Author + information
- aBaker-IDI Heart and Diabetes Institute, Melbourne, Australia
- bUniversity of Minnesota & VA Medical Center, Minneapolis, Minnesota
- cIcahn School of Medicine at Mount Sinai, New York, New York
- ↵∗Reprint requests and correspondence:
Dr. Jagat Narula, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, New York 10029.
In the world of drug and biomarker development, the “valley of death” sits between traditional academic research and industry research (1). It is so called because translational science is perceived as being of limited novelty—the “discovery” component having already been completed—so this seems of low priority for traditional research funding. At the same time, the absence of a clear clinical product makes this work unattractive to industry. This chasm is responsible in part for the delays in bringing new ideas to commercialization (1). In imaging research, we have such a process as well, relating to the steps between making physiological observations of clinical relevance and eventually applying these into clinical pathways (Figure 1). Imagers have been particularly poor at developing the strongest level of evidence—randomized controlled trials—for our new techniques and applications. This is perhaps no better exemplified than in developing the evidence base for routine, follow-up tests. Although these studies account for a substantial proportion of the work load in any imaging laboratory, many routine studies fall into the category of being of uncertain appropriateness, or even “rarely appropriate” (2). In some such instances, routine testing is devoid of benefit because the test is clearly unnecessary, providing no change in therapy or documentation of reassurance, or occurring when the next step in management has already been documented before the results of transthoracic echocardiography are provided. The solution to these situations is simple: we should find means of identifying and declining these tests. However, other instances are more nuanced: clinicians order tests because they consider the tests to provide information to guide management. The problem is that in the absence of strong evidence, it is hard to judge the value of imaging in clinical pathways. In this issue of iJACC, several papers demonstrate the importance of physiological signals for providing clinical guidance regarding the management of a variety of cardiac and noncardiac conditions. Will the next step be the inappropriate use of this information in unnecessary studies of unproven clinical value, or will we “cross the valley” to develop the requisite evidence base to justify their routine clinical adoption?
Cardiac allograft vasculopathy is a barrier to long-term survival in patients undergoing heart transplantation. In a study of 63 consecutive heart transplantation patients, Erbel et al. (3) used cardiac magnetic resonance to assess both myocardial strain and perfusion. Decreasing perfusion reserve and diastolic strain rate correlated with the findings of biopsy (to assess the microvasculature) and coronary angiography (to assess the epicardial vessels). The absence of vasculopathy was associated with good outcomes. This “discovery research” shows the information provided by the physiological signal. However, before we use these techniques for better surveillance of these patients, more work is needed to identify suitable cutoffs and the predictive value in multicenter studies. If such information comes to hand, these physiological signals from noninvasive testing can supplement or possibly even supplant the standard invasive approach.
Similarly, the development of pacing-lead endocarditis is a well-known but fortunately rare complication of cardiac pacing. In this situation, the identification of septic emboli with imaging techniques has immediate implications for clinical management. In this issue, investigators from France describe the identification of septic emboli using positron emission tomography of fluorodeoxyglucose uptake in nearly one-third of 35 consecutive patients with pacemaker lead endocarditis (4). The “discovery science” is that positron emission tomography can perform in a setting in which computed tomography is often insensitive, and cardiac magnetic resonance is often incompatible with the implanted pacemaker. However, before this discovery can be adopted as a routine follow-up test, multicenter studies are needed to show prognostic value, the availability of appropriate management responses, and the economic value of this additional step.
Hematologic conditions may have long-term effects on the myocardium because of infiltration or treatment with cytotoxic or radiotherapy. Much recent attention has focused on the association of chemotherapy with myocardial disease and heart failure, but the effects of therapy on the heart valves has received less attention. Murbraech et al. (5) report the finding of valvular disease in 22% of lymphoma survivors following autologous hematopoietic stem cell transplantation. Although it might be expected that this association was attributable to radiotherapy, valve abnormalities were reported in nearly 17% of patients treated with anthracycline alone, representing a 3-fold increased risk compared with control subjects. Likewise, sickle cell disease has been associated with restrictive cardiomyopathy and pulmonary hypertension. Investigators from Canada show impaired diastolic function in patients with sickle cell disease, with correlation among left atrial size, pulmonary pressure, and estimated left ventricular filling pressure (6), and verify their findings in a meta-analysis of 68 previous studies. The clinical translation of this work on hematologic conditions awaits evidence that the physiological markers of adverse outcomes can provoke a therapeutic response that changes this prognosis. In the absence of this, the routine screening of at-risk patients is likely to generate anxiety rather than better health.
Inherent in the application of these data is the need for a standardization. The GenTAC (National Registry of Genetically Triggered Thoracic Aortic Aneurysms and Cardiovascular Conditions) investigators took the opportunity of having core laboratory and site measurements of aortic size, in order to compare their consistency (7). These investigators showed that just as different imaging modalities provided different levels of reproducibility, so did the clinical centers influence the results. Clearly, even when the prognostic information and translational information are well known, the adoption of sequential routine follow-up measurements is dependent on the consistency of measuring techniques among sites.
At iJACC, we try consistently to select the best new discovery science, and we are proud of this issue’s examples. However, we are keen to see the next steps: well-done clinical trials and economic analysis that translate the excellent discoveries of the imaging community to appropriate, evidence-based clinical practice.
Dr. Narula has received research support from Philips and GE Healthcare in the form of equipment grant to the institution. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- American College of Cardiology Foundation
- Douglas P.S.,
- Garcia M.J.,
- Haines D.E.,
- et al.
- Erbel C.,
- Mukhammadaminova N.,
- Gleissner C.A.,
- et al.
- Amraoui S.,
- Tlili G.,
- Sohal M.,
- et al.
- Murbraech K.,
- Wethal T.,
- Smeland K.B.,
- et al.
- Niss O.,
- Quinn C.T.,
- Lane A.,
- et al.
- Asch F.M.,
- Yuriditsky E.,
- Prakash S.K.,
- et al.