Timing of Intervention in Asymptomatic Patients With Valvular Heart Disease

Helmut Baumgartner; Bernard Iung; Catherine M. Otto

Eur Heart J. 2020;41(45):4349-4356.

Abstract and Introduction

Abstract

Current management of valvular heart disease (VHD) seeks to optimize long-term outcome by timely intervention. Recommendations for treatment of patients with symptoms due to severe valvular disease are based on a foundation of solid evidence. However, when to intervene in asymptomatic patients remains controversial and decision requires careful individual weighing of the potential benefits against the risk of intervention and its long-term consequences. The primary rationale for earlier intervention is prevention of irreversible left ventricular (LV) myocardial changes that might result in later clinical symptoms and adverse cardiac events. A number of outcome predictors have been identified that facilitate decision-making. This review summarizes current recommendations and discusses recently published data that challenge them suggesting even earlier intervention. In adults with asymptomatic aortic stenosis (AS), emerging risk markers include very severe valve obstruction, elevated serum natriuretic peptide levels, and imaging evidence of myocardial fibrosis or increased extracellular myocardial volume. Currently, transcatheter aortic valve implantation (TAVI) is not recommended for treatment of asymptomatic severe AS although this may change in the future. In patients with aortic regurgitation (AR), the potential benefit of early intervention in preventing LV dilation and dysfunction must be balanced against the long-term risk of a prosthetic valve, a particular concern because severe AR often occurs in younger patients with a congenital bicuspid valve. In patients with mitral stenosis, the option of transcatheter mitral balloon valvotomy tilts the balance towards earlier intervention to prevent atrial fibrillation, embolic events, and pulmonary hypertension. When chronic severe mitral regurgitation is due to mitral valve prolapse, anatomic features consistent with a high likelihood of a successful and durable valve repair favour early intervention. The optimal timing of intervention in adults with VHD is a constantly changing threshold that depends not only on the severity of valve disease but also on the safety, efficacy, and long-term durability of our treatment options.

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Table 1. ESC/EACTS and AHA/ACC Guideline recommendations for intervention in asymptomatic patients with valvular heart disease
2014 and 2017 AHA/ACC Guidelines	2017 ESC/EACTS Guidelines
ASYMPTOMATIC SEVERE AORTIC STENOSIS
LV systolic dysfunction with LVEF ≤50 % (IB)	LV systolic dysfunction with LVEF <50% not due to another cause (IC)
Decreased exercise tolerance or exercise fall in blood pressure (IIaB)	Abnormal exercise test showing • symptoms clearly related to AS (IC) • fall in blood pressure below baseline (IIaC)
Low surgical risk and • very severe AS (V _max ≥ 5.0 m/s) (IIaB) or • rapid disease progression (≥0.3 m/s/year) (IIbC)	Low surgical risk and one of the following (IIaC) • very severe AS (V _max ≥ 5.5 m/s) • severe calcification and rate of V _max progression ≥ 0.3 m/s/year • markedly elevated BNP (>three-fold age- and sex-corrected range) • severe pulmonary hypertension (PA systolic pressure > 60 mmHg confirmed by invasive measurement) without other explanation
ASYMPTOMATIC CHRONIC SEVERE AORTIC REGURITATION
LV systolic dysfunction (LVEF < 50%) (IB)	LV systolic dysfunction (LVEF ≤ 50%) (IB)
Normal LV systolic function (LVEF ≥ 50%) but with severe LV dilation (LVESD > 50 mm) (IIaB)	Normal LV systolic function (LVEF > 50%) with severe LV dilatation: LVEDD > 70 mm or LVESD > 50 mm (or LVESDi > 25 mm/m² BSA in patients with small body size) (IIaC)
Normal LV systolic function (LVEF ≥ 50%) but with progressive severe LV dilation (LVEDD > 65 mm) if surgical risk is low (IIbC)
Bicuspid aortic valve: indications for surgery on the ascending aorta	Aortic root or tubular ascending aorta aneurysm ^a (irrespective of the severity of AR)
Diameter of the aortic sinuses or ascending aorta >50 mm and risk factor for dissection is present (family history of aortic dissection or if the rate of increase in diameter is ≥5 mm per year) (IIaC)	Patients with Marfan syndrome with maximal ascending aortic diameter ≥50 mm (IC)
Diameter of the aortic sinuses or ascending aorta >55 mm (IB)	Patients with aortic root disease and maximal ascending aortic diameter: (IIaC) • ≥45 mm in the presence of Marfan syndrome and additional risk factors,^b or patients with TGFBR1 or TGFBR2 mutation (including Loeys–Dietz syndrome)^c • ≥50 mm in the presence of a bicuspid valve with additional risk factors^b or coarctation • ≥55 mm for all other patients.
Patients with aortic valve surgery because of severe AS or AR if the diameter of the ascending aorta is >45 mm (IIaC)	Patients with primary indication for the aortic valve with maximal ascending aortic diameter ≥45 mm, particularly in the presence of a bicuspid valve.^d (IIaC)
ASYMPTOMATIC MITRAL STENOSIS
PMC for very severe mitral stenosis (mitral valve area ≤1.0 cm²) and favourable valve morphology in the absence of left atrial thrombus or moderate-to-severe mitral regurgitation (IIaC) PPMC for severe mitral stenosis (mitral valve area ≤1.5 cm²) and favourable valve morphology in the absence of left atrial thrombus or moderate-to-severe mitral regurgitation, with new onset of atrial fibrillation (IIbC)	Valve area ≤1.5 cm², without unfavourable clinical and anatomical characteristics for PMC^e and • high thromboembolic risk (history of systemic embolism, dense spontaneous contrast in the left atrium, new onset, or paroxysmal atrial fibrillation) (IIaC) and/or • high risk of haemodynamic decompensation (systolic pulmonary pressure > 50 mmHg at rest, need for major non-cardiac surgery, desire for pregnancy) (IIaC)
ASYMPTOMATIC CHRONIC SEVERE PRIMARY MITRAL REGURGITATION
LV systolic dysfunction (LVEF 30–60% and/or LVESD ≥ 40 mm) (IB)	LV systolic dysfunction (LVESD ≥ 45 mm or LVEF ≤ 60%) (IB)
Preserved LV function (LVEF >60% and LVESD <40 mm) and a high likelihood of a successful and durable repair with new onset of atrial fibrillation or PA systolic pressure at rest >50 mm Hg (IIaB)	Preserved LV function (LVEF >60% and LVESD <45 mm) and atrial fibrillation secondary to severe MR or PA systolic pressure at rest >50 mm Hg confirmed by invasive measurement (IIaB)
Preserved LV function (LVEF >60% and LVESD < 40 mm) if (all must be present): • likelihood of a successful durable repair is >95%, • expected surgical mortality is <1%, • valve repair if performed at a Heart Valve Center of Excellence (IIaB)	Normal LV function (LVEF > 60% and LVESD 40–44 mm) and all of the following: • a durable repair is likely, • surgical risk is low, • valve repair if performed at a Heart Valve Center, and • a flail mitral leaflet or severe LA dilation (volume >60 mL/m² in sinus rhythm) is present (IIaC)
Preserved LV function (LVEF > 60% and LVESD < 40 mm) with a progressive increase in LV size or decrease in EF on serial imaging studies (IIaC)

Adapted from Refs.^1–3
ACC, American College of Cardiology; AHA, American Heart Association; AR, aortic regurgitation; AS, aortic stenosis; AVR, aortic valve replacement; BSA, body surface area; EACTS, European Association for CardioThoracic Surgery; ECG, electrocardiogram; ESC, European Society of Cardiology; LA, left atrium; LV, left ventricle; LVEDD, left ventricular end-diastolic dimension; LVEF, left ventricular ejection fraction; LVESD, left ventricular end-systolic dimension; PA, pulmonary artery; PMC, percutaneous mitral commissurotomy; V _max, peak transvalvular velocity.
^aFor clinical decision-making, dimensions of the aorta should be confirmed by ECG-gated CT measurement.
^bFamily history of aortic dissection (or personal history of spontaneous vascular dissection), severe aortic regurgitation or mitral regurgitation, desire of pregnancy, systemic hypertension, and/or aortic size increase >3 mm/year (on repeated measurements using the same ECG-gated imaging technique, measured at the same level of the aorta with side-by-side comparison and confirmed by another technique).
^cIn females with low body surface area, presence of TGFBR2 mutation, or patients with severe extra-aortic features a lower threshold of 40 mm may be considered.
^dConsidering age, BSA, aetiology of valvular disease, presence of a bicuspid aortic valve, and intraoperative shape and thickness of the ascending aorta.
^eUnfavourable characteristics for percutaneous mitral commissurotomy can be defined by the presence of several of the following characteristics: (i) clinical characteristics: old age, history of commissurotomy, NYHA Class IV, permanent atrial fibrillation, and severe pulmonary hypertension. (ii) Anatomical characteristics: echo score >8, Cormier score 3 (calcification of mitral valve of any extent, as assessed by fluoroscopy), very small mitral valve area, and severe tricuspid regurgitation.