Author + information
- Received August 12, 1996
- Revision received March 24, 1997
- Accepted April 17, 1997
- Published online August 1, 1997.
- José Alberto San Román, MD, FESCA,*,
- Isidre Vilacosta, MD, FESCB,
- María Jesús Rollán, MDB,
- Juan Antonio Castillo, MDB,
- Joaquín Alonso, MD, FESCA,
- Juan Manuel Durán, MDA,
- Federico Gimeno, MD, PhDA,
- José Luis Vega, MD, FESCA,
- Luis Sánchez-Harguindey, MDB and
- Francisco Fernández-Avilés, MD, FESC, FACCA
- ↵*Dr. José Alberto San Román, Cardiology Department, Ramón y Cajal 3, 47011 Valladolid, Spain.
Objectives. We sought to analyze right ventricular contractility during dobutamine infusion in patients with right coronary artery disease and to elucidate whether the development of right ventricular asynergy aids in characterizing a right coronary artery stenosis.
Background. Clinical investigations are emphasizing the importance of right ventricular function in patients with coronary artery disease. Thus, prognosis of patients with inferior myocardial infarction is influenced by right ventricular function. This study describes the echocardiographic and electrocardiographic findings during dobutamine-atropine echocardiography in patients with right coronary artery disease.
Methods. We studied 31 patients with isolated right coronary artery disease and no previous myocardial infarction. Six patients with poor acoustic window were excluded (feasibility 80%). The remaining 25 patients underwent dobutamine-atropine echocardiography. A right coronary artery stenosis located before the origin of the right ventricular branches was considered proximal; otherwise, it was considered distal.
Results. Right ventricular asynergy during dobutamine-atropine testing developed in 17 patients (sensitivity 68%); 14 had proximal and 3 had distal right coronary artery disease. The following segments were involved: inferior (n = 17), lateral (n = 5) and outflow tract (n = 1). No patient showed anterior asynergy. All 17 patients had left ventricular asynergy as well. Ischemia-free time was 10.7 ± 6.2 (mean ± SD) min for the right ventricle and 8.9 ± 5.2 min for the left ventricle (p < 0.05). Ischemic ST changes were recorded in 15 patients (in standard leads in 14 and in right precordial leads in 8). All patients with right precordial changes showed ST elevation and had right ventricular asynergy (sensitivity and specificity for right ventricular asynergy 47% and 100%, respectively). A control group of 25 patients with no right coronary artery disease (5 with no disease, 15 with left anterior descending and 5 with left circumflex coronary artery disease) underwent dobutamine echocardiography. Right ventricular asynergy developed in two patients with left anterior descending artery stenosis (specificity 92%); in both, the anterior wall was affected.
Conclusions. Echocardiography during dobutamine infusion is a reliable technique for assessing right ventricular dysfunction in patients with right coronary artery disease. Right ventricular contractility can be assessed during dobutamine echocardiography in selected patients.
Increasing evidence from clinical investigation is emphasizing the importance of evaluating right ventricular function in patients with coronary artery disease [1–4]. The value of two-dimensional echocardiography in assessing regional right ventricular contraction after inferior myocardial infarction has been documented [5–7]. In patients with no previous myocardial infarction, right ventricular function is usually adequate at rest despite the existence of compromised right ventricular myocardial blood supply secondary to coronary artery disease. However, echocardiographic and ventriculographic [9, 10]studies have shown markedly abnormal performance during exercise in patients with right coronary artery disease. The appearance of transient right ventricular asynergy during pharmacologic stress echocardiography has heretofore not been evaluated. This prospective study describes the echocardiographic and electrocardiographic (ECG) findings during intravenous infusion of dobutamine in consecutive patients with right coronary artery stenosis. Our purpose has been to analyze right ventricular contractility during dobutamine infusion and to elucidate whether the development of right ventricular asynergy aids in characterizing a right coronary artery stenosis.
We prospectively studied 31 consecutive patients with isolated right coronary artery stenosis. Patients with prior myocardial infarction or with left coronary artery disease (either left main, left anterior descending or left circumflex) were excluded. All patients had angina (15 on effort and 16 at rest) and underwent coronary angiography as recommended by their referring physicians on the basis of clinical findings. Medical treatment was withdrawn 48 h before the study, with the exception of short-acting nitrates if needed. Informed consent was obtained in all cases.
Because inclusion in the study required adequate echocardiographic image, 6 (19%) of the 31 patients were excluded because a poor quality acoustic window precluded assessment of the right ventricle. The final study group comprised the remaining 25 patients (20 male; mean age 63 ± 11 years) who underwent dobutamine-atropine echocardiography.
In part 2 of the study, we assessed the specificity of right ventricular dysfunction during dobutamine administration. Systematic right ventricular segment analysis was performed in all patients with suspected coronary artery disease without coronary angiography who underwent dobutamine echocardiography in our department. Coronary angiography was performed subsequently in some patients if indicated by their referring physician. Our control group comprised the first 25 patients with no disease or with one-vessel disease (excluding the right coronary artery): 5 patients with no disease, 15 with left anterior descending and 5 with left circumflex artery disease.
1.2 Coronary angiography.
The coronary arteries were visualized with use of the Judkins technique and multiple standard projections. A coronary stenosis with >50% reduction of lumen diameter was considered significant. Evaluation was made by hand-held electronic calipers.
A right coronary artery stenosis located before the origin of the right ventricular branches was considered proximal (Fig. 1); otherwise, it was considered distal.
1.3 Dobutamine-atropine intravenous infusion.
Dobutamine was infused for 15 min. An initial rate of 10 μg/kg per min was increased by 10 μg/kg per min every 3 min up to an infusion rate of 40 μg/kg per min that was maintained for 6 min. At the end of the infusion, 1 mg of atropine was administered if 85% of the maximal predicted heart rate had not been achieved.
The infusion was interrupted prematurely for any one of the following situations: 1) achievement of maximal heart rate; 2) systolic or diastolic blood pressure >220 mm Hg or >120 mm Hg, respectively; 3) sustained ventricular arrhythmias; 4) symptomatic hypotension; 5) severe angina; 6) ST segment depression >0.3 mV or elevation >0.2 mV. The development of either right or left ventricular asynergy was not considered an end point, and infusion was continued unless right and left ventricular asynergy appeared together or one of the aforementioned situations occurred.
1.4 Echocardiographic examinations.
Continuous monitoring with two-dimensional echocardiography was carried out at baseline, during drug infusion and up to 10 min after cessation of infusion. M-mode echocardiography was performed when possible. Commercially available machines were used.
To visualize the right and left ventricles, six views were attempted in each patient. Thus, parasternal long- and short-axis, apical four- and two-chamber and subcostal long- and short-axis views were obtained when possible. If any view offered a poor quality image it was excluded from further analysis and the remaining views were considered.
The right ventricle was divided into four segments as previously described : anterior, lateral and inferior walls and wall of the outflow tract. The left ventricle was also studied to detect any wall motion abnormality not present before dobutamine infusion by using a 16-segment model . Segmental wall motion was graded as normal, hypokinetic, akinetic or dyskinetic. An echocardiographic result was defined as positive if areas of transient asynergy developed that had been absent or of lesser degree at baseline.
Recordings were stored by means of videotapes in conventional motion format with the possibility of frame by frame analysis. On-line and off-line analyses were qualitatively performed by two experienced observers (>300 studies analyzed). Decision was made by consensus in cases of disagreement (normal vs. hypokinesia in one patient; akinesia vs. hypokinesia in one patient).
1.5 ECG studies.
Standard 12-lead, right precordial leads (V3R and V4R) and blood pressure were obtained at baseline, every 2 min and when required by the echocardiographer. ECG findings were considered positive when >0.1 mV of ST segment depression or elevation from baseline at 0.08 s from the J point appeared.
Qualitative variables are expressed as percent. Quantitative variables are expressed as mean value ± SD and were compared by Student ttest. Significance was set at a value of p < 0.05.
Coronary angiography, right and left ventricular analysis and ECG results in patients with right coronary disease are depicted in Table 1. Angiography demonstrated right coronary artery stenosis in 25 patients (proximal in 17 and distal in 8). Patients 10 and 16 had coronary occlusion with collateral circulation. All patients had a dominant right coronary artery.
No patient had wall motion abnormalities at baseline or required premature interruption of drug infusion. Right ventricular asynergy during dobutamine infusion (Fig. 2and Fig. 3) was found in 17 patients (14 with proximal and 3 with distal right coronary artery disease) (sensitivity 68%). In this study, therefore, sensitivity and specificity of right ventricular asynergy during stress for proximal right coronary disease were 82% and 62%, respectively. The inferior segment of the right ventricle was involved in all 17 cases, the lateral in 5 and the ventricular outflow tract in 1. No patient showed anterior asynergy.
Asynergy of the left ventricle during dobutamine administration was found in 21 patients (16 with proximal and 5 with distal right coronary artery stenosis). All patients with right ventricular asynergy had left ventricular asynergy as well; that is, no patient showed isolated right ventricular asynergy. Left ventricular asynergy was mainly located in the inferior and inferoposterior segments. In two patients, asynergy extended to the posterior segments.
We have found the subcostal approach to be particularly useful. In most patients the right ventricular walls were well seen from this window. In addition, M-mode echocardiography was helpful in assessing wall motion. The apical view allows imaging of only one right ventricular segment, and the parasternal window offers a poor quality image in a high proportion of patients, thus limiting its practical value.
In the 17 patients with right and left ventricular asynergy, the time from the onset of infusion to the development of asynergy was 10.7 ± 6.2 min for the right ventricle and 8.9 ± 5.2 min for the left ventricle (p < 0.05). Left ventricular preceded right ventricular asynergy in 11 patients; in 4 patients, asynergy of both ventricles developed simultaneously after atropine infusion.
2.2 Specificity (control group).
In 2 of the 25 patients in the control group, right ventricular dysfunction developed in conjunction with left ventricular wall motion abnormalities. Both patients had left anterior descending artery stenosis and were noted to have akinesia of the anterior wall of the right ventricle during dobutamine administration. Thus, specificity of right ventricular dysfunction for right coronary artery disease was 92%. Left ventricular wall abnormalities appeared in 15 patients (70%) with coronary artery disease (12 with left anterior descending and 3 with left circumflex artery disease). Dobutamine echocardiographic findings were negative for ischemia of the left ventricle in the five patients with no disease.
2.3 ECG findings.
ECG results were positive for ischemia in 15 patients. In these patients, ST segment changes appeared later than wall motion abnormalities (12.1 ± 7.7 vs. 9.1 ± 5.8 min, p < 0.05).
An ischemic response in standard leads was found in 14 patients. All 14 had left ventricular asynergy (10 with proximal and 4 with distal right coronary artery stenosis). ST segment elevation was present in seven patients with proximal and two with distal stenosis.
Right precordial leads showed ST elevation in eight patients; all had right ventricular asynergy (six with proximal and two with distal right coronary artery disease). No patient had ST depression in right precordial leads. Thus, ST changes in right precordial leads during dobutamine infusion had a sensitivity and specificity for right ventricular asynergy of 47% and 100%, respectively. For proximal right coronary stenosis, ST changes in right precordial leads had a similar sensitivity (35%) and specificity (88%).
The development of right ventricular asynergy during pharmacologic stress echocardiography has not been previously reported. In this study, dobutamine infusion provoked right ventricular wall motion abnormalities in patients with right coronary artery disease. We demonstrated the high specificity of this sign: Right ventricular dysfunction developed in only two patients without right coronary artery disease. We also addressed the usefulness of searching for wall motion abnormalities in the right ventricle to better characterize a right coronary artery stenosis. Thus, the development of right ventricular asynergy during dobutamine administration suggests the presence of a proximal stenosis. Furthermore, the absence of right ventricular asynergy in patients with right coronary artery stenosis indicates the presence of a distal stenosis. However, some patients with distal disease showed right ventricular asynergy during the test because not only the right ventricular branches but also the posterior descending artery can irrigate the inferior wall of the right ventricle. Right ventricular asynergy appeared in patients in whom dobutamine already had provoked left ventricular asynergy and no patient had isolated right ventricular asynergy. From a practical standpoint, searching for right ventricular ischemia is justified for the following reasons when ischemia of the inferior wall of the left ventricle appears: 1) Isolated abnormalities of the posterobasal segment of the left ventricle are a well recognized cause of false positive results on stress echocardiography . The existence of right ventricular asynergy should be of help in distinguishing a false from a true positive echocardiographic result; 2) spatial and temporal coordinates help to stratify positive responses and to correlate them with the severity of coronary artery disease; 3) prognosis of patients with inferior myocardial infarction is adversely affected by the presence of right ventricular wall motion abnormalities. Likewise, it can be speculated that right ventricular ischemia during dobutamine echocardiography might indicate a worse prognosis.
3.1 Assessment of right ventricular function.
Some investigators have suggested that the left ventricular ejection fraction does not correlate with exercise performance in the failing heart. Rather, the right ventricular ejection fraction correlates with exercise capacity. In patients with coronary artery disease, the right ventricular ejection fraction was demonstrated by radionuclide ventriculography [9, 10]to decrease during exercise. Likewise, the significance of evaluating right ventricular wall motion abnormalities when searching for coronary artery disease was suggested in a study in which a small cohort of patients showed right ventricular dysfunction . Our study is the first to undertake right ventricular regional analysis during dobutamine echocardiography. Other investigators used different types of stress for the same purpose. Using radionuclide angiography, Parodi et al. demonstrated the presence of regional right ventricular dysfunction during pacing tachycardia in 95% of patients with a fixed right coronary artery stenosis. Their results and ours suggest that a systematic approach to the right ventricle when performing pharmacologic stress echocardiography assists in the diagnosis and better characterization of a right coronary artery stenosis. Although the prognostic value of this approach is not fully proved, the prognostic value of the right ventricular ejection fraction has been demonstrated in patients with coronary artery disease and congestive heart failure.
3.2 Echoanatomic correlations.
In right dominant hearts (90% of cases) the right coronary artery nourishes the entire right ventricle except for the anterior wall, which receives its blood supply from branches originating from the left anterior descending artery . The relation between left anterior descending artery disease and the anterior wall of the right ventricle has been pointed out in reports in which asynergy of the anterior margin of the right ventricle accompanied anterior myocardial infarction. In our study the anterior wall was not affected in any patient with right coronary disease because no patient had left anterior descending artery stenosis. In contrast, two patients with left anterior descending stenosis had akinesia of the anterior wall of the right ventricle. Therefore, if the anterior wall of the right ventricle is ignored when searching for right coronary artery disease, specificity of right ventricular wall motion abnormalities increases to up to 100%. In other words, asynergy in the inferior, lateral or ventricular outflow tract walls can be considered a hallmark of right coronary stenosis.
The lateral wall is irrigated by the marginal branches which, together with the posterior descending artery, irrigate the inferior wall . Dobutamine infusion most frequently provoked asynergy of the inferior wall, which is the wall usually involved in patients with inferior myocardial infarction of the left ventricle .
3.3 Ischemic threshold of the ventricles.
In our study, ischemia-free time was shorter in the left than in the right ventricle. In other words, the right ventricle had a higher ischemic threshold. To our knowledge, no other investigation has studied this issue. Anatomic factors contribute to explain the differences in the ischemic threshold of the two ventricles. For example, the right ventricle is protected from ischemic injury by the thebesian veins and thus is not always affected in proximal occlusions of a dominant right coronary artery. Furthermore, the right ventricle is a low pressure system that, in contrast to the left ventricle, not only has little myocardial oxygen demand but also augments coronary blood flow during systole. In keeping with this statement is the finding that right ventricular infarction did not develop in any of 51 pigs after right coronary artery occlusion. In addition, the right ventricle is much thinner than the left, another protective factor that favors coronary blood flow. The fact that in animal models right ventricular infarction is more frequent when the right ventricle is hypertrophied further corroborates these theoretic explanations.
3.4 ECG changes.
It is generally agreed that ST segment elevation in right precordial leads is a sensitive and specific marker of right ventricular infarction . Braat et al. noted that this alteration disappeared within 10 h after the onset of symptoms in half of their patients. In our study, 8 of 17 patients with right ventricular asynergy manifested transient ST elevation in right precordial leads that normalized within 15 min after cessation of dobutamine infusion. These data demonstrate that ST elevation in right precordial leads is related not only to right ventricular infarction but also to reversible ischemia. Thus, the clinical practice of routinely including right precordial leads when obtaining an ECG during chest pain at rest may prove useful in identifying right ventricular involvement in the ischemic event.
3.5 Limitations of the method.
Searching for right ventricular asynergy during dobutamine stress echocardiography has some limitations. In this study, feasibility was 80%, lower than that reported when searching for left ventricular asynergy. Parasternal and subcostal views are essential to interrogate the right ventricle. In practice, an apical view of sufficient quality for analysis of the left ventricle is not difficult to obtain; by contrast, poor parasternal and subcostal windows are relatively frequent. In addition, a “blind area” (the right ventricle is beneath the sternum) can preclude complete analysis of the right chamber. Radionuclide angiography overcomes this limitation, and its results in searching for right ventricular ischemia have been encouraging . Performance of stress echocardiography requires experienced observers . In all likelihood, the learning curve will be longer for the study of the right than of the left ventricle given complicated contractility and complex shape of the right chamber. Not simple mathematic formulas from a single plane, as in study of the left ventricle, but use of orthogonal images in different planes is demanded, and echocardiographers are not accustomed to this approach. In this sense, the analysis of right ventricular function is time-consuming and the echocardiographer may therefore miss abnormalities of new onset in the left ventricle.
Our results demonstrate that dobutamine administration can provoke right ventricular asynergy in patients with right coronary artery lesions. Ischemia-free time is longer in the right than in the left ventricle. Furthermore, assessment of right ventricular performance during dobutamine testing aids in characterizing right coronary artery stenosis. ECG changes in right precordial leads are a very specific marker of right ventricular asynergy. The prognostic value of right ventricular asynergy during dobutamine administration remains speculative.
We deeply appreciate the technical assistance of Josefina Albújar, Olga Alfonso, Ana España, Inés Gómez and Marı́a Sánchez.
- Received August 12, 1996.
- Revision received March 24, 1997.
- Accepted April 17, 1997.
- The American College of Cardiology
- Dell’Italia LJ,
- Starling MD,
- Crawford MH,
- Boros BL,
- Chaudhuri TK,
- O’Rourke RA
- Oldershaw P
- D’Arcy B,
- Nanda NC
- Brown KA,
- Okada RD,
- Boucher CA,
- Strauss HW,
- Pohost GM
- Bach DS,
- Muller DW,
- Gros BJ,
- Armstrong WF
- Parodi O,
- Neglia D,
- Marcassa C,
- Marzullo P,
- Sambuceti G
- Polak JF,
- Holman BL,
- Wynne J,
- Colucci WS
- Farrer-Brown G
- King SB III.,
- Douglas JS
- Braat SH,
- Brugada P,
- De Zwaan C,
- Coenegracht JM,
- Wellens HJ
- Picano E,
- Lattanzi F,
- Orlandini A,
- Marini C,
- L’Abbate A