce Free AccessEditorialPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessEditorialPDF/EPUBHearing the Right Heart's Sotto Voce Ashish Aneja, MD and Subha V. Raman, MD Ashish AnejaAshish Aneja From The Ohio State University, Columbus, OH. and Subha V. RamanSubha V. Raman From The Ohio State University, Columbus, OH. Originally published29 Aug 2012https://doi.org/10.1161/CIRCULATIONAHA.112.136598Circulation. 2012;126:1673–1675Other version(s) of this articleYou are viewing the most recent version of this article. Previous versions: January 1, 2012: Previous Version 1 The left ventricle (LV) typically dominates the conversation around cardiovascular risk. This includes symptoms stemming from LV ischemia, signs of increased LV voltage by electrocardiography in hypertensive heart disease, and, apparently, a focus on the LV to open an editorial devoted to the right ventricle (RV) in preclinical risk assessment.Article see p 1681That is not to say that the softer voice of the distressed RV cannot be heard. Although the RV generally labors in the shadow of the more massive LV, the astute clinician can "think right heart"1 in the appropriate context of, for instance, a history of pulmonary or congenital heart disease. Furthermore, RV abnormalities can be recognized on careful inspection of the ECG, albeit more easily appreciated in the absence of marked LV voltage increase.But what attention does the RV require in the general populace at risk of, but without, apparent cardiovascular disease? In this issue of Circulation, Kawut and colleagues2 address this question in reporting their analysis of cardiac magnetic resonance (CMR) examinations and subsequent outcomes in >4000 participants in the Multi-Ethnic Study of Atherosclerosis. After adjusting for hypertension, tobacco use, C-reactive protein level, body mass index, demographic variables, and LV mass, the presence of right ventricular hypertrophy (RVH) doubled the risk of incident heart failure (HF) and cardiovascular death. This was observed in a cohort of mildly overweight adults in their early 60s who were, on average, normotensive at the time of baseline examination. In 65% of the study sample who had pulmonary function tested roughly 2 years after baseline assessment, the incremental predictive value of RVH for HF or death over the same covariates remained significant.RVH may previously have been neglected in longitudinal, community-based studies because of lack of a technique for its reliable measurement. Electrocardiographic detection of ventricular hypertrophy (not surprisingly with more data accrued regarding LV hypertrophy3 versus RVH4) lacks sensitivity, an important feature for appropriate population-based screening. Even if ECG changes of RVH are appreciable over the din of left heart abnormalities, the reproducibility data presented in this work are consistent with prior studies establishing CMR as a reliable modality for RV quantification with efficient sample size requirements for clinical trials.5What we do not learn from this work is what incremental value RVH by CMR has over echocardiographic indices, especially estimation of pulmonary artery systolic pressure (PASP) using Doppler-based measurement of tricuspid regurgitation jet velocity. In 778 white individuals from Olmsted County, Minnesota without manifest cardiopulmonary disease at baseline evaluation, increased PASP conferred increased mortality in a stepwise fashion (age-adjusted hazard ratio of 2.74 per 10 mm Hg).6 In this study, 69% of subjects had measurable tricuspid regurgitation, considerably higher than a peak 26% prevalence (increasing with age and highest in octogenarian men) of mild or worse tricuspid regurgitation in the Framingham study.7 In contrast, 92% (4144/4484) of the present Multi-Ethnic Study of Atherosclerosis cohort had interpretable RV-CMR studies. Although these data suggest that RV mass is a more reliable biomarker of right heart disease in community-based cohorts, some context of RVH by CMR amid widely used echo-Doppler measurements would have been helpful.Is the RV speaking to us directly through Kawut and colleagues'2 parsimonious model, or is it simply a voice for so many unmeasured variables? Although a subset had pulmonary function tests that would presumably capture latent obstructive or interstitial lung disease, we do not know to what extent sleep disordered breathing, occupational or travel exposures, silent chronic thromboembolism, undiagnosed left to right shunts, and infections such as human immunodeficiency virus were responsible for right heart changes. Of these variables, sleep disordered breathing may be the most significant because of marked increases in its recognized prevalence coupled with a propensity to cause subclinical RV enlargement and dysfunction8 that may reverse with treatment.9 The inclusion of body mass index in their model may have captured some instances of obstructive sleep apnea, but body mass index alone is an inadequate surrogate for the varied forms of sleep disordered breathing.Events such as HF (n=78, 2%) and cardiovascular death (n=34, 0.8%) were expectedly low. This number of events still allowed for subset analysis by pulmonary function measures, but the primary analysis did not include several key risk factors for HF that were addressed in an earlier publication in this journal reporting HF events in the Multi-Ethnic Study of Atherosclerosis–RV cohort.10 In that work, a high prevalence of baseline hypertension, obesity, chronic obstructive pulmonary disease (COPD), smoking, LV hypertrophy, and LV systolic dysfunction were rated as significant contributors to subsequent HF. Those results remind us of the difficulty in attributing events to RV hypertrophy beyond what could be predicted by classic left HF risk factors.The finding of a higher event rate in subjects with RV hypertrophy in conjunction with a relatively low LV mass is interesting and perhaps accounted for by the propensity of the LV to overwhelm the independent contribution of the RV to symptoms in the majority of HF cases and cardiovascular deaths. This is evident in the moderating effect of LV indices on the clinical impact of the other RV measures that did not survive multivariable analysis, such as RV end-diastolic and end-systolic volumes. These data endorse an association between RV mass and events, but causation requires further investigation.Even as CMR offers a gold standard to quantify RV size and systolic function, the assessment of RV mass can be time-consuming and prone to significant interobserver variability without dedicated core laboratory facilities or clinical staff adept at RV endocardial and epicardial contour delineation. However, this should not deter further investigation into the independent role of the RV in cardiovascular events and deaths to focus more attention on right heart–centric therapeutic approaches. Clinical data do suggest an independent role of RV function in prognosis,11,12 and preserved RV function in the setting of left HF predicts improved outcomes and functional capacity.13 Future investigations should seek to elucidate related versus distinct pathways of RV and LV dysfunction.The right ventricle is susceptible to dysfunction concomitantly with the LV as a result not only of increases in afterload from pulmonary venous hypertension but also ventricular interdependence, shared cellular myopathic processes, and ischemia. Evidence describing separate LV and RV embryogenesis, with recent discovery of a second heart field from which the RV (but not the LV) develops,14 lends further credence to the existence of distinct LV and RV signaling mechanisms and processes that could serve as future diagnostic and therapeutic targets. Preclinical mechanistic studies challenge existing notions of RV failure associated with pulmonary hypertension and increased RV afterload. Bogaard and colleagues15 produced RV hypertrophy without failure via pulmonary artery banding in Sprague-Dawley rats, whereas RV failure ensued in an angioproliferative model of pulmonary hypertension. The latter was produced via administration of a vascular endothelial growth factor receptor blocker in the setting of hypoxia that, in turn, caused myocyte apoptosis, decreased RV capillary density, myocardial fibrosis, and decreased vascular endothelial growth factor mRNA and protein expression. In the angioproliferative model, RV function could be preserved with a dietary supplement that induced myocardial nuclear factor E2–related factor 2 and heme-oxygenase 1, preventing myocardial fibrosis and capillary loss.15 Such RV-targeted interventions remain poorly queried in clinical trials, just as descriptions of distinct molecular and signaling mechanisms to explain RV dysfunction in humans are gaining momentum but remain rudimentary compared with the LV.16 Recognizing these gaps, a working group of the National Heart, Lung, and Blood Institute has delineated a roadmap to target translational research in these critical areas.5This work is a valuable and provocative addition to the literature that lends a stronger voice to the soft-spoken RV, which may be the good listener among cardiac chambers—taking in the effects of a variety of other conditions and presenting it through structural changes to the attuned observer. This trial's meticulous measurement of RV parameters coupled with long-term follow-up represents an important step forward in population-based research that should foster novel translational efforts. Ultimately, multifaceted, longitudinal outcomes studies that track the onset and progression of structural and functional changes should yield better identification of at-risk individuals who would benefit from population-based strategies to prevent adverse cardiovascular events.AcknowledgmentDedicated to the memory of Charles F. Wooley, MD who taught so many to 'think right heart.'Sources of FundingThis was work was supported by National Institutes of Health grants R01HL095563 and R01HL102450.DisclosuresDr Raman receives research support from Siemens, Pfizer, and Novartis.FootnotesThe opinions expressed in this article are not necessarily those of the editors or of the American Heart Association.Correspondence to Subha V. Raman, MD, MSEE, FAHA, Professor and Medical Director, CMR/CT, The Ohio State University, Davis Heart and Lung Research Institute, 473 W 12th Ave, Suite 200, Columbus, OH 43210. E-mail raman.[email protected]eduReferences1. Raman SV, Sparks EA, Boudoulas H, Wooley CF. Tricuspid valve disease: tricuspid valve complex perspective. Curr Probl Cardiol. 2002; 27: 103–142.CrossrefMedlineGoogle Scholar2. Kawut SM, Barr RG, Lima JAC, Praestgaard A, Johnson WC, Chahal H, Ogunyankin KO, Bristow MR, Kizer JR, Tandri H, Bluemke DA. Right ventricular structure is associated with the risk of heart failure and cardiovascular death: the Multi-Ethnic Study of Atherosclerosis (MESA)-Right Ventricle Study. Circulation. 2012; 126: 1681–1688.LinkGoogle Scholar3. Jain A, Tandri H, Dalal D, Chahal H, Soliman EZ, Prineas RJ, Folsom AR, Lima JA, Bluemke DA. 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Chest. 2009; 135: 794–804.CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetails October 2, 2012Vol 126, Issue 14 Advertisement Article InformationMetrics © 2012 American Heart Association, Inc.https://doi.org/10.1161/CIRCULATIONAHA.112.136598PMID: 22932259 Originally publishedAugust 29, 2012 Keywordshypertrophy, right ventricularcardiac imaging techniquesEditorialsheart failureheart ventriclesrisk assessmentPDF download Advertisement SubjectsComputerized Tomography (CT)Congenital Heart DiseaseEpidemiologyEthics and PolicyHypertrophyMyocardial Biology
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