What is the Best Therapeutic Strategy in Patients with Low Flow, Low-Gradient Aortic Stenosis, and Wide QRS?

This editorial refers to ‘Prevalence and clinical impact of QRS duration in patients with low-flow/low-gradient aortic stenosis due to left ventricular systolic dysfunction,’ by F.A. Sebag et al., published in this issue on pages 639–647, and ‘Usefulness and limitations of contractile reserve evaluation in patients with low-flow, low-gradient aortic stenosis eligible for cardiac resynchronization therapy,’ by F. Garnier et al., published in this issue on pages 648–654. Aortic valve stenosis has reached endemic proportions in Western countries. Although population-based studies are scarce, its prevalence is estimated to be 2–5% in people older than 65 years.1 Severe aortic stenosis carries a dismal prognosis when associated with congestive heart failure, with an expected survival of less than 2 years when treated medically.2 The Euro Heart Survey showed an overall surgical mortality of 2.7% for standalone aortic valve replacement (AVR) and 4.3% for combined replacement and coronary revascularisation. Notably, 19% of patients operated on for aortic valve stenosis in Europe show some degree of left ventricular (LV) systolic dysfunction at the time of surgery and LV ejection fraction is lower than 0.30 in 2.9% of patients who undergo surgery.3 Particularly challenging is the population showing a small valve area (<1 cm2), impaired systolic function and a low mean pressure gradient (<40 mmHg). Although these patients represent <5% of patients with aortic stenosis, they represent the most controversial subset.4 Left ventricular dysfunction may be secondary to long-standing severe aortic stenosis with superimposed myocardial fibrosis, extensive coronary artery disease, previous myocardial infarction or LV dyssynchrony. Dobutamine stress echocardiography is useful for stratification of operative risk in the setting of low-flow/low-gradient aortic stenosis (LF/LGAS). Patients who do not experience a 20% increase in stroke volume on dobutamine stress echocardiography are considered to have LF/LGAS without contractile reserve. According to multicentre studies, patients with LV contractile reserve have a relatively low operative risk (5%), whereas patients without contractile reserve have a high operative mortality (22–32%).5, 6 Data show that LF/LGAS without contractile reserve on dobutamine stress echocardiography has a catastrophic long-term outcome when treated medically, with a 5-year mortality as high as 87%.6 Therefore, despite a high operative mortality risk, surgery should not be contraindicated for LF/LGAS patients solely on the basis of the absence of contractile reserve on dobutamine stress echocardiography. These patients present an unacceptably high mortality on medical management and have an acceptable long-term outcome after AVR with significant functional and LV ejection fraction improvement.7 Prolonged QRS duration is perceived as a marker of cardiac dyssynchrony. It is found that LV mechanical dyssynchrony is present at rest or during stress testing in 30–50% of patients with LV systolic dysfunction and can result in inefficient contraction and reduced ventricular performance.8 In this issue of the journal, Monin et al. evaluated the prevalence and clinical impact of QRS duration in patients with LF/LGAS and LV systolic dysfunction. Among 88 consecutive patients included retrospectively, 56% (n = 49) had QRS duration ≥130 ms.9 Thirty-two per cent (n = 28) of patients met the criterion for left bundle branch block (LBBB) and 24% (n = 21) met the criterion for right bundle branch block (RBBB). Notably, the prevalence of LBBB in their study was similar to that observed in other large series with similar patients. Haghjoo et al.10 reported that significant rest intraventricular dyssynchrony can be found in >2/3 of patients with LBBB, as opposed to >1/3 of patients with RBBB. On that basis, we can assume that approximately ≥60% of patients with wide QRS in Monin et al.'s study probably had significant intraventricular dyssynchrony (1/3 of all patients included). As the duration of QRS did not change in the subgroup of patients who had AVR, it is likely that intraventricular dyssynchrony was not reduced after surgery. Notably, broader QRS tend to be more frequent in the subgroup of patients without contractile reserve (47%) compared with patients with contractile reserve (18%). The effect of pharmacological stress testing on intraventricular cardiac dyssynchrony has rarely been studied. However, most authors agree that in patients with wide QRS, the prevalence and severity of dyssynchrony increases with dobutamine perfusion.11-13 In previous studies, it is therefore plausible that LV dyssynchrony could have contributed to the lack of contractile reserve evaluated by dobutamine stress echocardiography.14 In this issue of the journal, Eicher et al. demonstrated, in a population mainly constituted of patients with large QRS (13 patients with LBBB and 8 patients with permanent right ventricular pacing) and LF/LGAS, that contractile reserve was present in only 47% of the patients. They proposed to their patients a sequential therapeutic strategy based on cardiac resynchronization therapy (CRT) implantation followed by AVR with conventional surgery or Transcatheter Aortic Valve Implantation (TAVI) to the subgroup of patients with dyssynchrony, independently of the presence or absence of contractile reserve. Finally, 19 patients underwent CRT implantation and eventually 14 patients had subsequent AVR 4–8 months after CRT implantation. Only one patient died, yielding an operative mortality of 7%, which is much lower than anticipated. This finding suggests the presence of global LV viability in those patients that could not be demonstrated by dobutamine infusion, because of inotropically exacerbated dyssynchrony. Lancellotti et al.12 were the first to describe the dynamic characteristics of LV dyssynchrony during exercise in the absence of ischemia. Exercise increased LV dyssynchrony in 46% of patients with congestive heart failure. Lafitte et al.13 also described the changes in LV dyssynchrony from rest to exercise in heart failure patients in an exercise-echocardiography study. Three distinct groups were described: patients with no difference between rest and exercise; patients without dyssynchrony at rest but induced by exercise; and finally, a third group of patients with dyssynchrony at rest that normalized on exercise. Both local and global myocardial viability appear to be important factors modulating the response to CRT. The importance of viability has been evaluated in several studies using different non-invasive imaging techniques. Indeed, we have evaluated the importance of local viability in the left pacing lead implantation area for the prediction of acute response to CRT using dobutamine stress echocardiography. Acute responders to CRT were defined as having a ≥15% increase in LV stroke volume 24 hours following device placement, which was observed in 55% of the patients.15 We also studied the impact of local viability in the left pacing lead implantation area on the predicted response to CRT using dobutamine stress echocardiography. A positive response to CRT was characterized by reverse LV remodelling 6 months after CRT implantation (≥15% LV end-systolic volume reduction). Positive remodelling was present mostly (>80%) in patients with local viability.16 Briefly, in patients with wide QRS characterized by LBBB, acute increase of stroke volume and positive remodelling can be expected in most patients with viability in the left posterolateral wall as evaluated by dobutamine stress echocardiography.15, 16 Even if the number of patients studied is limited, preoperative CRT should be highly considered in patients with LBBB having no contractile reserve, because the expected mortality is so high in such patients with LF/LGAS. This recommendation is further supported by the proven benefits of CRT in many other settings. In presence of particularly precarious situation [low-output, New York Heart Association (NYHA) class IV], CRT implantation should be considered before AVR. However, if prior to AVR the clinician does not contemplate pre-CRT implantation, operative implantation of definitive epicardial LV lead should be considered. In the absence of an early increase of LV ejection fraction after AVR or in the presence of postoperative clinical deterioration in patients with LBBB, CRT implantation should be considered using epicardial lead. In the study by Eicher et al. (this issue), waiting 4–8 months after CRT implantation was not associated with a prohibitive mortality (7%). However, sooner AVR may be indicated depending on the clinical status. In almost all studies of patients with LF/LGAS, those with functional moderate to severe mitral regurgitation were excluded. As functional mitral regurgitation can have multiple aetiologies (asynchrony and alteration of mitral geometry), mitral regurgitation reduction can be anticipated in these patients after CRT implantation.15, 16 Thus CRT implantation should be an option in that population. In summary, Monin et al. (this issue) observed that wide QRS is prevalent in patients with LF/LGAS and Eicher et al. (this issue) demonstrated that CRT implantation before AVR might favourably influence perioperative mortality in patients with LBBB. Clearly, there is a need for a registry regarding patients with LF/LGAS with and without contractile reserve and wide QRS (LBBB and RBBB). Whether CRT therapy should be considered before AVR in all patients with wide QRS in the presence or absence of contractile reserve remains to be determined. Until then, your clinical judgment is still the best approach! Conflict of interest: none declared.

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