Clinical value, cost-effectiveness, and safety of myocardial perfusion scintigraphy: a position statement.

Mortality rates due to coronary artery disease (CAD) have declined in recent years as result of improved prevention, diagnosis, and management. Nonetheless, CAD remains the leading cause of death worldwide with most casualties expected to occur in developing nations. Myocardial perfusion scintigraphy (MPS) provides a highly cost-effective tool for the early detection of obstructive CAD in symptomatic individuals and contributes substantially to stratification of patients according to their risk of cardiac death or nonfatal myocardial infarction. MPS also provides valuable information that assists clinical decision-making with regard to medical treatment and intervention. A large body of evidence supports the current applications of MPS, which has become integral to several guidelines for clinical practice.     

Real-time three-dimensional echocardiography permits quantification of left ventricular mechanical dyssynchrony and predicts acute response to cardiac resynchronization therapy

Objective: To evaluate the value of real-time three-dimensional echocardiography (RT3DE) to predict acute response to cardiac resynchronization therapy (CRT).
Methods: Sixty consecutive heart failure patients scheduled for CRT were included. RT3DE was performed before and within 48 hours after pacemaker implantation to calculate both left ventricular (LV) volumes and LV dyssynchrony. LV dyssynchrony was defined as the standard deviation of the time taken to reach the minimum systolic volume for 16 LV segments (referred to as the systolic dyssynchrony index, SDI). Patients were subsequently divided into acute responders or nonresponders, based on a reduction ≥ 15% in LV end-systolic volume immediately after CRT.
Results: Four patients (7%) were excluded from further analysis because of either suboptimal apical acquisitions or significant translation artifacts. Out of the remaining 56 patients, 35 patients (63%) were classified as acute responders. Baseline characteristics were similar between responders and nonresponders, except for the SDI, which was larger in responders. Moreover, responders demonstrated a significant reduction of SDI immediately after CRT (from 9.7 ± 4.1% to 3.6 ± 1.8%, P < 0.0001), whereas SDI did not change in nonresponders (3.4 ± 1.8% vs 3.1 ± 1.1%, NS). ROC curve analysis revealed that a cut-off value for SDI of 5.6% yielded a sensitivity of 88% with a specificity of 86% to predict acute echocardiographic response to CRT (AUC 0.96).
Conclusion: RT3DE is highly predictive for acute response to CRT (sensitivity 88% and specificity 86%). In addition, RT3DE allows assessment of changes in LV volumes and LV ejection fraction before and after CRT implantation.     

Long-term prognostic value of ejection fraction changes during dobutamine-atropine stress echocardiography

OBJECTIVE: Dobutamine stress echocardiography (DSE), using subjective wall motion scoring, provides incremental prognostic information over clinical data. The aim of the study was to test the additional prognostic value of left ventricular ejection fraction (LVEF) changes during DSE at different stages. METHODS: The study population comprised 106 consecutive patients (mean age 60+/-11 years, 73% men) with suspected or known coronary artery disease referred for DSE. Stress-induced ischemia was defined as new or worsening wall motion abnormalities. LVEF was measured at rest, peak stress and recovery. Follow-up was successful in 104 (98%) patients. Four patients who underwent revascularization within 60 days were excluded from the analysis. End-points during follow-up were cardiac death, non-fatal myocardial infarction and late revascularization. RESULTS: During a mean follow-up of 5.3+/-2.1 years, 26% of patients died: 13% due to cardiac death, 6% patients experienced non-fatal myocardial infarction and 38% underwent late revascularization. Rest-to-peak LVEF increase was lower in patients who experienced cardiac death or non-fatal myocardial infarction (4.9+/-8.6 compared with 9.2+/-7.5, P=0.04) and any cardiac events (6.0+/-8.5 compared with 10.5+/-6.7, P=0.004). An inverse correlation was found between left ventricular ejection increase and the number of ischemic segments (P<0.0001). A multivariable Cox proportional hazard model demonstrated that, in addition to clinical data and new wall motion abnormalities, lower LVEF increase had an incremental prognostic value in predicting hard cardiac events (hazard ratio 1.1, 95% confidence interval 1.0-1.2). CONCLUSION: Failure of LVEF to significantly increase during DSE, denoting more extensive ischemia, identifies a higher-risk subgroup for late cardiac events.     

The significance of stress-induced ST segment depression in patients with inferior Q wave myocardial infarction

OBJECTIVES

This study was conducted to evaluate the relationship between ST segment depression (STD) during dobutamine stress tests in different electrocardiogram (ECG) leads and myocardial ischemia assessed by simultaneous single photon emission computed tomography (SPECT) imaging in patients with inferior Q wave myocardial infarction.

BACKGROUND

STD is a standard electrocardiographic sign of myocardial ischemia. Although STD may represent reciprocal changes in patients with previous myocardial infarction, studies of reciprocal changes during stress tests are scarce.

METHODS

Dobutamine (up to 40 μg/kg/min) stress and rest myocardial perfusion scintigraphy using technetium SPECT imaging was performed in 125 patients >3 months after Q wave inferior myocardial infarction. The location of STD at the ECG was defined as anterior (V_1–4), high lateral (I, aVL) and lateral (V_5,6). Ischemia was defined as reversible perfusion abnormalities.

RESULTS

STD occurred in the high lateral leads in 20 patients, in the anterior leads in 12 patients and in the lateral leads in 2 patients. ST segment elevation occurred in 25 patients in the inferior leads. High lateral STD was associated with inferior ST elevation in 16 patients (80%). There was a significant inverse linear correlation between the magnitude of ST segment shift from rest to peak stress in the inferior and the high lateral leads (r = −0.8, p < 0.0005), whereas no significant correlation was found between ST segment shift in the inferior and the anterior leads (r = −0.1, p = NS) or between the inferior and the lateral leads (r = 0.15, p = NS). Ischemia was detected in 45% of patients with and in 42% of patients without high lateral STD (p = NS). Patients with high lateral STD had a higher prevalence of fixed perfusion defects in the inferior wall (100% vs. 70%) and in the posterolateral wall (55% vs. 29%) compared with other patients (both p < 0.05). Ischemia was more prevalent in patients with anterior STD than without (75% vs. 39%, p < 0.05).

CONCLUSIONS

In patients with inferior Q wave myocardial infarction, stress-induced STD in high lateral leads should be recognized as a reciprocal change for ST elevation in the inferior leads, and therefore, should be interpreted with the consideration of the significance of ST elevation if present, rather than being indicative of myocardial ischemia on its own. The STD found in the anterior leads appears to be a sign of myocardial ischemia. These findings should be considered in the definition of a positive ECG stress test and in establishing the criteria for the termination of stress test.     

Improvement of left ventricular ejection fraction, heart failure symptoms and prognosis after revascularization in patients with chronic coronary artery disease and viable myocardium detected by dobutamine stress echocardiography.

OBJECTIVES: This study was designed to address, in patients with severe ischemic left ventricular dysfunction, whether dobutamine stress echocardiography (DSE) can predict improvement of left ventricular ejection fraction (LVEF), functional status and long-term prognosis after revascularization. BACKGROUND: Dobutamine stress echocardiography can predict improvement of wall motion after revascularization. The relation between viability, improvement of function, improvement of heart failure symptoms and long-term prognosis has not been studied. METHODS: We studied 68 patients with DSE before revascularization; 62 patients underwent resting echocardiography/radionuclide ventriculography before and three months after revascularization. Long-term follow-up data (New York Heart Association [NYHA] functional class, Canadian Cardiovascular Society [CCS] classification and events) were acquired up to two years. RESULTS: Patients with > or =4 viable segments on DSE (group A, n = 22) improved in LVEF at three months (from 27+/-6% to 33+/-7%, p < 0.01), in NYHA functional class (from 3.2+/-0.7 to 1.6+/-0.5, p < 0.01) and in CCS classification (from 2.9+/-0.3 to 1.2+/-0.4, p < 0.01); in patients with <4 viable segments (group B, n = 40) LVEF and NYHA functional class did not improve, whereas CCS classification improved significantly (from 3.0+/-0.8 to 1.3+/-0.5, p < 0.01). A higher event rate was observed at long-term follow-up in group B versus group A (47% vs. 17%, p < 0.05). CONCLUSIONS: Patients with substantial viability on DSE demonstrated improvement in LVEF and NYHA functional class after revascularization; viability was also associated with a favorable prognosis after revascularization.     

Cardiovascular mortality and heart failure risk score for patients after ST-segment elevation acute myocardial infarction treated with primary percutaneous coronary intervention (Data from the Leiden MISSION! Infarct Registry)

The risk scores developed for the prediction of an adverse outcome in patients after ST-segment elevation myocardial infarction (STEMI) have mostly addressed patients treated with thrombolysis and evaluated solely all-cause mortality as the primary end point. Primary percutaneous coronary intervention in patients with STEMI has improved the outcome significantly and might have changed the relative contribution of different risk factors. Our patient population included 1,484 consecutive patients admitted with STEMI who had undergone primary percutaneous coronary intervention. The clinical, angiographic, and echocardiographic data obtained during hospitalization were used to derive a risk score for the prediction of short-term (30-day) and long-term (1- and 4-year) cardiovascular mortality and hospitalization for heart failure. During a median follow-up of 30 months, 87 patients (6%) died from cardiovascular mortality or were hospitalized for heart failure. Multivariate Cox regression analyses identified age ≥70 years, Killip class ≥2, diabetes, left anterior descending coronary artery as the culprit vessel, 3-vessel disease, peak cardiac troponin T level ≥3.5 μg/L, left ventricular ejection fraction ≤40%, and heart rate at discharge ≥70 beats/min as relevant factors for the construction of the risk score. The discriminatory power of the model as assessed using the areas under the receiver operating characteristic curves was good (0.84, 0.83, and 0.81 at 30 days and 1 and 4 years, respectively), and the patients could be allocated to low-, intermediate-, or high-risk categories with an event rate of 1%, 6%, and 24%, respectively. In conclusion, the current risk model demonstrates for the first time that 8 parameters readily available during the hospitalization of patients with STEMI treated with primary percutaneous coronary intervention can accurately stratify patients at long-term follow-up (≤4 years after the index infarction) into low-, intermediate-, and high-risk categories.     

Dobutamine stress-redisstribution-reinjection versus rest-redistribution thallium-201 spect in the assessment of myocardial viability

The aim of this study was to evaluate the value of thallium-201 chloride (²⁰¹Tl) reinjection imaging following dobutamine stress (DRi) to identify viable myocardium in comparison with a rest-redistribution ²⁰¹Tl protocol (RR). The identification of viable myocardium bears important consequences for adequate selection of patients with poor left ventricular function, often unable to exercise, who are considered for revascularization. Twenty-six patients with chronic coronary artery disease and depressed left ventricular function (ejection fraction 36±10%) were studied by both DRi and RR single photon emission computed tomography (SPECT). Semi-quantitative analysis of regional ²⁰¹Tl activity (5-point score) and wall motion by echocardiography using a 16-segment model was performed. Regions were classified as viable (normal/reversible/fixed moderate defects) or non-viable (fixed severe defects) and related to regional wall motion. Target heart rate was reached in 25 patients. Myocardial viability was demonstrated in 353/416 (85%) by DRi SPECT and in 346/416 (83%) by RR SPECT. The agreement between the 2 protocols was 98% with a K-value of 0.94; similar results were obtained when the analysis was limited to dyscontractile segments. In conclusion, this study demonstrates the feasibility and diagnostic value of DRi SPECT to identify viable myocardium.     

Relation between ST segment elevation during dobutamine stress test and myocardial viability after a recent myocardial infarction.

OBJECTIVE: To assess the relation between ST segment elevation during the dobutamine stress test and late improvement of function after acute Q wave myocardial infarction. PATIENTS AND DESIGN: 70 patients were studied a mean (SD) 8 (3) days after acute myocardial infarction with high dose dobutamine-atropine stress echocardiography and a follow up echocardiogram at 85 (10) days. A score model based on 16 segments and four grades was used to assess left ventricular function. Functional improvement was defined as a reduction of wall motion score > or = 1 in > or = 1 segments at follow up. INTERVENTION: Myocardial revascularisation was performed in 23 patients (33%) before follow up studies. RESULTS: ST segment elevation occurred in 40 patients (57%). Late functional improvement occurred in 35 patients (50%). Functional improvement was more common in patients with ST segment elevation (68% v 30%, P < 0.005) and they had a higher mean (SD) number of improved segments at follow up (1.9 (2.2) v 0.5 (1.1), P < 0.005). The wall motion score index decreased between baseline and follow up in patients with ST segment elevation (1.54 (0.50) v 1.48 (0.43), P < 0.05) but not in patients without ST segment elevation (1.39 (0.60) v 1.45 (0.47)). The accuracy of ST segment elevation for the prediction of functional improvement was similar to that of low dose dobutamine echocardiography in patients with anterior infarction (80% v 83%) and in patients who underwent revascularisation (78% v 83% respectively). CONCLUSION: In patients with a recent Q wave myocardial infarction, dobutamine-induced ST segment elevation is a valuable marker of myocardial viability particularly when the test is performed without or with suboptimal echocardiographic imaging.     

pH-triggered,activated-state conformations of the influenza hemagglutinin fusion peptide revealed by NMR

The highly conserved first 23 residues of the influenza hemagglutinin HA2 subunit constitute the fusion domain, which plays a pivotal role in fusing viral and host-cell membranes. At neutral pH, this peptide adopts a tight helical hairpin wedge structure, stabilized by aliphatic hydrogen bonding and charge–dipole interactions. We demonstrate that at low pH, where the fusion process is triggered, the native peptide transiently visits activated states that are very similar to those sampled by a G8A mutant. This mutant retains a small fraction of helical hairpin conformation, in rapid equilibrium with at least two open structures. The exchange rate between the closed and open conformations of the wild-type fusion peptide is ∼40 kHz, with a total open-state population of ∼20%. Transitions to these activated states are likely to play a crucial role in formation of the fusion pore, an essential structure required in the final stage of membrane fusion.