Multiple Interventional Procedures as an Alternative to Cardiac TransplantationOpen Access

Introduction

A 64-year-old patient with a medical history of hypertension presented with dyspnea to the emergency department of a secondary care hospital. The electrocardiogram showed left bundle branch block (LBBB) with significant ST-segment elevation in the anterior leads. The patient was transferred to our hospital (Caen University Hospital) for primary percutaneous coronary intervention (PCI). On admission, he presented with cardiogenic shock requiring dobutamine support. Echocardiography showed severe left ventricular (LV) systolic dysfunction (LV ejection fraction [LVEF], 35%) with extensive akinesis of the anterior wall. Coronary angiography showed proximal left anterior descending artery occlusion and stenosis of the proximal circumflex artery (Video 1).

Question 1: What would be the preferred PCI strategy for multivessel coronary artery disease in the setting of acute myocardial infarction complicated by cardiogenic shock?

Answer 1: The most recent guidelines (1) recommend primary PCI only of the culprit lesion in this setting (Class III, Level of Evidence: B) on the basis of the results of the CULPRIT-SHOCK trial (Culprit Lesion Only PCI Versus Multivessel PCI in Cardiogenic Shock) (2), showing that multivessel primary PCI is associated with an increased risk of the composite outcome of all-cause mortality or severe renal failure, both at 30 days and 1 year, when compared with culprit lesion–only primary PCI.

However, when our patient was admitted, guidelines recommended multivessel PCI in this setting, so the patient underwent multivessel primary PCI with drug-eluting stents implanted in the left anterior descending and circumflex arteries (Video 2).

The patient recovered and was discharged to a cardiac rehabilitation center. He was readmitted 2 weeks later for recurrent cardiogenic shock requiring inotropic support. Transthoracic echocardiography during dobutamine infusion showed severely decreased LV function (LVEF, 21%), moderate mitral regurgitation (MR), and significant low-gradient aortic stenosis (AS) with a mean gradient of 21 mm Hg and an aortic valve area of 0.81 cm². BSA at the time of diagnosis of severe AS was 2.17 (height 182 cm, weight 92 kg) and so AVA indexed 0.37 cm² (0.81/2.17).

Question 2: Which approach should be used for the echocardiographic diagnosis of AS with low cardiac output?

Answer 2: In cardiogenic shock with low cardiac output, the transvalvular aortic valve gradients are significantly reduced, explaining why the diagnosis was missed on the initial echocardiogram. In low-flow, low-gradient AS with reduced LVEF, low-dose dobutamine echocardiography is recommended to distinguish truly severe AS from pseudo-severe AS, defined by an increase of the aortic valve area >1.0 cm² with flow normalization. The presence of a flow reserve is associated with improved outcome. In the absence of flow reserve, a high calcium score determined by computed tomography favors significant AS (3).

Question 3: What is the best treatment for AS in patients with severe LV dysfunction?

Answer 3: Although patients without flow reserve have a higher operative mortality, both surgical aortic valve replacement (SAVR) and transcatheter aortic valve replacement (TAVR) have been shown to improve LVEF and clinical status. The ability to identify patients with severe AS in this subgroup by computed tomography calcium scoring and the availability of TAVR have lowered the threshold to intervene (3).

The choice for intervention must be based on careful individual evaluation of technical suitability and the risks and benefits of each option. SAVR is recommended in patients at low surgical risk. TAVR is recommended in patients at high surgical risk, as assessed by the heart team.

Because of high surgical risk (EuroSCORE II >17%), our patient was selected for TAVR. The procedure was successfully performed in July 2016 with a 26-mm Sapien 3 valve (Edwards Lifesciences, Irvine, California).

Question 4: What is the expected evolution of LVEF after TAVR?

Answer 4: It depends on its cause. In patients with low-flow, low-gradient AS and reduced LVEF whose depressed LVEF is predominantly caused by excessive afterload, LVEF usually improves after intervention. LVEF improvement is uncertain if the primary cause is myocardial infarction or cardiomyopathy.

In October 2016, 3 months after successful TAVR, the patient still had persistent dyspnea and LV dysfunction (LVEF, 34%) with moderate MR. The electrocardiogram showed sinus rhythm with LBBB (QRS complex duration, 130 ms) on medical therapy, including ramipril 10 mg, bisoprolol 5 mg, spironolactone 25 mg, furosemide 125 mg, and ivabradine 10 mg daily.

Question 5: How would you optimize the management of the patient?

Answer 5: In case of persistent symptoms of heart failure (HF) in patients with sinus rhythm, QRS complex duration of 130 to 149 ms, LBBB configuration, and LVEF ≤35%, cardiac resynchronization therapy with an implantable defibrillator (CRT-D) is recommended to improve symptoms and reduce mortality (4).

According to the PARADIGM trial (Angiotensin–Neprilysin Inhibition versus Enalapril in Heart Failure), a combination of sacubitril and valsartan is recommended as a replacement for angiotensin-converting enzyme inhibitor therapy to reduce the risk of HF hospitalization and death further in ambulatory patients with reduced LVEF who remain symptomatic despite optimal treatment with an angiotensin-converting enzyme inhibitor, a beta-blocker, and a mineralocorticoid receptor antagonist (4).

The patient underwent CRT-D implantation, and ramipril was replaced by the sacubitril-valsartan combination. In November 2016, he remained severely symptomatic (New York Heart Association functional class III dyspnea), with high B-type natriuretic peptide levels (1,400 pg/ml) and low peak oxygen consumption (14 ml/kg/min). Control echocardiography (Videos 3, 4, 5, and 6) showed severe secondary MR (regurgitant orifice area, 0.3 cm²) and low LVEF (34%) with moderate remodeling (LV end-diastolic volume, 75 ml/m²).

Question 6: At this time, should the patient be considered for cardiac transplantation?

Answer 6: Because of poor prognosis and the absence of clinical and echocardiographic improvement on optimized treatment, mechanical circulatory support as destination therapy or heart transplantation should be considered in these patients (5).

After evaluation by the heart team, the patient was considered a candidate for heart transplantation. However, because of his relative stability and the known shortage of donor hearts, his expected waiting time was long. A percutaneous intervention on the mitral valve to reduce MR was decided after evaluation of its suitability by transesophageal echocardiography. A successful MitraClip (Abbott, Lake Bluff, Illinois) procedure with 1 clip was performed in December 2016 (Figure 1). In June 2018, the patient had no symptoms, and B-type natriuretic peptide levels were decreased to 348 pg/ml. Echocardiography (Video 7) showed mild residual MR, a mean transmitral gradient of 4 mm Hg, and a significantly increased LVEF (48%).

Question 7: Could the favorable effect of the MitraClip have been predicted in this patient? In our case, what should have been the optimal timing for MR treatment?

Answer 7: MR may be overestimated in patients with severe AS. Treating the AS first and decreasing LV pressure can reduce MR (6). Pre-existing MR in patients presenting for TAVR has been related to greater need for hemodynamic support, longer hospital stays, and higher in-hospital and 6-month mortality (6). Therefore, treatment of MR after TAVR should be considered.

Because a decrease in MR severity after TAVR is possible, staging the 2 interventions starting with TAVR seems more reasonable. Recent reviews show that a staged approach, beginning with TAVR and followed by MitraClip placement, is the most common strategy (7).

Recent randomized studies (8,9) comparing medical treatment versus MitraClip use in secondary MR with HF and decreased LVEF showed conflicting results. Unlike the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation) trial showing a significant benefit in terms of mortality, the MITRA-FR (Multicentre Randomized Study of Percutaneous Mitral Valve Repair MitraClip Device in Patients With Severe Secondary Mitral Regurgitation) trial, which included patients with less severe MR and more severe remodeling, failed to show a benefit.

Our patient was an adequate candidate for MitraClip after TAVR because despite severe HF and low LVEF, he had relatively moderate ventricular remodeling with significant MR. His long-term outcome was satisfactory, and heart transplantation or ventricular assist device implantation was avoided.

This case demonstrates that staged interventional procedures may lead to stabilization and regression of HF with multiple underlying mechanisms. A multidisciplinary approach with the heart team is essential in the management of advanced complex HF.

Footnotes