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Need for Stratification of Heart Failure with Preserved
Need for Stratification of Heart Failure with Preserved Ejection Fraction
Heart Failure with preserved Ejection Fraction (HFpEF) is a crucial problem among cardiovascular diseases for the lack of established treatment strategies. There must be a need for detailed observational cohort studies for HFpEF patients to elucidate the detailed clinical phenotypes and to find appropriate therapeutic strategies.
Akito Nakagawa, Division of Cardiovascular Medicine, Amagasaki-Chuo Hospital
Heart Failure (HF) is a critical social problem all over the world, and HF with preserved Ejection Fraction (HFpEF) has particularly been increasing and upcoming to a bothering issue. Complicated pathophysiology and multiple comorbidities with an aging population makes it rather difficult to find the best way to treat HFpEF patients, and none of specific strategies have been established for the prognostic improvement. In order to understand the characteristics, backgrounds, and underlying problems of current HFpEF patients, we considered detailed observational cohort study must be needed. Based on such a concept, professor Yasushi Sakata (Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Japan) launched multi-centre observational cohort study, named PURSUIT-HFpEF registry, from June 2016 to register up to 1,500 HFpEF patients until March 2021. Inclusion criteria were acute decompensated HFpEF diagnosed by the Framingham criteria for HF plus the following: (1) left ventricular ejection fraction ≥ 50 per cent and (2) N-terminal pro-brain natriuretic peptide (NT-proBNP) ≥ 400 pg/mL or brain natriuretic peptide (BNP) ≥ 100 pg/mL on admission. Exclusion criteria were age < 20 years, severe valvular disease, acute coronary syndrome on admission, life expectancy of < 6 months due to prognosis of non-cardiac diseases, and previous heart transplantation.
Importance of right heart function among HFpEF patients
Although Right Ventricular (RV) function had been de-emphasised in the consideration of left-sided HF for many years, it is now evident that RV dysfunction is highly prevalent and resulted in poor prognosis in patients with left-sided HF with HFpEF in the position statement of the Heart Failure Association of the European Society of Cardiology. Even among the parameters related to right heart dysfunction and failure, RV-Pulmonary Artery (PA) coupling has been extensively focused on the prognostic predictability.
Right ventricle is quite sensitive to changes in afterload, and the afterload dependence is even exaggerated in HFpEF patients. Although RV-PA coupling had been evaluated with invasive calculation with Swan-Ganz catheterisation, recent studies have revealed that RV-PA coupling was able to be examined in a non-invasive manner with Tricuspid Annular Plane Systolic Excursion (TAPSE) to Pulmonary Arterial Systolic Pressure (PASP) ratio on echocardiography. TAPSE represents right ventricular contractile function, and PASP is estimated with the pressure gradient of tricuspid
Fig 1. Shedding light on RV-PA uncoupling with echocardiography
Fig 2. RV-PA uncoupling reflected with echocardiographic TAPSE/PASP was associated with adverse outcomes among HFpEF patients.
regurgitation Doppler wave in addition to the estimated right atrial pressure, presumed with the diameter and inspiratory collapsibility of inferior vena cava. Reduced TAPSE/PASP ratio was associated with worse prognosis in HF (including HFpEF), and a prognostic cut-off value was generally identified as < 0.36 mm/mmHg.
Need for assessment of HFpEF patients in a real-world data Findings from PUTSUIT-HFpEF registry
From our multi-centre prospective observational study, we examined the prognostic importance of TAPSE/PASP ratio among 655 hospitalised HFpEF patients. The median age was as high as 83 years, which was comparable to the patient characteristics of the large cohort of GWTG-HF registry. We should state the patient characteristics of this cohort that 56 per cent were females, median body mass index was as small as 21.2 kg/ m2, atrial fibrillation coexisted as much as 40 per cent, and the median NT-proBNP level was 1,080 pg/mL. The median value of TAPSE/PASP at discharge was as high as 0.54 mm/mmHg, and the ideal cutoff value of predicting adverse
Although treatment strategies were evaluated with randomised clinical trials, there were unavoidable discrepancies between trial candidates and realworld patients. The clinical impact on HFpEF patients of Angiotensin II Receptor Blockers (ARBs) of irbesartan and candesartan had been evaluated with I-PRESERVE (n = 4,133) and CHARM-Preserved (n = 3,023) trials, which had been unfortunately failed in establishing desirable evidence of ARB on HFpEF patients. While the mean age of HFpEF patients reported from a large size of observational study of the heart failure component of Get with the Guideline (GWTG-HF) registry (n = 18,299, between 2005 and 2009) was as high as 82 years, the candidate ages of I-PRESERVE (mean of 72 years, age ≥ 75 years was 34 per cent) and CHARM-Preserved (mean of 67 years, age ≥ 75 years was 27 per cent) were quite different. Considering these discrepancies, we should reassume the pathophysiology and treatment strategy for HFpEF patients based on real-world data.
As described above, the prognostic importance of RV-PA coupling for HFpEF patients had been established, however, the prognostic importance of TAPSE/PASP < 0.36 mm/mmHg was proved based on HFpEF populations haemodynamically validated with right heart catheterisation, which is ethically inappropriate for HFpEF patients in general. In order to verify the clinical prognostic usability of TAPSE/PASP ratio, investigations based on widely included HFpEF patients should be needed.
Fig 2. HFpEF, heart failure with preserved ejection fraction; PASP, pulmonary artery systolic pressure; RV-PA uncoupling, right ventricular-pulmonary arterial uncoupling; TAPSE, tricuspid annular plane systolic excursion
outcomes, defined as a composite of all-cause death, HF re-admission, or cerebrovascular events, was also as high as 0.48 mm/mmHg (area under the curve of receiver operating curve analysis = 0.59, P< 0.0001).
Kaplan Meier curve analyses showed that TAPSE/PASP < 0.48 mm/ mmHg was sufficient to predict the poor outcome (Log-rank P< 0.0001 for composite endpoint), and multivariable Cox regression testing revealed that TAPSE/PASP <0.48 mm/mmHg was significantly associated with the composite endpoint independently from multiple covariates including age, female sex, atrial fibrillation, renal dysfunction, and NT-proBNP elevation (hazard ratio = 1.77, 95 per cent confidence interval; 1.34-2.32, P< 0.0001). As a matter of course, a lower generally accepted threshold of TAPSE/PASP< 0.36 mm/ mmHg was also able to predict the poor outcome; a higher threshold of 0.48 mm/mmHg was proved to be sufficient for the prognostic prediction in this cohort. There must be racial differences between Asians and Westerners which made the different meanings of TAPSE/ PASP ratio, however, the evidence derived from our registry should reflect the precise characteristics of the realworld HFpEF patients.
Although major pathophysiology among HF and the definition of the ejection fraction as HFpEF are derived from the left side of the heart, our findings suggested that RV-PA uncoupling, deeply related to the right side of the heart, observed in echocardiography had a crucial prognostic meaning even among elderly multiple comorbid HFpEF patients.
AUTHOR BIO
Suggestions for future HFpEF treatment
Findings from the PURSUIT-HFpEF registry suggest the necessity of a treatment strategy for HFpEF patients based on RV function and pulmonary circulation. For instance, the short term beneficial effects of -adrenergic agonists for HFpEF have been considered from such a viewpoint. Andersen et al. reported that dobutamine infusion caused greater pulmonary vasodilatation with enhanced reductions in PA resistance, greater increase in PA compliance, and a more negative slope in the PA pressureflow relationship in a prospective trial in HFpEF patients. Following this study, in a randomised, double-blind, placebocontrolled trial for HFpEF patients, Reddy et al. described the beneficial effects of an inhaled -adrenergic stimulant that improved the primary endpoint of exercise pulmonary vascular resistance. Both trials showed that beneficial effects on acute improvement were achieved with the improvement of RV-PA uncoupling with -adrenergic stimulation.
The abilities of these and other potential therapeutic agents for HFpEF patients to improve RV-PA uncoupling, and ultimately the prognosis are needed to be explored in further investigations.
References are available at www.asianhhm.com
Akito Nakagawa graduated from Kobe University School of Medicine (Japan) and completed his PhD from Osaka University Graduate School of Medicine (Japan). He is a general cardiologist of a private hospital in Japan, having concurrent research post at the department of Medical Informatics, Osaka University Graduate School of Medicine (Japan).
BUILDING RESILIENT AND SECURE INFRASTRUCTURE
FOR HEALTHCARE’S DIGITAL FUTURE
Powering the Internet of Healthcare with resilient, secure infrastructure, COVID-19 has demonstrated how emerging technologies, such the cloud, IoT and automation, can actively improve patient care outcomes and streamline hospital operations. Coupled with increasing connectivity and smartphone adoption across Asia, medical care is also expected to become more accessible and personalised. As healthcare institutions embark on their digitalisation journey to meet and balance the region’s growing needs, how can we ensure that our infrastructure sets up our adoption of these emerging technologies for success?
Richard Farrell, Director, Cloud & Data Centre Segment, Electrical Sector, APAC, Eaton
There’s no denying that Asia-Pacific (APAC) is the centre of growth when it comes to digital healthcare adoption.
Amidst a global decline in non-coronavirus care expenditure, Asia has been the only region to see an increase in healthcare spending in
2020, thanks to consistent economic performance. Healthcare Information Technology (IT) spending is a particular area of focus with an estimated compound annual growth rate of 7 per cent between 2019 and 2022, driven by investments in software and IT services.
These investments in digital technologies complement the continued rise in smartphone penetration and connectivity across APAC, which is improving the accessibility and personalisation of healthcare delivery to the region’s 4.3 billion population. Telehealth services for instance have grown significantly, surging in use over the past year as demand for medical care swelled.
Many of these digital products and services have demonstrated valuable contributions to the improvement of patient care outcomes and hospital operations, both in the battle against COVID-19 and beyond. In fact, healthcare organisations have barely scratched the surface when it comes to leveraging these new technologies.
However, their success hinges on the industry’s embrace and mastery of technologies like the cloud and the Internet of Things (IoT), which are providing medical professionals and hospital administrators realtime visibility into different systems and applications in order to manage resources better.
As the industry embarks on its transformation journey, organisations must ensure that their infrastructure investments set their digitalisation initiatives up for success.
The expanding Internet of Medical Things (IoMT)
It is essential to first recognise that a modern healthcare institution will be one that is built on a network of connected devices which function like a nervous system — collecting, processing and transmitting data vital to everyday operations. A hospital’s efficiency, like any modern data-driven organisation, will be increasingly judged based on its ability to share timely information with the parties that need it most, while ensuring that this data is kept securely.
Beyond transmitting data, these connected devices will also control some of the most critical core systems needed for operations to run smoothly. Essential components of any hospital, clinic or research centre such as heating, ventilation and air conditioning (HVAC) systems rely on this connectivity to enable uninterrupted diagnostic procedures and patient care, while helping to keep costs down.
The impact of this connectivity extends far beyond the four walls of the hospital. Many of such devices connect and exchange data on cloud platforms for patients, medical teams and hospital staff to access at their convenience.
For instance, fitness trackers, connected implants and mobile apps are empowering users to manage their long-term health from the comfort of their own homes. Increased access to these digital tools give people greater incentive to take ownership of their health, and allow clinicians to deliver more effective treatments, remotely and in-person, that are backed by richer, more accurate data.
Empowering patients through connected, self-service technologies like these will be important to relieve the growing pressure on Asia’s healthcare systems as the region’s population ages and the prevalence of chronic diseases rises.
Ensuring secure and always-on healthcare with edge computing
For medical professionals to make sense of all the data being generated and collected, healthcare organisations need to have the right tools in place in order to process and analyse information in real time, and extract valuable insights. In many instances, transmitting and handling such large amounts of data on aging network infrastructure has resulted in bandwidth and latency issues.This can have serious consequences if more medical services are expected to be delivered virtually.
To address some of these challenges, the healthcare sector has started to explore the potential of edge computing over the past couple of years. Edge computing brings data processing closer to where data is being gathered, using a wider network of smaller “micro” data centres and reducing the reliance on a centralised data centre facility.
This is especially useful in scenarios where delays in processing cannot be afforded or connectivity is poor, and is likely to dramatically improve healthcare access for communities living in remote areas or elderly patients living alone. Wearables, bandwidthintensive video streaming and other monitoring devices can be deployed more efficiently to provide insights, detect falls or changes in behaviour, and raise alarms, ultimately ensuring that more patients can be cared for effectively round the clock.
Another key advantage of processing data at the edge is its security and reliability. Healthcare institutions no longer need to depend solely on third-party cloud service providers or networks to relay data, and the impacts of power outages or
network downtime from cyber threats can be minimised. Combining these benefits with the speed and latency of other emerging technologies like 5G can have an amplifier effect on the potential applications of advanced solutions such as remote surgery or the use of autonomous vehicles for emergency response.
The move towards a more distributed edge computing environment is only possible if healthcare institutions have the right power management infrastructure to keep these IoT networks up and running. Infrastructure managers in healthcare organisations will need to pay attention to a range of threats - from environmental risks to power anomalies beyond the hospital compound, to keep mission-critical applications and devices running longer, and protect servers from sudden, unexpected data loss in the field.
To this end, having a reliable critical backup power solution combined with an electrical power monitoring software platform will enable infrastructure managers to predict and manage any power related incident before they happen. This also allows for patient data to be available on-demand even when connectivity disruptions or power outages occur.
Defending digital healthcare assets against cyberattacks
The proliferation of connected devices and networks need to be supported by a rigorous approach to cybersecurity. IoT networks have become popular attack vectors for many cybercriminals due to the sheer number of potentially unsecured devices that offer multiple entry points to an organisation’s more sensitive corporate networks. Hospitals and medical institutions themselves are increasingly popular targets of cyberattacks as well, for reasons ranging from the theft of personal medical information to intentional disruption of a city’s critical infrastructure.
Beyond the loss of information, cyberattacks can cripple hospital operations and adversely impact lives. Last year, Brno University Hospital (one of the Czech Republic's biggest COVID-19 testing laboratories) was shut down for hours due to an attack; while in Thailand, ransomware attacks hit public hospitals and companies, slowing down operations by blocking access to their own data.
Cyberattacks have become a matter of when, not if. However, if appropriate steps are taken to plug the necessary gaps, the transformative impacts of these new technologies will far outweigh any potential risks.
To mitigate these security issues, infrastructure managers should ensure that their organisation’s infrastructure is regularly updated and patched. A thorough assessment of existing infrastructure should also be carried out before introducing any new system or tool, in order to get a more accurate understanding of each organisation’s existing cybersecurity risks. One often overlooked area is the operational technology (OT) environment, which includes systems and devices such as power, cooling and building management systems that form part of the physical infrastructure. When performing cybersecurity audits, healthcare organisations should take into account both IT and OT environments to ensure that they have a comprehensive picture of potential vulnerabilities that they might be exposed to.
When it comes to deploying new solutions, infrastructure managers should work with technology partners to implement systems and tools that comply with international and thirdparty certifications and standards managed by established organisations such as UL or the International Electrotechnical Commission. IoT and connected devices should also always be manufactured with a “secure by design” approach to aid infrastructure owners in their management of cybersecurity risks throughout the product’s lifecycle.
Managing and securing power in an increasingly complex and volatile future
In recent months, many of these transformation and digitalisation initiatives have been accelerated by COVID-19. Healthcare institutions have gone to great lengths to leverage technology as a means of reducing in-person contact and exposure to the virus. Siriraj Hospital in Bangkok, for instance, has begun trialing unmanned vehicles for the contactless delivery of medicines and supplies, while Singapore’s National University Health System has begun using robots and drones for building maintenance and security.
Many of these connected tools and systems will also be used to support mass COVID-19 vaccination rollouts across the world this year. Technologies such as smart RFID tags will be used to track shipments and inventory, while an array of sensors are likely to be deployed to monitor temperature, humidity and light fluctuations,
to ensure that the complex storage requirements of these vaccines are met.
All this information will need to be shared between hospitals, clinics and health authorities in real-time as stock data and distribution streams are optimised and synchronised at a city or even national level. Given the complexity of this endeavour, a loss of power at any stage in the highly-data dependent distribution stream would be a major setback in the fight against the disease.
Pandemic activities aside, many of the modern digital systems hospitals have come to rely on would grind to a halt without a proper power back-up strategy. The reach of these systems spans from hospital administration to patient care and research. As hospitals’ reliance on digital infrastructure and power consumption grow, generators and other traditional back-up solutions will no longer be sufficient to meet this growing energy appetite.
Energy costs are skyrocketing and hospitals today are already using more than twice the amount of power compared to other public buildings. Furthermore, adverse climate events from wildfires to flooding are occurring in greater frequency and intensity. Healthcare organisations will need to have the right power management tools that not only protect hospitals from wider grid disruptions, but can also be scalable to support an upsurge in patients that typically follows such incidents.
A new generation of back-up strategies are emerging to address this challenge, from the use of microgrids, to lithium-ion batteries and Uninterruptible Power Supply solutions. These solutions often utilise IoT and the cloud tools themselves to provide intelligent 24/7 monitoring. When paired with predictive analytics tools, such critical power solutions can provide constant power even under the most adverse environmental power conditions.
Powering our smart hospital ambitions
Moving to the edge, cybersecurity and having a back-up power strategy are just three of the first major steps towards the adoption of digital initiatives. As with any new systems, hospitals will need to apply the people, process and technology framework, in order to ensure that these new investments are well supported and positioned for success.
Many experts still recognise that getting the ‘people’ aspect right is often the most important determinant factor of success when it comes to issues like cybersecurity or digitalisation. This shift towards the cloud and IoT will need to be accompanied by well-planned training, resources, and strategic collaboration to unlock their full value, safely.
In these challenging times, the role of the hospitals as critical infrastructure nodes for communities cannot be overstated. Making the right strategic investments today will go a long way to ensure their resilience amidst the uncertainty in the years ahead.
AUTHOR BIO
Rich is a technology evangelist, strategist & consultant with over 20 years of experience in the IT, Data Centre, and Hyperscale Cloud space. In his current role at Eaton, he collaborates with customers across the Asia-Pacific region to shape their cloud strategy and advises on data centre build best practice and industry innovations.
