Continuous-flow left ventricular assist device (CF-LVAD) therapy is now standard of care in the treatment of advanced heart failure as a bridge to transplant or destination therapy with patient survival approaching 70% at 2 years in the latter population.1,2 The CF technology relies on a rotary pump to move blood continuously from the left ventricle to the aorta throughout the cardiac cycle. This alters the normal pulsatile physiology to a continuous-flow physiology, with a notable feature of a reduced or absent pulse pressure (PP). Because of this diminished PP, the standard method of noninvasive blood pressure (BP) measurement is not feasible in CF-LVAD patients. This limitation has been overcome by measuring the return of circulation pressure using Doppler ultrasound to obtain a Doppler BP (DopBP), which originally was shown to be a surrogate for mean arterial pressure (MAP),3 slow cuff deflation method, and use of pulse oximetry waveform combined with manual sphygmomanometry.4,5 Because it is now evident that CF-LVAD physiology reflects a spectrum of low pulsatile (PP) flow rather than true nonpulsatile flow,6 the validity of DopBP as a surrogate for MAP is in question. This concern was recently illustrated in a larger study that demonstrated that DopBP has only modest correlation with MAP and is more closely correlated with systolic BP (SBP).5 Based on this concern, the DopBP target at many centers for CF-LVAD patients is dichotomized based on the presence or absence of a palpable pulse. Theoretically, patients with a palpable pulse have a higher PP and therefore a greater difference between DopBP and MAP (Figure 1). Despite this practice, the use of a palpable pulse as a measure of PP has not been scientifically investigated.
In addition to the challenges of BP measurement and management, CF-LVADs have raised questions regarding the impact of low pulsatile flow on end-organ function. At present, lack of pulsatility is implicated in the development of mucosal bleeding in the gastrointestinal tract in the form of arteriovenous malformations7,8 and increased aortic stiffness.9 Study of these and other associations has been limited by the use of noninvasive measures of pulsatility that have not yet been validated.
Given these concerns, in the current study, we aimed to prospectively evaluate the readily available noninvasive measures of pulsatility—the HeartMate II (HMII) pulsatility index (PI), aortic valve opening (AVO), and assessment of a palpable pulse—in comparison to the gold standard, invasively obtained arterial PP via an arterial catheter. We also sought to evaluate the impact of the presence or absence of a palpable pulse in the noninvasive assessment of BP during CF-LVAD support.
We prospectively enrolled 23 patients who underwent either primary CF-LVAD implant or a pump exchange or CF-LAVD patients who were admitted to the cardiothoracic intensive care unit (ICU) and had an arterial line, at Montefiore Medical Center between September 2015 and April 2016. The study protocol was approved by the Institutional Review Board. Patients were excluded from the study if they were less than 18 years of age, received mechanical right ventricular support, had previous radial artery surgery, or were unable to give informed consent. Patients with both axial (HMII) and centrifugal (HeartWare) pumps were enrolled in the study. After obtaining informed consent, baseline demographic data on each subject were collected. All the following measurements were obtained while the patients were in ICU with arterial line between postoperative days 1 and 5.
Assessment of Pulsatility
Pulse Pressure Via Arterial Catheter
Daily measurement of SBP, diastolic BP (DBP), and MAP was collected over a 60 second average after leveling and zeroing the arterial catheter. Pulse pressure was calculated as the difference between the SBP and DBP (SBP − DBP).
The presence or absence of a radial pulse was assessed daily by four health care providers (HCPs) comprising of two heart failure physicians and two critical care nurses while the patients had an arterial line in place. The radial artery on the arm contralateral to the arterial line was assessed by the standard palpatory method for 60 seconds. The examiners were blinded to each other’s assessment and the arterial catheter pressure tracing.
Aortic Valve Opening
All patients had one echocardiogram to assess for AVO simultaneous to PP assessment. The AVO score was calculated based on a 10-beat average: 0 = no opening, 1 = intermittent opening, and 2 = regular opening (every beat, if atrial fibrillation >7/10 beats).
The HMII calculates the PI as (maximum power – minimum power)/(average power) averaged over 15 seconds. This value was displayed by the device monitor and was retrieved daily, simultaneous to PP assessment along with the LVAD speed (rpm), flow (L/min), and power (W).
Assessment of Doppler Blood Pressure
Doppler blood pressure was measured daily simultaneous to the PP assessment described above. First, a Doppler probe (Summit Doppler L350 with 8 MHz transducer, Wallach Surgical Devices, Trumbull, CT) was used to locate the brachial artery in the antecubital fossa. Then, a standard BP cuff was inflated to obliterate the blood flow in the brachial artery, identified by the disappearance of the Doppler signal. The cuff was deflated slowly, and the pressure at which there was return of circulation, identified by the reappearance of the Doppler signal, was recorded as the DopBP. The average of three consecutive measurements was recorded.
A descriptive summary of baseline patient characteristics is presented as mean (standard deviation [SD]) or median (interquartile range [IQR]) for continuous variables and frequencies (%) for discrete variables. Reliability of radial pulse assessment was evaluated using kappa statistic along with 95% CI employing bootstrap sampling.10 The assessment of association between variables of interest was carried out using generalized estimating equations to account for within patient clustering.11 Results are presented as effect estimate and associated 95% CI. Statistical significance is claimed at a computed p value ≤0.05 or in instance when associated 95% CI excluding the null.
The study group comprised 23 patients who were supported by a CF-LVAD. Table 1 describes the patient’s demographics. Of note, 70% (16) of the patients were male and 73% (17) had a nonischemic cause of cardiomyopathy. Seventeen patients were primary implants while three were pump exchanges, and 87% (n = 20) of the patients had an axial pump (HMII) while 13% (n = 3) had centrifugal pump (HeartWare).
Interobserver Agreement and Correlation of Pulse Pressure to Radial Pulse
By consecutive daily assessments, 57 sets of radial pulse evaluation were collected on 23 patients. Each dataset comprised the daily pulse finding of four HCPs and the simultaneously recorded PP from the arterial catheter. The interobserver agreement for the presence of a palpable pulse was moderate (k = 0.41; 95% CI, 0.28–0.60). A palpable pulse was found to be linearly associated with PP with an odds ratio (OR) of 1.58 (95% CI, 1.21–2.05; p = 0.0006).
In the entire study population, the median PP was 14 mm Hg (IQR, 10–21). A prior study has suggested that a PP of ≥15 represented the ideal target during CF-LVAD support and we therefore stratified our cohort accordingly.12 If the PP was ≥15 mm Hg, a radial pulse was palpated 82% of the time, whereas when the PP was <15 mm Hg, a radial pulse was palpated only 35% of the time (Figure 2, A and B).
Correlation of Doppler Blood Pressure to Mean Arterial Pressure Based on Presence of Palpable Pulse
The measurement of DopBP was added to the protocol after the initial seven patients had completed their assessments. Therefore, there were only 31 sets of DopBP, SBP, and MAP collected in the remaining 16 patients. This group was divided into pulsatile and nonpulsatile cohort based on the presence or absence of a radial pulse from HCP 1. Figure 3 demonstrates the correlation between the DopBP and MAP/SBP based on the presence or absence of palpable pulse. In the pulsatile cohort, there was a strong correlation between DopBP and SBP (r = 0.94; 95% CI, 0.82–0.99), whereas the correlation between DopBP and MAP was much weaker (r = 0.42; 95% CI, 0.19–0.96). In the nonpulsatile cohort, there was a strong correlation between both the DopBP and SBP (r = 0.94; 95% CI, 0.80–1.0) and DopBP and MAP (r = 0.87; 95% CI, 0.77–1.00). When HCP 2, 3, or 4 was used, there were no significant changes in these findings.
Pulsatility Index, Aortic Valve Opening, and Pulse Pressure
In our study population, 20 patients were supported by HMII. In the HMII patients, 49 sets of daily measurements of PP and corresponding PI were analyzed. Pulse pressure was significantly associated with PI with a regression coefficient of 0.30 (95% CI, 0.14–0.45; p = 0.0002). For every 5 mm increase in PP, the PI increased by 0.30. All 23 patients in the study had one echo done simultaneous to PP measurement. Only two patients had intermittent AVO, and therefore, they were combined with the regular AVO group. Pulse pressure was not significantly associated with AVO (OR, 1.41; 95% CI, 0.70–2.83; p = 0.33). Figure 4 demonstrates the variability in the PP in these two groups.
In the current study, we sought to investigate the impact of a palpable pulse on the measurement and interpretation of DopBP and the relationship between PP and the readily available noninvasive measures of pulsatility. Our principal findings are as follows: 1) a palpable pulse is linearly associated with PP and has moderate interobserver agreement; 2) a palpable pulse allows for dichotomization of the DopBP to reflect the SBP in its presence and the MAP in its absence; and 3) the HMII PI is significantly associated with the PP.
We now understand that CF-LVADs do not create a truly continuous-flow physiology but rather a low pulsatile flow state with varying degrees of PP. This is well illustrated in our cohort where the PP ranged from 3 to 42 mm Hg and the median was 14 mm Hg. In comparison, the mean PP was 47 mm Hg in patients with advanced heart failure,13 whereas in young normotensive adults, the mean PP was 42.3 ± 9.9.14 Appreciating this nuance is critical for interpretation of BP measurements because pulsatility significantly affects the relationship between DopBP and MAP (Figure 1).
As illustrated in Figure 1, the use of DopBP is a poor surrogate of MAP as pulsatility increases. In a well-conducted contemporary study, Lanier et al.5 previously demonstrated that DopBP correlated more closely to SBP than MAP, our findings in this regard should be considered confirmatory. Expanding upon this observation, and using the presence or absence of a palpable radial pulse, we are able to dichotomize patients into two groups along the pulsatility spectrum: 1) pulse present – DopBP reflects SBP and 2) pulse absent – DopBP reflects MAP (Figure 3). We have additionally validated this premise by demonstrating that the presence of a palpable pulse is indeed linearly associated with increasing PP. Finally, we found that there is moderate interobserver agreement among a variety of HCPs (physicians and nurses) in their ability to palpate a pulse in CF-LVAD patients. This suggests a promising prospect for its appropriateness as a tool in clinical practice. Given the findings of this study, we feel that larger studies examining a palpable pulse and BP management are now necessary. In fact, at present, there is no prospective study on BP management despite strong retrospective data demonstrating the importance of BP control in mitigating adverse events.15,16
The HMII PI is one of the commonly used noninvasive measures of pulsatility, and multiple studies have used PI as the marker of pulsatility. Nonetheless, to our knowledge, the relationship between PI and PP has never been explored. Our data are therefore notable as the first to validate that the HMII PI has an association with pulsatility. Finally, our data did not find an association between AVO and PP. This important finding emphasizes the difference between PP peripherally and the pressure gradient across the aortic valve. As seen in Figure 5, there are patients with very low PP who are able to open the aortic valve, whereas on the other hand, some patients with very high PP do not open their aortic valve. This may also explain why the association between AVO and arterio-venous malformation is less robust than the HMII PI.
Our study has a number of limitations that are worth mentioning. First, as is common to most LVAD studies, the small sample size, in addition to being from a single center, may limit the generalizability of the findings. Similarly, study assessments were repeated multiple times on the same subjects, and although this was accounted for in most of the analysis, the combination with a small cohort could have significantly affected the results as the potential for very few patients contributing more observations is high, especially in the case of some of the subgroup analyses. Finally, it is not clear that PP as the gold standard assessment of pulsatility during CF-LVAD support is adequate to explain the hemodynamics and physiologic response at the end-organ and cellular level. Some authors have advocated the use of measures of hemodynamic energy changes during the cardiac cycle such as energy equivalent pressure or surplus hemodynamic energy.17
Despite these limitations, our findings may have a significant impact on the management of patients with CF-LVAD and in further understanding adverse events associated with CF-LVAD. We have highlighted how assessment of the radial pulse can be important in longitudinal outpatient BP management. In addition, we are the first to systematically evaluate the relationship of noninvasive measures of pulsatility, notably finding that HMII PI is a potential surrogate.
In conclusion, a palpable pulse and the HMII PI are reliable noninvasive measures of pulsatility in patients with a CF-LVAD. Incorporating a palpable radial pulse into the algorithm of BP management as illustrated in Figure 5 may be important for optimal treatment and to negate adverse events.
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