Identification of viable myocardium by dipyridamole-induced improvement in regional left ventricular function assessed by echocardiography in myocardial infarction and comparison with thallium scintigraphy at rest

doi:10.1016/0002-9149(92)90545-A

The American Journal of Cardiology

Volume 70, Issue 7, 15 September 1992, Pages 703-710

https://doi.org/10.1016/0002-9149(92)90545-A Get rights and content

Abstract

In patients with coronary artery disease and left ventricular impairment, the distinction between ventricular dysfunction due to myocardial fibrosis and postischemic, viable, although dyssynergic, myocardium has important clinical implications. Experimental studies have shown that dipyridamole can increase myocardial function in stunned segments, outlining a potential role of dipyridamole-induced functional recovery as an ultrasonic marker of myocardial viability. The aim of this study was to assess whether the increase of regional left ventricular function early during dipyridamole infusion in basally asynergic segments could identify viable myocardium recognized by rest injected, delayed (>14 hours from tracer injection) thallium and (in a subset of patients) late functional recovery evaluated by a follow-up echocardiogram at rest. Twenty-two patients with angiographically documented coronary artery disease and regional dysfunction in resting conditions (average left ventricular ejection fraction 43 ± 8%) were studied by echocardiography. All patients underwent a dipyridamole-echocardiographic test (up to 0.84 mg/kg over 10 minutes) and a delayed planar thallium study. A 13-segment model was used for both techniques. A score index ranging from 1 (normokinesia) to 4 (dyskinesia) was used for echocardiography. Thallium-201 activity was expressed in each segment as the percentage of maximal activity in the corresponding view. After dipyridamole, the wall motion score was assigned to each segment in resting conditions and at peak hyperkinesia before possible mechanical signs of ischemia. A segment was considered viable when there was a regional activity >55% of peak thallium and when a resting dyssynergy (echocardiographic score ≥2) showed an improvement of ≥1 grade by dipyridamole. In all, 80 basally asynergic segments were scored. Dipyridamole and thallium had concordant results in 21 of 26 thallium-viable and 52 of 54 thallium-necrotic segments. The 23 segments viable by dipyridamole had a higher thallium score than did the 57 necrotic by dipyridamole (73 ± 9 vs 42 ± 9; p < 0.01). In a subset of 15 patients, a follow-up echocardiogram at rest was obtained at 3.4 ± 2.7 months after the initial study. A significant functional recovery (improvement of ≥1 grade) was found in 15 of 19 segments with and only 5 of 39 without dipyridamole-induced improvement (79 vs 13%; p < 0.01). These observations suggest that dipyridamole-induced recovery in the contractile function of basally asynergic segments (possibly linked to the inotropic effect of increased flow) identifies areas with myocardial viability.

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In the setting of reduced resting blood flow and no or limited flow reserve, hibernating myocardium may manifest contractile reserve at a low dose stage and then show deterioration of function at higher doses due to ischemia (biphasic response). Contractile reserve can also be assessed using low level exercise, phosphodiesterase inhibitors, vasodilators (dipyridamole, adenosine, and nitroglycerin) and after induction of a premature ventricular beat.229-231 Dobutamine is the preferred agent for viability assessment.
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Vasodilator-induced hypotension is generally beneficial because of the associated decrease in an LV wall tension, but an excessive reduction in perfusion pressure may be harmful (Kattus and Gregg, 1959). Other possible mechanisms are sympathetic activation secondary to the systemic vasodilatation or a decrease of ventricular afterload (Picano et al., 1992; Lucarini et al., 1992). In addition, dipyridamole has documented anti-inflammatory properties, including antioxidant effects (Weyrich et al., 2005).
Successful protection against post-resuscitation myocardial injury is not available for trauma patients. Whereas intensive improvement in resuscitation strategies reduce myocardial injury, death among trauma patients are among the highest in the world due to myocardial dysfunction and multiple organ failure. Dipyridamole is a nucleoside transport inhibitor. Recent studies have shown that elevation of serum adenosine caused by dipyridamole improve cardiac function. The purpose of the present study was to examine the myocardial protective effects of dipyridamole therapy following 1 h of hemorrhagic shock.
Sprague–Dawley rats were used. The study consisted of three phases: Phase I to examine the direct effects of dipyridamole on myocardial function by perfusion of the isolated hearts with Krebs Henseleit buffer (KHB) + dipyridamole on the Langendorff apparatus. Phase II examined the protective effects of dipyridamole following 60 min of hemorrhagic shock (HS) by ex vivo treatment with dipyridimole 20 μg/L for 5 min followed by resuscitation with KHB for 55 min. Phase III: 60 min HS followed by in vivo treatment by injecting 1 ml of (20 μg/L) dipyridamole intra-arterially, and resuscitation for 30 min. Myocardial protection was assessed by measuring left ventricular generated pressure (LVGP) and end diastolic pressures (LVEDP).
During ex vivo resuscitation, hearts from dipyridamole treated animals had significantly higher LVGP, and significantly lower LVEDP versus controls.
Dipyridamole therapy produces protection against post-resuscitation myocardial injury in rats.
Clinical and prognostic role of pressure-volume relationship in the identification of responders to cardiac resynchronization therapy
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In patients with depressed ejection fraction (<35%), the identification of contractile reserve during dobutamine stress echocardiography has been shown to provide important prognostic information27 in revascularized ischemic cardiomyopathy,28 as well as in nonischemic cardiomyopathy patients on medical therapy,29,30 and in low-flow, low-gradient severe aortic stenosis patients undergoing valve replacement.31 Contractile reserve is a specific marker of underlying myocardial viability, which can also be assessed with similar accuracy by nuclear medicine and cardiac magnetic resonance (CMR) techniques.32,33 These techniques also showed that the extent of viable myocardium and/or transmural scar tissue play an important role in identifying responders to CRT.5-8,34,35
The identification of responders remains challenging in cardiac resynchronization therapy (CRT). Pressure-volume relationship (PVR) is a method to evaluate left ventricular myocardial contractility during stress. The aim of the study was to assess the role of PVR to identify responders to CRT.
Seventy-two patients (57% with ischemic etiology) referred to CRT: ejection fraction ≤35%, New York Heart Association ≥III and QRS duration ≥120 milliseconds, underwent dobutamine stress echocardiography (up to 40 μg/kg per minute). PVR was defined as systolic cuff pressure/end-systolic volume index difference between rest-peak dobutamine stress echocardiography. Responders were identified by clinical and/or echocardiographic (end-systolic volume decrease ≥15%) follow-up criteria. We divided retrospectively the patient population into 2 groups, accordingly to the presence of myocardial contractile reserve that was set at the value of PVR (0.72 mm Hg/mL per square meter) obtained by a receiver operating characteristic analysis.
During a median follow-up of 12 months, 8 patients (11%) died. Patients with lower PVR, showed higher brain natriuretic peptide levels (853 ± 1211 vs 342 ± 239, P = .044) larger left ventricular end-diastolic (196 ± 82 mL vs 152 ± 39 mL, P = .005) and end-systolic (147 ± 66 vs 112 ± 30 mL, P = .006) volumes. Intraventricular dyssynchrony was similar in the 2 groups (88 ± 45 vs 70 ± 32 milliseconds, P = .175). Patients with higher PVR presented a larger incidence of clinical (86% vs 46% P < .001), and echocardiographic responders to CRT (79% vs 40%, P = .002). Event-free survival was significantly better in patients with higher PVR (log rank = 5.78, P = .01).
Patients with preserved contractility, assessed by PVR during stress echocardiography show a favor clinical outcome and left ventricular reverse remodeling after CRT. In particular, PVR may have a significant clinical role in patients undergoing CRT, providing critical information for risk stratification.
Stress Echocardiography with Nonexercise Techniques: Principles, Protocols, Interpretation, and Clinical Applications
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Prognostic Value of Pharmacologic Stress Echocardiography in Patients With Idiopathic Dilated Cardiomyopathy: A Prospective, Head-to-Head Comparison Between Dipyridamole and Dobutamine Test
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All of these studies showed a beneficial effect of inotropic reserve on prognosis, although disparate methodology, selection criteria, and prognostic end points were used.5–14 In ischemic heart disease the low dipyridamole dose stress echocardiography was shown to be an effective tool in the detection of myocardial viability,20,21 and the extent of myocardial viability was associated with a higher survival probability.3 In patients with DCM, only one study demonstrated the prognostic significance of contractile reserve induced by a high dipyridamole dose.14
Inotropic reserve identified by dobutamine or dipyridamole stress echocardiography is associated with a better outcome in patients with idiopathic dilated cardiomyopathy (DCM), although the relative prognostic value of each remains unsettled. The purpose of the present study was to assess the relative prognostic value of dobutamine versus dipyridamole stress echocardiography for the prediction of all-cause death in patients with idiopathic DCM.
Eighty-seven patients (63 were male, aged 54 ± 12 years) with DCM and an ejection fraction less than 35% underwent both dipyridamole and dobutamine stress echocardiography on different days and in a random order. In all patients, wall motion score index and ejection fraction were evaluated at baseline and peak stress. All patients were followed up for an average of 52 months. All-cause death was identified as the prognostic end point. During the follow-up, 26 all-cause deaths occurred (29.8%). On multivariate analysis, either dobutamine echocardiography (relative risk 0.299; P = .02; 95% confidence interval 0.084–0.835) or dipyridamole echocardiography (relative risk 0.161; P < .00; 95% confidence interval 0.07–0.394) added significantly to a prognostic model based on clinical and resting echocardiographic variables. Survival was 83% in patients with dobutamine and 84% in patients with dipyridamole-induced contractile reserve.
Dobutamine and dipyridamole stress echocardiography have similar feasibility and prognostic accuracy in DCM risk stratification.
Predictive value of biphasic response during dipyridamole echocardiography test in the low-risk group of patients after acute myocardial infarction
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To investigate whether biphasic response during dipyridamole echocardiography test (DET), which represents viable but potentially ischemic myocardium in the infarcted region, affects prognosis of patients after uncomplicated acute myocardial infarction, we performed high-dose DET in 80 consecutive patients younger than 65 years with first acute myocardial infarction and preserved left ventricular function. Patients were followed up for 27 ± 12 months for new coronary events. According to DET results all patients were classified into 4 groups: group 1 consisted of 20 patients with biphasic response; group 2 included 14 patients with sustained improvement in regional contractility; group 3 consisted of 24 patients showing no change in contractility; and group 4 included 22 patients with worsening response. Cumulative survival free of total coronary events was significantly lower in group 1 patients compared with all other groups (P < .05). By multivariate Cox analysis biphasic response was the strongest independent predictor of stable angina pectoris (odds ratio = 12.1, P = .0002), followed by hyperlipoproteinemia (odds ratio = 5.9, P = .006). On the other hand, development of acute coronary syndromes could not have been predicted by actual clinical or DET parameters.

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Identification of viable myocardium by dipyridamole-induced improvement in regional left ventricular function assessed by echocardiography in myocardial infarction and comparison with thallium scintigraphy at rest

Abstract

Am Heart J

J Am Coll Cardiol

J Am Call Cardiol

J Am Coll Cardiol

Am J Cardiol

Am J Cardiol

Am J Cardiol

J Am Coll Cardiol

J Am Coll Cardiol

J Am Coll Cardiol

Am Heart J

J Am Coll Cardiol

Prog Cardiovasc Dis

J Am Coll Cardiol

Am Coll Cardiol

J Am Coll Cardiol

Myocardial viability. What does it mean and how do measure it?

Circulation

Identification of viable myocardium in patients with chronic coronary artery disease and left ventricular dysfunction. Comparison of thallium scintigraphy with reinjection and PET imaging with F-fluorodeoxyglucose

Circulation