Author + information
- Paul W. Armstrong, MD∗ ( and )
- Justin A. Ezekowitz, MBBCh, MSc
- Canadian VIGOUR Centre, Department of Medicine (Cardiology), University of Alberta, Edmonton, Canada
- ↵∗Address for correspondence:
Dr. Paul W. Armstrong, Canadian VIGOUR Centre, University of Alberta, 2-132 Li Ka Shing Centre for Health Research Innovation, Edmonton, AB T6G 2E1, Canada.
“You pays your money and you takes your choice.”
—Mark Twain (1)
The contributions of cardiac devices to the well-being and longevity of heart failure (HF) patients are well established. However, much of the data underpinning their efficacy has occurred in patients meeting specific clinical trial entry criteria that are often not transferrable to the complexity characterizing clinical choices. Whereas implantable cardioverter-defibrillator (ICD) implantations has reduced the likelihood of mortality extracted by arrhythmia-induced sudden death in patients with chronic HF and reduced ejection fraction, concerns about concomitant augmentation of the risk of progressive HF death, device-related infection, and inappropriate shocks have prompted a call for carefully weighing these trade-offs during individual decision making (2). Recent evidence has also questioned the continuing role of ICDs in HF patients without coronary artery disease (CAD) whose risk of sudden death is less than that of their CAD counterparts (3).
The advent of cardiac resynchronization therapy (CRT) has been a welcome addition to the HF therapy quiver because it not only improves symptoms and quality of life, but also survival. The MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy) trial established that early intervention with CRT with defibrillator (CRT-D) was superior to ICD alone in reducing long-term mortality and HF-related events in minimally symptomatic HF patients with a left ventricular ejection fraction (LVEF) of ≤30% and left bundle branch block (LBBB) (4).
Notwithstanding this welcome clarity, all engaged in HF management recognize that patient factors, such as advanced age, comorbidities, and personal preferences conspire to complicate therapeutic choices related to the use of cardiac devices. In this issue of the Journal, Zeitler et al. (5) attempt to unravel the influence of baseline comorbidities on the role of CRT-D in a long-term follow-up of the MADIT-CRT study. Not surprisingly from prior observations, they found that as the comorbidity burden rises, so too did the likelihood of death or a HF event, especially in patients assigned an ICD alone (5,6). Reassuringly however in this population restricted to patients with LBBB, those receiving a CRT-D device still derived benefit as compared to the ICD group, irrespective of the number of their comorbidities.
Before accepting these observations at face value, we contend that it is useful to reflect on some missing pieces to this puzzle that might inform us as to how better integrate the authors’ findings into practice. It is surprising that we are unable to separately discern the impact of the 8 selected baseline comorbidities on mortality and HF events because cause specific mortality data have been reported elsewhere (7). Because the long-term follow-up of MADIT-CRT trial (which also included the non-LBBB patients) reported the benefit of CRT-D versus ICD separately, this would have been of particular interest, given that mortality occurred less frequently than HF events (8). Of additional note is a 2015 MADIT-CRT trial report indicating that about two-thirds of the deaths in the MADIT-CRT trial were cardiac, of which 60% were assessed as pump failure and 25% due to arrhythmia (7). This previous report also described an increased mortality hazard related to renal disease, diabetes, and prior chronic HF. Understanding mortality outcomes separately in this low-risk group would have been especially important considering the initial MADIT-CRT trial report did not demonstrate an early reduction in mortality, but rather a decline in HF hospitalization rates with CRT-D therapy (4).
The left atrial volume (LAV) imaging data in the current report deserve special consideration, as there were baseline differences across the comorbidity categories; LAV increased as the burden of additional disease accumulated (5). This is not surprising given the influence of older age, diabetes, and lower estimated glomerular filtration rate. However, CRT-D was associated with a ∼30% relative reduction in LAV regardless of comorbidities. It is heartening to observe that even in those with substantial comorbidities reverse atrial remodeling seems possible. Because an enlarged left atrium may presage atrial fibrillation, this response to CRT-D (or other therapies) most likely modulated by altered loading conditions or atrial fibrosis, may have implications for assessing future risk.
Not all comorbidities are created equal, nor are they likely to remain static after their baseline ascertainment during the subsequent patient journey. Examination of Table 1 in the current report suggests a break point between comorbidity groups 0 and 1 from those above: the former patients are younger, are more often women, have better renal function, and have less CAD, hypertension, and cerebral vascular disease. Clearly, the presence of CAD, poorly controlled diabetes, and advanced kidney disease are likely to be large players on the future horizon of such patients. Whereas age and sex are immutable, smoking habits, hypertension, and other factors are eminently treatable; moreover, CRT-D may well reduce the burden of comorbidities by improving cardiac function and quality of life. Hence a positive response to CRT-D may carry with it improvement in renal function, skeletal muscle performance, and mood or cognitive impairment.
What implications are there for the clinician here? HF is a complex syndrome that rarely occurs in isolation from other ailments. Chronic obstructive lung disease, sleep apnea, peripheral vascular disease, depression, anxiety, cognitive impairment, and dementia are an incomplete list of other factors that merit consideration in a holistic model of HF care such as is delivered in multidisciplinary HF clinics. In addition, a frailty assessment adds a more comprehensive portrait to the insights gained from a listing of comorbidities and is easily undertaken (9). New pharmacologic therapeutic options have recently emerged that take both time and care to implement and evaluate (10,11). These deserve full exploration before proceeding with a device intervention that is life altering and costly. Finally, when weighing individual patient choices it is wise to recall that even though comorbidities should not preclude CRT-D or CRT pacemaker implantation they also carry an increased likelihood of procedural complications.
What need is there for further evidence and research to guide us in the future? We believe that once a clear baseline picture is established for each patient we need to better recognize the dynamic and evolving nature of risk that incorporates not only the natural history of the primary disease but integrates a comprehensive view of other patient factors at play (12). Once a device is implanted, a unique window into subclinical events such as paroxysmal atrial fibrillation is established. How to respond to this rich source of knowledge is a new and unmet challenge. The progress made in weighing the strength of nonfatal clinical outcomes comprising composite endpoints may also provide analogous future insights into the relative influence of various comorbidities on prognosis (13).
The MADIT-CRT investigators have reminded us to invest our resources carefully as we make complex choices for our patients with HF.
The authors acknowledge the expert editorial assistance of Lisa Soulard.
↵∗ Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology.
Both authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- 2017 American College of Cardiology Foundation
- Twain M.
- Allen L.A.,
- Stevenson L.W.,
- Grady K.L.,
- et al.
- Køber L.,
- Thune J.J.,
- Nielsen J.C.,
- et al.
- Zeitler E.P.,
- Friedman D.J.,
- Daubert J.P.,
- et al.
- Steinberg B.A.,
- Al-Khatib S.M.,
- Edwards R.,
- et al.
- Perkiomaki J.S.,
- Ruwald A.C.,
- Kutyifa V.,
- et al.
- Bakal J.A.,
- Roe M.T.,
- Ohman E.M.,
- et al.