Author + information
- Received October 16, 2013
- Revision received November 11, 2013
- Accepted November 21, 2013
- Published online June 1, 2014.
- Kalpa De Silva, MBBS, PhD∗,
- Matthew Lumley, MBBS, BSc∗,
- Balrik Kailey, BSc∗,
- Jordi Alastruey, PhD†,
- Antoine Guilcher, PhD‡,
- Kaleab N. Asrress, MA, BM, BCh∗,
- Sven Plein, MD, PhD†,§,
- Michael Marber, PhD∗,
- Simon Redwood, MBBS, MD∗ and
- Divaka Perera, MA, MD∗∗ ()
- ∗King's College London British Heart Foundation Centre of Excellence, National Institute for Health Research Biomedical Research Centre at Guy's and St. Thomas's National Health Service Foundation Trust, Cardiovascular Division, The Rayne Institute, London, United Kingdom
- †Department of Biomedical Engineering, Division of Imaging Sciences and Biomedical Engineering, King's College London, King's Health Partners, St. Thomas's Hospital, London, United Kingdom
- ‡Department of Clinical Pharmacology, St. Thomas's National Health Service Foundation Trust, London, United Kingdom
- §Multidisciplinary Cardiovascular Research Centre, Leeds Institute of Genetics, Health and Therapeutics University of Leeds, Leeds, United Kingdom
- ↵∗Reprint requests and correspondence:
Dr. Divaka Perera, Cardiovascular Division, The Rayne Institute, St. Thomas's Hospital, 123 Coldharbour Lane, London SE1 7EH, United Kingdom.
Objectives This study sought to identify the effect of coronary autoregulation on myocardial perfusion during intra-aortic balloon pump (IABP) therapy.
Background IABP is the most commonly used circulatory support device, although its efficacy in certain scenarios has been questioned. The impact of alterations in microvascular function on IABP efficacy has not previously been evaluated in humans.
Methods Thirteen patients with ischemic cardiomyopathy (left ventricular ejection fraction: 34 ± 8%) undergoing percutaneous coronary intervention were recruited. Simultaneous intracoronary pressure and Doppler-flow measurements were undertaken in the target vessel following percutaneous coronary intervention, during unassisted and IABP-assisted conditions. Coronary autoregulation was modulated by the use of intracoronary adenosine, inducing maximal hyperemia. Wave intensity analysis characterized the coronary wave energies associated with balloon counterpulsation.
Results Two unique diastolic coronary waves were temporally associated with IABP device use; a forward compression wave and a forward expansion wave caused by inflation and deflation, respectively. During basal conditions, IABP therapy increased distal coronary pressure (82.4 ± 16.1 vs. 88.7 ± 17.8 mm Hg, p = 0.03), as well as microvascular resistance (2.32 ± 0.52 vs. 3.27 ± 0.41 mm Hg cm s–1, p = 0.001), with no change in average peak velocity (30.6 ± 12.0 vs. 26.6 ± 11.3 cm s–1, p = 0.59). When autoregulation was disabled, counterpulsation caused an increase in average peak velocity (39.4 ± 10.5 vs. 44.7 ± 17.5 cm s–1, p = 0.002) that was linearly related with IABP–forward compression wave energy (R2 = 0.71, p = 0.001).
Conclusions Autoregulation ameliorates the effect of IABP on coronary flow. However, during hyperemia, IABP augments myocardial perfusion, principally due to a diastolic forward compression wave caused by balloon inflation, suggesting IABP would be of greatest benefit when microcirculatory reserve is exhausted.
In excess of one-third of all coronary revascularization procedures occur in the context of underlying impaired left ventricular function, with an associated increase in morbidity and mortality (1–3). The intra-aortic balloon pump (IABP) is commonly used during percutaneous coronary intervention (PCI) with the aim of increasing coronary blood flow through augmentation of the diastolic aortocoronary pressure gradient. Additionally, IABP therapy decreases myocardial oxygen demand, by reducing the end-diastolic pressure, and, therefore, the afterload, making it an attractive means of ameliorating ischemia and consequently enhancing cardiac output. However, recent randomized control data, in clinical scenarios where IABP therapy is commonly employed, have shown limited efficacy with routine placement of the device (4–6). The physiological basis for this lack of benefit remains unclear, but it may relate to the interaction of the device with the innate homeostatic coronary autoregulatory mechanisms that govern myocardial perfusion, particularly in regard to the vasomotor control at the level of the microcirculatory resistance vessels. IABP therapy may only provide additional hemodynamic support when myocardial perfusion is outside the normal physiological range, when autoregulation has been pathologically disabled, in conditions such as profound cardiogenic shock or persistent ischemia.
Regional and global left ventricular perfusion and function are closely related to the microvascular integrity of the relevant myocardial territories, with microvascular dysfunction leading to left ventricular impairment and vice versa. The advent of pressure and Doppler sensor-tipped guidewire technology has allowed detailed in vivo interrogation of microcirculatory physiology (7,8). Wave intensity analysis (WIA) of phasic coronary pressure and flow profiles has allowed further characterization of the microcirculation and its impact on coronary flow in a number of stable and acute clinical settings (9–11). These studies demonstrate that mechanical impedance of the coronary microcirculation by the myocardium is the predominant factor that governs myocardial perfusion, with a backward traveling (microcirculatory) expansion wave (BEW), and a forward traveling (aortic) compression wave (FCW) identified as being the most influential in generating diastolic coronary flow (12–14). WIA has not previously been used in humans to assess the effect of IABP counterpulsation therapy on the energy transfer within the coronary circulation.
The aim of this study was to characterize the effects of IABP therapy on the coronary circulation by simultaneously assessing coronary flow, microvascular resistance, and wave energy. Using these indices, we assessed whether microcirculatory autoregulation modulates the effects of IABP therapy in patients with chronic ischemic cardiomyopathy undergoing PCI.
Patients scheduled to undergo high-risk single-vessel or multivessel PCI were considered for inclusion in the study. High risk was defined as the presence of impaired left ventricular function (ejection fraction <40% on cardiac magnetic resonance imaging, echocardiography, or left ventricular angiography) and a large amount of myocardium subtended by stenosed vessels, characterized by the BCIS-JS (British Cardiovascular Intervention Society Jeopardy Score) of 6 or greater. The BCIS-JS has been described previously (15), but in brief, it is a modification of the Duke Jeopardy Score (16), which allows broader classification of coronary anatomy, including left main coronary artery stenoses and bypass grafts (the total score ranges from 0 to 12). Exclusion criteria were a prior diagnosis of significant aortic valvular disease, nonischemic cardiomyopathy, severe peripheral artery disease precluding insertion of the IABP catheter, an acute coronary syndrome within the preceding 48 h, or cardiogenic shock.
Cardiac catheterization, IABP, and intracoronary measurement protocol
All patients were preloaded with aspirin (300 mg) and clopidogrel (600 mg). Coronary angiography was performed using a standard Judkins technique via a femoral artery approach. A 40-cc IABP catheter (Maquet Cardiovascular, Rastatt, Germany) was inserted via the contralateral femoral artery and deployed in the descending aorta distal to the left subclavian artery origin at the start of the procedure and counterpulsation was commenced at 1:1 augmentation ratio. Intracoronary nitroglycerin was administered before diagnostic angiography and intracoronary physiological measurements to ensure maximal epicardial arterial vasodilation. Hemodynamic measurements were obtained in the target vessel at least 5 min following final balloon occlusion during PCI. Aortic pressure (Pa) was measured via the coronary guiding catheter. Intracoronary pressure (Pd) and average peak velocity (APV) were measured via a 0.014-inch dual pressure and Doppler sensor-tipped guidewire (ComboWire, Volcano Corp., San Diego, California), the tip being positioned in the distal vessel. Simultaneous pressure and Doppler measurements were repeated 3× for each condition to reduce acquisition error, ensuring the resumption of steady state between measurements, defined as a return of APV to the baseline value.
First, basal measurements were obtained (with auto-regulation “switched on”) during 1:1 IABP augmentation. Then, measurements were obtained after transiently disabling autoregulation, with 1:1 IABP augmentation. Autoregulation was disabled by inducing maximal hyperemia via sequentially increasing doses of intracoronary adenosine, with the maximal tolerable dose dictated by the onset of atrioventricular conduction block or systemic symptoms (up to 60 μg were administered in the right and up to 96 μg in the left coronary arteries, respectively). Basal and hyperemic measurements were then repeated in unassisted conditions, after placing the IABP on “stand-by” mode, and allowing at least 4 min for return of basal steady-state conditions.
Phasic pressure and flow analysis
Data were sampled at 200 Hz and analyzed off-line, using a customized program developed in Matlab (Mathworks, Inc., Natick, Massachusetts). A Savitzky-Golay convolution method (17) was adopted, using a polynomial filter to refine the derivatives of the Pa and APV signals. Three to 6 consecutive cardiac cycles were selected for resting and hyperemic conditions, gated on the electrocardiographic R-wave peak, with ensemble averaging of Pa, Pd, APV, and heart rate. For the purposes of WIA, it has been considered that diastole commences with the onset of ventricular relaxation, signified by the dicrotic notch on the arterial pressure waveform, as previously described (14). Net coronary wave intensity (δI) was calculated from the time-derivatives (δt) of ensemble-averaged coronary pressure and flow velocity (U) as δI = δPd/δt × δU/δt (10,18). Coincident (microcirculation-derived) backward and (aorta-derived) forward propagating waves were separated assuming blood density to be 1,050 kg/m3 and estimating coronary wave speed using the sum of squares method (18,19). The peak energies (in W m–2 s–2 × 105) carried by the 3 most prominent wave energies identified were analyzed. These were the positive, aorta-derived FCW, occurring at the onset of systole; the concurrently occurring negative, backward (microcirculation-derived) compression wave, and BEW, the first negative wave occurring at the onset of ventricular relaxation, identified by the onset of diastole. Additionally, the waveforms that were associated with inflation and deflation of the IABP balloon in diastole were also analyzed. Total wave energy (area under the curve) was also determined to identify the relative changes occurring during unassisted and IABP-assisted conditions. The investigators who performed the data analyses were blinded to all clinical patient data.
Pulse-wave and mean-per-beat pressure-flow analysis
Pulse wave analysis was performed using custom-made programs (Matlab) in both unassisted and assisted aortic arterial waveforms. The area under the systolic phase of the pressure tracing (tension time index, TTI), and diastolic phase, (diastolic time index, DTI), were determined using the dicrotic notch (Fig. 1). TTI relates to myocardial oxygen demand and DTI to coronary perfusion (20). The Buckberg index was also calculated, providing a ratio of myocardial oxygen supply and demand, which is the quotient of diastolic to systolic pressure-time integral, representing the potential relationship between subendocardial blood supply (DTI) and afterload (TTI), respectively (20). To assess the effect of the IABP device on the timing of the cardiac cycle, diastolic time fraction was calculated. This represents the ratio of time in diastole to duration of a complete heart cycle.
Velocity time integral was calculated as follows:where t represents time during the cardiac cycle from t-start to t-end, vt is the instantaneous flow velocity at time t, and δt represents the interval between successive measurements.
Hyperemic and nonhyperemic (basal) microvascular resistance were calculated as the ratio of mean Pd to APV (mm Hg cm s–1) during maximal hyperemia or basal conditions, respectively, obtained through simultaneous intracoronary pressure-flow measurements, during 3 to 6 consecutive cardiac cycles (8,21).
Statistical analysis was performed using IBM SPSS (version 20, Armonk, New York). D'Agostino and Pearson omnibus normality test was performed to ensure a nonskewed distribution. Two-way analysis of variance without replication was performed for each measured variable when comparing to ≥2 different (nominal) conditions. Correlation analysis was used to quantify the relationship between variables. A 2-tail test for significance was performed in all analyses; p ≤ 0.05 was considered statistically significant. Data are represented as mean ± SD, unless otherwise stipulated.
The study protocol was approved by the U.K. National Health Service research ethics committee (Reference: 11/H0804/10). All participants were provided with an information sheet detailing the study protocol prior to providing informed verbal and written consent.
Thirteen patients with ischemic cardiomyopathy were recruited, 11 (age 67 ± 11 years) with a left ventricular ejection fraction of 34 ± 8% completed the study protocol. Two patients became hemodynamically compromised during the procedure and did not complete the study protocol and were therefore excluded from the final analysis. Of our study group, 82% (n = 9) were hypertensive, 91% (n = 10) were hypercholesterolemic, and all had prior myocardial infarction. The high-risk nature of this cohort was typified by the elevated logistic EuroSCORE (European System for Cardiac Operative Risk Evaluation) (11 ± 5%) and significant degree of coronary artery disease burden, with a mean BCIS-JS of 9 ± 2. Patient characteristics are outlined in Table 1.
Effects of hyperemia on unassisted coronary hemodynamics
Heart rate and aortic and distal coronary pressures remained unchanged during intracoronary adenosine-induced hyperemia (p = 0.41, 0.93, and 0.26, respectively). There was a reduction in microvascular resistance (R2 = 0.61, p = 0.003) with a corresponding increase in coronary flow (APV) (R2 = 0.62, p = 0.01). Furthermore, there was an increase in the microcirculatory BEW (R2 = 0.57, p = 0.02). Table 2 provides a summary of the hemodynamic observations.
IABP effects with “switched on” autoregulation
Systemic and Pulse Wave Parameters
During basal conditions, heart rate remained unchanged following the introduction of IABP device (66.3 ± 14.1 vs. 66.4 ± 12.3 beats/min, p = 0.87). Mean Pa altered significantly with balloon-pump assistance (92.2 ± 16.4 vs. 95.4 ± 20.4 mm Hg, p = 0.03). A nonsignificant trend in reduction of TTI was observed (30.1 ± 15.2 vs. 27.8 ± 13.9, p = 0.08) with balloon augmentation. Whereas the device did not alter the duration of diastole, with diastolic time fraction remaining unchanged (0.65 ± 0.07 vs. 0.64 ± 0.08 s, p = 0.87), diastolic pressure-time index, DTI, increased in conjunction with diastolic augmentation of mean Pa with counterpulsation therapy (43.9 ± 11.9 vs. 54.2 ± 13.4, p = 0.007). The ratio of myocardial oxygen supply (DTI) to demand (TTI), the Buckberg index, increased (1.70 ± 0.68 vs. 2.08 ± 0.57, p = 0.03).
Mean Coronary Indices
Whereas balloon pump augmentation led to an increase in distal coronary pressure (82.4 ± 16.1 vs. 88.7 ± 17.8 mm Hg, p = 0.04), there was no corresponding change in mean flow velocity (APV) (32.3 ± 11.1 vs. 26.6 ± 11.3 cm s–1, p = 0.08) in the presence of a functioning autoregulation. Similarly, velocity time integral remained unchanged during basal IABP-assisted conditions (26.8 ± 12.3 vs. 22.8 ± 7.5 cm, p = 0.51). Microvascular resistance during basal conditions was observed to increase significantly during counterpulsation therapy (2.32 ± 0.5 vs. 3.27 ± 0.41 mm Hg cm s–1, p = 0.001).
Coronary Wave Intensity Analysis
The 3 previously described wave energies (FCW, backward compression wave, and BEW) were identified in all patients. Figure 2 demonstrates a typical coronary wave intensity profile. Additionally coronary WIA of the circulation during IABP counterpulsation showed 2 additional wave energies (Fig. 3) relating to the inflation and deflation of the balloon. Inflation resulted in an aortic-originating (forward traveling) accelerating compression wave (IABP-FCW), with the subsequent deflation of the balloon causing an aortic-originating (forward traveling) decelerating expansion wave (IABP-FEW). Furthermore, during balloon-pump assistance peak BEW was reduced compared with unassisted conditions (–2.21 ± 0.64 vs. –1.62 ± 0.67 W m–2s–2 × 105, p = 0.004). During unassisted conditions, the relative acceleratory energies provided by FCW and BEW were 39% and 61%, respectively, whereas during IABP-assistance, FCW was 36%, BEW reduced to 30%, with the IABP-FCW accounting for 34% of total wave energy.
IABP effects with “switched off” autoregulation
Systemic and Pulse Wave Parameters
Balloon counterpulsation during intracoronary adenosine-induced hyperemia did not alter the heart rate (69.2 ± 14.2 vs. 69.1 ± 12.6 beats/min, p = 0.85), diastolic time fraction (0.60 ± 0.09 vs. 0.61 ± 0.09 s, p = 0.33), or mean Pa (93.4 ± 16.4 vs. 92.1 ± 15.4 mm Hg, p = 0.57) compared with unassisted conditions. TTI was reduced (although this was not statistically significant: 31.4 ± 11.6 vs. 27.9 ± 8.7, p = 0.11), and there was an increase in DTI (39.5 ± 13.0 vs. 46.5 ± 14.5, p = 0.01), with a corresponding increase in Buckberg index (1.31 ± 0.37 vs. 1.91 ± 0.56, p = 0.01), mirroring observations during basal conditions.
Mean Coronary Indices
Similar to basal conditions, balloon-pump assistance in the hyperemic setting was accompanied by an increase in distal coronary pressure (82.4 ± 16.1 vs. 89.7 ± 14.4 mm Hg, p = 0.02). However, in contrast to the basal state, there was an increase in APV (39.4 ± 10.5 vs. 44.7 ± 17.5 cm s–1, p = 0.002). Furthermore, velocity time integral was observed to increase during balloon assistance (25.8 ± 15.1 vs. 32.4 ± 15.7, p = 0.009). Hyperemic microvascular resistance was unchanged in unassisted and assisted conditions (2.21 ± 0.42 vs. 2.25 ± 0.78 mm Hg cm s–1, p = 0.45).
Coronary Wave Intensity Analysis
Augmentation of coronary flow with balloon counterpulsation (ΔAPV = APVIABP – APVunassisted) related proportionately with the IABP-FCW wave energy (p = 0.001, R2 = 0.71) (Fig. 4) with maximal hyperemia; there was no relationship between these parameters in basal conditions. IABP-FEW also related with augmentation of APV (p = 0.003, R2 = 0.60). Multiple linear regression, confirmed that augmentation in APV was primarily as a result of IABP-FCW (p = 0.01) rather than IABP-FEW (p = 0.14), with ΔAPV = 2.2 × 10–5(FEW) + 5.7 × 10–5(FCW) + 6.13. The dominant microcirculatory wave, BEW, tended to decrease during hyperemic balloon-pump assistance (2.43 ± 0.63 vs. 1.98 ± 0.76 W m–2 s–2 × 105, p = 0.07) compared with unassisted conditions.
We have comprehensively characterized the effects of intra-aortic balloon counterpulsation on coronary and microvascular hemodynamics, including the first clinical application of coronary WIA in this setting. Using these techniques, we have shown that the effects of IABP therapy are intimately linked to innate microvascular function and that the processes of autoregulation may ameliorate the potential benefits of this therapy. However, when autoregulation is disabled, IABP therapy was seen to augment myocardial perfusion. These findings help to explain the results of recent randomized control trials of balloon counterpulsation and also indicate the potential utility of this therapy in clinical scenarios accompanied by exhausted microcirculatory reserve.
Coronary autoregulation and IABP
Coronary blood flow is tightly controlled and matched to the oxygen demands of the heart by adapting the caliber of the coronary resistance arteries, via inter-related processes involving mechanisms intrinsic to the vascular wall, as well as metabolic and neurohumoral factors (22,23). The 2 major determinants of coronary flow are coronary arterial pressure and myocardial oxygen consumption. Coronary autoregulation is the mechanism that maintains coronary flow independent of arterial pressure for a given level of oxygen consumption or changing oxygen requirements at a constant perfusion pressure (24). In the presence of an epicardial coronary stenosis there is intramural microcirculatory vasodilation, reduction in resistance, accommodating for the reduction in pressure distal to the stenosis (25). Ischemia ensues as a result of the inability of this vasodilatory response to match the oxygen requirements, because the threshold of maximal microcirculatory vasodilation has been exceeded, and resistance cannot be reduced any further. Therefore in the presence of persistent ischemia, the autoregulatory mechanisms are completely exhausted, so that myocardial flow becomes proportional to perfusion pressure. This condition of minimal resistance is mimicked by pharmacological administration of adenosine, which causes maximal vasodilation and reduction in microvascular resistance, switching “off” the normal autoregulatory pathways. During this state, we have demonstrated that IABP therapy leads to an increase in distal coronary pressure, which proportionately increases coronary flow. However, when autoregulation is intact, the counterpulsation-related increase in Pd is accompanied by an increase in microvascular resistance, as a consequence of which coronary flow remains unchanged.
Clinical data on IABP efficacy and the impact of autoregulation
The efficacy of IABP therapy has come in to question in recent years in light of several randomized control trials that have failed to demonstrate the efficacy of routine IABP placement in different clinical settings. The first of these was BCIS-1 (4), in which IABP was deployed in patients who were hemodynamically stable at the outset, but were at increased risk of major complications during PCI, who showed no reduction in incidence of major adverse cardiovascular and cerebrovascular events, compared with those randomized to have unassisted PCI. Given that most patients enrolled in BCIS-1 are likely to have had perfusion pressures within the autoregulatory range and that patients with active ischemia and shock were excluded, the findings of the current study may explain why a strategy of routine IABP placement in unselected patients failed to show benefit. On the other hand, 1 in 8 patients who were randomized to receive unsupported PCI experienced hemodynamic compromise sufficient to warrant rescue IABP insertion. There is a signal that those requiring “bail-out” may be patients at the extreme end of the spectrum of diminished physiological reserve, severity of coronary artery disease, and therefore microvascular dysfunction. The CRISP AMI (Counterpulsation to Reduce Infarct Size Pre-PCI Acute Myocardial Infarction) trial (26) assessed the role of routine use of IABP in patients presenting with large anterior STEMIs within 6 h of symptom onset without cardiogenic shock. Pre-procedure IABP insertion failed to reduce infarct size in this study. Although this result appears to be at odds with the physiological observations seen in the current study, this lack of effect may have been due to the relatively brief period of counterpulsation prior to mechanical reperfusion being achieved. From our observations, the subgroup who stands to gain most benefit from counterpulsation therapy may be the one that had persisting ischemia despite reperfusion. Analysis of this subset of patients in CRISP-AMI may be instructive.
The most recent of these randomized clinical trials was IABP-SHOCK II (Intra-aortic Balloon Support for Myocardial Infarction With Cardiogenic Shock) (6), which assessed the utility of IABP in acute myocardial infarction complicated by cardiogenic shock. A strategy of elective IABP insertion failed to reduce 30-day mortality in this study. Although hypotension is central to the clinical diagnosis of cardiogenic shock, it is interesting to note that systolic blood pressure was in excess of 90 mm Hg in approximately 50% of all patients enrolled in IABP-SHOCK II, falling within the normal range of coronary autoregulation. Applying the observations of our current study, it could be postulated that the presence of a working autoregulatory system may have limited the effect of IABP therapy in many patients of the IABP-SHOCK II cohort.
The effect of autoregulation on the efficacy of mechanical hemodynamic support may also be applicable to devices that aim to directly unload the left ventricular cavity. Remmelink et al. (27) previously observed in a cohort of patients undergoing PCI with left ventricular dysfunction with adjunctive Impella device (Cardiotechnik, Aachen, Germany) support that during basal conditions, increased distal coronary pressure did not lead to an augmentation of coronary flow, though a linear increase was evident during hyperemic conditions. Analogous with the current study, an increase in basal microvascular resistance, due to the presence of a functioning microcirculatory autoregulation, diminished the beneficial effect of the device.
Wave intensity analysis of IABP counterpulsation
Kolyva et al. (28,29) previously demonstrated the effect of the IABP balloon on aortic hemodynamics during in vivo and ex vivo experiments, delineating the unique ability of WIA in assessing the hemodynamic effects of the device, highlighting the relationship of device inflation and deflation to wave propagation in the aorta. The current study represents the first application of WIA to pressure and flow measurements in the coronary circulation during counterpulsation in humans. We have demonstrated that IABP therapy is associated with a characteristic WIA morphology, with 2 unique diastolic waves observed, the first, a further FCW, corresponds with inflation of the balloon, and the second with balloon deflation. These novel parameters allow comprehensive assessment of the effects of IABP therapy integrated with innate microvascular and contractile function and may prove to be useful in future counterpulsation research, aimed at distinguishing responders from nonresponders and for assessing the relative efficacy of newer iterations of pulsatile assist devices.
Using these techniques, we have demonstrated that IABP augmentation of aortic and distal coronary pressure does not necessarily translate to an improvement in coronary flow or perfusion of the heart, as previously thought. Instead, we have shown that the energy driving myocardial perfusion during counterpulsation is entirely different to the patterns in unassisted conditions, with the added beneficial energy of the IABP-FCW being offset by a decrease in the BEW (in turn due to an increase in microvascular resistance due to autoregulation) such that net coronary flow remains unchanged. In contrast, during hyperemic conditions, when autoregulation is disabled, there is no diminution of the BEW during counterpulsation, such that the effect of the IABP-FCW and the BEW are summative, resulting in augmentation of coronary flow. In the presence of hyperemia, the energy from the balloon inflation (IABP-FCW) related linearly to the increase in peak coronary flow velocity (ΔAPV) (Fig. 5). These observations may explain the lack of benefit seen when the IABP is employed prophylactically rather than in cases when autoregulatory mechanisms have been rendered dysfunctional, such as in the presence of persistent ischemia or shock.
We have described a novel experimental model to characterize the effects of intra-aortic balloon counterpulsation on myocardial perfusion and to compare its efficacy in 2 settings, with and without functioning autoregulation. These techniques have the potential to be applied to investigation of other circulatory assist devices, including those that allow direct left ventricular unloading and iterations of the balloon pump itself, in a variety of clinical and experimental settings.
This was a small, single center study, but it is the first in human study to describe the relationship and effects of the use of intra-aortic balloon counterpulsation on coronary wave intensity and the effects of modulating coronary autoregulation on the utility of IABP therapy. As a consequence of the small sample sizes and the use of unadjusted statistical tests adopted within the studies, there is potential for a type 1 error affecting the results. Therefore, further investigation is warranted to confirm these initial findings.
Autoregulation ameliorates the effect of IABP on coronary flow by increasing microvascular resistance in response to increased distal coronary pressure. However, during hyperemic conditions, IABP augments myocardial perfusion, principally due to a diastolic FCW caused by balloon inflation. These findings suggest IABP will be of greatest benefit when regional microcirculatory reserve is exhausted.
This research was supported by an unrestricted educational grant from Maquet Cardiovascular. Dr. De Silva has received funding from a Heart Research U.K. fellowship grant (#RG2593/10/12). Dr. Alastruey has received funding from a British Heart Foundation fellowship grant (#FS/09/030/27812), the Centre of Excellence in Medical Engineering (funded by the Wellcome Trust and Engineering and Physical Sciences Research Council under grant #WT 088641/Z/09/Z) and the National Institute for Health Research Biomedical Research Centre at Guy's and St. Thomas's National Health Service Foundation Trust and King's College London. Dr. Plein has received funding from a British Heart Foundation fellowship (FS/1062/28409). Dr. Guilcher is a shareholder in Centron Diagnostics Ltd. Dr. Perera has received financial support from the U.K. Department of Health via the National Institute for Health Research Comprehensive Biomedical Research Centre Award to Guy's and St. Thomas's National Health Service Foundation Trust in partnership with King's College London. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Abbreviations and Acronyms
- average peak velocity
- backward expansion waves
- diastolic time index
- forward compression wave
- forward expansion wave
- intra-aortic balloon pump
- aortic pressure
- percutaneous coronary intervention
- intracoronary pressure
- tension time index
- wave intensity analysis
- Received October 16, 2013.
- Revision received November 11, 2013.
- Accepted November 21, 2013.
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