Carlo Caiati

Validation of a new noninvasive method (contrast-enhanced transthoracic second harmonic echo Doppler) for the evaluation of coronary flow reserve: Comparison with intracoronary Doppler flow wire

OBJECTIVES We tested the hypothesis that coronary flow reserve (CFR) in the left anterior descending coronary artery (LAD) as assessed by a new noninvasive method (contrast-enhanced transthoracic second harmonic echo Doppler) is in agreement with CFR measurements assessed by intracoronary Doppler flow wire. BACKGROUND Contrast-enhanced transthoracic second harmonic echo Doppler is a novel noninvasive method to detect blood flow velocity and reserve in the LAD. However, it has not yet been validated versus a gold-standard method. METHODS Twenty-five patients undergoing CFR assessment in the LAD by Doppler flow wire were also evaluated by contrast-enhanced transthoracic Doppler to record blood flow in the distal LAD at rest and during hyperemia obtained by adenosine i.v. infusion. In five patients CFR was evaluated twice (before and after angioplasty). RESULTS As a result of the combined use of i.v. contrast and second harmonic Doppler technology, feasibility in assessing coronary flow reserve equaled 100%. The agreement between the two methods was high. In fact, in all but five patients the maximum difference between the two CFR measurements was 0.38. Overall, the prediction (95%) interval of individual differences was -0.69 to +0.72. Reproducibility of CFR measurements was also high. The limits of the agreement (95%) between the two measurements were -0.32 to +0.32. CONCLUSIONS Coronary flow reserve in the LAD as assessed by contrast-enhanced transthoracic echo Doppler along with harmonic mode concurs very closely with Doppler flow wire CFR measurements. This new noninvasive method allows feasible, reliable and reproducible assessment of CFR in the LAD.

Improved Doppler detection of proximal left anterior descending coronary artery stenosis after intravenous injection of a lung-crossing contrast agent: a transesophageal Doppler echocardiographic study.

OBJECTIVE This study was designed to verify the usefulness of transesophageal Doppler recording of blood flow velocity in the proximal left anterior descending coronary artery, after a peripheral injection of a lung-crossing contrast agent (SHU 508A), in detecting and locating a hemodynamically significant stenosis (vessel narrowing > or = 50%) affecting this portion of the vessel. BACKGROUND Transesophageal Doppler echocardiography has a limited diagnostic impact on the evaluation of proximal left anterior descending coronary artery stenoses. Peripheral injection of SHU 508A, a lung-crossing contrast agent enhancing Doppler signal to noise ratio in coronary arteries, may allow recording of localized disturbed blood flow velocity at the stenosis site even in the absence of a clear B-mode visualization of the vessel. METHODS Transesophageal Doppler echocardiography, before and after echo contrast injection, was performed in 31 patients who underwent coronary angiography. Using color Doppler as a guide, pulsed wave Doppler recording of blood flow velocity in the left anterior descending coronary artery was attempted to detect a localized increase in blood flow velocity. B-mode evaluation of the vessel was also performed. RESULTS Angiography showed a significant proximal left anterior descending coronary artery stenosis in 16 patients (group 1) and no stenosis in 15 patients (group 2). In 15 of 16 group 1 patients, Doppler after contrast injection revealed a localized velocity increase of at least 50% of the reference value; mean (+/-SD) percent increase in velocity was 150 +/- 89% (range 367% to 0%). In group 2 Doppler after contrast injection revealed a mild localized increase in velocity in four patients and no increase in velocity in the remaining 11 patients; mean (+/-SD) percent increase in velocity was 5 +/- 7% (range 21% to 0%, p < 0.001 vs. percent increase in group 1). When a percent velocity increase > or = 50% of the reference value was considered a positive criterion for detecting significant stenosis, the sensitivity and specificity were 92% and 100% respectively. The sensitivity of the evaluation before contrast injection or considering B-mode imaging alone was much lower (25% and 19%, respectively, p < 0.001 vs. evaluation after contrast injection). In addition, color Doppler after contrast injection correctly located the stenosis along the vessel, as compared with angiography. CONCLUSIONS Blood flow evaluation of the proximal left anterior descending coronary artery by transesophageal Doppler echocardiography after contrast injection is a feasible and reliable method for detecting and locating significant stenoses affecting this part of the vessel and is an improvement over the traditional ultrasound approach.

Improved Doppler signal intensity in coronary arteries after intravenous peripheral injection of a lung-crossing contrast agent (SHU 508A)

OBJECTIVES We tested the hypothesis that SHU 508A, a new lung-crossing contrast agent capable of increasing the Doppler signal to noise ratio in the right heart as well as left heart cavities after intravenous injection, could increase Doppler signal intensity in coronary arteries, thus improving the feasibility and quality of transesophageal Doppler echocardiographic evaluation of coronary blood flow velocity. BACKGROUND Coronary blood flow velocity can be evaluated by transesophageal Doppler echocardiography. However, an adequate Doppler tracing is obtainable in a relatively low percent of patients. METHODS Transesophageal Doppler echocardiography of coronary arteries was performed in 35 patients before and after SHU 508A injection at four different dosages (200 mg/ml in 5 ml, 200 mg/ml in 10 ml, 300 mg/ml in 5 ml and 300 mg/ml in 10 ml). Color Doppler mapping of coronary flow and pulsed wave Doppler measurement of coronary blood flow velocity were attempted in all patients. RESULTS Color Doppler flow mapping of 105 evaluated coronary segments (left main, left anterior descending and circumflex in 35 patients) was not detectable or was weak in 88% of patients before and 33% of patients after echo contrast injection (p < 0.0001); it was optimal (that is, well delineated with complete flow mapping of the explored vessel) in only 11% of patients before and 67% after echo contrast injection (p < 0.0001). In addition, pulsed wave Doppler signal quality improved after echo contrast injection: Pulsed wave Doppler recording of coronary blood flow velocity was not obtainable or was weak in 78% of cases before and 34% after echo contrast injection (p < 0.0001); pulsed wave Doppler recording of coronary blood flow velocity was optimal (that is, there was a complete and well defined outline of diastolic coronary blood flow velocity in 23% of cases before and 66% after echo contrast injection [p < 0.0001]. Both length and width of color Doppler mapping in the left anterior descending coronary artery increased after SHU 508A injection (from 5.75 +/- 5.32 and 1.51 +/- 1.17 to 17.04 +/- 8.76 and 4.21 +/- 1.78 mm, respectively, mean +/- SD, p < 0.0001). CONCLUSIONS The feasibility and quality of recording coronary blood flow velocity by transesophageal Doppler echocardiography are considerably improved by intravenous injection of SHU 508A. The improved feasibility of this new semi-invasive method for evaluating coronary blood flow velocity and flow reserve can considerably increase its research and clinical utilization.

Prediction of cardiac events after uncomplicated myocardial infarction by cross-sectional echocardiography during transesophageal atrial pacing

Atrial pacing can safely be utilized shortly after myocardial infarction. To evaluate the prognostic value of wall motion abnormalities induced by such pacing 83 consecutive patients with recent uncomplicated myocardial infarction underwent transthoracic cross-sectional echocardiography during transesophageal atrial pacing and upright bicycle exercise stress test. Patients were followed-up for 14 +/- 5 months. During the atrial pacing and the echocardiography, patients were defined at high risk if abnormalities of wall motion were detected in left ventricular regions remote from the infarcted area. Then, during the exercise stress test, high risk patients were those with ST segment depression greater than or equal to 1 mm. On the other hand, patients were considered to be at low risk if they had no abnormalities of wall motion during atrial pacing in remote regions or, in the case of the stress test, if they did not develop ST depression greater than or equal to 1 mm. Of the 83 patients, 21 had major cardiac events during the period of follow-up. Cardiac events occurred in 15/23 (65%) and 5/60 (8%, P less than 0.001) patients assigned to the groups adjudged to be at high and low risk, respectively, on the basis of echocardiographic results. Exercise testing was less reliable in identifying patients at risk of future cardiac events. Major events occurred in only 6 of the 19 patients with a positive stress test (32%, P less than 0.05 vs positive stress echocardiography) and in 14 of the 64 patients with a negative exercise stress test (22%, P = NS vs positive exercise stress test, P less than 0.05 vs negative atrial pacing echocardiography).

Detection, location, and severity assessment of left anterior descending coronary artery stenoses by means of contrast-enhanced transthoracic harmonic echo Doppler

AIMS Contrast-enhanced second harmonic Doppler (ED) is a new ultrasound modality that increases the feasibility of recording blood flow velocity (BFV) in the left anterior descending coronary artery (LAD) using a transthoracic approach. Blood flow velocity convective acceleration is a reliable marker of coronary stenosis and can be used to assess the percentage area reduction at the stenosis site by applying the continuity equation. To detect, locate, and assess the severity of significant stenosis throughout the LAD by means of an ED recording of BFV acceleration at the stenosis site. METHODS AND RESULTS Fifty-three consecutive patients undergoing coronary angiography (CA) underwent a colour-guided pulsed-wave ED recording of BFV in the proximal/mid and distal portions of the LAD, and maximal and reference BFV was obtained in each of the two arterial segments. Maximal velocity was much higher in the diseased segments (>or=50% lumen narrowing) than in the normal segments (143 +/- 84 vs. 38 +/- 20 cm/s; P < 0.001); as the reference velocity was similar (37 +/- 13 vs. 31 +/- 12; P = 0.03), the percentage increase in velocity was also higher (290 +/- 233 vs. 20 +/- 37%; P < 0.001). Using a cut-off value of an 82% increase in velocity, sensitivity and specificity vs. CA was, respectively, 86 and 95%. The reduction in the percentage area of stenosis calculated using the continuity equation agreed with that determined by means of quantitative CA (r = 0.7). CONCLUSION Blood flow velocity evaluation in the LAD by means of transthoracic ED is feasible and reliable in detecting, locating, and assessing the severity of LAD stenosis.

Early Noninvasive Evaluation of Coronary Flow Reserve after Angioplasty in the Left Anterior Descending Coronary Artery Identifies Patients at High Risk of Restenosis at Follow-Up

BACKGROUND Coronary restenosis is the most important clinical limitation after percutaneous coronary intervention (PCI), and coronary flow reserve (CFR) is reduced in the presence of significant coronary stenosis. This study evaluated whether detection of early reduction of Doppler echocardiographically derived CFR in the left anterior descending coronary artery can identify patients at high risk for developing restenosis after successful PCI. METHODS Doppler echocardiographically derived CFR was studied in 124 consecutive patients at 1-month and 6-month follow-up after PCI in the left anterior descending coronary artery, together with coronary angiography. RESULTS Restenosis was detected in 39 angiographic examinations (group A) and no coronary restenosis in the remaining 85 (group B) at 6 months. At 1 month, CFR was reduced in group A compared with group B (P < .0001), and a significant reduction of CFR in group A (P < .0001) but not in group B (P = .89) was detected at 6 months. CFR ≤ 2.5 at 1 month was 67% sensitive and 87% specific for predicting significant restenosis, with positive and negative predictive values of 67% and 87%, respectively. CONCLUSIONS CFR ≤ 2.5 detected 1 month after PCI in the left anterior descending coronary artery has the potential to identify patients at higher risk for developing coronary restenosis and indicates the need for close clinical follow-up.

Sudden cardiac death secondary to demonstrated reperfusion ventricular fibrillation in a woman with Takotsubo cardiomyopathy

Takotsubo cardiomyopathy is a left ventricle cardiomyopathy characterized by a reversible dyskinesia responsible for the typical apical ballooning aspect. The disease is considered benignant with a full recovery within a few weeks. We present the case of a 52-year-old woman who presented with angina diagnosed with Takotsubo cardiomyopathy on the basis of both noninvasive (electrocardiography, echocardiography) and invasive (angiography) exams. At discharge, a Holter monitor was fitted to the patient. During the recording the patient faced sudden cardiac death. The analysis of the Holter traces allowed some speculations on the mechanism of this unexpected arrhythmic death. The cause of the fatal ventricular fibrillation appears to be the fast reperfusion following a short occlusion of an epicardial coronary artery. This case highlights the epicardial vasospasm as an important pathogenic mechanism of the syndrome and the possible usefulness of diagnostic tests able to elicit the spasm susceptibility and guide a more targeted pharmacological therapy. Some considerations are also possible on the cellular processes linking the rapid reperfusion and the arrhythmias onset.

Transesophageal echo-Doppler studies of coronary arteries — identification, assessment of flow reserve and value of contrast enhancement

Blood flow in the left coronary artery usually has a biphasic pattern with a greater diastolic and a smaller systolic component. The diastolic component is greater because in diastole coronary resistance is lower and the pressure gradient between the aortic root and left ventricle (i.e. the driving pressure) is higher. The amount of coronary blood flow (or flow velocity), its baseline characteristics and the changes induced by drugs capable of decreasing coronary resistance (and thus increasing forward flow) represent an important aspect of clinical and research cardiology studies. A better understanding of coronary pathophysiology is, in fact, extremely useful for the comprehension of the underlying angina mechanisms in some non “coronary artery diseases” characterized by effort chest pain (patients with reduced coronary flow reserve), for the evaluation of the effects of coronary active drugs and for the assessment of resting flow alterations in coronary arteries produced by different cardiac diseases.

The importance of stress-induced cardiac wall motion abnormalities in the evaluation of drug intervention

SummaryStress-induced wall motion abnormalities are a sensitive marker of myocardial ischaemia. Stress echocardiography has recently been the subject of increasing interest because of its improved feasibility and compatibility with new and effective alternative stresses. Transoesophageal atrial pacing (TAP) with 2-dimensional echocardiography (2-D echo) is a recently developed echocardiographic stress procedure that has been shown to be reliable and effective in both the diagnosis and evaluation of stress-induced myocardial ischaemia.TAP with 2-D echo was performed after treatment with placebo and intravenous gallopamil 0.03 mg/kg in 12 patients with stable, reproducible angina of effort. Compared with placebo, gallopamil treatment increased the time to 1mm ST-segment depression (6.6 vs 5.3 minutes; p < 0.05) and improved the ventricular wall motion score at a heart rate of 130 beats/min (17 vs 15; p < 0.01) and 150 beats/min (13 vs 11; p = 0.07). Three patients who developed angina after placebo administration were symptom-free after gallopamil. Thus, gallopamil exerts a beneficial effect on atrial pacing-induced ischaemia, by increasing the pacing time to the ischaemic threshold and reducing the extent of dysfunctional myocardium during ischaemia.

Transesophageal echocardiographic assessment of coronary flow reserve and coronary artery stenosis using echo enhancement

Echocardiography has been used to visualize proximal portions of coronary arteries since the advent of the technique [1, 2]. Transesophageal echocardiography (TEE) produces high quality images due to the proximity of the probe to the heart and the use of high frequency transducers, and has reawakened interest in the coronary echocardiographic field. Using transesophageal Doppler echocardiography, evaluation of the left main coronary artery (LMCA) has improved, and this is now a useful tool for detecting left main coronary artery stenosis [3–5]. In addition, transesophageal Doppler echocardiography has been used to record blood flow velocity in proximal left anterior descending coronary artery (LAD) in resting conditions and after pharmacological vasodilatation to explore the maximal amount of flow that the coronary vascular bed can accommodate above normal (coronary flow reserve) [6–8]. The importance of coronary flow reserve assessment lies in the fact that it is considered a better indicator of the functional significance of a coronary stenosis [9] — visual inspection by angiography of the anatomical severity of a coronary stenosis does not accurately reflect its physiological importance [10]. However, several limitations have impeded the widespread clinical application of TEE to coronary artery visualization and, consequently, stenosis detection and coronary blood flow reserve assessment. First, apart from the LMCA, the rest of the proximal left coronary tree is poorly visualized by TEE. In particular, the success rate in imaging an adequate portion of the proximal left anterior descending coronary artery, whose pathology carries important clinical and prognostic implications for the patient [11, 12], is low, with a consequent relatively poor diagnostic impact of TEE on the evaluation of proximal LAD coronary stenosis. On the other hand, TEE coronary flow reserve evaluation has a rather long learning-curve and, even after that, the ability to attain a good quality time—velocity curve (especially the systolic curve) in LMA bifurcation is suboptimal. For these reasons the attention of some research groups has been directed towards a lung-crossing contrast agent which, when injected i.v., could enhance the intensity of Doppler signal and thus the signal-to-noise ratio in coronary arteries, improving the quality and feasibility of coronary blood flow velocity Doppler recording. In this chapter we will discuss the clinical usefulness of the lung-crossing contrast agent, SHU 508A in improving assessment of coronary flow reserve and detection of proximal left anterior descending coronary artery stenosis during transesophageal Doppler echocardiography.