Heart failure module 6: surgical management

Released7 May 2020     Expires: 07 May 2022      Programme:

Sponsorship Statement: Vifor Pharma UK has provided an unrestricted educational grant to fund this activity and has not had any input into any aspect of this learning resource.

Introduction

Medical and device therapy has provided great benefit for many millions of patients with heart failure: treatment with angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), mineralocorticoid receptor antagonists (MRAs), beta blockers and sacubitril/valsartan is associated with a 63% reduction in all-cause mortality versus placebo.1 Although around 15% of patients with heart failure due to a reduced ejection fraction (HeFREF) recover their left ventricular function within three years with optimal medical treatment,2 the same proportion will progress to end-stage disease and surgical intervention is sometimes necessary.3

Surgical treatment for heart failure includes:

  • mechanical circulatory support
    • left ventricular 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 heart failure who require advanced therapy (such as LVAD or transplantation) is more difficult. As many as one quarter of patients with end-stage heart failure may have an unrecognised need for advanced therapies.4

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 waiting for a heart transplant per year as receive one.5

Left ventricular assist devices (LVAD)

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 left ventricular assist devices (LVADs) (figure 1).

Figure 1. HeartMate II® (Thoratec Corporation)
Figure 1. An example of a left ventricular assist device

Until recently, 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).6

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).7 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.

Heart failure module 6 - Figure 2. Contemporary indications for left ventricular assist device implantation
Figure 2. Contemporary indications for left ventricular assist device implantation

LVADs are used as DT more commonly than other indications worldwide (figure 2).7 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.

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

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.

Development (click here to find out more about LVAD design)

The first generation of these devices (e.g. HeartMate® I) were large, pulsatile displacement pumps. The haemodynamic benefits were offset by significant morbidity from extensive surgical dissection required for a large device, high rates of infection due to the high calibre driveline, and limited durability necessitating reoperation.

The second-generation pumps (e.g. HeartMate® II, Jarvik 2000) are smaller devices with impeller pumps that provide continuous flow compared to biphasic flow of first generation devices. In head-to-head trials with first-generation technology, the HeartMate® II device was associated with higher survival rates (figure 3) and lower complications rates, possibly due to the smaller size.8

Heart failure module 6 - Figure 3. Improved survival with second-generation technology
Figure 3. Improved survival with second-generation technology

Various third-generation devices are now in use or undergoing further evaluation. An example is the HeartWare® HVAD®, which has a miniaturised centrifugal pump that uses magnetic and hydrodynamic forces to levitate and rotate the impeller, theoretically avoiding wear on bearings. The smaller device size allows for quick and less invasive implantation athough the adverse event rate remains stubbornly high – see the ENDURANCE trial below.

Despite developments in design, the morbidity associated with LVAD therapy continues to impede progress in the field: 70% of patients with either continuous or pulsatile LVAD suffer a first episode of infection, bleeding, device malfunction, stroke or death within one year (figure 4).9

Heart failure module 6 - Figure 4. Graph showing time to first major event with 70% of patients suffering an adverse event during the first year following implant for mechanical circulatory support
Figure 4. Graph showing time to first major event with 70% of patients suffering an adverse event during the first year following implant for mechanical circulatory support

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 develop acquired von Willebrand factor deficiency. The tiny pulse pressure with continuous flow pumps is associated with gastrointestinal bleeding due to angiodysplasia. 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 to handle the volume returned to it by the assisted left ventricle (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 to the LVAD speed, or insertion of a right-sided 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 left ventricle, 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 insufficiency at 18 months, and the problem is difficult to treat. Options include open or transcatheter valve replacement, or cardiac transplantation.

High adverse event rates are inevitable in severely unwell and unstable patients such as those suitable for LVAD therapy. Trials of LVADs in patients with less severe disease have had mixed results.

REVIVE-IT (Randomised Evaluation of VAD Interventillation before Inotropic therapy), a randomised controlled trial of LVADs in patients who were less ill than patients currently eligible for destination therapy (New York Heart Association [NYHA] class II–IV with ‘advanced heart failure’ defined by markers such as hyponatraemia or high natriuretic peptide), was discontinued because of the high adverse event rate.10

In the ROADMAP (Risk Assessment and Comparative Effectiveness of Left Ventricular Assist Device and Medical Management in Ambulatory Heart Failure Patients) study, investigators enrolled 200 patients (average age 64 years, median brain natriuretic peptide [BNP] 547 pg/mL in the LVAD arm) who were eligible for LVAD therapy with a second-generation device (HeartMate II™). Treatment was assigned per patient wishes to either LVAD implantation or optimal medical therapy. The primary end point was survival on original therapy with >75 metre improvement in six-minute walk distance at one year. More patients in the LVAD group met the primary endpoint, with the difference increasing at two years’ follow up (30% vs. 12%; p=0.012).6,7 In an as-treated analysis, LVAD implantation was associated with a better one year survival (80% vs. 63%, p=0.02), but because 30% of patients in the OMT group had LVAD implantation over two years, there was no significant difference in intention-to-treat analysis.11,12 While the results are promising, it is essential to bear in mind that treatment with an LVAD in the ROADMAP study was not randomised: almost a third of patients in the ‘control’ arm changed their mind and opted for an LVAD during the two-year study period. The data are compromised as a result.

In the ENDURANCE (The HeartWare™ Ventricular Assist System as Destination Therapy of Advanced Heart Failure) trial, investigators enrolled 446 patients (average age 64 years, NYHA III–IV average left ventricular ejection fraction [LVEF] 17%) all of whom were eligible for LVAD therapy but ineligible for heart transplantation (i.e. the LVAD was a destination therapy or bridge to candidacy – common indications for implantation in America but not in the UK).13 Patients were randomised to either the commonly used HeartMate II™ device with an axial rotating pump implanted in the abdominal cavity or the newer HeartWare HVAD™ with a smaller, magnetically levitated pump implanted in the pericardium. The absence of bearings in the magnetically levitated pump was hypothesised to reduce the risk of device failure, thrombus formation and stroke.

The primary end point was a composite of survival free from disabling stroke, urgent transplantation or device explant or replacement due to complications two years after implantation. The primary end point was similar between the two devices suggesting non-inferiority of the HeartWare HVAD™compared to the HeartMate II™device. However, adverse event rates were high in both arms: while patients with the HeartMate II™ device were more likely to require device replacement, explantation or urgent transplantation (16% vs. 9%, p=0.03), they were less likely to have a stroke (12% vs. 30%, p<0.001), right heart failure (27% vs. 39%, p=0.02) or sepsis (15% vs. 24%, p=0.05) compared to the HeartWare HVAD™.13

In the very similar MOMENTUM 3 (Multi-centre Study of MagLev Technology in Patients Undergoing MCS Therapy With HeartMate 3) trial, investigators enrolled 294 patients with end-stage heart failure who were randomised to either the HeartMate II™ device or the HeartMate III™ device (similar to the HeartWare HVAD™ device with a magnetically levitated centrifugal pump that is implanted in the pericardial space).14 More patients in the HeartMate III™ arm met the primary end point of survival free of disabling stroke or device explant or replacement due to complications six months after implantation (86% vs. 77%, p<0.001), suggesting non-inferiority (p<0.001). Although the study was not powered to detect superiority, the HeartMate III™ did appear to be the better device (p=0.04). Adverse event rates were again high but similar in the groups.

A retrospective cohort analysis comparing outcomes amongst patients in the UK implanted with the HeartMate II™device or the HeartWare HVAD™ device found no significant difference in outcome or adverse event rates between the devices.15

In the UK, data on LVAD implantation is collected by the NHS Organ Donation and Transplant Service, which releases annual activity reports: in 2018–19, there were 161 LVAD implantations for long-term bridging (n=102 – the majority of whom were stable but requiring inotropic support), short-term bridging (n=50 – the majority of whom were in cardiogenic shock) and primary graft dysfunction after heart transplantation (n=9). While outcome has improved (three-year survival post-implant in 2018–19 was 58% vs. 47% in 2016–17), it remains poor:16 more patients die on support (35%) than are transplanted (18%) or have the device explanted due to recovery (10%).

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 heart failure (or when there is serious co-morbidity) and thus outcome is poor and the only viable long-term treatment – transplantation – is often contraindicated. Thus 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 heart failure despite its inherent risks and complications (figure 5).17

Figure 5. Long-term survival for adult recipients after cardiac transplantation
Figure 5. Long-term survival for adult recipients after cardiac transplantation

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 (figure 6).17

The size of the UK heart transplant waiting list has grown by 132% since 2010. In the UK in 2018–19, there were 608 patients on the heart transplant waiting list; of the 1,600 organ donors, 186 hearts were donated of which 180 were used. Between 2015 and 2018 amongst patients on the non-urgent transplant list, 19% had been transplanted within two years of listing, whilst 29% were still waiting, 29% had progressed to the urgent list and 11% had died while waiting.18

Heart failure module 6 - Figure 6. Number of heart transplants to all recipient ages, categorised by year (1982−2011) and geographical region
Figure 6. Number of heart transplants to all recipient ages, categorised by year (1982−2011) and geographical region

Patient selection

Good cardiac transplant candidates have advanced and severely symptomatic heart failure but do not have end-organ complications or co-morbidities associated with high peri-operative risk or which adversely affect long-term outcome. The aim is to identify those patients with a sufficiently poor prognosis to justify the increased early mortality risk with better long-term survival the reward. In-patient referral may be considered for patients admitted with acute heart failure with intractable inotrope dependence or cardiogenic shock.

Clinical features that should prompt consideration for transplant are:19

  • >2 admissions with acute heart failure in last 12 months
  • persistent signs and symptoms of heart failure despite maximal therapy
  • evidence of right ventricular dysfunction or increasing pulmonary arterial pressure
    • aim to refer before pulmonary artery pressure is >50 mmHg
  • end-organ damage that is attributable to heart failure and may be correctable with transplant
    • weight loss
    • liver dysfunction
    • anaemia
    • hyponatraemia
    • renal dysfunction preventing increasing dose of diuretics sufficient to treat congestion
    • aim to refer before estimated glomerular filtration rate <40 ml/min/1.73m2

The criteria for heart transplantation are:20

  • left ventricular systolic dysfunction not due to a correctable cause such as valve disease or coronary artery disease
  • NYHA class III or IV
  • optimal medical and device therapy (if indicated)
  • evidence of a poor prognosis
  • reduced peak oxygen consumption on cardiopulmonary exercise testing
  • significantly raised natriuretic peptides
  • high risk on established prognostic scoring systems such as heart failure survival score (HFSS).

Criteria for urgent in-patient referral are:20

  • persistent cardiogenic shock due to primary cardiovascular cause
  • continuous intravenous inotropic support
  • mechanical circulatory support
  • ongoing coronary ischaemia with no revascularisation treatment options
  • no contraindication to transplantation.

Contraindications for heart transplantation are:20

  • primary end-organ damage i.e. not secondary to advanced heart failure
    • renal dysfunction
    • liver dysfunction
  • pulmonary hypertension
    • pulmonary vascular resistance >5 Wood units
    • transpulmonary gradient >15 mmHg
    • pulmonary arterial systolic pressure (PASP) >60 mmHg
  • active infection or sepsis
  • recent pulmonary embolism
  • microvascular complications of diabetes other than non-proliferative retinopathy
  • obesity*
    • body mass index >32 kg/m2
  • active malignancy other than localised non-melanoma skin cancer*
  • symptomatic peripheral or cerebrovascular disease*
  • auto-immune disease*
  • infiltrative cardiac disease*
    • sarcoidosis
    • amyloidosis
  • severe skeletal myopathy with associated cardiomyopathy*
  • smoking*
  • excessive alcohol use*
  • history of non-compliance / non-adherence to treatments*

* = relative contraindications.

Patients who undergo transplantation require life-long follow up, monitoring and treatment: a stable home life with adequate social support and psychological evaluation are also important aspects of patient selection.19

Transplant assessment is summarised in table 1.19,20

Table 1. Summary of transplant assessment
Table 1. Summary of transplant assessment

Donor organ selection and peri-operative management

Figure 7. HeartMate II® (Thoratec Corporation)
Figure 7. Key aspects of donor organ selection for cardiac transplantation

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 7). 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.

The surgical transplant operation has evolved over time;21

  1. the bi-atrial technique: this left some recipient right atrium in situ and required long, sometimes fallible atrial anastomoses (figure 8a).
  2. the total orthotopic technique: this involved separate anastomoses for each pulmonary vein and the great vessels (not pictured)
  3. the bicaval technique. Here the insertion of the recipient’s pulmonary veins into the left atrium remains in situ, with the donor left atrium anastamosed to this remnant and the donor right atrium anastamosed to the great veins (figure 8b).
Heart failure learning module 6 - Figure 8. Evolving surgical technique, with the donor organ in red, recipient structures in blue, and surgical instruments in grey. Panel A shows the biatrial technique where the recipient right atrium remains in situ necessitating a long atrial anastamosis but retaining more normal haemodynamics with native structures. Panel B shows the bicaval technique, where the recipient right atrium is removed and great veins anastamosed to the donor atrium
Figure 8. Evolving surgical technique, with the donor organ in red, recipient structures in blue, and surgical instruments in grey. Panel A shows the biatrial technique where the recipient right atrium remains in situ necessitating a long atrial anastamosis but retaining more normal haemodynamics with native structures. Panel B shows the bicaval technique, where the recipient right atrium is removed and great veins anastamosed to the donor atrium

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

Table 2. Perioperative problems to anticipate following cardiac transplantation
Table 2. Problems to anticipate following cardiac transplantation

Long-term management

Cardiac transplant dramatically improves survival and quality of life in the right patient. One-year survival is 81%. For those who survive the first year, five-year survival is 85%.

However, morbidity rates are high. 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 calcineurin inhibitors, tacrolimus and ciclosporin, form the mainstay of therapy and are most often used with corticosteroids and a cell-cycle agent, such as mycophenolate for long-term maintenance.

Induction immunosuppression given pre-operatively is sometimes included. The drugs all target T cells, which drive cellular rejection. They have many side effects, many of which being dose-dependent make monitoring of drug levels mandatory.

Key factors to consider in long-term follow-up are:

  • Anticipation and early treatment of allograft rejection: frequent studies of left ventricular dimensions and wall thickness by echocardiography, accompanied usually by endomyocardial biopsy for histological assessment are required early after the transplant. If rejection is identified, treatment depends on the underlying mechanism.
    • cellular rejection (most common) responds to high dose corticosteroids
    • antibody-mediated rejection (e.g. due to pre-existing or de novo human leukocyte antigen (HLA) sensitisation) can require inhibition of B cells and antibody removal, for example by plasmapheresis.
  • Monitoring for evidence of chronic allograft dysfunction; usually ‘cardiac allograft vasculopathy’ (CAV) which 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 heart failure, or as sudden death.22 CAV is often diffuse and therefore not amenable to revascularisation. Careful symptomatic (anti-anginals) and preventative (statin) medical therapy is a priority; most patients are started on low-dose atorvastatin (10 mg once daily) due to lower incidence of myositis compared with other statins.
  • Stringent monitoring of drug levels and renal function is essential to prevent nephropathy. Kidney disease can be exacerbated by other factors such as pre- or peri-transplant renal injury, coexistent diabetes and hypertension.
  • Careful management of hypertension and hyperlipidaemia, both common pre-morbid diagnoses that can be caused or exacerbated by immunosuppressive drugs. Cardiac denervation may also contribute to hypertension. Together, these can increase the risk of CAV.
  • Prompt treatment of infection, due to ongoing susceptibility with immunosuppression, and the possibility of superadded bone marrow suppression due to the drugs.
  • Monitoring for immunosuppression-associated malignancy, particularly non-melanoma skin tumours and B-lymphomas.

The Organ Donation (Deemed Consent) Act 2019 will became law in March 2020 in England, Wales and Northern Ireland meaning that all adults are presumed to have given consent for organ donation unless there is a documented decision otherwise. The act may increase the availability of organs for heart transplantation.

Revascularisation and ventricular restoration

Revascularisation

Inadequate myocardial perfusion can cause impaired contractility; this can be either fixed (infarction) or reversible (hibernation). Differentiating hibernating myocardium from infarcted tissue can be done with dobutamine stress echocardiography or thallium scintigraphy. Coronary revascularisation in heart failure aims to improve myocardial function by restoring perfusion to hibernating myocardium, so reducing left ventricular volumes and improving left ventricular function (figures 9a and 9b).

Figure 9a. Echocardiogram before coronary artery bypass grafting in the setting of hibernating myocardium (Click arrow below to play, or bottom-right for full screen)

Figure 9b. Echocardiogram after coronary artery bypass grafting in the setting of hibernating myocardium. On the postoperative scan, the left ventricular volumes have reduced and there is improved left ventricular function (Click arrow below to play, or bottom-right for full screen)

Until publication of the STICH (Surgical Treatment for Ischaemic Heart Failure) trial results in 2011, the practice of revascularising hibernating myocardium was common but based on largely anecdotal evidence.

The STICH trial (n=1,212, median age 59 years, NYHA I–IV, median left ventricular ejection fraction [LVEF] 27% in the treatment arm) was designed to test whether revascularisation improved outcomes in patients with heart failure and underlying coronary disease without angina severe enough to warrant revascularisation on its own merits. There was no significant difference in all-cause mortality between patients treated by revascularisation with coronary artery bypass grafting (CABG) plus optimal medical therapy (OMT) and those treated with OMT alone (figure 10).23 There was no requirement for patients to undergo functional testing before entering the trial thus investigators were unable to differentiate between hibernating or infarcted myocardium.

Heart failure module 6 - Figure 10. Primary outcome from the STICH trial, showing no significant difference in all-cause mortality between those patients treated with coronary artery bypass grafting and those treated with optimal medical therapy
Figure 10. Primary outcome from the STICH trial, showing no significant difference in all-cause mortality between those patients treated with coronary artery bypass grafting and those treated with optimal medical therapy

The HEART (Heart Failure Revascularisation Trial) study (n=138, average age 65 years, two-thirds of whom were NYHA I–II, median wall motion index 0.8 [equivalent to LVEF of 24%]) was a randomised trial of OMT vs. OMT plus angiography with the intent to revascularise either via percutaneous coronary intervention (PCI) or CABG. Unlike STICH, all eligible patients underwent perfusion testing and the presence of myocardial viability was an inclusion criterion. However, like STICH, there was no difference in mortality between the OMT group and the revascularisation group. The study was closed early due to slow recruitment, sponsor withdrawal and the start of the STICH study – the results are underpowered as a result.24

The results were controversial, at least in part because many investigators and researchers thought that they ‘knew’ the result already: the anecdote in clinical medicine is very powerful. Many excuses were advanced for the neutral result:

  • the majority of patients complained of angina rather than dyspnoea
  • myocardial viability testing, while central to the studied hypothesis, was not an inclusion criterion for STICH
  • on later core lab analysis, many patients were found to have LVEF <35%
  • patients with left main stem disease are prime candidates for revascularisation but were excluded.

There matters rested until the STICH extension (STICHES) was published in 2016.25 The original patient cohort from STICH was followed for almost 10 years, and at that point, there was a small, but definite, survival advantage for the surgically treated group. It is important to note that the patients in STICH had a mean age just short of 60 years and that it took a very long time for the survival advantage to appear. There is thus a reasonable argument that selected younger patients with heart failure (in whom angina is not a prominent symptom) should be offered coronary angiography with a view to surgical revascularisation.

A recent meta-analysis suggested that revascularisation (either with CABG or PCI) in patients with coronary artery disease and an LVEF <40% was associated with reduced mortality risk compared to medical therapy alone.26 However, of the 21 studies included, only three were randomised controlled trials, and these trials involved fewer than 2,000 patients. STICH and STICHES remain the only reliable randomised data on which decisions regarding revascularisation in patients with heart failure can be made.

The REVIVED-BCIS2 (Efficacy and Safety of Percutaneous Coronary Intervention to Improve Survival in Heart Failure) study is currently recruiting patients for a randomised controlled trial of PCI plus OMT vs. OMT alone in patients with HeFREF. The presence of myocardial viability is an inclusion criterion and the primary outcome is a composite of all-cause mortality or heart failure hospitalisation (NCT01920048).27 Recruitment is nearly complete.

Surgical ventricular restoration

Surgical ventricular restoration (SVR) involves exclusion of scar on the ventricular wall from previous myocardial infarction.

The aims of SVR are to:

  • normalise ventricular geometry
  • improve myocardial perfusion
  • reduce left ventricular work
  • improve left ventricular 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 11a–d). It is usually done during CABG for patients with ischaemic cardiomyopathy and anterior wall akinesia or severe dyskinesia. It adds about 20 minutes to the procedure time without increasing operative risk.

Figure 11b. Surgical ventricular restoration by the Dor procedure. An interventricular stitch is placed to create a neoventricle
Figure 11b. Surgical ventricular restoration by the Dor procedure. An interventricular stitch is placed to create a neoventricle
Figure 11a. Surgical ventricular restoration by the Dor procedure. First the area of scar is identified and partially excised
Figure 11a. Surgical ventricular restoration by the Dor procedure. First the area of scar is identified and partially excised
Figure 11d. Surgical ventricular restoration by the Dor procedure. Finally the remaining scar is used to cover the patch or excised, and the defect is closed
Figure 11d. Surgical ventricular restoration by the Dor procedure. Finally the remaining scar is used to cover the patch or excised, and the defect is closed
Figure 11c. Surgical ventricular restoration by the Dor procedure. A Dacron patch is placed to create a neoventricle
Figure 11c. Surgical ventricular restoration by the Dor procedure. A Dacron patch is placed to create a neoventricle

In non-randomised studies, SVR improves LVEF and other haemodynamic variables. However, hypothesis 2 of the STICH trial compared outcomes of patients randomised to CABG plus SVR to CABG alone and found no significant difference in the composite endpoint of all-cause mortality or cardiovascular hospitalisation.

Percutaneous ventricular restoration has also been investigated: the Parachute device, a percutaneously delivered device that partitions the left ventricle as a means of ventricular restoration, appears safe and feasible in patients with heart failure and left ventricular dilatation.28 However, a phase III trial was terminated in June 2017.29

There may yet be sub-groups who do benefit from surgical or percutaneous ventricular restoration and, similar to the story with revascularisation, this book is not yet closed.

Valve surgery

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

In these cases, transcatheter aortic valve implant (TAVI) should be considered as being a lower risk alternative. 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.

A more difficult problem is that of mitral valve surgery. Functional mitral regurgitation is very common in heart failure as a consequence of valve ring dilation together with tethering of the posterior leaflet of the valve. There are no adequately powered randomised trials of surgical mitral intervention, but registry studies all suggest that a surgical approach is associated with a neutral (or worse) outcome. There are two randomised controlled trials of the Mitraclip® device in patients with HeFREF and mitral regurgitation with conflicting results.

In the COAPT (Transcatheter Mitral-Valve Repair in Patients with Heart Failure) study, investigators enrolled 614 patients with LVEF <50% and moderate-severe or severe functional mitral regurgitation (average age 72 years, ~90% NYHA II–III, average NTproBNP 5,174 ng/L, average LVEF 31%, 51% severe mitral regurgitation) who were randomised to either transcatheter mitral valve repair with the Mitraclip® device or OMT. The primary end point was heart failure hospitalisations with 24 months follow up. Of the 302 patients in the treatment group, 287 successfully underwent device implantation. Treatment with the device was associated with a reduced risk of hospitalisation with heart failure (36% per patient-year vs. 68%, p<0.001) and reduced mortality (a non-powered secondary end point; 18% vs. 22%, p<0.001) compared to medical treatment alone.30

In the MITRA-FR (Percutaneous Repair or Medical Treatment for Secondary Mitral Regurgitation) study, investigators enrolled 304 patients with LVEF <40% and severe functional mitral regurgitation (average age 70 years, 91% NYHA II–III, median NTproBNP 3407 ng/L, average LVEF 33%) who were randomised to mitral valve repair with the Mitraclip® device or OMT. The primary outcome was all-cause mortality or hospitalisation with heart failure. Of the 152 patients in the treatment group, 138 had the device successfully implanted. There was no difference in the primary end point between the groups after 12 months (55% vs. 51%, p=0.51).31

It is not clear why two very similar trials have yielded two very different results. One explanation may be that medical supervision of the control group was far more strict and the number and changes in medication were greater in the MITRA-FR trial than the COAPT study. For example, despite the high number of hospitalisations with heart failure in the COAPT study, there were no significant changes in heart failure medications (including diuretics) during the study period: it may be that mitral valve repair in patients with HeFREF is beneficial only when compared to inadequate medical management. Another favoured explanation is that the patients in COAPT had smaller left ventricular volumes for a given severity of mitral regurgitation, implying that they had mitral regurgitation out of proportion to their left ventricular impairment. They were therefore more likely to respond to mitral intervention.32

Quite 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 heart failure, appropriate and timely patient selection will be key to effective use.

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References

  1. Burnett H, Earley A, Voors AA, et al. Thirty years of evidence on the efficacy of drug treatments for chronic heart failure with reduced ejection fraction: a network meta-analysis. Circ Heart Fail 2017;10:e003529. https://doi.org/10.1161/CIRCHEARTFAILURE.116.003529
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