Michelle M. Kittleson, MD, PhD

The panel concludes by discussing the future of ATTR-CM care. They highlight continued progress in disease-modifying therapies, with growing interest in determining how best to sequence or potentially combine treatments as evidence evolves. The group notes that as patients are diagnosed earlier, the goals of therapy may increasingly shift from slowing decline to preserving long-term function and quality of life. They emphasize the importance of expanding awareness and education across specialties so that more patients are recognized before advanced cardiac dysfunction develops. Improving access to therapy remains an essential area of focus, as cost and insurance barriers continue to influence treatment decisions. The panel also anticipates advances in monitoring disease progression, including the use of biomarkers and imaging to better assess response over time. Ultimately, the experts express optimism that ongoing research, broader recognition, and more refined care pathways will continue to improve outcomes for individuals living with ATTR-CM.

The panel discusses the importance of shared decision-making in the care of patients with ATTR-CM. They emphasize that treatment conversations are often ongoing rather than single moments, as patients and families may need time to understand the diagnosis, the goals of therapy, and what to expect over time. The clinicians highlight the role of clear, honest communication, particularly when addressing uncertainty around disease progression or response to therapy. The group describes how patient preferences can influence treatment selection, including the choice between oral therapies and periodic injections, the desire to minimize medication burden, and the importance of maintaining independence and daily routines. They also note that caregivers are crucial partners in supporting adherence, appointment planning, and monitoring changes in function or symptoms. Ultimately, the panel agrees that successful care depends on making decisions with patients, ensuring they understand their options, and aligning treatment plans with their values, goals, and quality-of-life priorities.

The panel focuses on how quality of life considerations shape ATTR-CM management. Beyond survival and hospitalization outcomes, many patients most value being able to remain mobile and independent—continuing activities such as walking, gardening, or caring for grandchildren. Even subjective concerns like weight loss or appearing “frail” can meaningfully affect how patients feel about their health. Managing symptoms of congestion and reducing the need for frequent diuretic adjustments also plays an important role in daily well-being. The discussion then highlights recent data from HFSA showing that vutrisiran was associated with fewer gastrointestinal symptoms, such as diarrhea and constipation. The panel found this particularly interesting in wild-type ATTR-CM, where GI involvement is not always recognized. Improvements in GI comfort can support better nutrition, energy, and overall day-to-day function. Across the conversation, the experts emphasize that maintaining function and stability over time is often the clinical outcome patients value most.

The panel discusses decision-making around monotherapy versus dual therapy in ATTR-CM. They explain that while there is not definitive, statistically significant evidence supporting routine dual therapy for all patients, there is also no evidence of harm when stabilizers and silencers are used together. Because the two therapeutic classes work through different mechanisms, dual therapy is considered reasonable in selected patients, particularly when the goal is to slow progression as much as possible. The panel emphasizes that treatment decisions should be individualized, guided by disease stage, symptom burden, neurologic involvement, patient priorities, and access considerations. They stress that ATTR-CM is not a uniform disease, and two patients with the same diagnosis may have completely different clinical needs. Ultimately, the group agrees that the only clearly inappropriate choice is providing no disease-modifying therapy at all.

The panel discusses how clinicians approach selecting disease-modifying therapy once ATTR-CM is confirmed. They emphasize that treatment choice is individualized and begins with assessing disease stage and overall cardiac function. If a patient is extremely advanced and unlikely to benefit, the conversation may shift toward goals of care. For most patients, the next consideration is whether neuropathy is present, particularly in hereditary variants, where a silencer such as vutrisiran may be preferred because it addresses both cardiac and neurologic manifestations. Cost and access are also significant factors, and the panel notes that insurance coverage may determine which agent is feasible. Finally, patient preference plays an important role: some prefer a daily oral therapy, while others favor a less frequent injection to avoid managing multiple medications. The experts emphasize shared decision-making, stating that the key principle is to initiate approved therapy, as the only clearly wrong choice is receiving no treatment.

The panel reviews key insights related to transthyretin amyloidosis therapies discussed at the AHA 2025 Scientific Sessions. They emphasize that the new data presented are largely “on the margins,” reinforcing findings already established in pivotal trials: the major disease-modifying therapies for ATTR-CM are effective and safe, and the most important mistake is not initiating any therapy once the diagnosis is confirmed. One topic highlighted from recent analyses is atrial arrhythmias in ATTR-CM. The panel notes that while patients with atrial arrhythmias often represent more advanced disease, the presence of arrhythmias does not diminish the efficacy of available treatments. The discussion also touches on renal function data, where improvements are believed to reflect better heart failure status and reduced diuretic need, rather than a direct renal effect of therapy. Overall, the panel emphasizes individualized management and careful clinical interpretation rather than one-size-fits-all assumptions.

The panel discusses the importance of monitoring and supporting vitamin status in patients receiving ATTR-CM therapies, particularly those on transthyretin silencers that reduce hepatic production of TTR. Because TTR transports retinol-binding protein, lowering TTR levels can affect vitamin A transport. The clinicians explain that when silencing therapy is used, patients should receive vitamin A supplementation, but at the appropriate physiologic dose, not excess replacement. They caution that high-dose vitamin A can be harmful and stress the need to avoid overcorrection, particularly in older adults. The panel also notes that education is essential, as patients may assume all supplements are beneficial or may take additional over-the-counter vitamins without disclosing them. Clear counseling helps ensure patients understand what to take, what to avoid, and why. Overall, the discussion emphasizes thoughtful, monitored supplementation as part of comprehensive care, rather than a standalone intervention.

The panel discusses the role of transthyretin (TTR) stabilizers in the management of ATTR-CM, focusing on tafamidis and acoramidis. They explain that both agents work by stabilizing the TTR tetramer to prevent dissociation and subsequent amyloid fibril formation. Tafamidis is highlighted as the first approved stabilizer with demonstrated benefit in reducing morbidity and mortality in ATTR-CM. Clinicians note that many patients experience stable disease over time with tafamidis, and its favorable tolerability profile, with minimal need for laboratory monitoring, is especially helpful for older adults seeking consistent, manageable treatment. The discussion then shifts to acoramidis, which is designed to strongly stabilize the TTR protein. The panel describes clinical impressions that acoramidis has shown promising results in trials and represents an important emerging option. They emphasize that having multiple stabilizers broadens therapeutic choice and may help align treatment selection with patient needs and disease characteristics, reinforcing the importance of earlier diagnosis and appropriate therapy initiation.

The panel reviews the HELIOS-B Phase 3 trial evaluating vutrisiran, a transthyretin silencer, in patients with ATTR-CM. Participants were randomized to receive vutrisiran or placebo, with approximately 40% already taking tafamidis at trial entry, particularly in the United States. The study was designed with predefined primary and secondary endpoints, assessing outcomes both in the overall population and in those not on baseline tafamidis. The trial demonstrated statistically significant results across all major endpoints, including reductions in all-cause mortality and cardiovascular hospitalizations, with notable benefit observed both in monotherapy and combination-therapy subgroups. The panel highlights the magnitude of treatment effect and notes that these findings supported FDA approval of vutrisiran for ATTR-CM. They also emphasize its favorable safety profile, explaining that common adverse events—such as cardiac failure and arrhythmias—reflect the underlying disease rather than the drug itself. Overall, the experts describe vutrisiran as a meaningful and well-tolerated therapeutic advancement for patients with ATTR-CM.

The panel discusses the concept of achieving a rapid reduction, or “knockdown,” of transthyretin (TTR) production in ATTR-CM. They note that the rationale is intuitive: slowing or halting new amyloid formation as early as possible may help interrupt disease progression. The comparison is made to AL amyloidosis, where shutting down the source of the abnormal protein is central to treatment. However, the panel emphasizes that ATTR-CM develops gradually over many years, and as a result, even when TTR production is reduced, clinical improvement is typically gradual rather than immediate. The experts highlight the importance of setting realistic patient expectations—treatment reduces ongoing injury but does not rapidly remove existing amyloid deposits. They also discuss the need to understand which symptoms are truly amyloid-related versus coincidental, and they stress the long-term, supportive relationships clinicians build with patients and families, particularly when helping individuals adjust goals and maintain quality of life over time.

The panel reviews the two major therapeutic strategies for treating ATTR-CM: transthyretin (TTR) silencers and stabilizers. Stabilizers work by binding to the TTR protein and preventing it from misfolding into amyloid fibrils, helping maintain the protein’s native structure. Silencers, by contrast, act at the genetic level to reduce the production of TTR protein in the liver through RNA interference or antisense mechanisms. Together, these approaches aim to reduce amyloid formation and slow disease progression. The experts note that patients are often highly informed and eager to understand the differences between these therapies. They emphasize the importance of clear, patient-centered discussions that explain how the treatments work, why both options exist, and how therapy selection may depend on disease stage, phenotype, genetic background, and emerging clinical evidence. As research evolves, clinicians continue to refine how these mechanisms complement one another and how combination or sequential strategies may shape future care.

The panel shifts to remaining unmet needs in ATTR-CM care, emphasizing that despite progress in diagnosis and available therapies, gaps persist across patient identification, treatment access, and long-term management. One ongoing challenge is recognizing early disease and distinguishing ATTR-CM from other common cardiac conditions, particularly in older adults with preserved ejection fraction. The experts stress that clinicians must think beyond labeling HFpEF as a final diagnosis by seeking its underlying cause. Therapeutically, the group notes that while stabilizers and silencers have expanded treatment options, navigating these therapies requires careful consideration of patient characteristics, tolerance, and evolving evidence. Cost and access barriers continue to affect who receives treatment and when. The panel also highlights the need for more data on disease monitoring and response assessment, particularly regarding biomarkers and imaging changes over time. Finally, greater patient and provider education, coordinated care pathways, and earlier referrals remain essential to improving outcomes.

The panel discusses how advances in imaging and biomarkers have transformed the diagnostic approach to ATTR-CM. Historically, diagnosis required invasive endomyocardial biopsy, but cardiac radionuclide scintigraphy with bone-avid tracers now enables noninvasive identification in many patients. This imaging modality is widely accessible and interpretable for cardiologists, making earlier diagnosis more feasible. However, the group emphasizes the critical importance of ruling out monoclonal protein before relying on radionuclide uptake, as AL amyloidosis can produce misleading results and requires urgent, different treatment. The conversation also highlights the evolving role of biomarkers, including high-sensitivity troponin, NT-proBNP, and prealbumin (TTR) levels, both for staging and potentially monitoring disease or therapeutic response, though standardized guidance is still developing. Additionally, the panel notes that interpretation of imaging requires nuance, particularly with borderline or focal uptake patterns. Collectively, these diagnostic advancements support earlier detection, but clinical context, careful interpretation, and structured testing pathways remain essential.

The panel explores strategies to improve collaboration across specialties to accelerate diagnosis of ATTR-CM. They note that while clinicians who frequently treat cardiac amyloidosis easily recognize red flags, most patients initially present in orthopedic, neurology, or primary care settings where awareness may be limited. The group emphasizes the importance of education rather than universal screening: common conditions like bilateral carpal tunnel syndrome are widespread, and only a minority will be linked to amyloid. Instead, these findings should be viewed as risk factors that prompt thoughtful clinical review rather than routine tissue sampling. Effective models of care involve strengthening communication channels between specialists and building workflows that encourage referral when constellation patterns emerge. Advanced practice providers often serve as key connectors, helping evaluate history, coordinate testing, and reinforce awareness. The panel highlights that integrating these teams can enable earlier identification, reduce missed opportunities, and help patients access disease-modifying therapies before significant cardiac decline occurs.

The panel focuses on recognizing extra-cardiac manifestations that often precede cardiac symptoms in ATTR-CM. Orthopedic signs—such as bilateral carpal tunnel syndrome, cervical or lumbar spinal stenosis, biceps tendon rupture, trigger finger, and recurrent joint replacements—may occur five to ten years before cardiac involvement. Neurologic and autonomic features, including peripheral neuropathy, orthostatic hypotension, constipation, diarrhea, urinary retention, and erectile dysfunction, also serve as early clues, though frequently attributed to aging or unrelated conditions. The discussion emphasizes the importance of educating clinicians across specialties to identify these signals and consider amyloidosis when patterns cluster. The panel notes that orthopedic surgeons, neurologists, primary care physicians, and geriatricians play key roles in spotting early presentations. Advanced practice providers can also help bridge communication and referral pathways. Rather than screening every patient with common conditions, the group recommends viewing these findings as risk indicators and prompting coordinated evaluation to facilitate earlier diagnosis and treatment.

The panel opens by outlining the significant clinical burden of ATTR-CM. Patients often initially present with atrial arrhythmias or conduction abnormalities before developing heart failure, which commonly manifests first as exercise intolerance. Without treatment, the disease follows a progressive course that impacts both patients and caregivers, many of whom are unfamiliar with amyloidosis at diagnosis. The discussion highlights notable delays in identifying hereditary ATTR-CM, particularly among Black and Caribbean patients with the V142I variant, emphasizing the need for improved community and provider awareness. The conversation then shifts to trends in diagnosis. While recognition of ATTR-CM has increased and patients are being diagnosed earlier—with outcomes improving when therapy is initiated sooner—significant barriers remain. A major challenge is persistent misperception of ATTR-CM as rare. The panel stresses reframing heart failure with preserved ejection fraction as a syndrome requiring etiologic evaluation and encourages clinicians to consider ATTR-CM in older patients with increased ventricular wall thickness, prompting timely, appropriate diagnostic workup.

Andrew Wang, MD; James Januzzi, MD; Michelle M. Kittleson, MD, PhD; and Milind Desai, MD, MBA, share a look into the future of oHCM treatment.

Michelle M. Kittleson, MD, PhD, comments on remaining unanswered questions regarding CMIs in treatment of oHCM, highlighting disease modification.

Expert cardiologists share approaches to implementing mavacamten and aficamten in the clinical treatment of oHCM.

Andrew Wang, MD, and Anjali Owens, MD, review the clinical trials of aficamten, a CMI used for treating patients with oHCM.

Milind Desai, MD, MBA, and Michelle M. Kittleson, MD, PhD, review the clinical trial data of mavacamten, the first FDA-approved cardiac myosin inhibitor for the treatment of oHCM.

Andrew Wang, MD, discusses the use of cardiac myosin inhibitors (CMIs) as a new, less invasive option for treating oHCM.

Milind Desai, MD, MBA, comments on the broadening knowledge in the oHCM space, leading to the development of new therapies.

Expert cardiologists share approaches to the challenges that come with septal reduction therapy, as well as access to oHCM treatment.

Andrew Wang, MD, comments on the treatment algorithm for symptomatic oHCM, highlighting treatment guidelines, and James Januzzi, MD, reviews treatment selection for oHCM through the lens of the patient’s quality of life.

Expert cardiologists discuss treating patients with symptomatic vs asymptomatic oHCM.

Milind Desai, MD, MBA, leads a discussion on the importance of accurate imaging in oHCM and aortic stenosis, highlighting the echocardiogram and doppler tests.

Milind Desai, MD, MBA, comments on risk stratification for sudden cardiac death (SCD) in oHCM.

Cardiology experts discuss the importance of an accurate and prompt diagnosis of oHCM, as well as effectively educating the patient about the condition.

Michelle M. Kittleson, MD, PhD, and James Januzzi, MD, review signs that point to oHCM, highlighting family history and details on the diagnostic evaluation.