Heart failure module 5: surgical management and palliative care of HF

Introduction

Although left ventricular (LV) systolic function recovers in around 15% of patients with heart failure due to a reduced ejection fraction (HFrEF) within three years with optimal medical treatment (OMT),¹ the same proportion will progress to end-stage disease and surgical intervention is sometimes necessary.²

Surgical treatment for heart failure (HF) includes:

• mechanical circulatory support
  • LV assist devices (LVAD)
• cardiac transplantation
• coronary revascularisation
• surgical ventricular restoration
• valve surgery.

While identifying the need for mechanical circulatory support in a patient with cardiogenic shock may be easy enough, identifying ambulatory patients with chronic HF who require advanced therapy (such as LVAD or transplantation) is more difficult.

Donor organ shortage is a frequently cited reason for the low rate of heart transplantation in the UK – according to Eurotransplant (a non-profit organisation that co-ordinates organ transplantation across continental Europe) there are approximately twice as many patients awaiting heart transplant per year than those who receive one.⁴

Mechanical circulatory support

LVADs

Mechanical circulatory support (MCS) was developed as a rescue therapy for patients in intractable cardiogenic shock. The first devices were conceived as a continuation for patients who were unable to come off cardiopulmonary bypass (CPB) and have progressed to separate, implantable LVADs (figure 1).

Historically, LVADs were only indicated as a holding measure until an organ became available or until a decision was made regarding cardiac transplantation; so-called ‘bridge-to-transplantation’ (BTT) or ‘bridge-to-decision’ (BTD).

However, in 2015, the National Institute for Health and Clinical Excellence (NICE) published guidelines also recommending LVADs as long-term therapy for patients ineligible for transplantation, so-called ‘destination therapy’ (DT).⁵

In America, LVADs are licenced for a third indication known as ‘bridge-to-candidacy’, whereby the LVAD is implanted in a patient ineligible for heart transplantation with the hope that the improvement in haemodynamics may enable the patient to become eligible for transplant at a later date.

LVADs are used as DT more commonly than other indications worldwide (figure 2).⁶ In a minority of patients, the haemodynamic relief provided by the LVAD can allow recovery of myocardial function and explant of the device, though the majority will require continued support.

Adapted from the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS)6

The standard LVAD circuit pumps blood from the LV cavity through the device into the ascending aorta, creating a mechanical bypass of the LV outflow. The left ventricle is thus off-loaded (and the aortic valve may remain closed). Cardiac output is thus increased.⁷

Beneficial effects of LVAD include:

• increased systemic blood pressure
• improved organ perfusion and subsequent beneficial neuro-hormonal changes
• reduced cardiac chamber size
• reduced left atrial and pulmonary pressures.

Complications of LVAD therapy¹⁰

The most frequent problems encountered during LVAD therapy are:

Bleeding and thrombosis
• All patients require anticoagulation, with the specific regime varying between devices
• All patients also develop acquired von Willebrand factor deficiency
• The tiny pulse pressure with continuous flow pumps is associated with gastrointestinal bleeding due to the development of angiodysplasia (much like in severe aortic stenosis)
• Device thrombosis is a difficult problem manifested by increased power consumption, clinical or laboratory signs of haemolysis (e.g. elevated bilirubin, plasma haemoglobin and lactate dehydrogenase levels) or device stoppage. It can be treated with intravenous heparin, fibrinolytics or surgery (pump exchange or urgent transplant).
Infection
• The risk of infection is high; the artificial surfaces of the pump itself create sites for colonisation and the percutaneous driveline that delivers power is an extremely common site of infection
• Severity of infection can vary from asymptomatic driveline site colonisation to deep abscesses or device-related endocarditis. Wound care requires specialist nursing oversight.
Right ventricular failure
• This is precipitated by failure of the right ventricle (RV) to handle the volume returned to it by the assisted LV (particularly because the right ventricle can be involved in the underlying disease process)
• This can be manifested by distended neck veins, liver congestion and increasing oedema, accompanied by a deterioration in exercise capacity and increasing natriuretic peptides
• Treatment is with diuretics, adjustment of the LVAD speed, or insertion of a right-sided ventricular assist device (VAD) in extreme cases.
Stroke
• Both types of stroke – ischaemic due to embolism or haemorrhagic due to bleeding – are often catastrophic, if they occur
• Haemorrhagic stroke is especially feared; anticoagulation cannot be stopped due to the high likelihood of device thrombosis and failure.
Acquired aortic regurgitation
• LVAD therapy creates a large pressure gradient from the aorta to the LV, transmitted across the aortic valve; this can lead to aortic regurgitation, which decreases the efficacy of support and longevity of the device
• Up to 50% will have moderate to severe aortic regurgitation at 18 months, which is difficult to treat. Options include open or transcatheter valve replacement or cardiac transplantation.
Arrhythmia
• Both atrial and ventricular arrhythmia are common in patients with LVAD. Patients with LVADs are unique in regard to ventricular arrhythmia in that an episode of VF does not lead to death as peripheral blood flow is maintained by the pump. Cardioversion is still required!

In the UK, data on LVAD implantation is collected by the NHS Organ Donation and Transplant Service which releases annual activity reports. In 2021/22, there were 334 LVAD implantations for long-term bridging.¹⁷ The median time on an LVAD was 1,101 days.¹⁷ The majority of patients were listed for a heart transplant within a year of LVAD implantation but only 5% of patients underwent transplantation within that time frame. While outcome has improved, it remains poor – more patients die on support (31%) than are transplanted (13%) or have the device explanted due to recovery (5%).¹⁷

The future of LVADs lies not only in developing technology to reduce the morbidity and cost of long-term therapy, but also in their appropriate deployment. Many patients are referred too late in the natural history of HF (or when there is serious co-morbidity) and thus outcomes are poor and the only viable long-term treatment – transplantation – is often contraindicated. The timing of LVAD insertion remains critical. The economic argument will only carry weight when the up-front cost is a great deal lower. No publicly funded health care system can afford the present costs of a device in even larger numbers of patients than at the moment.

Cardiac transplantation

Cardiac transplantation has evolved significantly since its inception in the 1960s and remains the best long-term therapy for advanced HF, despite its risks and complications (figure 3).¹⁸

Data obtained from NHS BTCAG-H, 202218

Clinically, the key challenges are management of patient selection, donor organ selection, the peri-operative period and long-term follow up, in addition to availability of donor organs. Practically, the key challenge is shortage of available donor organs, which limits the expansion of the transplant population.¹⁹

By the end of March 2023 in the UK, there were 254 adult patients on the heart transplant waiting list.¹⁷ Between 2018 and 2020 amongst 302 patients on the non-urgent transplant list, 20% had been transplanted within three years of listing, whilst 27% were still waiting, 29% had progressed to the urgent list and 10% had died while waiting.¹⁷

Patient selection¹⁹

Good cardiac transplant candidates have advanced and severely symptomatic HF, but do not have other end-organ complications or co-morbidities associated with high peri-operative risk or which adversely affect long-term outcome. In-patient referral may be considered for patients admitted with acute HF with intractable inotrope dependence or cardiogenic shock.^19,20

Transplant assessment is summarised in table 1.^20,22

Donor organ selection and peri-operative management¹⁹

Specialised teams based at cardiac transplant centres carry out organ retrieval. Techniques for selecting suitable organs are complex and usually involve clinical examination, electrocardiography (ECG), haemodynamic studies using a pulmonary artery catheter, and direct visual inspection (figure 4). This is complemented by data from echocardiography or cardiac catheterisation, if available. The organ is transferred to the centre in cold storage or in an organ care system that maintains a warm, perfused state, where available.

Key: ECG = electrocardiography; Echo = echocardiography; PA = pulmonary artery

Performing a heart transplant

The surgical transplant operation has evolved over time.²² The bi-atrial technique left some recipient right atrium in situ and required long, sometimes fallible atrial anastomoses (figure 5a). The total orthotopic technique involved separate anastomoses for each pulmonary vein and the great vessels (not pictured). The bicaval technique involved the insertion of the recipient’s pulmonary veins into the left atrium remains in situ, with the donor left atrium anastamosed to the remnant and the donor right atrium is anastamosed to the great veins (figure 5b).

Reproduced with kind permission from Hunt22

The operation and post-operative recovery can vary from the routine (such as in a stable patient with a first sternotomy) to extremely high-risk (such as in patients with several previous sternotomies, a VAD in situ, or in patients who are critically ill). Specific early problems that should be anticipated are summarised in table 2.

Table 2. Problems to anticipate following cardiac transplantation¹⁹

Right ventricular failure
Right ventricular function is particularly susceptible to ischaemia and this becomes aparent after ceasing CPB. This can be compounded by high recipient pulmonary vascular resistance and multiple blood transfusion
Bradyarrhythmia
Usually sinus bradycardia or sinus arrest. Most centres use expectant temporary atrial pacing or isoprenaline to maintain an early relative tachycardia. This overcomes the initially low stroke volume that normalises with improving ventricular compliance
Systemic inflammatory response
This particularly occurs with prolonged CPB or pre-existing infection (e.g. chronic LVAD infection), often requiring high-dose vasopressors
Haemorrhage
Frequently this is due to coagulopathy rather than a surgical cause. Pericardial bleeding can be exacerbated by the presence of potential space after removal of the enlarged heart, or by size mismatch of the donor organ
Biventricular failure
In the early phase, this raises concern for primary graft failure and hyperacute rejection
Key: CPB = cardiopulmonary bypass; LVAD = left ventricular assist device

Long-term management

Cardiac transplant dramatically improves survival and quality of life (QoL) in the right patient. Based on the NHS’ annual report on heart transplantation in the UK published in 2023, the national rate of patient survival following adult heart transplant at one and five years is 85.9% and 71.4% respectively.¹⁷

However, morbidity rates are high.²³ The crux of follow-up lies in careful management of immunosuppression, finding the balance between avoidance of rejection and avoidance of side effects of therapy.

The immunosuppressant therapies all target T-cells, which drive cellular rejection. Induction immunosuppression given pre-operatively is sometimes included. The calcineurin inhibitors, tacrolimus and ciclosporin, are the mainstay of therapy and are often combined with corticosteroids and a cell-cycle agent, such as mycophenolate, for long-term maintenance. The drugs have many side effects, many of which are dose-dependent making monitoring of drug levels mandatory.²⁴

Cardiac allograft vasculopathy (CAV) is the most common late complication (weeks to months from transplantation). It is an accelerated form of coronary artery disease in a transplanted heart. As only around 10–30% of patients regain any innervation to the heart post-transplant, angina symptoms are uncommon and patients often present with breathlessness following silent myocardial infarction, or with HF, or as sudden death.²⁵ CAV is often diffuse and therefore not amenable to revascularisation. Careful symptomatic (anti-anginals) and preventative (statins) medical therapy is a priority; most patients are started on low-dose atorvastatin (10 mg once daily) due to the lower incidence of myositis compared with other statins.²⁶

Revascularisation, ventricular restoration and valve surgery

Patients with HF are commonly considered for coronary revascularisation and valve surgery. Surgical ventricular restoration (SVR) involves exclusion of scar on the ventricular wall from previous myocardial infarction and is not commonly performed. Such decisions are difficult, not least because patients with HF often have multiple co-morbidities, including frailty, which makes the long-term benefit of invasive treatment less certain. However, there may be a subset of patients who benefit from certain treatments. As ever, patient selection and shared decision-making is key.²⁷

Revascularisation

Inadequate myocardial perfusion can cause impaired contractility; this can be either fixed (infarction leading to scar) or reversible (hibernation). Differentiating hibernating myocardium from infarcted tissue can be done, for example with dobutamine stress echocardiography or thallium scintigraphy. Coronary revascularisation in HF aims to improve myocardial function by restoring perfusion to hibernating myocardium, so reducing LV volumes and improving LV function (figures 6a and 6b).

There is a reasonable argument that selected younger patients with HF (in whom angina is not a prominent symptom) should be offered coronary angiography with a view to surgical revascularisation. There is no role for PCI for the treatment of LV systolic dysfunction, even in the presence of so-called viable myocardium.

Surgical ventricular restoration²⁷

The aims of surgical ventricular restoration (SVR) are to:

• normalise ventricular geometry
• improve myocardial perfusion
• reduce LV work
• improve LV contraction.

The early procedures were similar to partial left ventriculectomy for aneurysm, while the contemporary SVR involves resection of the non-functional myocardium before placement of an endoventricular Dacron patch to exclude the scar (figures 7a–d). It is usually done during CABG for patients with ischaemic HF and anterior wall akinesia or severe dyskinesia. It adds about 20 minutes to the procedure time without increasing operative risk.

With kind permission from Gemma Price	With kind permission from Gemma Price
With kind permission from Gemma Price	With kind permission from Gemma Price

Valve surgery

An important cause of the HF syndrome is valvular heart disease. Every patient presenting with HF should be assessed for valvular disease; aortic stenosis is a particularly common cause. Appropriate patients should be offered aortic valve replacement as a potentially curative procedure. Many patients, however, may be too frail for surgical valve replacement by the time they present with HF.

In these cases, transcatheter aortic valve implantation (TAVI) should be considered as being a lower-risk alternative.³⁵ TAVI is certainly superior to medical therapy in inoperable patients and is increasingly being shown in trials to be as effective as surgical valve replacement in lower-risk patients.³⁵

A more difficult problem is that of mitral valve surgery. Functional mitral regurgitation (MR) is very common in HF as a consequence of valve ring dilation, together with tethering of the posterior leaflet of the valve.³⁶

How transcatheter mitral valve repair will fit into future guidelines is not clear, but it is certain that, as with all surgical treatment options for HF, appropriate and timely patient selection will be key to effective use.

Summary

Revascularisation, either by CABG or PCI, is commonly performed with patients with LV systolic dysfunction. However, there is little evidence that it influences prognosis outside of an acute coronary syndrome. If HF is thought to be due primarily to valve disease, then treatment of the valve is likely to benefit the patient only if they are fit for the intervention; patient selection for surgical or transcatheter valve interventions is difficult, but key to success.

Palliative care in HF

Palliative care is an approach that improves the QoL of patients and their families

At any stage of the disease, patients with HF have poorer QoL than the general population,^41,42 largely due to the significant symptom burden which worsens as the disease progresses.⁴³ In those patients where surgical intervention is not appropriate, or in end-stage disease, end-of-life and palliative care should be implemented.

There is very little data on the benefits of palliative care in patients with HF. A recent meta-analysis of all randomised controlled trial data involving 921 patients with HF found that palliative care interventions were associated with an improvement in QoL and symptom burden, and reduced hospitalisations compared to usual care. The European Society of Cardiology (ESC) and NICE HF guidelines recognise the need for supportive and palliative care services for patients with end-stage HF.^44–46

Integrated working between primary care, HF services and specialist palliative care is essential but a palliative approach to care and access to palliative care is patchy, both nationally and internationally.⁴⁷

Barriers to effective palliative care in patients with HF include:

• unpredictable disease trajectory
• poor communication between members of the multidisciplinary team (MDT) – for example, a lack of clarity about the appropriate ceiling of medical therapy
• reluctance of clinical staff to have the difficult conversations around the end of life due to concerns about destroying hope
• healthcare services are poorly set up for timely and effective palliative interventions.

What is palliative care?

Palliative care (table 3) aims to improve the QoL of patients with chronic or terminal illness and help their families face the problems associated with life-threatening illness. The primary goal is the prevention and relief of suffering by early identification, assessment and treatment of pain and/or psychological distress, as well as addressing spiritual needs.

Palliative care for patients with HF is provided by an MDT led by a palliative care specialist, in conjunction with a HF specialist, with access to other relevant services for persistent or complex needs. It involves a problem-based integrated approach to advanced care planning, communication and symptom control. In order to explore the palliative care of patients with HF, each aspect will be addressed in turn.

There are several common misunderstandings about palliative care. These include:

• a belief that palliative care is only applicable to patients for whom there is clearly apparent irreversible deterioration with death expected within days to months
• requires a handover of the patient to the palliative care team
• only relates to physical symptom control in the dying patient and can only be provided once all other therapeutic options are exhausted.

Problem-based integrated approach

Educating the patient, carers and families about the condition allows for informed joint decision-making. This should be an ongoing process across multiple clinical encounters; the unpredictable trajectory of HF means constant reassessment of a patients’ risk of adverse outcomes and, therefore, potential need for palliative care services is essential.

The level of palliative care intervention at different stages in a patient’s disease process will vary from patient-to-patient, dependent on their needs. Most patients can be cared for in primary care and by their usual secondary care teams, but some require access to specialist palliative care services. This integrated approach allows patients to receive palliative care depending upon need rather than prognosis.^48,49

Important considerations in patients with HF receiving palliative care include:

• Frailty and malnutrition

Regardless of how they are defined, frailty and malnutrition are common in HF, affecting over 50% of patients.^50,51 Patients with frailty and/or malnutrition have more severe disease; are less likely to be treated with disease-modifying drugs; and are at greater risk of hospitalisation or death.^51–54 The majority of hospitalisations or deaths occurring in frail patients are due to non-cardiovascular causes.⁵² Indeed, in all patients with chronic HF – whether frail or not – non-cardiovascular causes account for the majority of morbidity and mortality in the last year of life.⁵⁵

All disease-modifying therapies for HFrEF are given on the basis that they reduce HF hospitalisation and cardiovascular mortality.⁴⁶ Thus, the presence of frailty or malnutrition (or the suspicion that the patient may be in or near the last year of life – see below) should prompt discussions about discontinuing HF therapies, especially if the patient is experiencing side effects.

• Advance care planning



Advance care planning is defined by the General Medical Council as “the process of discussing the type of treatment and care that a patient would or would not wish to receive in the event that they lose capacity to decide or are unable to express a preference.”⁵⁰

Advance care planning is important to many patients; it increases the likelihood of end-of-life wishes being carried out and improves the quality of care for both patients and their carers.^51–54

One aspect of advance care planning is decision-making about preferred place of care. In the UK, there is a gross disparity between preferred place of care for cancer patients and HF patients.⁵⁶ Palliative care services tend to be structured to meet the needs of patients with cancer, many of whom have a predictable disease trajectory; as a consequence, most patients will die at home or in a hospice. In contrast, patients dying from cardiovascular diseases, including HF, are much more likely to die in hospital (59%) with fewer than 1% dying in a hospice.^55,57

For example, decisions regarding deactivation of an implantable cardioverter-defibrillator (ICD) in a patient predicted to be in the last few weeks of life can be particularly difficult but are an essential aspect of care; if an ICD is not re-programmed to pacemaker mode only, dying may be complicated by repeated shocks.⁵⁸

• Communication

Guidance and training have been developed to help physicians and the many patients with HF who want to discuss end-of-life issues.^59,60 Patients are involved in decisions about their future care, despite uncertain disease trajectories by “hoping for the best, and preparing for the worst.”^61–66 Such discussions should be ongoing through the natural history of disease and not reserved for when a patient displays clear signs of end-stage disease. Regarding ICDs, it is good practice to inform the patient that the time may come at which treatment with an ICD is no longer appropriate as part of counselling before implantation.

• Symptom control

Breathlessness (figure 8) is the predominant symptom of end-stage HF. Decisions on investigations and treatment must be taken in the context of the patient’s wishes and stage of the disease.⁶⁷

For example, intravenous (IV) diuretics, vasodilators and inotropes are not appropriate for someone in the last few days of life whose primary wish is to be kept comfortable in whom less aggressive treatments are essential.

Box 7. Palliative management of breathlessness68 Assessment and treatment of reversible causes, dependent upon the patient’s wishes and stage of illness SC furosemide infusion, which may be as effective as IV treatment for venous congestion and may prevent admission to hospital in patients with advanced HF69,70 Cardiac exercise programmes, which also address patient education and psycho-social support are available, even for severely limited patients64 Handheld fans may ease the sensation of dyspnoea71 Low-dose opioids may improve symptoms of breathlessness in patients with HF.72 However, as the largest trial to date was closed early due to poor recruitment, the data in support of long-term opiate use for breathlessness in patients with HF remain scant73 Benzodiazepines may be helpful. However, there is very little evidence to support their use; they should only be used as second-line agents.74 Key: HF = heart failure; IV = intravenous; SC = subcutaneous

Courtesy of the British Heart Foundation

Pragmatic approach to HF treatment

Many medications used to treat HF lower blood pressure or heart rate, yet confer prognostic benefit. Postural hypotension is common among elderly patients⁷⁷ and is associated with an increased risk of falls and injury.⁷⁸ In patients with HF who are approaching the end of their lives who often require high-dose oral diuretics, continuing high-dose medications such as beta blockers, ACE inhibitors and mineralocorticoid receptor antagonists may cause more harm than long-term benefit.

How do we know a patient with HF is nearing the end of their life?

The natural history of HF is defined by periods of relative stability punctuated by periods of unpredictable and often sudden decline from which the patient may, or may not, recover. Thus, distinguishing patients whose conditions are salvageable from those who are entering the last few weeks of life is difficult. The ESC list five criteria, the presence of one or more of which ought to prompt consideration of end-of-life care for patients in whom advanced treatment, such as with heart transplantation or LVADs, has been deemed futile⁴⁴:

• Progressive functional decline and increasing dependence with activities of daily living
• Severe symptoms and poor QoL, despite optimal HF management
• Frequent hospital admissions or other severe decompensation episodes, despite OMT
• Cardiac cachexia
• Clinically judged to be end-of-life for another reason, such as severe infection or advanced cancer.

Summary

Incorporation of a palliative care approach in response to patient need rather than estimated prognosis will result in better care for patients with advanced HF. Interventions to support the patient and family with symptom control with the aim of improving QoL should be used alongside optimal HF management. Palliative care should be provided by the usual clinical teams in primary and secondary care, with access to specialist palliative care services when needed for persistent or complex problems.

close window and return to take test

References

1. Kalogeropoulos AP, Fonarow GC, Georgiopoulou V et al. Characteristics and outcomes of adult outpatients with heart failure and improved or recovered ejection fraction. JAMA Cardiol 2016;1:510–8. https://doi.org/10.1001/jamacardio.2016.1325
2. Kalogeropoulos AP, Samman-Tahhan A, Hedley JS et al. Progression to stage d heart failure among outpatients with stage C heart failure and reduced ejection fraction. JACC Heart Fail 2017;5:528–37. https://doi.org/10.1016/j.jchf.2017.02.020 [Epub ahead of print]
3. Lund LH, Trochu JN, Meyns B et al. Screening for heart transplantation and left ventricular assist system: results from the ScrEEning for advanced Heart Failure treatment (SEE-HF) study. Eur J Heart Fail 2018;20:152–60. https://doi.org/10.1002/ejhf.975 [Epub ahead of print]
4. Eurotransplant. Statistics Report Library. Yearly Statistics Overview 2022. Available from http://statistics.eurotransplant.org/index.php?search_type=overview&search_text=9023 (accessed 11 January 2024)
5. National Institute for Health and Care Excellence. Implantation of a left ventricular assist device for destination therapy in people ineligible for heart transplantation [IPG516]. London: NICE, 2015. Available from: https://www.nice.org.uk/guidance/ipg516 (accessed 31 October 2023)
6. Kirklin JK, Naftel DC, Pagani FD et al. Seventh INTERMACS annual report: 15,000 patients and counting. J Heart Lung Transplant 2015;34:1495–504. https://doi.org/10.1016/j.healun.2015.10.003 [Epub ahead of print]
7. Tedford RJ, Leacche M, Lorts A, Drakos SG, Pagani FD, Cowger J. Durable Mechanical Circulatory Support: JACC Scientific Statement. J Am Coll Cardiol 2023;82:1464–81. https://doi.org/10.1016/j.jacc.2023.07.019
8. Berardi C, Bravo CA, Li S et al. The history of durable left ventricular assist devices and comparison of outcomes: HeartWare, HeartMate II, HeartMate 3, and the future of mechanical circulatory support. J Clin Med 2022;11:2022. https://doi.org/10.3390/jcm11072022
9. Slaughter MS, Rogers JG, Milano CA et al. HeartMate II Investigators. Advanced heart failure treated with continuous-flow left ventricular assist device. N Engl J Med 2009;361:2241–51. https://doi.org/10.1056/NEJMoa0909938 [Epub ahead of print]
10. Kirklin JK, Naftel DC, Kormos RL et al. Quantifying the effect of cardiorenal syndrome on mortality after left ventricular assist device implant. J Heart Lung Transplant 2013;32:1205–13. https://doi.org/10.1016/j.healun.2013.09.001 [Epub ahead of print]
11. Pagani FD, Aaronson KD, Kormos R et al. The NHLBI REVIVE-IT study: Understanding its discontinuation in the context of current left ventricular assist device therapy. J Heart Lung Transplant 2016;35:1277–83. https://doi.org/10.1016/j.healun.2016.09.002 [Epub ahead of print]
12. Estep JD, Starling RC, Horstmanshof DA et al. Risk assessment and comparative effectiveness of left ventricular assist device and medical management in ambulatory heart failure patients: results from the ROADMAP study. J Am Coll Cardiol 2015;66:1747–61. https://doi.org/10.1016/j.jacc.2015.07.075
13. Starling RC, Estep JD, Horstmanshof DA et al; ROADMAP Study Investigators. Risk assessment and comparative effectiveness of left ventricular assist device and medical management in ambulatory heart failure patients: the ROADMAP study 2-year results. JACC Heart Fail 2017;5:518–27. https://doi.org/10.1016/j.jchf.2017.02.016 [Epub ahead of print]
14. Rogers JG, Pagani FD, Tatooles AJ et al; ENDURANCE Investigators. Intrapericardial left ventricular assist device for advanced heart failure. N Engl J Med 2017;376:451–60. https://doi.org/10.1056/NEJMoa1602954
15. Mehra MR, Naka Y, Uriel N et al; MOMENTUM 3 Investigators. A fully magnetically levitated circulatory pump for advanced heart failure. N Engl J Med 2017;376:440–50. https://doi.org/10.1056/NEJMoa1610426 [Epub ahead of print]
16. Parameshwar J, Hogg R, Rushton S et al. Patient survival and therapeutic outcome in the UK bridge to transplant left ventricular assist device population. Heart 2019;105:291–6. https://doi.org/10.1136/heartjnl-2018-313355 [Epub ahead of print]
17. National Health Service. Blood and transplant. Annual report on heart transplantation. Report for 2022/2023. Available from: https://nhsbtdbe.blob.core.windows.net/umbraco-assets-corp/30881/nhsbt-heart-transplantation-report-2223.pdf (accessed 10 January 2024)
18. National Health Service. Blood and Transplant Cardiothoracic Advisory Group – Heart. Long-term Conditional Survival Post-Heart Transplant. 2022. Available at: https://nhsbtdbe.blob.core.windows.net/umbraco-assets-corp/30608/item-123-ctagh-22-52-conditional-survival-final.pdf (accessed 10 January 2024)
19. Banner NR, Bonser RS, Clark AL et al. UK guidelines for referral and assessment of adults for heart transplantation. Heart 2011;97:1520e1527. https://doi.org/10.1136/heartjnl-2011-300048
20. Dar O, Banner NR. Cardiac transplantation: who to refer and when. Br J Hosp Med (Lond) 2013;74:258–63. https://doi.org/10.12968/hmed.2013.74.5.258
21. McDonagh TA, Metra M, Adamo M et al; ESC Scientific Document Group. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: Developed by the Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). With the special contribution of the Heart Failure Association (HFA) of the ESC. Eur J Heart Fail 2022;24:4–131. https://doi.org/10.1002/ejhf.2333
22. Hunt SA. Taking heart – cardiac transplantation past, present, and future. N Engl J Med 2006;355:231–5. https://doi.org/10.1056/NEJMp068048
23. Dew MA, Kormos RL, Roth LH, Murali S, DiMartini A, Griffith BP. Early post-transplant medical compliance and mental health predict physical morbidity and mortality one to three years after heart transplantation. J Heart Lung Transplant 1999;18:549–62. https://doi.org/10.1016/s1053-2498(98)00044-8
24. Crespo-Leiro MG, Costanzo MR, Gustafsson F et al. Heart transplantation: focus on donor recovery strategies, left ventricular assist devices, and novel therapies. Eur Heart J 2022;43:2237–46. https://doi.org/10.1093/eurheartj/ehac204
25. Aranda JM Jr, Hill J. Cardiac transplant vasculopathy. Chest 2000;118:1792–800. https://doi.org/10.1378/chest.118.6.1792
26. Chih S, Chong AY, Mielniczuk LM, Bhatt DL, Beanlands RS. Allograft vasculopathy: the Achilles’ heel of heart transplantation. J Am Coll Cardiol 2016;68:80–91. https://doi.org/10.1016/j.jacc.2016.04.033
27. Hegeman RRMJJ, Swaans MJ, van Kuijk JP, Klein P. State-of-the-art review: Technical and imaging considerations in hybrid transcatheter and minimally invasive left ventricular reconstruction for ischemic heart failure. J Clin Med 2022;11:4831. https://doi.org/10.3390/jcm11164831
28. Velazquez EJ, Lee KL, Deja MA et al; STICH Investigators. Coronary-artery bypass surgery in patients with left ventricular dysfunction. N Engl J Med 2011;364:1607–16. https://doi.org/10.1056/NEJMoa1100356 [Epub ahead of print]
29. Velazquez EJ, Lee KL, Jones RH et al; STICHES Investigators. Coronary-artery bypass surgery in patients with ischemic cardiomyopathy. N Engl J Med 2016;374:1511–20. https://doi.org/10.1056/NEJMoa1602001 [Epub ahead of print]
30. Cleland JG, Calvert M, Freemantle N et al. The heart failure revascularisation trial (HEART). Eur J Heart Fail 2011;13:227–33. https://doi.org/10.1093/eurjhf/hfq230 [Epub ahead of print]
31. Perera D, Clayton T, O’Kane PD et al; REVIVED-BCIS2 Investigators. Percutaneous revascularization for ischemic left ventricular dysfunction. N Engl J Med 2022;387:1351–60. https://doi.org/10.1056/NEJMoa2206606 [Epub ahead of print]
32. Brener MI, Uriel N, Burkhoff D. Left ventricular volume reduction and reshaping as a treatment option for heart failure. Structural Heart 2020;4:264–83. https://doi.org/10.1080/24748706.2020.1777359
33. Costa MA, Mazzaferri EL Jr, Sievert H, Abraham WT. Percutaneous ventricular restoration using the parachute device in patients with ischemic heart failure: three-year outcomes of the PARACHUTE first-in-human study. Circ Heart Fail 2014;7:752–8. https://doi.org/10.1161/CIRCHEARTFAILURE.114.001127 [Epub ahead of print]
34. US National Institutes of Health. ClinicalTrials.gov. A multinational trial to evaluate the parachute implant system (PARACHUTE). Available from: https://clinicaltrials.gov/show/NCT01286116 (accessed 01 November 2023)
35. Prendergast BD, Baumgartner H, Delgado V et al. Transcatheter heart valve interventions: where are we? Where are we going?. Eur Heart J 2019;40:422–40. https://doi.org/10.1093/eurheartj/ehy668
36. Clark AL, Alamgir MF, Nair RK, Thackray ST. Percutaneous surgery for mitral valve disease. Heart 2009;95:1850. https://doi.org/10.1136/hrt.2009.167536
37. Stone GW, Lindenfeld J, Abraham WT et al; COAPT Investigators. Transcatheter mitral-valve repair in patients with heart failure. N Engl J Med 2018;379:2307–18. https://doi.org/10.1056/NEJMoa1806640 [Epub ahead of print]
38. Obadia JF, Messika-Zeitoun D, Leurent G et al; MITRA-FR Investigators. Percutaneous repair or medical treatment for secondary mitral regurgitation. N Engl J Med 2018;379:2297–306. https://doi.org/10.1056/NEJMoa1805374 [Epub ahead of print]
39. Grayburn PA, Sannino A, Packer M. Proportionate and disproportionate functional mitral regurgitation: a new conceptual framework that reconciles the results of the MITRA-FR and COAPT Trials. JACC Cardiovasc Imaging 2019;12:353–62. https://doi.org/10.1016/j.jcmg.2018.11.006 [Epub ahead of print]
40. Stone GW, Abraham WT, Lindenfeld J et al; COAPT Investigators. Five-year follow-up after transcatheter repair of secondary mitral regurgitation. N Engl J Med 2023;388:2037–48. https://doi.org/10.1056/NEJMoa2300213 [Epub ahead of print]
41. Teno JM, Weitzen S, Fennell ML, Mor V. Dying trajectory in the last year of life: does cancer trajectory fit other diseases? J Palliat Med 2001;4:457–64. https://doi.org/10.1089/109662101753381593
42. Hobbs FDR, Kenkre JE, Roalfe AK, Davis RC, Hare R, Davies MK. Impact of heart failure and left ventricular systolic dysfunction on quality of life. A cross-sectional study comparing common chronic cardiac and medical disorders and a representative adult population. Euro Heart J 2002;23:1867–76. http://dx.doi.org/10.1053/euhj.2002.3255
43. Barclay S, Momen N, Case-Upton S, Kuhn I, Smith E. End-of-life care conversations with heart failure patients: a systematic literature review and narrative synthesis. Br J Gen Pract 2011;61:e49–62. http://dx.doi.org/10.3399/bjgp11X549018
44. Ponikowski P, Voors AA, Anker SD et al. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur J Heart Fail 2016;18:891–975. https://doi.org/10.1002/ejhf.592
45. Rogers JG, Patel CB, Mentz RJ et al. Palliative care in heart failure: the PAL-HF randomized, controlled clinical trial. J Am Coll Cardiol 2017;70:331–41. https://doi.org/10.1016/j.jacc.2017.05.030
46. McDonagh TA, Metra M, Adamo M et al; ESC Scientific Document Group. 2023 Focused Update of the 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J 2023;44:3627–39. https://doi.org/10.1093/eurheartj/ehad195 [Erratum in: Eur Heart J 2023 Nov 23]
47. Harrison N, Cavers D, Campbell C, Murray SA. Are UK primary care teams formally identifying patients for palliative care before they die? Br J Gen Pract 2012;62:e344–e52. http://dx.doi.org/10.3399/bjgp12X641465
48. Sepúlveda C, Marlin A, Yoshida T, Ullrich A. Palliative care: the World Health Organization’s global perspective. J Pain Symptom Manage 2002;24:91–6. http://dx.doi.org/10.1016/S0885-3924(02)00440-2
49. Hogg KJ, Jenkins SMM. Prognostication or identification of palliative needs in advanced heart failure: where should the focus lie? Heart 2012;98:523–24. http://dx.doi.org/10.1136/heartjnl-2012-301753
50. Haga K, Murray S, Reid J et al. Identifying community-based chronic heart failure patients in the last year of life: a comparison of the Gold Standards Framework Prognostic Indicator Guide and the Seattle Heart Failure Model. Heart 2012;98:579–83. http://dx.doi.org/10.1136/heartjnl-2011-301021
51. Sze S, Pellicori P, Zhang J, Weston J, Clark AL. Identification of frailty in chronic heart failure. JACC Heart Fail 2019;7:291–302. https://doi.org/10.1016/j.jchf.2018.11.017 [Epub ahead of print]
52. Sze S, Pellicori P, Kazmi S et al. Prevalence and prognostic significance of malnutrition using 3 scoring systems among outpatients with heart failure: a comparison with body mass index. JACC Heart Fail 2018;6:476–86. https://doi.org/10.1016/j.jchf.2018.02.018 [Epub ahead of print]
53. Sze S, Pellicori P, Zhang J, Weston J, Squire IB, Clark AL. Effect of frailty on treatment, hospitalisation and death in patients with chronic heart failure. Clin Res Cardiol 2021;110:1249–58. https://doi.org/10.1007/s00392-020-01792-w [Epub ahead of print]
54. Sze S, Pellicori P, Zhang J, Clark AL. Malnutrition, congestion and mortality in ambulatory patients with heart failure. Heart 2019;105:297–306. https://doi.org/10.1136/heartjnl-2018-313312 [Epub ahead of print]
55. Sze S, Pellicori P, Zhang J, Weston J, Clark AL. The impact of malnutrition on short-term morbidity and mortality in ambulatory patients with heart failure. Am J Clin Nutr 2021;113:695–705. https://doi.org/10.1093/ajcn/nqaa311
56. French M, Keegan T, Anestis E, Preston N. Exploring socioeconomic inequities in access to palliative and end-of-life care in the UK: a narrative synthesis [published correction appears in BMC Palliat Care 2021 Dec 12;20:188]. BMC Palliat Care 2021;20:179. https://doi.org/10.1186/s12904-021-00878-0
57. Abel AAI, Samuel NA, Cuthbert JJ et al. Hospital admissions in the last year of life of patients with heart failure. Eur Heart J Qual Care Clin Outcomes 2023;10:168–75 https://doi.org/10.1093/ehjqcco/qcad047 [Online ahead of print]
58. General Medical Council. Treatment and care towards the end of life: good practice in decision-making. 2022. Available from: http://www.gmc-uk.org/guidance/ethical_guidance/end_of_life_care.asp (accessed 01 November 2023)
59. Auerbach S. Should patients have control over their own health care?: Empirical evidence and research issues. Ann Behav Med 2000;22:246–59. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4118537/
60. Kelner M. Activists and delegators: elderly patients’ preferences about control at the end of life. Soc Sci Med 1995;41:537–45. https://doi.org/10.1016/0277-9536(94)00381-3
61. Flynn KE, Smith MA, Vanness D. A typology of preferences for participation in healthcare decision making. Soc Sci Med 2006;63:1158–69. http://dx.doi.org/10.1016/j.socscimed.2006.03.030
62. Detering KM, Hancock AD, Reade MC, Silvester W. The impact of advance care planning on end of life care in elderly patients: randomised controlled trial. BMJ 2010;340:c1345. http://dx.doi.org/10.1136/bmj.c1345
63. Billingham MJ, Billingham SJ. Congruence between preferred and actual place of death according to the presence of malignant or non-malignant disease: a systematic review and meta-analysis. BMJ Support Palliat Care 2013;3:144–54. http://dx.doi.org/10.1136/bmjspcare-2012-000292
64. National End of Life Care Intelligence Network. Deaths from cardiovascular diseases: implications for end of life care in England. NHS National End of Life Care Programme 2013. Available from: http://www.endoflifecare-intelligence.org.uk/resources/publications/deaths_from_cardiovascular_diseases (accessed November 2023)
65. Beattie JM, Connolly MJ, Ellershaw JE. Deactivating implantable cardioverter defibrillators. Ann Intern Med 2005;143:690–1. https://dx.doi.org/10.3238/arztebl.2012.0535
66. Allen LA, Stevenson LW, Grady KL et al. Decision making in advanced heart failure. Circulation 2012;125:1928–52. http://dx.doi.org/10.1161/CIR.0b013e31824f2173
67. Solano JP, Gomes B, Higginson IJ. A comparison of symptom prevalence in far advanced cancer, AIDS, heart disease, chronic obstructive pulmonary disease and renal disease. J Pain Symptom Manage 2006;31:58–69. https://doi.org/10.1016/j.jpainsymman.2005.06.007
68. National Institute of Health and Care Excellence. Improving supportive and palliative care for adults with cancer [CSG4]. London: NICE, 2004. Available from: https://www.nice.org.uk/guidance/csg4 (accessed 30 January 2024)
69. Zacharias H, Raw J, Nunn A, Parsons S, Johnson M. Is there a role for subcutaneous furosemide in the community and hospice management of end-stage heart failure? Palliat Med 2011;25:658–63. https://doi.org/10.1177/0269216311399490
70. Gilotra NA, Princewill O, Marino B et al. Efficacy of intravenous furosemide versus a novel, pH-neutral furosemide formulation administered subcutaneously in outpatients with worsening heart failure. JACC Heart Fail 2018;6:65–70. https://doi.org/10.1016/j.jchf.2017.10.001 [Epub ahead of print]
71. Galbraith S, Fagan P, Perkins P, Lynch A, Booth S. Does the use of a handheld fan improve chronic dyspnea? A randomized, controlled, crossover trial. J Pain Symptom Manage 2010;39:831–8. http://dx.doi.org/10.1016/j.jpainsymman.2009.09.024
72. Oxberry S, Bland J, Clark A, Cleland J, Johnson M. Repeat dose opioids may be effective for breathlessness in chronic heart failure if given for long enough. J Palliat Med 2013;16:250–5. http://dx.doi.org/10.1089/jpm.2012.0270
73. Johnson MJ, Cockayne S, Currow DC et al. Oral modified-release morphine for breathlessness in chronic heart failure: a randomized placebo-controlled trial. ESC Heart Fail 2019;6:1149–60. https://doi.org/10.1002/ehf2.12498 [Epub ahead of print]
74. Simon ST, Higginson IJ, Booth S, Harding R, Bausewein C. Benzodiazepines for the relief of breathlessness in advanced malignant and non-malignant diseases in adults. Cochrane Db Syst Rev 2010;20:CD007354. http://dx.doi.org/10.1002/14651858.CD007354.pub2
75. Cranston Josephine M, Crockett A, Currow D. Oxygen therapy for dyspnoea in adults. Cochrane Db Syst Rev 2008;16:CD004769. http://dx.doi.org/10.1002/14651858.CD004769.pub2
76. Clark AL, Johnson M, Fairhurst C et al. Does home oxygen therapy (HOT) in addition to standard care reduce disease severity and improve symptoms in people with chronic heart failure? A randomised trial of home oxygen therapy for patients with chronic heart failure. Health Technol Assess 2015;19:1–120. https://dx.doi.org/10.3310/hta19750
77. Ong HL, Abdin E, Seow E et al. Prevalence and associative factors of orthostatic hypotension in older adults: results from the well-being of the Singapore elderly (WiSE) study. Arch Gerontol Geriatr 2017;72:146–52. https://doi.org/10.1016/j.archger.2017.06.004
78. Finucane C, O’Connell MD, Donoghue O, Richardson K, Savva GM, Kenny RA. Impaired orthostatic blood pressure recovery is associated with unexplained and injurious falls. J Am Geriatr Soc 2017;65:474–82. https://doi.org/10.1111/jgs.14563