The New Duo in Heart Failure Management?
Niklas Lidströmer Karolinska Institutet, MD, MSc, specialist physician, postgraduate researcher in AI in medicine, senior advisor in AI and medical investments, former AI entrepreneur and founder of an AI-powered medical platform, former head of Medical AI at a variety of med-tech companies, and also previous co-leader of a handful of successful medical start-ups. Currently Chief Medical Officer, Acorai, firstname.lastname@example.org , he authored the“Redefining Heart Failure” blog series, where he explored the context of readmission statistics and their relevance for understanding the cause for admission.
He is also a Physician champion of medical artificial intelligence applications and the lead editor of the largest reference work on AI in Medicine published by Springer Nature and also the editor of a follow-on Springer Nature title recently published on AI in Covid-19
We may witness the marriage of two macro trends in heart failure management – of the recently further manifested advantages of using NT-proBNP and of the routine use of a wireless heart monitor. Will the routine test happily live ever after with a non-invasive intracardiac pressure device?
Cardiologists are well aware of the scarcity of evidence for dosage and up-titration of medical therapy of patients on wards with acute heart failure.
A few days ago, in November 2022, in the Lancet(1) the STRONG-HF trial was published. This large international (87 hospitals in 14 countries), open-label, randomised, parallel-group trial had been completed, and had included patients aged 18-85 years with acute heart failure. These patients had not been given the full doses of guideline-directed medical therapy (GDMT). Before their discharge from the hospital, they were randomised (1:1) and stratified by left ventricular ejection fraction with blocks and subblocks designating them to normal standard of care or high-intensity care. The normal care definition followed local guidelines. The high-intensity care included up-titration regimens emanating in 100% of recommended dosage levels within a fortnight, followed by a series of outpatient check-ups over the coming two months. The latter included clinical examination, lab tests and NT-proBNP levels. The study continued if no primary endpoints were reached, e.g., rehospitalisation, until the 180th day.
Important take-home messages
It is worth highlighting that the trial had originally 1,800 enrolled patients, but was ended at 1,000, since the effect of the NT-proBNP usage was so striking, that a continued study was deemed unethical. Blockbuster figures were reported, with a reduction of -28% in cardiovascular death, a composite endpoint of rehospitalisation and mortality of -34% and a reduced rehospitalisation of -44%. The significance was affected by the closure preterm per se.
The study showed the intensive regimen with brisk up-titration, frequent check-ups of acute heart failure was both willingly accepted the patients, since it clearly reduced their symptoms, reduced rehospitalisation, and improved life quality, among other benefits.
Hence, the Roche Elecsys® NT-proBNP biomarker has proved to be an integral part of the acute heart failure treatment strategy, entailing speedy up-titrations and frequent check-ups after an admission.
However, for admitted patients we still have the problem with inadequate monitoring tools in the heart failure workflow resulting in high readmission rates, poor outcomes, and a large cost burden for hospitals and society. The difficulty in accurately assessing heart failure leads to 43% of patients being discharged when unstable, i.e., congested.(2) This leads to one of the highest readmission rates (50%),(3, 4) and deterioration in cardiac function and survival rates in patients. For example, the results are losses of $8k+ per heart failure admission, and $108bn in annual costs to the US health system alone (calculation of average Medicare claims reimbursement payments for DRG291-293).
A cautionary tale
A challenge is that NT-proBNP is a biomarker with a slow reaction time to improvements and deteriorations of patient status. This is probably demonstrated the most in the 90-day adverse event rate in the Strong-HF trial being higher than in the control arm. The most likely hypothesis for this is the dehydration of patients leading to kidney injury. We, of course, recognise from the Champion trial (5) and hemodynamic first principles that removing fluid is the single most important aim of heart failure treatment to reduce hospitalisations, yet this does carry a non-insignificant risk of CKD if not closely monitored.
So the light in the tunnel, though, is that heart failure readmissions are preventable through intracardiac pressure monitoring (ICPM).(6) Hence, there is also a need for a low-cost and accurate ICPM solution. With such a device, with a performance equivalent to the invasive clinical gold standard, it would improve the quality of care, with more efficient and accurate personalized care. It would also reduce readmissions, avoid complications, reduce the average length of stay and improving patients’ quality of life too, and furthermore lead to direct cost savings to hospitals.
The real-world view
Presently the alternative is the invasive cardiac catheterisation, giving extensive information about the heart condition, but being performed seldom per patient, and hence not suited for monitoring several times per day, week, or month.
With a heart monitor, usable both on ward and in outpatient settings, it would be possible to both titrate the GDMT much more forcefully and accurately and obtain a daily transparency about patient stability in combination with long term biomarker monitoring.
With the present heart failure management and the uneven availability and distribution of care, kismet rules over a patient’s chances. But with a well-balanced combination of both NT-proBNP in the follow up and an intracardiac pressure monitor during and after admission, a much more individual, precise, and early treatment would be possible, through accurate, absolute, and actionable insights.
Looking to the future
Possibly NT-proBNP and intracardiac pressure monitoring would be two parallel entities in a clinical setting, providing mutually intelligible support, one strengthening the actionability of the other. We may stand at the doorstep of a new clinical management of heart failure, with this new couple as intertwined as a double helix of valuable diagnostics. It would be intriguing to research this relationship further.
- Mebazaa Aea. Safety, tolerability and efficacy of up-titration of guideline-directed medical therapies for acute heart failure (STRONG-HF): a multinational, open-label, randomised, trial. The Lancet. 2022;Online 7th November. https://pubmed.ncbi.nlm.nih.gov/36356631/
- Abraham J BV, Burkhoff D, Pahuja M, Sinha SS, Rosner C, Vorovich E, Grafton G, Bagnola A, Hernandez-Montfort JA, Kapur NK. Heart Failure-Related Cardiogenic Shock: Pathophysiology, Evaluation and Management Considerations: Review of Heart Failure-Related Cardiogenic Shock. . J Card Fail. 2021;Oct;27(10):1126-1140. https://www.ahajournals.org/doi/abs/10.1161/CIRCHEARTFAILURE.121.009279
- Bragazzi NL, Zhong W, Shu J, Abu Much A, Lotan D, Grupper A, et al. Burden of heart failure and underlying causes in 195 countries and territories from 1990 to 2017. European Journal of Preventive Cardiology. 2021;28(15):1682-90. https://academic.oup.com/eurjpc/article/28/15/1682/6133248
- Muhammad Shahzeb Khan JS, Noman Lateef, Marwan S. Abougergi, Stephen J. Greene, Tariq Ahmad, Stefan D. Anker, Gregg C. Fonarow and Javed Butle. Trends in 30- and 90-Day Readmission Rates for Heart Failure. Heart Failure. 2021;14:e008335. https://www.ahajournals.org/doi/full/10.1161/CIRCHEARTFAILURE.121.008335
- Abraham WT, et al Wireless pulmonary artery haemodynamic monitoring in chronic heart failure: a randomised controlled trial, Lancet 2011 https://doi.org/10.1016/S0140-6736(11)60101-3
- Desai AS, Stevenson LW. Rehospitalization for Heart Failure. Circulation. 2012;126(4):501-6. https://www.ahajournals.org/doi/full/10.1161/circulationaha.112.125435