Article

Cardiac biomarkers to aid in diagnosis and management in AMI and HF

Early detection of heart disease with cardiac biomarkers improves patient outcomes
Misdiagnosis of AMI and the need for early detection of HF in women

Video watch time 8:56min. Article read time 5min. 

 

Video: Interview with expert Dr Vaduganathan on a patient advocacy story related to long term consequences of AMI misdiagnosis

Article: Deep dive into the challenges around the early diagnosis of AMI and HF in women, and the benefits of early detection of heart disease with cardiac biomarkers to improve patient outcomes

 

Misdiagnosis of  AMI and the need for early detection of HF 

 

Cardiovascular disease (CVD) continues to be one of the highest causes of mortality worldwide and accounts for approximately 35% of female deaths each year,1 this is more than all cancers combined. Owing to a lack of awareness of female-specific symptoms among healthcare practitioners and the general public, underrepresentation of women in clinical research, CVD continues to be under-recognised, under-diagnosed and under-treated in women.2 The implementation of cardiac biomarkers in clinical practice could serve as a tool to enhance the early detection, diagnosis, and management of CVD in women, thereby reducing mortality rates and improving patient outcomes.3,4

There is a diverse range of presenting symptoms for CVD and heart disease which are often different in women versus men.5,6 A meta-analysis of 27 studies found that even though there are multiple common symptoms in both men and women, women were more likely to report symptoms such as shoulder blade pain, nausea, vomiting, and shortness of breath, whereas men predominantly experienced chest pain and diaphoresis.7 This frequently leads to misdiagnosis of CVD and heart disease in women, or results in their symptoms being dismissed as anxiety-related.2,5 The misdiagnosis risk is heightened by the fact that women frequently show subtle electrocardiographic changes and higher incidences of unstable angina (UA) and non-ST-segment elevated myocardial infarction (NSTEMI) over ST-segment elevated myocardial infarction (STEMI), along with minor increases in troponin levels, therefore implementing sex-specific thresholds and high-sensitive troponin assays may help reduce diagnostic delays.8-10

Acute MI (AMI) requires hospitalisation and  rapid access to specialised treatment. Evidence suggests that delays to guideline-directed therapies & interventions are associated with increased mortality.11,12 Therefore, an  initial misdiagnosis of AMI needs to be corrected quickly to ensure the best possible recovery and to inform both short- and long-term treatment decisions. 

Early detection of HF is also shown to be vital for reducing patient morbidity and mortality.4 The majority of HF diagnoses occur in an acute care setting.4 In a study of 124,126  patients there were low rates of echocardiography and natriuretic peptide testing in those with HF. Of patients included in the study 51% were diagnosed in the inpatient setting with a significant trend towards greater inpatient diagnosis. Of all incident HF diagnoses, 57% underwent echocardiography, 55% underwent natriuretic peptide testing and 25% did not undergo either diagnostic test.13 The increasing rates of inpatient HF diagnoses indicates lost opportunities for earlier treatment initiation and better patient outcomes.13 It is important to note that nearly all aspects of heart failure (HF) are influenced by sex, from epidemiology and risk factors to response to treatment and outcomes: i.e. women more frequently present with HFpEF, while men are predisposed to HFrEF; traditional risk factors as obesity, diabetes and mental stress are stronger risk factors in women, while at the same time women also face additional sex-specific risk factors as breast cancer-related chemoradiation therapy and peripartum cardiomyopathy (PPCM).6

A significant issue contributing to current sex disparities in HF is the under-representation of women in HF clinical trials (only 20–25% of participants), leading to treatment guidelines that are primarily based on male-derived data, and to amassing knowledge gaps in sex-specific mechanisms, optimal drug dosages for women, and criteria for device therapy.6  

The importance of addressing these issues to enable early detection of heart disease was highlighted by patient Rhonda Monroe, who describes her HF journey after suffering an acute MI, which was misdiagnosed at the age of 36, in an article available on Roche.com. Rhonda is now a vocal patient advocate, sharing her experiences and raising awareness on the issues surrounding her personal story.

Dr Muthiah Vaduganathan, a cardiologist at Brigham and Women's Hospital and faculty at Harvard Medical School commented on Rhonda’s HF journey from her misdiagnosed AMI through to her recovery and continued advocacy for improvements of diagnostic tools. Additionally, he shares his expert opinion on the inclusion of new generation of biomarkers such as high-sensitivity troponin (hs-troponin) and N-terminal pro-B-type natriuretic peptide (NTproBNP) in improved care pathways in order to achieve earlier diagnosis of AMI and HF, respectively. 

 

The value of cardiac biomarkers for the early detection of heart failure

 

HF and MI are critical health issues globally, with as many as 64.3 million people estimated to suffer from HF.14 Whilst MI symptoms are well recognised, HF symptoms are more subtle and complex, often leading to delayed recognition and reporting by patients.15 Symptoms such as fatigue and shortness of breath are frequently mistaken for normal ageing, causing significant delays in seeking medical attention.15 Additionally, traditional symptom reporting methods are insufficient, necessitating newer diagnostic approaches. Over the past two decades, the use of biomarkers has revolutionised the diagnosis for AMI in acute settings and has shown promise in early screening, diagnosis, and management of HF.16-18

Whilst there are multiple contributing factors to HF such as obesity, diabetes and chronic kidney disease, Dr. Vaduganathan confirmed that MI remains the principal cause, despite advancements in timely revascularisation and other MI directed therapies.18 Dr. Vaduganathan stated, that “time is muscle” and early diagnosis and management of MI is as crucial as it ever was because timely intervention can significantly reduce the risk of developing HF.

Dr Vaduganathan suggested that there is a broad and invaluable role for cardiac biomarkers, such as NT-proBNP, when screening, diagnosing and managing HF at earlier stages.

 

Nowadays we have more accurate tools for timely diagnosis of acute MI and HF using biomarkers.

Dr. Vaduganathan

 

In addition to ECGs, cardiac biomarkers could be utilised by paramedics and emergency department physicians to diagnose patients prior to hospital admission to help facilitate prompt diagnosis and treatment.

HF is often perceived as the end stage of cardiovascular care, but it encompasses a broad spectrum, including patients with mild or moderate symptoms. Patients are core partners in managing their health and educating them on HF and its various phenotypes is crucial. Usage of cardiac biomarkers can play a critical role and help educate patients on their heart health status. Once HF is diagnosed, multiple medications are typically prescribed and patients are keen to understand if their heart health is improving.17,18 Cardiac biomarkers can provide evidence to guide patient conversations, help motivate patients, encourage engagement with their physicians and allow the physician to demonstrate the efficacy of medications and the associated risk reductions.

Dr Vaduganathan’s final point on cardiac biomarkers is that they are extensively used in the acute care settings, and their application in chronic or follow-up care stages is underutilised. Broadening the use of these cardiac biomarkers can maximise their potential in clinical practice, improving patient outcomes and care quality. 

Standardised care pathways can minimise missed opportunities and maximise opportunities for quality improvement. These pathways help physicians diagnose and manage patients more efficiently and effectively. Chest pain and AMI care pathways are well-established globally and incorporate cardiac biomarkers like hs-troponin, which has helped facilitate earlier diagnosis and management.16

 

Patient and symptom diversity in clinical trials and clinical research of heart failure

 

When discussing the diversity of patients and their symptom presentation in HF and MI, Dr. Vaduganathan explained that symptoms can vary significantly between men and women, necessitating diverse communication strategies and inclusion of greater patient representation in clinical trials and research. Clinical research infrastructure must continue to evolve to allow greater diversity in clinical trials and clinical research. 

 

New efforts are underway to try to at an earlier timepoint involve patients in clinical trials and involve them in study leadership as investigators and partners in trials to help recruit patients who most represent the people who we routinely encounter in clinical practice.

Dr. Vaduganathan

 

Addressing the challenges of late and missed diagnoses of HF and AMI requires a multifaceted approach. This includes leveraging biomarkers for early diagnosis, implementing standardised care pathways, educating patients and ensuring diverse patient representation in clinical research. By embracing these strategies, healthcare providers can improve early diagnosis, management and outcomes for patients with HF and AMI.

 

Interested in reading a personal experience? Read the story of Rhonda Monroe here.

Video transcript

0:10
Unfortunately, late diagnoses and missed diagnoses of heart failure and myocardial infarction are actually quite common at the global level.


0:21
While symptoms of heart attacks are now becoming more widely recognised in recent years, symptoms of heart failure might be more insidious, might be more complex in terms of their presentations, and so patients often may not be able to themselves recognise that these symptoms are reflective of heart failure.


0:46
And so patients may go for several days, weeks, months without reporting important symptoms like fatigue and shortness of breath that they may pass off as a usual part of ageing or deconditioning.


1:02
And so because of that, heart failure especially, is missed or is only diagnosed late in the time frame today. We now have newer approaches beyond simply symptom reporting to help us aid in the early diagnosis of heart failure and myocardial infarction that includes biomarkers.


1:24
And the evolution over the last 20 years since Rhonda's initial presentation has actually dramatically transformed how we approach diagnosis of myocardial infarction in acute settings as well as heart failure in both screening for diagnosing early and managing heart failure.

 

1:59
So unfortunately today, myocardial infarction or a heart attack is still the principal mechanism in which people develop heart failure. And there's a wide variety of other causes of heart failure like obesity, like chronic kidney disease and diabetes.


2:16
But ultimately myocardial infarction, despite all the improvements we've had in terms of timely revascularisation and other therapies targeting heart attacks, it still remains the number one cause of heart failure, and so, we often say “time is muscle”.


2:36
And so the earlier we reach patients in the field, the earlier those symptoms are reported, the earlier heart attacks are diagnosed and managed, the lower the chances and risks of heart failure would ensue in the future.


2:54
And so in this case, I think there would be a tremendous value in moving upstream and trying to diagnose heart attacks at an earlier stage. And that includes deployment of biomarkers like high sensitivity troponins, but also in terms of reaching patients earlier in the field.


3:15
And so even paramedics and emergency department clinicians are utilising electrocardiograms and biomarkers even before patients reach hospitals, and that actually allows for the more timely diagnosis of these conditions as well.


3:46
Yeah, heart failure is all often viewed as the end stage component of cardiovascular care.


3:53
And I think as a community, we now need to embrace that heart failure is a broad umbrella that occurs even at earlier stages and may affect people with mild or moderate symptom burden. And so educating patients about what is heart failure and the different types of heart failure is going to be of paramount importance because patients are ultimately our core partners in managing conditions.


4:24
And I think biomarkers are a very helpful communication tool to help communicate exactly what is happening in the heart because once we diagnose heart failure, we often start multiple medications. But patients often want to say, “is my heart improving?” And we often have limited evidence to provide them with.


4:52
There are longitudinal changes in the, for instance, heart structure and function to guide that conversation. I think biomarkers such as NT-proBNP can be quite useful as a motivating factor to keep patients engaged in their care and to communicate that their risk is truly declining with effective medications.


5:27
Yeah, ultimately standardised pathways are what is going to move us forward in terms of minimising missed opportunities and maximising opportunities for quality improvement. And chest pain and myocardial infarction are paradigms of standardised care pathways.


5:47
And so today in 2024, we have standardised chest pain pathways across the globe in a variety of healthcare settings in which biomarkers such as high sensitivity troponins are used upfront and then incorporated into standardised algorithms that clinicians can respond to and move patients towards a clear-cut diagnosis at an earlier time point from presentation.


6:28
I think that it starts in patient education and in the clinical community. We often have representations of chest pain and myocardial infarction as men presenting with these symptoms.  But we know that there's a diversity of patients that are affected by these conditions, but also the presenting symptoms might actually be different in men and women.


6:55
And so ultimately, I think our own communication strategies and representation should similarly be diverse in terms of the clinical research infrastructure. We too need to redesign those efforts.


7:10
Ultimately without ensuring diverse patient enrollment and recruitment in these trials, we ultimately won't be able to influence and affect large segments of the population because they may feel that they weren't appropriately represented in those pivotal studies.


7:32
And so new efforts are underway to try to, at an earlier time point, involve patients in clinical trials, involve them in study leadership and as investigators and partners in trials to help recruit patients that most represent people that we routinely encounter in clinical practice.


8:09
I think these biomarkers now have a core home in acute care settings and I think clinicians, especially in the emergency departments are facile in using these biomarkers in the urgent evaluation of patients.


8:27
I think the broader role of these biomarkers in the chronic care management of patients and in serial monitoring after an acute event or in a chronic disease state is under appreciated, and so broadening those horizons for these biomarkers I think will maximise their potential in clinical practice.

Key facts

  • To ensure equitable care for all patients, both clinical trials and standardised care pathways must include diverse patient groups and a range of presenting symptoms. This approach will provide opportunities for early diagnosis and management of cardiovascular disease.
  • The incorporation of new generations of biomarkers into clinical care pathways not only in acute care settings can be a highly relevant addition to aid some particularly challenging clinical assessments, during which HCPs are faced with the identification of a greater diversity of presenting symptoms, such as heart failure symptom differences between men and women.
  • Utilising biomarkers such as high-sensitivity cardiac troponin or N-terminal-pro-B-type natriuretic peptide in the timely diagnosis of either acute myocardial infarction (AMI) or the management of patients with heart failure (HF) respectively  can support timely diagnosis and early detection of worsening conditions, and provide a clear metric for patients in regards to their treatment .16-17

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References

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