Heart failure is a leading cause of morbidity and mortality in the developed world. Individuals with heart failure are an aging patient population with multiple comorbid conditions, which impact the complexity of the symptom burden of the disease. Whereas many providers are adept at managing the challenges of neurohormonal modulation, volume status, dyspnea and angina, they may lack the skill to manage depression, anxiety, fatigue and pain. There is a significant burden of pain experienced by the heart failure patient. In fact, 75% or more of patients with heart failure experience significant pain at the advanced stages of their disease . In the recently completed Pain Assessment, Incidence & Nature in Heart Failure (PAIN-HF) study, which evaluated the experience of pain in 347 outpatients with advanced heart failure, pain anywhere in the body was experienced by 84% of patients and almost 40% of patients had multiple sites of pain [2▪▪]. Pain is often unrecognized and undertreated. The medical and psychosocial complexities of the heart failure patient affect the experience of pain and present challenges for the management of pain which may not exist for other patient populations, especially at the end of life. We will review the pathophysiology of pain, discuss the limited available data regarding the understanding and management of pain in heart failure, attempt to understand the sources of pain and influencing factors which modulate pain and finally discuss current treatment options and the most recent research aimed at understanding cause and treatment options.
PATHOPHYSIOLOGY OF PAIN
The experience of pain is individual. In some instances (such as trauma or postsurgery) the cause of pain is clear and apparent. In other cases the description and cause require a practitioner to take time to fully elucidate the characteristics of a pain experience to guide treatment. Pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage’ . Pain is multifactorial and a multifaceted approach is needed to understand and manage pain-irrespective of cause.
Dr Cicely Saunders defined ‘total pain’  to conceptualize pain at the end of life, though it can be extended to a chronic life-limiting, highly symptomatic disease, such as heart failure. Physical, emotional, social or interpersonal, and spiritual or existential facets contribute to the experience of ‘total pain’. We will briefly review all four, with a focus on understanding and managing physical pain in the heart failure patient (Fig. 1).
Physical pain, the most common form of pain that most practitioners treat, can be discussed in the context of the neurophysiology of pain and described as nociceptive versus neuropathic. Somatic and visceral pains are nociceptive pains. Nociception is the conscious experience of pain from somatosensory nervous system transmission of noxious stimuli to the brain. The response to stimuli encoding into an action potential can be autonomic, for example a change in heart rate or blood pressure with the perception of pain, or it can be behavioral, for example withdrawing a hand from a painful stimulus such as a hot stove. Nociceptive pain is the ‘pain that arises from actual or threatened damage to non-neuronal tissue and is due to the activation of nociceptors’ . Somatic pain is associated with the pain from injury or nociceptor activation in the skin, soft tissues, including bones and joints. Often this pain is well localized and the descriptors of this pain include ‘throbbing, aching and stabbing’. Visceral pain is ‘deep pain’ encountered due to stimulation of the nociceptors which line the viscera of the organs, for example the capsule that covers the liver. This pain can be associated with symptoms such as nausea, vomiting, diaphoresis and often is characterized as deep pressure, cramping or squeezing. Figure 2 is a graphic representation of the main neurophysiologic processes involved in the perception and response to nociceptive pain .
In contrast with nociceptive pain, neuropathic pain is caused ‘by a lesion of disease of the somatosensory nervous system’ . Peripheral injury leads neurons to become exquisitely sensitive and become more reactive and excitable, even to stimuli that may not have normally caused pain (peripheral sensitization). Central sensitization occurs when the lesion is within the central nervous system (dorsal horn of the spinal cord/spinothalamic tract). This is experienced as more continuous pain over a larger area and a painful response to nonnoxious stimuli. Neuropathic pain is described as painful dysesthesias (abnormal sensations), hyperalgesia (increased sensitivity to painful stimuli) or allodynia (pain from generally innocuous stimuli). Neuropathic pain is often difficult to treat and associated with other systemic illnesses (cancer, multiple sclerosis, diabetes, etc).
Finally, pain can also be characterized temporally as acute or chronic. Acute pain is generally a pain of less than 3 months duration which is associated with a known injury. This pain in general responds to analgesics including opioids and may often resolve with nonpharmacologic interventions (heat, cold, massage). Most practitioners can treat acute pain with relative proficiency. Chronic pain adds a level of complexity that is often uncomfortable for many prescribers. Chronic pain last more than 3 months from an acute injury and is associated with changes in the transduction, transmission and modulation of the painful stimuli. Chronic pain may be related to ongoing painful stimuli such as persistent inflammation or it may be the result of sensitization of central or peripheral neurons. Peripheral pain is described as ‘shooting, burning, electric’ and central as ‘vise-like and throbbing’. The main goals of treating chronic pain are to relieve distress and restore maximal function . With acute pain there is often autonomic hyperactivity, for example release of catecholamines leads to tachycardia, rise in blood pressure and often muscle rigidity in the area of injury, whereas chronic pain tends to have little or no autonomic hyperactivity.
Many practitioners underestimate the importance of the other areas that contribute to the experience of total pain. Psychological pain incorporates various psychological illnesses and stressors into the pain experience. Whereas much of the literature regarding pain in chronic, life-limiting illness comes from work with cancer patients, the same principles apply to heart failure, with depression and anxiety as people deal with the meaning of heart failure in their lives. Patients with heart disease are at higher risk for depression than others and there is considerable morbidity associated with the dual diagnosis of heart failure and depression. Issues such as grief and loss figure prominently into this aspect of pain in heart failure – -the grief of loss of life, of functionality and of roles in family and community. Often these aspects of pain are least addressed by many practitioners. Untreated psychiatric illness may lead to an inability to adequately treat physical pain and suffering. This may in part explain why many patients with advanced heart failure experience uncontrolled pain at the end of their lives.
Social or interpersonal pain results from challenges that patients with heart failure have in relationships with family and caregivers that can be strained by the progressive and chronic nature of heart failure. As patients go on to receive advanced therapies such as mechanical circulatory support and transplant, these social networks become even more crucial. Many individuals living with heart failure experience the pain of loss of their role within their family and physical and psychological stressors of the disease may limit their ability to fully participate in their normal lives. Care providers often do not address the loss of work, life and financial stability as part of routine heart failure care and we miss the opportunity to understand the impact of nonphysical dimensions on the experience of pain. For many patients and their families, chronic illness leads to significant financial issues and even bankruptcy. Fear and worry contribute to patient and family experience of pain. Unresolved family discord often is exacerbated by severe, chronic illness and interventions to help deal with this conflict, especially at the end of life may help individuals regain a sense of control and comfort.
Spiritual pain and suffering is expressed in different ways for different individuals and often is not related to religious faith or practice. Existential pain comes from redefining their own personal value as a human being in the context of their illness and attempting to better understand the meaning of their lives and the impact of heart failure on that. To address spiritual and existential pain clinicians must be willing to engage the patient regarding their personal values of self and experiences of their lives, or partner with others who perform this task. Heart failure is a real and often overwhelming threat to patients’ personal and relational identity and may be fraught with a sense of hopelessness, loss, disappointment and fear of death. A lack of understanding in the general population of what heart failure truly is and its’ impact on morbidity and mortality often leads to patients and families being ‘shocked’ and ‘surprised’ when they reach the end stages of disease and are offered palliation/hospice and/or transplant and mechanical support. One often hears the comment ‘I didn’t realize I was this sick’ or ‘I didn’t really know I could die from this’. These experiences can lead to significant existential crises for patients which can often lead to noncompliance with recommended treatments and a disconnect between patients and providers. This conflict needs to be addressed early and frequently in order to avoid unnecessary suffering.
PAIN IN THE HEART FAILURE PATIENT
Pain is a significant part of the experience of HF patients. Much of the data identify pain in patients who are in the advanced stages of heart failure or are in the final stages of dying. For example, The Study to Understand Prognoses and Preferences of Outcomes and Risks of Treatments (SUPPORT) identified that in the last 3 days of life family caregivers felt 41% of patients with heart failure experienced moderate to severe pain . There is limited information regarding community dwelling heart failure patients with potentially less severe heart failure. The Help Veterans Experience Less Pain Study trial assessed symptoms, functional status and psychological, social and spiritual factors in community patients with the diagnosis of diastolic or systolic heart failure. In one analysis they found that 55% of patients reported pain (over 1/3 as moderate to severe) and pain severity correlated with other psychological, social and spiritual domains, demonstrating the multifactorial nature of the problem . Another view of their data compared it to a non-heart failure population controlling for age, comorbidities and cancer disorders and found the incidence and severity of pain was similar in both groups pointing to the unrecognized problem of pain in the heart failure population .
Most recently, the PAIN-HF trial attempted to define the location, character, severity, frequency and other correlates of pain in advanced heart failure patients, and analyzed quality of life, mortality and current treatments for pain. Over 80% of patients with advanced heart failure reported pain with more than one-third reporting pain at multiple sites. The most common site of pain was the ‘legs below the knees’ in one-third of patients (despite lack of edema) and pain at sites other than the chest was reported in 76% of individuals [2▪▪]. Patients reported severe to very severe pain one-third of the time (more so when pain was not ‘chest’ pain) and the strongest predictors of pain were concomitant degenerative joint disease (DJD), dyspnea and angina. Acetaminophen, NSAIDs, gabapentin, glucosamine/chondroitin, corticosteroids and cyclooxygenase-2 inhibitors were reported without significant relief of pain. Opioids used in 34% of patients were the only agent which reported to relieve pain. Ischemic heart disease is the most common cause for heart failure and yet anginal pain was reported in only 30% of patients [2▪▪]. A recent study by Clark and Goode [12▪] found chest pain in systolic heart failure to be fairly uncommon, even in patients with ischemic heart disease, although it weakly (but not statistically significantly) predicted a worse outcome.
The heart failure patient experiences pain from multiple sources. Understanding what is driving the discomfort is essential in determining how to approach the management of these symptoms.
Cardiac pain/intractable angina
Pain which is concerning for angina is approached with accepted evidence-based treatments for the management of chronic angina. These include the ongoing use of nitrates and beta blockers if tolerated by blood pressure, a limiting factor for many heart failure patients. Calcium channel blockers specifically dihydropyridines, which do not have a negative inotropic effect, may be added. Hypoperfusion of the myocardium with inadequate systemic pressures leading to global ischemia, especially in patients with nonrevascularizable myocardium may increase angina. Ranolazine modulates calcium overload in the myocyte and decreases anginal symptoms and improves exercise capacity in patients with chronic stable angina when added to a standard antianginal regimen.
Several mechanical therapies investigated in the treatment of intractable chronic angina have limited efficacy data and require more data on intermediate and long-term outcomes. Enhanced external counterpulsation (EECP) decreases anginal episodes although without significant benefit with regards to exercise tolerance and use of nitrates. Although a relatively unproven procedure, spinal cord stimulation at the T1 to T2 level is relatively well tolerated, decreases ischemic effects, improves functional status, decreases hospitalizations and improves quality of life. Transmyocardial laser revascularization (TMLR) opens chronic total occlusions in complex coronary disease including drug eluting stents and new devices, yet its burden of complications resulted in less of a role for TMLR. Finally, one last approach is the use of thoracic epidural analgesia. A recent study by Richter et al.[13▪] of a 10-year experience found long-term home self-treatment with thoracic epidural analgesia to be well tolerated, with symptomatic improvement of angina and improved quality of life. Catheter dislodgement occurred but there were no major complications.
Nonanginal pain is a significant component in the pain experience of heart failure patients who are older, may have other comorbid conditions, such as arthritis or diabetes and because of their heart failure and/or associated renal dysfunction, have limited treatment options. Trepidation among heart failure practitioners about the use of opioids in these patients prevents adequate relief. Clinicians should inquire about pain frequency, location, duration, precipitants and what relieves pain. It is critical that we approach pain management in the heart failure population as we would in any other chronic and/or life limiting illness. We must discuss with patients their goals (improving function and quality of life or minimizing pain), the likelihood of success in pain management and concerns they and their entire care team have. The basic principles of pain management are to use oral analgesics when able (adding adjuvant treatments), administer analgesics at regular intervals and adjust to the level of pain.
Figure 3, is an ‘analgesic ladder’ adapted from Vargas-Schaffer's  review of the validity of the WHO guideline in the current era. For heart failure patients, NSAIDs are not an option given interactions with neurohormonal modulation, renal dysfunction and fluid retention. Understanding of the severity of pain is critical and a willingness to climb the ladder, with caution, is equally as important.
Acetaminophen is reasonable to try in patients with mild pain. Opioids are well tolerated in heart failure patients but must be chosen cautiously in those with renal dysfunction. Several opioids, notably morphine, have neurotoxic renally excreted metabolites that accumulate with chronic use. Methadone, which can be quite effective in managing chronic pain and has the advantage of gastrointestinal excretion, accumulates in tissues over time thus maintaining a serum concentration for 30 h or longer. At high doses, methadone may cause QT prolongation and torsades de pointes, so the electrocardiogram should be monitored periodically. Opioid-naïve patients should receive short acting opioids until the total daily dose required for pain control is assessed and potentially a long acting opioid can be introduced.
Adjuvant medications such as the tricyclic antidepressants (TCAs), steroids and anticonvulsants can provide added relief for neuropathic and chronic pain. The anticholinergic effects of TCAs and the fluid retention of steroids and anticonvulsants (i.e. gabapentin) require close monitoring and careful attention to whether they are provided symptomatic benefit. Topical analgesics, including over-the-counter salicylates, reduce some localized pain. Physical therapy, massage, hydrotherapy, acupuncture and mindfulness meditation are a few of the possible alternative medicine/complementary treatments that help manage chronic or recurrent pain. Nutritionists and pharmacists can help the patient and provider sift through herbal and nutritional supplements to minimize risk of drug interactions and side effects. Palliative medicine or pain specialists may offer other options including interventional pain management techniques such as localized injections to manage painful conditions without systemic effects. Table 1 provides general guidelines for opioid and adjuvant medications in the heart failure patient.
Pain is a very real experience for the heart failure patient and it represents a significant threat to their quality of life. Very often the cause of that pain is not entirely clear, but, as the PAIN-HF trial described, for 14% of patients with advanced heart failure the total experience of pain was ‘horrible or excruciating’ and for 53% of patients it was ‘discomforting or distressing’ [2▪▪], truly pointing to the critical nature of this issue. Research needs to be directed at understanding the cause of pain syndromes in heart failure, how pain relates to volume status and ischemia, well tolerated and effective treatments in heart failure patients with arthritic pain and how the interplay of psychologic, social and spiritual stressors mediates the experience of pain. Improving communication with patients and caregivers is critical to the process of providing individualized and effective pain management. Expanding the relationships with palliative teams and heart failure providers can improve care by using the expertise of both groups to foster innovation and add to broaden our understanding of how addressing both aspects of the patient's disease process could lead to better outcomes.
Conflicts of interest
The authors have no relevant conflicts of interest to report.
REFERENCES AND RECOMMENDED READING
Papers of particular interest, published within the annual period of review, have been highlighted as:
- ▪ of special interest
- ▪▪ of outstanding interest
Additional references related to this topic can also be found in the Current World Literature section in this issue (p. 117).
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