Changes in speckle-tracking-derived mechanical dispersion index are associated with 30-day readmissions in acute heart failure

Once a diagnosis of acute heart failure (AHF) has been established, conventional 2D and Doppler echocardiography techniques provide limited relevant information to guide treatment decisions at the point-of-care (POC) [1]. Left ventricular ejection fraction (LVEF) is the most extensively investigated echocardiographic parameter, but it does not appreciably change during the acute treatment phase of AHF [2] and it provides limited actionable information when it comes to the selection of specific therapies that may be most suitable for a given patient with AHF [3, 4].

LV strain utilizing speckle-tracking technology is a relatively new quantitative method for evaluating LV systolic function, and while it has been well studied in chronic HF [5‐9], to date, there has been only one published report prospectively investigating its use, pre-treatment, in AHF [10]. Although there are numerous ways to measure LV strain utilizing speckle-tracking, global longitudinal peak systolic strain (GLS) is the most well studied [11]. GLS represents a summative measure of the degree of longitudinal shortening of each of the segments of the LV (typically 16–18 depending on the vendor and software being utilized) that are analyzed. GLS has been found to be associated with AHF readmission, independent of and incremental to clinical and basic echocardiographic parameters [12].

LV mechanical dispersion index (MDI) is the standard deviation (SD) of the time-to-peak longitudinal strain in each of the segments of the LV that are analyzed [13] and provides unique insight into mechanical dyssynchrony. While LV MDI has previously been shown to be a predictor of ventricular arrhythmias post-myocardial infarction, a predictor of adverse events following cardiac resynchronization therapy (CRT), and a discriminator of hypertrophic cardiomyopathy versus athlete’s heart [13‐15], it has yet to be considered as a potential measure of treatment effectiveness in AHF. A recent investigation by Chan et al. [16] found LV MDI to be an independent predictor of outcome in AHF patients after adjustment for baseline variables. The objective of the present study was to evaluate the relationship between the speckle-tracking-derived parameters LV MDI and GLS obtained pre- and 23-h post-treatment, and 30-day post-discharge outcomes (death and readmission to the hospital) in patients with AHF.

We present preliminary but highly promising data regarding the potential role of strain-based echocardiographic parameters in determining response to treatment and association with 30-day readmissions for patients hospitalized with AHF. To our knowledge, this is the first study of its kind prospectively evaluating MDI as a treatment response variable in AHF.

Our results are unique and informative, as they provide the first report of speckle-tracking-derived MDI data obtained from pre-treatment POC echocardiograms in patients with AHF. The change in MDI from the baseline echocardiogram to 23-h follow-up has never been reported in the published literature on AHF. Mechanical dispersion is an index of inter-segmental discoordination of contraction which evaluates the differences in time-to-peak shortening for each of the LV segments that are analyzed. A key strength of MDI is that it can be assessed using the same recording(s) as GLS and thus adds very little time to the interpretation.

Previous research has shown impaired GLS to be associated with poor outcomes in patients with HF, MDI, however, is far less studied in HF than GLS. In fact, until recently, nearly, all of the literature on MDI focused on its association with ventricular arrhythmias and its role in CRT [13, 17, 18]. A recent study by Chan et al. investigated both MDI and GLS as predictors of outcomes in hospitalized patients with HF with reduced ejection fraction (HFrEF), reporting that both GLS and MDI were independent predictors of long-term outcome after adjustment for baseline variables [16]. GLS > − 7.8% and MDI > 72 ms were predictive of all-cause mortality or need for heart transplantation. Limitations of this study include the inclusion only of HFrEF subjects as well as the timing of echocardiograms with a median interval between admission and echocardiography of 10 days, rendering this measure less meaningful to the physician at the POC. This study does, however, lend support to the notion that MDI is a predictor of post-discharge outcomes in hospitalized HF patients, results that are consistent with our findings.

A potential mechanistic explanation for the observed change in MDI during treatment is that in patients with AHF, LV filling pressure is invariably increased. This elevated intra-cavitary pressure has the greatest impact on the subendocardial fibers as a result of their location immediately adjacent to the LV cavity. These fibers are oriented in a longitudinal fashion, thereby leading to the longitudinal strain parameters (including GLS and MDI) being the most sensitive of all the various strain measures [19]. Time-to-peak systolic strain for a given segment of the LV (the standard deviation of which is MDI) may be impaired by either: (1) decreased blood flow through the compromised small circulatory beds in the subendocardium which is the terminus of epicardial-to-endocardial coronary blood flow (the classical subendocardial ischemia model) or (2) pressure-induced decline in conduction velocity in areas with a high density of conducting fibers (i.e., the interventricular septum) [20, 21]. We suspect that during AHF episodes, a combination of these factors causes derangement in LV function. Thus, treatments geared towards reducing LV pressure (i.e., afterload reduction through vasodilation and non-invasive positive pressure ventilation) may be the key to maximizing improvements in GLS and MDI during the first 23 h of AHF therapy. In the present study, 23-h change in MDI proved to be a superior predictor than 23-h change in GLS; one reason for this may lie in the contractile potential of cardiomyocytes in AHF patients. There are likely limitations to the degree to which deformation (GLS) can improve with optimal treatment and thus many patients in our study exhibited substantially improved coordination of contraction timing (MDI) but only experienced small improvements in GLS after 23 h.

Our study has several important limitations, including small sample size and non-consecutive sampling of patients based on study team availability. Despite the relatively long time frame for the project, a study team member was available to enroll eligible subjects on average 2 days a month thereby placing significant limitations on our ability to capture patients. As previously mentioned, 13 patients had to be excluded from the final data analysis because of technical issues related to image quality or ECG-tracing quality. The majority of the ECG exclusions occurred early on during the study as our team was gaining familiarity with the precise timing necessary to capture clips that had three consecutive sinus beats with a good ECG waveform. The small number of subjects included for the final analysis thus raises the possibility of selection biases. To evaluate for this bias, we present data in Table 1 comparing the data from our study population with that of an AHF registry study also being conducted at our institution. The similarity between these 2 cohorts suggests that we captured a cohort of patients that was similar to the general population of AHF patients admitted at our institution.

We enrolled a fairly homogenous group of AHF patients, primarily a hypertensive, exclusively African-American cohort, and did not specifically evaluate or differentiate between patients with HFpEF versus HFrEF. It is possible that inclusion of a more diverse group of patients would alter our results; future studies are needed to address these questions. There were also differences in rates of CAD between the favorable outcome and readmitted cohorts (50% vs. 76.9%). Although this difference did not achieve statistical significance, it is certainly quite likely that CAD may have been the primary factor differentiating the primary outcome and this study was not powered to detect this difference. Future investigations would be wise to explore the role of CAD in LV longitudinal strain and how it influences short-term outcomes. Owing to the observational nature of this study, there is potential confounding from differences in treatments between patients. Another result of the observational and non-interventional design of the study is that invasive hemodynamic data (such as central venous pressure, pulmonary capillary wedge pressure, and central venous oxygen saturation) was not available for any of the patients in the study cohort. Comparison between the non-invasively derived indices of contractility using speckle-tracking and these established invasive parameters would have allowed for further hypothesis generation about the nature of the changes in speckle-tracking parameters that the study patients underwent. Future studies should ideally include these comparative data as well as echocardiography data on diastolic parameters obtained at the same time as the speckle-tracking data. Finally, there is some element of selection bias owing to the inherent limitations of speckle-tracking techniques—patients with atrial dysrhythmias or heart rate greater than 120 cannot be included; these limitations should not, however, preclude its use when feasible.

Based on the results of this study, the speckle-tracking-derived LV strain parameters MDI and GLS appear to undergo significant change during the treatment of AHF, and the magnitude of this change demonstrated an association with 30-day readmission rates. While our study is limited by a small sample size in a distinct patient population, data are promising, hypothesis generating only, and supportive of the need for further investigation of MDI and GLS as variables to help guide treatment and predict short-term outcome in AHF.