CLINICAL RESEARCH: INTERVENTIONAL CARDIOLOGY
Acute Left Ventricular Dynamic Effects of Primary Percutaneous Coronary InterventionFrom Occlusion to Reperfusion
Maurice Remmelink, MD,
Krischan D. Sjauw, MD,
José P.S. Henriques, MD, PhD,
Marije M. Vis, MD,
René J. van der Schaaf, MD,
Karel T. Koch, MD, PhD,
Jan G.P. Tijssen, PhD,
Robbert J. de Winter, MD, PhD,
Jan J. Piek, MD, PhD and
Jan Baan, Jr, MD, PhD*
Department of Cardiology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands
Manuscript received October 15, 2008;
revised manuscript received December 9, 2008,
accepted December 15, 2008.
* Reprint requests and correspondence: Dr. Jan Baan, Jr., Department of Cardiology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105AZ Amsterdam, the Netherlands (Email: j.baan{at}amc.uva.nl).
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Abstract
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Objectives: We studied the left ventricular (LV) dynamic effects of primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI) by directly obtaining pressure–volume (PV) loops during the procedure.
Background: An acute myocardial infarction causes a decrease in LV compliance. The instantaneous effects of primary PCI on LV compliance are unknown.
Methods: We studied 15 consecutive patients (10 males, ages 59 ± 12 years), who presented with their first acute anterior STEMI within 6 h after onset of symptoms, and in whom coronary angiography revealed an occluded left anterior descending coronary artery. Before performing primary PCI, we inserted a pressure-conductance catheter in the LV to continuously obtain PV loops.
Results: Immediately after successful reperfusion, significant improvements were observed in LV diastolic function, as indicated by an increased end-diastolic compliance with a 6.0 ± 2.8 mm Hg (p < 0.0001) downward shift of the compliance curve. There was a decrease in end-diastolic pressure of 24 ± 18% (p = 0.0002), in stiffness of 27 ± 18% (p = 0.0003), and in wall stress of 20 ± 24% (p = 0.004). Systolic function mainly showed an immediate improvement in apical contractility from 40 ± 17% to 54 ± 15% (p = 0.01).
Conclusions: Primary PCI in anterior STEMI patients causes an immediate improvement in diastolic function, assessed by online PV loop measurements.
Key Words: acute myocardial infarction • hemodynamics • left ventricular function • pressure–volume relations • primary angioplasty
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Abbreviations and Acronyms
| | CO = cardiac output | | EDP = end-diastolic pressure | | EDV = end-diastolic volume | | EES
= end-systolic elastance | | EF = ejection fraction | | ESP = end-systolic pressure | | ESV = end-systolic volume | | LV = left ventricular | | PCI = percutaneous coronary intervention | | PV = pressure–volume | | STEMI = ST-segment elevation myocardial infarction | | SV = stroke volume | | SW = stroke work | | TIMI = Thrombolysis In Myocardial Infarction |
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In acute myocardial infarction, left ventricular (LV) compliance decreases and correlates directly with prognosis (1). Recent studies also have shown elevated filling pressures in ST-segment elevation myocardial infarction (STEMI) patients directly after primary percutaneous coronary intervention (PCI) (2,3).
The goal of reperfusion therapy is to restore coronary circulation to reduce infarct size and improve clinical outcome. Primary PCI is recognized as the best reperfusion modality. Whether primary PCI causes direct changes in LV dynamics is unknown because direct LV dynamic data during primary PCI procedures are unavailable.
Therefore, we studied LV dynamic responses to reperfusion throughout primary PCI for acute STEMI by continuously measuring LV pressure–volume (PV) loops using the combined pressure-conductance catheter (4).
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Methods
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Patients.
The study population consisted of 15 consecutive patients (10 males, mean age 59 ± 12 years) who presented with their first acute anterior STEMI within 6 h after onset of symptoms. Patients were included when coronary angiography revealed an occluded left anterior descending artery before primary PCI (Table 1).
Exclusion criteria were cardiogenic shock, refractory ventricular arrhythmias, congestive heart failure, previous myocardial infarction, significant valvular disease, and left ventricular thrombus. The study complied with the Declaration of Helsinki and was approved by the institutional research and ethics committee. All patients gave written informed consent.
Study protocol.
Patients were treated with aspirin, clopidogrel, and heparin before PCI. Heart rate and surface 12-lead electrocardiograms were monitored and aortic pressure was measured via the guiding catheter. Blood samples for hematology and chemistry including cardiac markers were drawn. Before performing primary PCI, the 7-F pigtail-equipped combined pressure-conductance catheter (CD Leycom, Zoetermeer, the Netherlands) was placed in the LV through the contralateral femoral artery (4). Between the outer electrodes of the conductance catheter a dual electric field is generated, and the inner 8 electrodes are used to generate segmental volume signals. The pressure and volume signals were continuously displayed on the monitor (CFL 512, CD Leycom) after analog-to-digital conversion at 250 Hz. The LV pressure and volume were continuously assessed. After completion of the PCI procedure, a 5-ml blood sample was used to measure blood resistivity rho, and a Swan-Ganz catheter (Edwards Lifesciences LLC, Irvine, California) was placed in the pulmonary artery via the femoral vein. Cardiac output was determined by thermodilution and parallel conductance by hypertonic saline injections to calibrate the volume signals of the conductance catheter (4). The PV loop assessment continued for approximately 30 min after the most optimal angiographic PCI results were achieved.
LV dynamic measurements and analysis.
The LV dynamics were recorded continuously during the PCI and were analyzed off-line. The initial pre-PCI (baseline) recordings were compared with the recordings at 25 min after achievement of an angiographically satisfactory PCI result. Per-beat averages of the recorded variables were calculated as the mean of all beats during a steady state of at least 12 s and covering 2 respiratory cycles. It was accounted for that selected recordings were obtained during stable hemodynamic conditions, without interference of pharmaceuticals (e.g., nitroglycerin). The following indexes were obtained: heart rate, cardiac output (CO), cardiac index as CO/body surface area, ejection fraction (EF), stroke volume (SV), stroke work (SW) as the area of the pressure-volume loop, end-systolic volume (ESV), end-diastolic volume (EDV), end-systolic pressure (ESP), end-diastolic pressure (EDP), and peak positive derivative of left ventricular pressure (dP/dtmax). The relaxation time constant Tau, as an index for the active diastolic LV properties during isovolumetric relaxation, was defined as the time required for the cavity pressure at dP/dtmin to be reduced by one-half (5). The end-systolic elastance (EES), as the slope of the end-systolic pressure-volume relation was estimated by ESP/ESV, and the end-diastolic stiffness (EED), as the slope on the end-diastolic pressure-volume relation was estimated by EDP/EDV (6). Effective arterial elastance (EA), an index of LV afterload, was calculated by ESP/SV (7). Subsequently, the ventricular–arterial coupling ratio was calculated by EES/EA, which describes the interaction between LV performance and the systemic arterial system (8). Regional cycle efficiency was calculated for the most basal and apical volume segment by SW/( PLV·VLV), as previously described (9). End-diastolic wall stress (WSED) and peak wall stress were calculated from the instantaneous LV pressure and volume signals, and from LV mass as derived from post-procedural echocardiography, by P·(1 + 3·V/LV mass) (10). The change in the passive diastolic LV properties indicated by the shift of the compliance curve was expressed by the mean pressure value over which the overlapping portion of the PV loop had moved (Pm), as previously described (11).
Statistical analysis.
Data are expressed as mean ± SD or n (%). The 2-tailed paired t test was used to compare LV dynamic data obtained before and after the PCI. SPSS release 12.0.2 statistical software package for Windows (SPSS Inc., Chicago, Illinois) was used for analyses. A value of p < 0.05 was considered statistically significant.
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Results
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Patient characteristics.
The baseline characteristics of the 15 patients are shown in Table 1. Coronary angiography showed a right dominant system in 11 (73%) patients. In 4 patients the location of the occlusion was in the proximal and in 11 patients in the mid-coronary segment. The time from symptom onset to reperfusion was 4.36 ± 2.94 h, from door to balloon was 41.56 ± 21.13 min, and from arterial access to reperfusion was 22.53 ± 4.91 min.
LV dynamics at baseline.
The left panel of Table 2
shows diastolic, systolic, and global LV dysfunction at baseline. All diastolic indexes were increased. Systolic and global LV indexes showed relatively small values of EF, SW, EES, and EES/EA, in combination with an increased EA and above normal dP/dtmax.
Effect of primary PCI on LV dynamics.
The PCI resulted in angiographic Thrombolysis In Myocardial Infarction (TIMI) flow grade 2 (n = 3) and TIMI flow grade 3 (n = 12). The right panels of Table 2 illustrate LV dynamics after reperfusion was achieved.
Diastolic Function
The main effects of reperfusion were observed on diastolic function. The response on diastolic function was uniform. There was an immediate improvement in EDP, EED, and WSED, whereas Tau remained unchanged. Compliance increased, as quantified by a Pm of –6.0 ± 2.8 mm Hg (p < 0.0001), indicating a downward shift of the compliance curve (Fig. 1).
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Figure 1 Illustration of a Pressure–Volume Loop in a Typical STEMI Patient
(A) Before primary percutaneous coronary intervention (PCI). (B) The downward-shifted pressure–volume loop after PCI. Note the improved and downward-shifted (arrows) left ventricular (LV) compliance curve caused by coronary reperfusion. Also, note the increased stroke volume in this patient. STEMI = ST-segment elevation myocardial infarction.
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Systolic Function
The effects of reperfusion on systolic function were variable. The PCI decreased the EES because the rightward shift of the PV loop occurred with a concomitant decrease in ESP, whereas regional cycle efficiency of the apical segment improved from 40 ± 17% to 54 ± 15% (p = 0.01). The basal segment showed no change (Fig. 2). The data in Table 2 showed small changes in dP/dtmax and no net effect of PCI on LV volumes and EF.
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Figure 2 Illustration of the Reperfusion-Induced Change in Regional Cycle Efficiency of the Apical and Basal LV Segment
For visual purposes, data are shown as mean ± SEM. Note that cycle efficiency of the apical segment increased(*p = 0.01), whereas the cycle efficiency of the basal segment showed no change. Abbreviations as in Figure 1.
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Discussion
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This study is the first to show direct effects of primary PCI on LV dynamics by online and load-independent data from PV loops. Coronary reperfusion caused an immediate improvement in diastolic function by increasing LV compliance and in systolic function by increasing apical contractility in STEMI patients.
Diastolic function.
All of our studied STEMI patients presented with diastolic dysfunction. The main effect of reperfusion on LV dynamics was an immediate improvement in the passive diastolic properties of the myocardium, whereas active LV relaxation remained unchanged. Previous findings are mainly based on data from experimental studies (12,13), and on data obtained after thrombolytic therapy (14). Primary PCI is recognized as the best (and most direct) reperfusion treatment modality. Data from clinical studies in the setting of primary PCI were usually obtained hours or days after completion of the procedure by echocardiography (15), and did not show immediate effects of reperfusion on LV function. Previous experimental (16) and later clinical (1) studies had shown that acute myocardial infarction caused a decrease in LV compliance indicated by an upward shift of the compliance curve, and a return of LV chamber stiffness toward normal within 1 week (13,14,17). We showed that these changes occur immediately after reperfusion, well within 1 h, although they do not return to normal values. Also, in line with our data, recent studies showed invasively measured elevated filling pressures in STEMI patients directly after primary PCI (2,3), but the immediate effects of primary PCI on LV dynamics have not been studied.
Immediate improvement of the intrinsic passive diastolic LV properties by primary PCI was observed in all 15 patients. This marked and beneficial effect of primary PCI is illustrated by the fact that immediate improvement of diastolic function occurred, whereas echocardiographic data failed to show immediate beneficial effects on diastolic function during reperfusion by thrombolytic therapy (14). Interestingly, the improvement in diastolic function observed in these STEMI patients is in line with invasive clinical studies evaluating LV function during a demand ischemic state during pacing (18) and ischemia induced by balloon coronary occlusion during elective PCI (19,20). Data from elective PCI for stable angina showed an upward and rightward shift of the PV loop during temporary ischemia and an immediate return to baseline after reperfusion (19,21), suggesting that primary PCI may result in an improved LV compliance, as is now confirmed. Obviously, the extent of the effects depends on the reversibility of the myocardial damage, as is confirmed by our data showing that the LV compliance does not return to normal values.
Active diastolic relaxation in our studied myocardial infarction patients was prolonged, but remained unchanged by reperfusion. Previous clinical studies of LV relaxation during myocardial ischemia, induced by temporary coronary occlusion in the setting of elective PCI, found prolongation of ventricular relaxation and return to normal after balloon deflation (19,21). Interestingly, the extent of the prolongation in our study population was the same as that during the temporary coronary occlusion in elective PCI (19). It seems, however, that unlike the passive function, the active relaxation of the infarcted ventricle shows no immediate recovery. Delayed (partial) recovery may be expected from experimental studies (13), but remains to be studied in primary PCI patients.
Systolic function.
Most of our studied STEMI patients presented with systolic dysfunction. The response to reperfusion was variable. Immediately after reperfusion by primary PCI, apical cycle efficiency improved significantly, whereas global systolic function showed no or only small changes. Growing evidence supports that improvement in apical function allows for increased storage of potential energy during systole (22,23). This stored potential energy is then converted to kinetic energy during isovolumetric relaxation. This kinetic energy allows for rapid reconfiguration of the LV back to its pre-ejection state, which creates a rapid decline in LV pressure (24). Although we could not document an improvement in the active relaxation time constant Tau during the acute phase, an improved systolic apical function may account for the improved diastolic function in the longer term.
Direct systolic effects of reperfusion by primary PCI have never been studied, whereas the prognostic implications of systolic function days or months after the onset of acute myocardial infarction (25,26) and well after primary PCI (2,27) have been studied extensively. Effects of reperfusion on systolic function have mostly been studied in thrombolytic therapy studies (28,29), which showed small improvements in wall motion abnormalities after 1 week (28), but obviously gave no information on acute effects of reperfusion. Our data do show that reperfusion by primary PCI indeed causes not only diastolic effects, but also systolic effects, and this may be of prognostic value in the long term.
Study limitations.
Myocardial loading and unloading interventions to determine the end-systolic and -diastolic pressure-volume relation were not performed because we considered these unethical (i.e., delay of reperfusion and possible hemodynamic consequences) for the patients under these circumstances. The EED estimated from steady-state PV loops by EDP/EDV underestimates the real slope of the end-diastolic pressure-volume relation at higher filling pressures because of its nonlinearity. Otherwise, our results would probably have shown even more pronounced changes in EED by PCI. Furthermore, because we collected acute data of reperfusion, we have no information on outcome, and additionally, outcome data would require a larger sample size.
Clinical implications.
Previously, LV function parameters for prognosis after acute myocardial infarction have been mainly systolic parameters (25). However, in the last decade there has been increasing attention on the prognostic importance of diastolic dysfunction because patients with preserved systolic function after acute myocardial infarction, but with pulmonary congestion caused by impaired diastolic function, have a poor prognosis (30).
The present study is the first clinical study to show the immediate effects of primary PCI on diastolic function: improved compliance and apical contractility via the assessment of online arithmetical and load-independent data from PV loops. The illustrated improved diastolic function during the acute phase may be of relevance to the LV remodeling process, which is well known for determining the long-term outcome of STEMI patients (31).
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Conclusions
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Online PV loop assessment during primary PCI showed that coronary reperfusion caused an immediate improvement in diastolic function by increasing LV compliance and in systolic function by increasing apical contractility in STEMI patients.
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Acknowledgments
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The authors thank the nursing staff of the cardiac catheterization laboratory for their skilled assistance, especially W. J. Rohling, RN, T. Wagenaar, RN, W. R. Rozendaal, RN, and S. van Gilst, RN.
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