Emerging cardio-rheumatology clinics manage ‘broad and vast’ crossover population
Rheumatologists and cardiologists have long co-managed patients out of necessity and without much formal collaboration or guidance.
However, in recent years, cardio-rheumatology clinics have begun to proliferate, offering more evidence-based algorithms for physicians who treat this crossover patient population.
“To understand the rise of cardio-rheumatology, we need to look at the rise of cardio-immunology, which is the research field investigating the relationship between the immune system and the heart,” Luigi Adamo, MD, director for cardiac immunology at the Johns Hopkins University division of cardiology, told Healio Rheumatology. “Over the past 25 years, cardio-immunology has demonstrated that the immune system is connected to every aspect of cardiac function, from contractility to the conduction of electrical stimuli, to cardiac structure and adaptation to injury.”
This knowledge has empowered the scientific community to look more critically and more carefully at patients with immune system dysfunction, according to Julie J. Paik, MD, MHS, associate professor of medicine in the division of rheumatology at the Johns Hopkins University School of Medicine.
“The scientific community is also empowered to appreciate several effects of this immune dysfunction on the heart that were previously ignored,” she said.
According to Paik, rheumatology is critical to understanding these very specific intersections, as it is “arguably the area of medicine where we currently have the best appreciation of the relationship between immune dysfunction and organ damage.”
“Therefore, it is the natural place to start seeking clinical application of the growing knowledge in cardiac immunology,” she added.
The progression to cardio-rheumatology would be the natural next step.
According to Brittany Nicole Weber, MD, PhD, director of the Cardio-Rheumatology Clinic in the division of preventive cardiology at Brigham and Women’s Hospital, an important component of the relationship between the specialties pertains to inflammation.
“Cardiovascular manifestations of immune-inflammatory disorders are diverse, including atherosclerosis, pericarditis, myocarditis, heart failure, valvular and arrhythmias,” she told Healio Rheumatology. “We have recognized that cardiac manifestations of autoimmunity are broad and vast — much more than atherosclerosis, although atherosclerotic risk is integral to identify and treat.”
Weber added that the complexity of rheumatologic and autoimmune diseases makes this patient group particularly challenging to manage.
“For example, there are a host of ways patients with lupus can present to cardiology,” she said. “The same is true for rheumatoid arthritis, psoriatic arthritis, psoriasis and others.”
Weber, who hosts a monthly online clinical conference series where all topics pertaining to cardio-rheumatology are discussed, noted that patients within this population are often relieved when given the option of receiving care from a clinic knowledgeable in both specialties.
“Patients with autoimmune diseases are often scared of having cardiac disease,” she said. “They are appreciative that there are specialists who specialize in this intersection.”
With this in mind, cardio-rheumatology experts aspire to create models that optimize care for this diverse patient population. However, this is no small task.
“The field is absolutely necessary, but it is still evolving,” Weber said.
At the moment, there is not one uniform model for cardio-rheumatology clinics, according to Heba Wassif, MD, MPH, director of cardio-rheumatology and inpatient clinical cardiology in the Tomsich Family Department of Cardiovascular Medicine, at the Cleveland Clinic’s Sydell and Arnold Miller Family Heart, Vascular & Thoracic Institute.
“It is still fairly new, usually with just one or two individuals at any institution identifying as cardio-rheumatologists,” she said.
However, as the downstream cardiac and cardiovascular effects of autoimmune diseases draw into sharper focus, cardio-rheumatology clinics are likely to become more common.
‘The Time has Come’ for Crossover Clinics
In a 2023 paper published in the Journal of the American Heart Association, Weber and colleagues outlined some considerations for cardio-rheumatology clinic operations.
“The time has come to define an evolving subspecialty focused on the intersection of the dysregulated immune response, inflammation and cardiovascular system — termed cardio-rheumatology,” the authors wrote. “The expansion of the breadth and depth of cardiovascular medicine has led to an increase in sub-specialization. The concept of cardio-rheumatology is not new, and clinical programs exist at a few academic centers, but we are now at a crossroad where it has come to the forefront.”
In their paper, Weber and colleagues proposed a cardio-rheumatology subspecialty focused on the effects inflammation has on the cardiovascular system.
“Other terms such as ‘cardio-inflammation’ could similarly be used, but the core features are the same” they added. “It includes understanding the cardiovascular impact of immune-mediated inflammatory diseases.”
Although the associations between inflammation and both cardiology and rheumatology are well documented, it is important to consider the varying ways rheumatologists and cardiologists approach them, according to Adamo.
“Cardiology and rheumatology often look at inflammation from two different angles,” he said. “Rheumatology typically looks at inflammation as a driver of disease and prescribes immunosuppressive agents to treat the targeted disease. For example, a rheumatologist might prescribe mycophenolate to control disease activity in a patient with idiopathic inflammatory myopathy.”
Meanwhile, the most common cause of inflammation in the cardiology setting is obesity, according to Joshua F. Baker, MD, associate professor of medicine in rheumatology at the Hospital of the University of Pennsylvania, and the Veteran’s Administration Medical Center in Philadelphia.
“In many settings, it remains controversial whether obesity-related inflammation can contribute to immune-mediated inflammation,” he said. “One area where this is likely to occur is in psoriasis, where obesity seems to be an important driver of the immune-mediated disease.”
This is just one of many such treatment and management details to be sorted out. As cardio-rheumatology clinics continue to grow and evolve, defining the boundaries will be critical to their success.
‘Should All Patients With Autoimmune Diseases be Seen by a Cardiologist?’
According to Weber, collaboration should start with communication.
“The primary need is that we talk to each other,” she said. “There should be shared decision-making regarding therapies and other management strategies.”
However, providers do not — and should not — have to wait to for a formal clinic to begin establishing cross-specialty dialogue and collaboration, Wassif said. Ideally, they should already be trading notes.
“I have my own clinic, and rheumatology has their own clinic,” Wassif said. “They are not combined, but there are open lines of communication.”
She added that efforts are currently underway in some clinics to use electronic medical records to facilitate communications between the specialties. However, as many physicians have reported, electronic medical records often create as many problems as they solve.
Until EMRs begin operating as advertised, Weber suggested that cardiologists and rheumatologists managing patients together should establish a shared workflow.
“Patients with systemic inflammatory disorders are referred to my clinic and the indication can range from prevention/risk stratification to chest pain,” she said. “I am still a prevention cardiologist. Risk assessment is still a critical part of my job and a critical component of the cardio-rheum collaboration.”
However, the parameters of risk assessment in these patients — eg, exactly which patients seen by a rheumatologist should be referred to cardiology — have largely yet to be defined.
“Should all patients with autoimmune diseases be seen by a cardiologist? That is tough to say, particularly because many rheumatologists have limited bandwidth,” Weber said. “They already have a lot they are taking care of, so they cannot be expected to manage everything — such as weight loss, lipid-lowering therapy and risk assessment, as well. This is why we need this field.”
Moreover, rheumatologists already understand that certain patient populations, such as those with systemic lupus erythematosus, are at particularly elevated risk for cardiovascular outcomes. However, current risk models underestimate cardiovascular risk and therefore imaging modalities — such as coronary calcium score — could be helpful, according to Wassif.
“Based on the current equations used to evaluate cardiovascular risk, we are underestimating the risks for certain patients with autoimmune disorders,” she said. “Because the current risk models underestimate the risk, other imaging modalities are needed.”
All of that said, risk assessment is only part of the plan. To fill all the current gaps in this crossover population, rheumatologists and cardiologists require more information on not only prediction and assessment, but also interventions, including when to start treatment.
‘Each Case is Different’
In 2022, EULAR offered recommendations for cardiovascular risk management in rheumatic and musculoskeletal diseases.
The final document included 19 recommendations, including information for gout, vasculitis, mixed connective tissue disease, myositis, systemic sclerosis, systemic lupus erythematosus and antiphospholipid syndrome. Topics included cardiovascular prediction tools, as well as interventions for traditional and disease-related cardiovascular factors.
“Most of the recommendations are coming from the rheumatology side,” Wassif said. “However, a consensus statement is coming in the future because there are still no clear guidelines for topics like when to start treatment. This field is in evolution.”
In the absence of clear guidelines, many health centers are charting their own path.
“In our Center for Cardiac Immunology, rheumatologists refer patients with a specific question,” Adamo said. “Typically, either there are treatment challenges — for instance, stubborn recurrent pericarditis or hard-to-manage hypertension — or there are specific conditions, such as chest pain or exercise intolerance, for which the rheumatologist thinks that the involvement of a cardiologist might have an impact on the plan of care.”
These conditions may include myocarditis, chest pain with concern for coronary artery disease, exercise intolerance of unclear etiology or palpitations, according to Paik.
“In our center, we believe in a care team approach,” she said. “The cardiologist makes recommendations and determines necessary testing, and then the team — including the cardiologist, the referring rheumatologist, and any other relevant specialists consulted along the way — decides how to proceed. However, each case is different.”
One way toward a more streamlined workflow in managing these patients could be through advances in imaging.
In a 2023 paper published in the Journal of the American College of Cardiology, Weber, Paik and colleagues made their case that emerging multimodality imaging techniques could allow for earlier, and more precise, diagnoses, as well as improve screening and disease activity monitoring.
“The integrated application of these technologies lead to earlier diagnosis and noninvasive monitoring of cardiac involvement in systemic inflammatory diseases that will aid in preclinical studies, enhance patient selection, and provide surrogate endpoints in clinical trials, thereby improving clinical outcomes,” they wrote.
According to Weber, imaging modalities could prove illuminating even in cases where the patient’s unique characteristics would normally spell uncertainty.
“Because every patient is different, I do not have one algorithm that will be effective every time,” Weber said. “I can take their calcium score and assess their symptoms, but if I am worried about a complication like macrovascular dysfunction l will order a PET scan. These images can help us figure out the patient’s risk profile over time.”
Indeed, PET scans could be particularly useful in this patient population, according to Wassif.
However, she cautioned that PET scans are not yet in practice.
“PET imaging is a specialized modality that helps identify microvascular disease as well as ischemia due to macrovascular disease,” Wassif said. “Furthermore, newer modalities such as the pericoronary fat attenuation index, using coronary CTA to identify coronary inflammation, may have role in the future in this population, but it is very early.”
It is likely that advanced imaging modalities will be an essential component of this broader team care approach, especially considering the sheer number of cases that could potentially fall within the scope of a cardio-rheumatology framework.
‘Enormous’ Numbers
One of the most impactful epidemiological studies within the cardio-rheumatology crossover cohort was published in 2022 by Conrad and colleagues in The Lancet. The population-based study included records for more than 22 million individuals accrued from the Clinical Practice Research Datalink, GOLD and Aurum datasets across the United Kingdom. The aim was to determine whether autoimmune diseases increase the risk for cardiovascular disease.
The final analysis included 446,449 participants with autoimmune diseases and 2,102,830 matched controls.
The results, after more than 6 years of follow-up, suggested that incident cardiovascular disease occurred in 15.3% of 68,413 patients with autoimmune diseases, and in 11% of 231,410 individuals without autoimmune diseases. For individuals with one autoimmune disease, there was a 1.4-fold increase (HR = 1.41; 95% CI, 1.37-1.45) in risk.
However, this risk increased progressively for individuals with two autoimmune diseases (HR = 2.63; 95% CI, 2.49-2.78), as well as those with three or more autoimmune diseases (HR = 3.79; 95% CI, 3.36-4.27).
“The numbers in this study are enormous,” Wassif said. “It showed that the associations are not only atherosclerosis or pericardial disease, and that risk is different from one autoimmune disease population to another.”
Further data from the Conrad study showed that patients with SSc demonstrated the highest risk for cardiovascular disease (HR = 3.59; 95% CI, 2.81-4.59), followed by Addison’s disease (HR = 2.83; 95% CI, 1.96-4.09), SLE (HR = 2.82; 95% CI, 2.38-3.33) and type 1 diabetes (HR = 2.36; 95% CI, 2.21-2.52).
Many experts believe such findings should be a wake-up call to all rheumatologists treating patients with systemic inflammation.
“Patients with autoimmune diseases can have autoimmune disease manifestations that involve the heart, such as lupus affecting the heat muscle or surrounding tissue,” Baker said. “Similarly, patients with ankylosing spondylitis and some forms of vasculitis can have involvement of the large vessels around the heart. Over the past several decades, it has also become apparent that longstanding systemic inflammation of the whole body is bad for the heart and can increase the risk for heart failure, heart attacks and strokes over the long-term.”
The findings from Conrad and colleagues are just one part of a larger picture of associations between cardiology and rheumatology.
In a 2022 paper published in Angiology, Wang and colleagues assessed 258 patients with SLE to determine cardiovascular outcomes. Results suggested that pericardial disease occurred in 33.3% of patients, while valve disease was reported in 18%, cardiomyopathy in 9.6%, and stroke in 7.4%. Five deaths occurred over 3 ± 2.2 years of follow-up after index SLE clinic visit, along with cardiovascular events in 9.3% of the cohort, and SLE-related hospitalizations in 17.1%.
“Lupus can cause inflammation in the muscle of the heart, leading to poor function,” Baker said. “Inflammation due to autoimmune disease also can increase the risk for plaque formation and may result in the destabilization in those plaques, making them more likely to rupture and lead to a heart attack.”
Gaining a deeper understanding how each of these combinations and associations may progress can inform workflow between cardiologists and rheumatologists.
“The rheumatologist and the cardiologist can both guide the treatment of myocarditis or pericarditis in connective tissue diseases such as lupus or myositis,” Adamo said.
According to Paik, cardiologists might be better equipped to lead care in these areas, but added that rheumatologists can also be effective on their own.
“Another potential area of overlap is the management of hypertension in patients with connective tissue disorders and renal involvement, classically in lupus,” she said. “Also, here, a cardiologist might be more experienced than a rheumatologist in managing hypertension, but both cardiologists and rheumatologists are specialists in internal medicine and are well-equipped to manage hypertension.”
The list of overlapping and comorbid conditions grows with each new publication and presentation. As clinicians become more familiar with the specific patient populations and subpopulations that enter their clinic with autoimmunity and cardiovascular disease, they should also be aware of an ever-shifting treatment landscape.
Ill Communication
According to Weber, in her experience caring for this crossover population, rheumatologists typically handle administration of biologic medications while she, as a cardiologist, handles statins, aspirin, and GLP-1 receptor agonists.
“As the team model grows, the idea is that we would be doing this collaboratively,” she said. “For example, I may see a patient who is already on a statin and I can discuss CV risk and intensify therapies as appropriate.”
Devising a treatment plan for any given cardio-rheumatology patient should come back to the basic idea of cross-specialty communication. According to Adamo, a lack of sufficient communication may lead to suboptimal care.
“Rheumatologists often treat pericarditis with steroids, something that has been proven to be generally suboptimal in the cardiology literature,” he said. “Or, rheumatologists may diagnose pericarditis based on clinical criteria, which is incompatible with cardiology guidelines.”
However, Paik does not blame either specialist for these miscommunications.
“We are working to understand whether these differences in practice are meaningful,” she said. “Still, simply the fact that in 2024, there is not already clear data to answer this question indicates that communication has been lacking.”
Paik and Adamo have observed similar phenomena in myocarditis treatment.
“The cardiology literature supports the use of significant doses of steroids to treat virus-negative myocarditis, but this literature is not typically considered among rheumatologists,” Paik said. “I expect that soon, we will see many of these discrepancies come to light, and we will see data-driven efforts to define a common ground for the benefit of the patients.”
Perhaps the most important consideration moving forward will be the adverse event profile of the treatments used in these patients. The association between Janus kinase inhibition and cardiovascular outcomes is well-worn territory, but there are other concerns, as well.
“TNF inhibitors can increase the risk for heart failure,” Paik said. “Rituximab (Rituxan, Genentech) can cause arrhythmias and heart failure, interleukin (IL)-6 inhibitors can cause hypertension, and IL-1 inhibitors as well as IL-6 inhibitors and IL-17 inhibitors can cause dyslipidemia.”
Combination therapies may also raise questions, according to Wassif.
“Can we use two biologics safely?” she said. “That is a difficult question.”
Wassif added that collaboration will be essential to understanding the risks involved with all new medications that appear on the market.
“There needs to be a multidisciplinary approach to understand new drugs and the effects they will have on our patients,” she said.
Looking beyond biologics, hydroxychloroquine can cause various types of cardiomyopathy, while tacrolimus can cause myocardial hypertrophy, according to Adamo.
“The cardiovascular toxicities of immunomodulatory drugs confirm the most basic tenant of cardio-immunology — the cardiovascular system and the immune system are closely connected,” he said. “All in all, this shows that cardiologists and rheumatologists should often work together.”
- References:
- Conrad N, et al. Lancet. 2022;doi:10.1016/S0140-6736(22)01349-6.
- Drosos GC, et al. Ann Rheum Dis. 2022;doi:10.1136/annrheumdis-2021-221733.
- Wang TKM, et al. Angiology. 2022;doi:10.1177/00033197221078056.
- Weber BN, et al. J Am Coll Cardiol. 2023;doi:10.1016/j.jacc.2023.09.819.
- Weber BN, et al. JAHA. 2023;doi:10.1161/JAHA.122.02784.
- For more information:
- Luigi Adamo, MD, can be reached at 5501 Hopkins Bayview Circle, Floor 1, Baltimore, MD 21224; email: ladamo2@jhmi.edu.
- Joshua F. Baker, MD, can be reached at 3400 Civic Center Blvd., Philadelphia, PA 19104; email: joshua.baker@pennmedicine.upenn.edu.
- Julie J. Paik, MD, MHS, can be reached at 5501 Hopkins Bayview Circle, Floor 1, Baltimore, MD 21224; email: jpaik1@jhmi.edu.
- Heba Wassif, MD, MPH, can be reached at 9500 Euclid Ave., Cleveland, OH 44195; email: wassifh@ccf.org.
- Brittany Nicole Weber, MD, PhD, can be reached at 75 Francis Street, Boston, MA 02115; email: bwe-ber@bwh.harvard.edu.
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