Fig. 5.1
On the left panel, a continuous wave Doppler signal of a mitral regurgitation with a presystolic component can be observed that disappears with the pacemaker activation as shown on the right panel. On the other hand, the signal intensity is reduced after CRT activation, suggesting an improvement of the regurgitation severity
Improvement in papillary muscles dyssynchrony [4] together with an increase in the rate of LV pressure increase [5], which counteracts tethering forces and leads to more effective mitral valve closure with the consequent reduction of the MR orifice area, explains the immediate decrease of MR with CRT-activation [6, 7]. It has also been observed an acute beneficial change in MV geometry after CRT in patients who would be responders in the follow-up (defined by echocardiographic criteria as a reduction in end-systolic LV volume >15 %) [5]. This acute effect on the mitral valve is pacing dependent as the interruption of CRT causes an immediate recurrence of MR [4]. Another described acute effect of CRT is the correction of the atrioventricular delay in CRT that eliminates diastolic or pre-systolic MR, when present.
In the mid-long run, the reduction of MR induced by CRT can also extend in relation to a global (LV volumes) and local (mitral valve geometry) resynchronization-related reverse remodeling [7] (Fig. 5.2).
Fig. 5.2
Mitral regurgitation improvement after 6-month CRT. Reduction in the left ventricle volume can also be observed
Another factor that has to be considered in the response to CRT, including MR improvement, is the presence of myocardial viability. Traditionally, it has been accepted that patients with ischemic cardiomyopathy, large scar tissue and particularly with severe MR at baseline, present lesser LV reverse remodeling and clinical response at follow-up when treated with CRT [8]. Other studies show that ischemic patients do also respond to CRT but to a lesser extent [9]. This discrepancy between studies suggests that response to CRT is a multifactorial process and that the presence and location of myocardial viability is an important factor together with the presence of a mechanical abnormality that is amenable to be electrically corrected [10]. A direct relationship between the extent of myocardial contractile recruitment during a stress echo and the extent of LV remodeling has been shown. Also, the precise status of the myocardium at the site of the lead placement is important; in this sense some studies have shown that the coincidence of the site of the lead implantation on scar tissue is related to a poorer response to CRT [11].
Indications
According to current Guidelines [12], CRT is indicated in symptomatic HF patients in functional class II-IV despite receiving optimal medical treatment, severe left ventricle systolic dysfunction with a left ventricular ejection fraction (LVEF) ≤ 35 % and presenting with a wide QRS on the ECG (QRS width ≥ 120 ms) preferably with a LBBB pattern.
Use of CRT to treat functional MR without fulfilling the previous conditions is still not contemplated in the guidelines, although growing evidence exists about the benefits of CRT in reducing the severity of mitral regurgitation by at least one degree, and for this reason, the possibility to postpone surgical treatment in the CRT- responder patients. The pooled data from 5 major studies including more than 350 patients treated with biventricular pacing, followed up for more than 6 months, showed a decrease in the amount of MR by 30–40 % [13].
Identification of patients who will benefit with CRT treatment is still a matter of controversy, despite recent approaches based on understanding the mechanisms leading to cardiac dyssynchrony amenable to be electrically corrected have been proposed. Some studies [10, 14] have demonstrated that the presence of a correctable mechanical abnormality is almost mandatory to obtain a positive response with CRT. The presence of a septal flash (Fig. 5.3) is the mechanical abnormality that can be most easily corrected with CRT and most related to a clear response. Moreover, patients without any mechanical abnormality are largely non-responders. It is important to use an integral approach when assessing cardiac dyssynchrony, taking into account all kinds of possible subtypes of dyssynchrony, since all of them are potentially correctable with CRT and can lead to a substantial improvement in patient outcome. The presence of these mechanical abnormalities is an independent predictor of echocardiographic response and midterm cardiovascular mortality, along with creatinine level and LV diameters, which reflect severity and evolutive status of the disease. A correctable mechanical abnormality not only detects patients with a higher probability of reverse remodeling, but also has a real impact on survival. However, the extent of response will be variable depending on other baseline parameters such as myocardial substrate (viability), underlying disease (renal insufficiency), and clinical status [10].
Fig. 5.3
M-mode scan across the left ventricle depicting the typical motion of the septum in patients with intraventricular dyssynchrony that correspond to the septal flash. The septal flash (arrows) can be detected in M-mode imaging as an early rapid contraction and relaxation of the interventricular septum. The lateral wall contraction is delayed
Some authors have also tried to identify baseline characteristics that may point to the best candidates for CRT regarding MR reduction after CRT. In this sense a very severe MR with a baseline tenting area of >3.8 cm2 would identify patients in whom CRT would not be effective to reduce MR, suggesting that the more advanced LV remodeling and the more distorted LV geometry, the lower the probability of effective treatment for functional MR [7] (Fig. 5.4). The fact is that response to CRT is modulated by several factors and acute and long-term benefits depend not only on the presence of LV dyssynchrony but also on the extent of residual myocardial viability in ischemic patients and severity of MR.
Fig. 5.4
The changes of mitral geometry together with left ventricle remodeling explain the reduction of mitral regurgitation with CRT. A baseline tenting area of >3.8 cm2 would identify patients in whom CRT would not be effective to reduce MR
A less invasive percutaneous approach to treat MR in non-responder patients to CRT using the Mitraclip device has been recently proposed in order to avoid a high-risk surgery in this population of very fragile patients [15].
Results of Treatment
Large prospective studies have demonstrated the additional clinical benefit of CRT in HF patients medically treated with suboptimum response. CRT results in improvement in symptoms, quality of life and survival in patients with advanced heart failure and wide QRS [16, 17], especially if associated to a cardioverter – defibrillator [18, 19]. Echocardiographically, a progressive LV reverse remodelling (with even normalization of LV dimensions) is found with a reduction in LV volumes and dyssynchrony. Moreover, a significant reduction of MR severity of at least one degree is expected in around 30–40 % of the patients [4] independently of the etiology of the underlying cardiomyopathy [7]. These benefits, which are very congruent in all published studies, have helped to expand the indications of CRT, and nowadays, the tendency is to start CRT in less advanced stages of heart failure patients.
The influence of MR severity on CRT response is also conflicting. Some investigators have shown that patients with severe MR have less chance of a positive response to CRT [13, 20, 21]. Others, like from those participating in the CARE-HF study, which was a randomized trial including a large number of patients, conversely showed that patients who did not respond to CRT were likely to have less MR as compared to responders [22]. Nonetheless, the presence of severe MR at baseline is usually associated with lower response to CRT as it usually indicates a more advance stage of the disease (50 % clinical and 40 % echocardiographic response instead of 70 and 50 %) [7].
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