Whole‐Body Imaging Procedures in Resistant Hypertension: Evaluating for Secondary Causes or to Define End‐Organ Damages?

In an editorial from almost 10 years ago, Dr Marvin Moser, Editor‐in‐Chief of the Journal at that time, cautioned against indiscriminate use of technology, to replace basic good hypertension and medical care in general.1 The subject of the debate at that time involved an emerging technology, impedance cardiography, which was not currently widespread in clinical practices. Dr Moser argued that clinicians not utilizing the newest technology should not be viewed by default as “antiacademic or antiprogress; almost all patients can be treated effectively without them.” In the past decade, magnetic resonance imaging (MRI) emerged as a sensitive technology to define end‐organ damage arising from hypertension in the brain, heart, and kidneys. Important papers in this Journal bear witness to this evolving understanding. For example, white matter lesions (WMLs) in the brain were found to correlate with both higher blood pressure (BP) at baseline and worse BP control among woman participating in the Women's Health Initiative Memory Study.2 Increased pulse pressure is associated with cognitive decline with such lesions3 and, as argued in an accompanying commentary, WMLs may represent a sensitive and meaningful intermediary target for antihypertensive therapeutic interventions.4 Similar associations have been observed with 24‐hour ambulatory BP monitoring (ABPM)–derived systolic and diastolic BPs, lacunes, perivascular spaces, and microbleeds.5 Yet another value is the capacity of specialized MRI to assess impaired organ perfusion, eg, in patients with chronic kidney disease, blood oxygen level–dependent MRI observed improved tissue oxygenation after renin‐angiotensin inhibitor administration.6

The article by Burchell and coworkers7 in this current issue of the Journal introduces an interesting concept on the diagnostic side of hypertension management, suggesting that a whole‐body MRI could answer most of the diagnostic questions and assist in making an etiologic diagnosis for hypertension in a single session.7 Such thinking is somewhat analogous to the concept of the “polypill,” as suggested by some to treat hypertension and cardiovascular risk factors with a small amount of multiple agents.8, 9, 10 The concept of a single diagnostic screening tool is actually quite attractive—just like the polypill—because with one test, a lot of other testing could be supplanted with a perhaps more expeditious arrival to the right diagnosis. We believe this suggestion should be heard and discussed in the community of hypertension experts. The idea of using such a screening tool in the hypertensive subpopulation where difficult cases are referred may sound “wild and outlandish” or overly expensive but its merits should be considered nonetheless. Undoubtedly, it is only a matter of time until MRI‐based imaging will largely replace computed tomography (CT)–based imaging, and with increasing availability of MRI exposure to ionizing radiation, CT will be less and less acceptable for us. We agree with the authors' conclusion that MRI is “safe”; however, the concept of “efficacy” is much to be debated—rather, we would call it a “safe and emerging” technology. We found it striking that even such comprehensive imaging failed to establish a clear etiology of treatment‐resistant hypertension in the majority of the patients. Yet, all this expensive image‐generating technology completely lacks the biochemical aspects of a hypertension workup. Most clinicians would likely consider biochemistry (low potassium, abnormal aldosterone/renin ratio) as a starting point of a workup for resistant hypertension. Anxiety‐related hypertension or obstructive sleep apnea are of additional concern; it is extremely unlikely that MRI could shortcut history‐taking and anthropometrics (eg, neck size) to assess the risk of obstructive sleep apnea.11 Most importantly, the study did not address—although mentions—the costs of the total‐body MRI. One important reason why others have not come up with this idea of total‐body MRI is because of its prohibitive cost. There are European countries where patients wait for months for an MRI and even in the United States, insurance preapproval may be needed. Perhaps reviewing the potential limitation of the study by Burchell and colleagues7 in more detail would offer us a glimpse into the future.

The article spends a considerable amount of energy and effort on going into great lengths to describe how well left ventricular (LV) hypertrophy (LVH) can be detected by MRI using cardiac magnetic resonance (CMR) imaging. While it may be true that this diagnostic tool gives us an extremely accurate level of insight into the left ventricular geometry, weight, and trabeculation, these are diagnostic results that are probably the least important information in the diagnostic workup of hypertension. To what degree describing anatomical structure beyond a certain detail would meaningfully add to the clinical decision‐making remains to be seen. The presence of LVH may be important to note—and indeed, they are part of various guidelines—but this is the least actionable information! A clinician would treat all of his or her patients to target BP values whether or not the patient had increased or decreased trabeculation in the heart. More importantly than anything, we should also recognize that LVH may be much more a consequence of insufficiently controlled hypertension than an etiology of a secondary cause. At this point in time, such technology is perhaps better conceptualized as a description of “cardiovascular health,” perhaps, than a true test to disclose causes of secondary hypertension. Notwithstanding even these limitations, we suffer from the lack of true gold standards. While CMR imaging can be an important and accurate tool to assess LVH and LV mass, it is not the gold standard to evaluate LVH! The article mentions “gold standard” for assessing LV mass and LVH five times, but it is not the gold standard in clinical practice. One of the referenced authors included (Pennel) and cited by Burchell writes, when discussing CMR imaging accuracy and reproducibility: “The gold‐standard validation of comparing in vivo images with subsequent postmortem weights has not been performed in humans, and this important comparison remains to be done.”12 For a gold standard to be such, it needs to be universally accepted to be the reference point and comparator to all other tests. CMR imaging is not at such stage (yet). Guidelines do not recommend using CMR imaging and it is not the standard of care as the universal test for establishing LVH—because it is not the gold standard!

Importantly, the MRI‐detected adrenal abnormalities were not necessarily helpful in diagnosing the etiology of hypertension in this population. The authors found 12 adrenal masses and only one or perhaps two were causing hypertension at all. This could be construed as a case for arguing against the MRI testing, as the diagnosis (the cause of hypertension) was not made and the findings did not produce more than patient stress and anxiety at a high price. This reminds us of the term the American College of Physicians calls “harmful testing,” that is, coming up with a finding of no actionable diagnosis that only raises the possibility of intervention‐related complications, anxiety, and cost but no benefit to the patient. Additionally, considering that some authors report the prevalence of hyperaldosteronism to be as high as 29%, the detection rate by MRI in this study was rather low.13 The story with renal artery stenosis (RAS) is similar; of 10 cases, only two had undergone stenting and the others received medications that would normally be given to people who have LVH anyway. Even though there were 10 patients who were found to have RAS, 80% of the findings were nonactionable findings that generated more testing and anxiety to the patient. Similarly, the significance of “thyroid abnormalities” would also be very doubtful, and, in the current study, almost all (6 of 7) proved of no consequence or relationship to the accelerated hypertension.

It is possible that the total‐body MRI gives us such a crisp image of the patient that we discover things that are possibly there but require no intervention for the abnormality. What good is this “crisp image” then if we cannot or should not do anything with the findings? Do we really want to look in a concave mirror to see all the wrinkles, freckles, and blemishes on our faces? Will anybody pay for these tests? Insurance companies likely would refuse coverage at the current time and such approach for the foreseeable future to remain a research tool or for the very wealthy willing to pay cash directly for the services. The authors carefully emphasize the importance of limiting such expensive technology to the tertiary care center settings rather than recommending it for the routine use as workup of simple hypertension.

Beyond these conceptual concerns, several practical issues remain unclear to us. While the referred cohort was stated to have “drug‐resistant hypertension,” “uncontrolled hypertension,” hypertension at young age, or “other difficult‐to‐treat hypertension,” there are no data on home BP or ABPM values prior to this extensive investigation. The true extent and impact of medical therapy adjustment prompted by MRI results for the cohort's participants remains unknown. Also, not too many new renal diseases were found—likely reflecting a preselection bias.

In summary, we are unable to agree with the authors' conclusion that “given the high prevalence of target organ damage reported… we recommend that MRI should be used as the primary imaging modality in tertiary hypertension clinics.”7 We would view this very interesting technology as a work in progress and belonging exclusively to the realm of clinical research at the present time. We regard this effort by the authors as a worthy undertaking for working on finding the causative diagnosis of hypertension rather than simply adding to treatment guidelines and protocols.