Heart Online First, published on May 29, 2015 as 10.1136/heartjnl-2015-307641
Long-term outcomes in coarctation of the aorta: an evolving story of success and new challenges Ami B Bhatt, Doreen Defaria Yeh Individuals with coarctation of the aorta have historically had poor long-term outcomes with a mean life expectancy of 35 years. Natural history studies demonstrated 90% of individuals dying before age 50 years. Over the past several decades, improvements in prenatal diagnosis, paediatric cardiac surgery, intensive care and adult congenital care have led to a robust success story with the majority of adults living to older ages. The Heart article by Choudhary et al1 studies the modern day adult coarctation population and defines a new trajectory for longevity. Although reintervention appears to be inevitable in many cases, with late complications including recoarctation, aneurysm development and cardiovascular death, the overall population demonstrates improved outcomes in those who reach adolescence with very good long-term survival to age 60 years. Despite this optimistic outlook, the authors recognise that atherosclerotic cardiovascular disease (ASCVD) and cerebrovascular events comprise the majority of late morbidity and mortality. The observed deaths were primarily sequelae of acute or chronic hypertension; however, the only identified predictor of hypertension was late repair. Until we are able to better risk stratify which individuals are at the greatest risk for hypertension and late adverse events, adult and paediatric cardiologists must be vigilant with all patients including those with repaired coarctation regarding aggressive primary prevention of ASCVD. In coarctation of the aorta, hypertension, endothelial dysfunction and increased aortic stiffness contribute to subsequent development of premature coronary artery disease and diastolic heart failure. It is likely that these factors are significantly interrelated in their aetiology and therefore hopefully in their treatment.
Department of Cardiology, Massachusetts General Hospital, Boston, Massachusetts, USA Correspondence to Dr Ami B Bhatt, Department of Cardiology, Massachusetts General Hospital, 55 Fruit Street, Yawkey 5B, Boston, MA 02114, USA;
[email protected]
HYPERTENSION: AN ONGOING PROBLEM, A CLEAR OPPORTUNITY Patients with coarctation who have not undergone repair invariably present with systemic arterial hypertension measured in the upper extremities. It is important to realise that even those who undergo early repair have a 30% 10-year incidence of hypertension, despite having achieved a lasting anatomic result.2 Choudhary et al reveal that nearly half of repaired individuals are hypertensive in this modern day cohort, and initial surgical approach was not a significant predictor. Mechanisms of hypertension may include upregulation of the renin–angiotensin system, impaired vasoreactivity, aortic arch geometry abnormalities, baroreflex dysfunction and abnormal aortic distensibility.3 Hypertension may be a better predictor that lipid levels for carotid intimal medial thickness (CIMT) progression (as a surrogate marker for ASCVD) among patients with coarctation. A recent study demonstrated that 3 years of treatment with high-dose atorvastatin did not reduce CIMT progression despite significant reduction in serum total cholesterol and low-density lipoprotein levels.4 In that same study, however, there was a close association of the presence of hypertension with CIMT. Although deaths were relatively few in the current study by Choudhary et al, prior studies confirm that hypertension contributes to and accelerates heart failure, premature atherosclerosis, cerebrovascular and progressive aortic disease as a cause of death. Hypertension may therefore have a predominant role in vascular wall dysfunction and its reversal may be essential in diminishing ASCVD risk. Targeting ‘ideal blood pressure’ over time in a repaired coarctation population to assess future ASCVD risk has not yet been undertaken and is an important next step in prevention of cardiovascular morbidity and mortality in this population.
VASCULAR DYSFUNCTION: THE TWO-HIT HYPOTHESIS Another potential target for therapy in coarctation of the aorta is endothelial dysfunction, demonstrated to persist many years after repair. Upper limb hypertension prior to repair may cause long-term Bhatt AB, et al. Heart Month 2015 Vol 0 No 0
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baroreceptor dysfunction5 or structural and functional abnormalities in the arterial wall resulting in endothelial dysfunction. Even normotensive individuals with well-repaired coarctation may demonstrate endothelial dysfunction. Prerepair hypertension may not be in the causal pathway of endothelial dysfunction as abnormal vascular function does not correlate with age at repair. In addition, a recent study revealed no significant difference in endothelial function between their patients with coarctation and healthy controls.6 These conflicting data now raise the possibility that only select individuals with coarctation have an overt intrinsic arteriopathy leading to vascular dysfunction. When present, endothelial dysfunction may be a key initiating event in atherogenesis in coarctation as has been demonstrated in other entities. It is unclear if the superimposition of systemic hypertension accelerates this process in these at-risk individuals, and presents an important direction for future research.
COARCTATION IS MORE THAN AORTIC DISEASE: LV MYOCARDIAL FUNCTION Rates of clinical heart failure rise after the fourth decade of life among patients with repaired coarctation. The unique and chronic afterload presented to the LV in individuals with aortic coarctation may accelerate diastolic abnormalities and heart failure. LV mass is a predictor of heart failure and increases over time in select normotensive individuals with coarctation despite repair. Ambulatory or exercise blood pressure measurements may reveal a haemodynamic contribution to this process. However, aortic dimensions, distensibility and flow patterns all present unique loads to the LV and may be equally relevant to long-term myocardial function.7 Impaired diastolic LV function is evident by echocardiography using tissue Doppler imaging several years after early childhood repair even before systolic function is affected. Cardiac MRI further reveals subtle impairment in LV systolic function (global longitudinal and radial strain) over time despite normal LVEF.8 These abnormalities of LV function correlate with degree of residual narrowing of the aorta in the absence of hypertension. These findings suggest that residual or recurrent coarctation with minimal gradient may not be a benign finding. We can also extrapolate that anatomic variations in aortic dimension (ie, long narrow segments, presence of native transverse arch, stented segments of grafts) may also significantly affect myocardial load. As we address the ageing individual with 1
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Figure 1 Longitudinal outcomes in coarctation. Superimposed pathophysiological changes and related clinical consequences over the lifespan are demonstrated. coarctation of the aorta, recognising, studying and modifying the ventriculoarterial relationship may alleviate LV afterload and future rates of clinical heart failure.
ASCVD RISK IN COARCTATION OF THE AORTA: A LONGITUDINAL ROADMAP Despite successful repair of aortic coarctation, individuals remain at elevated risk of premature atherosclerosis and early mortality. Coronary artery disease is documented in 25%–37% of cases and remains the most common cause of death.9 To better understand the aetiology of ASCVD in this population, known cardiovascular risk factors including hypertension, diabetes, overweight, smoking and sedentary lifestyle must be assessed and aggressively controlled. Choudhary and colleagues have demonstrated the improvement in patient with coarctation survival in the modern era as well as the concerns for long-term aortic 2
complications, including restenosis, aneurysm and hypertension, and need to be vigilant in this population. As the life expectancy of this population increases, validating potential surrogate measures of coronary atherosclerotic risk,10 such as CIMT will be important in supporting investigational efforts.9 While physiological research into the vascular and ventricular function and interactions in this population continue, there is a clear indication for large-scale studies of long-term cardiovascular risk factors and events in this population as well as investigation into treatment strategies for this population. Aggressive blood pressure control surfaces time and again as essential to the foundation of any coarctation treatment strategy. ‘Simple’ or ‘isolated’ coarctation of the aorta is an example of a disease process requiring us as clinicians to understand the interaction of inherent risk (genetic determinants, intrinsic arteriopathy) with
superimposed anatomic (native and intervened aortic), physiological (compliance, blood pressure, flow) and environmental (smoking, overweight, diabetes, sedentary lifestyle) modifiers, in a longitudinal construct (figure 1). Fortunately, Choudhary and colleagues tell us that with improved survival, we now have more time to evaluate this population longitudinally. The challenge is to further extend longevity while improving the quality of that time for this unique and complex population. Contributors ABB and DDY participated in the writing, editing and finalising of this editorial paper. Competing interests None declared. Provenance and peer review Commissioned; internally peer reviewed. To cite Bhatt AB, Defaria Yeh D. Heart Published Online First: [ please include Day Month Year] doi:10.1136/heartjnl-2015-307641
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▸ http://dx.doi.org/10.1136/heartjnl-2014-307035
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