Effects of haemodynamically atrio-ventricular optimized His bundle pacing on heart failure symptoms and exercise capacity: the His Optimized Pacing Evaluated for Heart Failure (HOPE-HF) randomized, double-blind, cross-over trial.

AIMS: Excessive prolongation of PR interval impairs coupling of atrio-ventricular (AV) contraction, which reduces left ventricular pre-load and stroke volume, and worsens symptoms. His bundle pacing allows AV delay shortening while maintaining normal ventricular activation. HOPE-HF evaluated whether AV optimized His pacing is preferable to no-pacing, in a double-blind cross-over fashion, in patients with heart failure, left ventricular ejection fraction (LVEF) ≤40%, PR interval ≥200 ms and either QRS ≤140 ms or right bundle branch block. METHODS AND RESULTS: Patients had atrial and His bundle leads implanted (and an implantable cardioverter-defibrillator lead if clinically indicated) and were randomized to 6 months of pacing and 6 months of no-pacing utilizing a cross-over design. The primary outcome was peak oxygen uptake during symptom-limited exercise. Quality of life, LVEF and patients' holistic symptomatic preference between arms were secondary outcomes. Overall, 167 patients were randomized: 90% men, 69 ± 10 years, QRS duration 124 ± 26 ms, PR interval 249 ± 59 ms, LVEF 33 ± 9%. Neither peak oxygen uptake (+0.25 ml/kg/min, 95% confidence interval [CI] -0.23 to +0.73, p = 0.3) nor LVEF (+0.5%, 95% CI -0.7 to 1.6, p = 0.4) changed with pacing but Minnesota Living with Heart Failure quality of life improved significantly (-3.7, 95% CI -7.1 to -0.3, p = 0.03). Seventy-six percent of patients preferred His bundle pacing-on and 24% pacing-off (p < 0.0001). CONCLUSION: His bundle pacing did not increase peak oxygen uptake but, under double-blind conditions, significantly improved quality of life and was symptomatically preferred by the clear majority of patients. Ventricular pacing delivered via the His bundle did not adversely impact ventricular function during the 6 months.

Optimizing atrio-ventricular delay in pacemakers using potentially implantable physiological biomarkers.

BACKGROUND: Hemodynamically optimal atrioventricular (AV) delay can be derived by echocardiography or beat-by-beat blood pressure (BP) measurements, but analysis is labor intensive. Laser Doppler perfusion monitoring measures blood flow and can be incorporated into future implantable cardiac devices. We assess whether laser Doppler can be used instead of BP to optimize AV delay. METHODS: Fifty eight patients underwent 94 AV delay optimizations with biventricular or His-bundle pacing using laser Doppler and simultaneous noninvasive beat-by-beat BP. Optimal AV delay was defined using a curve of hemodynamic response to switching from AAI (reference state) to DDD (test state) at several AV delays (40-320 ms), with automatic quality control checking precision of the optimum. Five subsequent patients underwent an extended protocol to test the impact of greater numbers of alternations on optimization quality. RESULTS: 55/94 optimizations passed quality control resulting in an optimal AV delay on laser Doppler similar to that derived by BP (median absolute deviation 12 ms). An extended protocol with increasing number of replicates consistently improved quality and reduced disagreement between laser Doppler and BP optima. With only five replicates, no optimization passed quality control, and the median absolute deviation would be 29 ms. These improved progressively until at 50 replicates, all optimizations passed quality control and the median absolute deviation was only 13 ms. CONCLUSIONS: Laser Doppler perfusion produces hemodynamic optima equivalent to BP. Quality control can be automatic. Adding more replicates, consistently improves quality. Future implantable devices could use such methods to dynamically and reliably optimize AV delays.

Independent and incremental value of stress echocardiography over clinical and stress electrocardiographic parameters for the prediction of hard cardiac events in new-onset suspected angina with no history of coronary artery disease.

AIMS: Recent data have shown that exercise electrocardiogram (ECG) has no incremental prognostic value over clinical and rest ECG parameters in chest pain patients without a history of coronary artery disease (CAD). The incremental prognostic value of stress echocardiography (SE) in this population is unknown. METHODS AND RESULTS: Accordingly, 547 consecutive patients (68 ± 4.9 years) with chest pain but no previous history of CAD, referred for SE (exercise and dobutamine), were identified. Patients were followed up for death and acute myocardial infarction (AMI). At a median follow-up period of 28 months, there were a total of 35 hard cardiac events (5 deaths and 30 non-fatal AMI). Among the prognostic clinical, resting/stress ECG, and SE data, univariate predictors were the Framingham risk score (P = 0.025), diabetes (P = 0.06), hypercholesterolaemia (P = 0.06), stress ECG ischaemia (P = 0.044), stress heart rate (P = 0.019), and SE-determined ischaemic burden (stress-rest wall thickening score index; P < 0.001). In a multivariate model, ischaemic burden was the only independent predictor of events (P < 0.001). SE also showed incremental prognostic value over and above clinical (Framingham's risk score) and stress ECG changes in a global χ(2) model. This was true also for patients undergoing only exercise SE (n = 347). CONCLUSION: SE provides both independent and incremental prognostic value for the prediction of hard cardiac events in chest pain patients without a previous history of CAD-over and above clinical, ECG, and stress ECG data.

Myocardial contrast echocardiography versus single photon emission computed tomography for assessment of hibernating myocardium in ischemic cardiomyopathy: preliminary qualitative and quantitative results.

BACKGROUND: Single photon-emission computed tomography (SPECT) is widely used for the assessment of hibernating myocardium (HM). The aim of this study was to test the hypothesis that myocardial contrast echocardiography (MCE), because of its better spatial and temporal resolution, would be superior to SPECT for the detection of HM. METHODS: Thirty-nine consecutive patients with symptomatic ischemic cardiomyopathy underwent rest and vasodilator SPECT and MCE. Of these, 23 survived to undergo assessment 3 months after revascularization for the recovery of left ventricular (LV) function (spontaneous recovery or dobutamine induced), which is the definition of HM. RESULTS: Of the 214 dysfunctional segments, 156 segments demonstrated HM in the 23 patients, of whom 16 showed significant improvement in LV function. Logistic regression analysis showed that both qualitative and quantitative MCE were independent predictors for the detection of HM (P < .0001 vs P = .06 for qualitative MCE vs qualitative SPECT, respectively, and P < .01 vs P = .25 for all quantitative myocardial contrast echocardiographic parameters vs quantitative SPECT, respectively). Using clinical and LV functional data, SPECT, and MCE for predicting the recovery of LV function, MCE was the only independent predictor (P = .03). CONCLUSION: MCE was superior to SPECT for the assessment of HM in ischemic cardiomyopathy.

Resting myocardial blood flow, coronary flow reserve, and contractile reserve in hibernating myocardium: implications for using resting myocardial contrast echocardiography vs. dobutamine echocardiography for the detection of hibernating myocardium.

AIMS: Controversy exists regarding the relative status of resting myocardial blood flow (MBF), coronary flow reserve (CFR), and contractile reserve (CR) in hibernating myocardium (HM). We hypothesized that CFR is more profoundly affected than resting MBF parameters in HM. Thus, resting MBF assessed by myocardial contrast echocardiography (MCE) will be more sensitive than CR elicited by dobutamine stress echocardiography (DSE) for the detection of HM. METHODS AND RESULTS: Accordingly 27 patients with ischaemic cardiomyopathy underwent resting MCE and DSE prior to revascularisation, of which 23 patients underwent follow-up echocardiography at 179 ± 66 days after revascularization. Qualitative and quantitative MCE [contrast intensity (A, dB)], MBF (represented by blood velocity ß, dB/s), and CFR (vasodilator ß/rest ß, ß reserve) were obtained. CR was obtained during DSE. Resting contrast intensity (7.2 ± 2.3 dB) and ß (0.67 ± 0.47 dB/s) were significantly (P < 0.005 and <0.01, respectively) reduced in HM vs. remote normal myocardium but significantly higher compared with non-viable segments (4.4 ± 2.3 dB and 0.43 ± 0.32 dB/s, respectively). However, CFR was significantly (0.82 ± 3.2 (P = 0.01)) lower in HM compared with normal (1.8 ± 1.02) but not significantly reduced when compared with non-viable myocardium (1.1 ± 3.3). Sensitivity for the detection of HM with qualitative and quantitative MCE were 82 and 87%, respectively, compared with 67% (P < 0.0001) by DSE with similar specificity of 55 and 67%, respectively, compared with 63% with DSE. CONCLUSION: Resting MBF but not CFR distinguished HM from non-viable myocardium. Resting MCE and not DSE was more accurate for the prediction of HM.

Prognostic value of myocardial contrast echocardiography in patients presenting to hospital with acute chest pain and negative troponin.

We hypothesized that myocardial contrast echocardiography (MCE) could be used to stratify risk in patients with suspected acute coronary syndrome but a nondiagnostic electrocardiogram and negative troponin. Pretest Thrombolysis In Myocardial Infarction (TIMI) scores were determined. Exercise electrocardiographic data in those patients undergoing treadmill stress echocardiography as part of risk evaluation were analyzed independently of echocardiographic data. On a separate day, low-power MCE at rest and during vasodilator stress was performed. All patients were followed for cardiac events (cardiac death, myocardial infarction, and revascularization). Of 148 patients, 27 demonstrated abnormal myocardial contrast echocardiographic results and had higher cardiac event rates compared with those with normal myocardial contrast echocardiographic findings (59% vs 7%, p <0.0001) at follow-up (8 +/- 5 months). Hard cardiac event rates (death and nonfatal myocardial infarction) were low (3%) in patients with normal myocardial contrast echocardiographic findings. Cardiac events in patients with abnormal myocardial contrast echocardiographic findings (59%) were significantly higher than those predicted by a high-risk TIMI score (33%, p = 0.0023) and compared with those predicted by high-risk exercise electrocardiography (80% vs 57%, p = 0.0003). In conclusion, stress MCE was superior to TIMI risk score and exercise electrocardiography in the assessment of risk in patients with suspected acute coronary syndrome, nondiagnostic electrocardiogram, and negative troponin.

Clinical and economic impact of stress echocardiography compared with exercise electrocardiography in patients with suspected acute coronary syndrome but negative troponin: a prospective randomized controlled study.

AIMS: Patients attending hospital with suspected acute coronary syndrome (ACS), non-diagnostic electrocardiogram (ECG), and negative troponin present a diagnostic dilemma for admitting physicians. We sought to determine the clinical and economic impact of stress echocardiography (SEcho) when compared with exercise ECG (ExECG) in the assessment of these patients. METHODS AND RESULTS: Following pre-test assessment by (Thrombolysis in Myocardial Infarction) TIMI score, patients were randomized to ExECG (n=218) or SEcho (n=215). Subsequently, low-risk patients were discharged; those considered high risk were referred for coronary angiography. Patients were followed-up for cardiac events and a cost-analysis performed. SEcho was superior to ExECG in stratifying patients as low risk (77 vs. 33%, respectively, P<0.0001) with no difference in cardiac event rate (5 vs. 3%, respectively). SEcho classified fewer patients as intermediate risk (3 vs. 39%, respectively, P<0.0001) and fewer patients required further tests when compared with ExECG (3 vs. 47%, respectively, P<0.0001). Costs for detection of coronary artery disease were significantly less in patients undergoing SEcho (pound366.63 vs. pound515.48, P=0.004). CONCLUSION: SEcho is superior to ExECG in the risk stratification of patients with suspected ACS but negative troponin. SEcho resulted in less diagnostic uncertainty, fewer referrals for further investigation, and hence, a significant cost benefit over ExECG.

Clinical significance of perfusion techniques utilising different physiological mechanisms to detect myocardial viability: a comparative study with myocardial contrast echocardiography and single photon emission computed tomography.

Myocardial uptake using (99m)Tc-sestamibi single photon emission computed tomography (SPECT) depends largely on myocardial microvascular volume. Myocardial contrast echocardiography (MCE) is a relatively new technique that detects not only microvascular volume but also blood flow. These differing mechanisms may affect the relative accuracies of MCE and SPECT for detecting myocardial viability (MV) early after acute myocardial infarction (AMI) and thrombolysis. Accordingly 56 patients underwent resting transthoracic echocardiography, low-power MCE and SPECT 7+/-2 days following first AMI and thrombolysis. Contractile reserve (CR) was assessed 3 months following revascularization. The sensitivity and specificity of MCE and SPECT were 83% and 78% (p=ns) and 78% and 45% (p<0.01) respectively. MCE was the only multivariate predictor of global recovery of function and CR (OR=3.5, p=0.01). The different physiological mechanisms employed by MCE and SPECT translate into different relative accuracies for the detection of MV.

Contrast echocardiography versus gated single photon emission computed tomography for the assessment of parameters of left ventricular remodeling after acute myocardial infarction.

BACKGROUND: Assessment of parameters of left ventricular (LV) remodeling after acute myocardial infarction (AMI) has both therapeutic and prognostic implication. Contrast echocardiography (CE) has the advantage of simultaneously assessing myocardial perfusion and LV remodeling. We aimed to evaluate the accuracy of CE to assess LV remodeling after AMI compared with technetium-99m sestamibi gated single photon emission computed tomography (SPECT). METHODS: Accordingly, 36 consecutive patients underwent gated SPECT, CE, and cardiovascular magnetic resonance imaging (CMR) 7 to 10 days after AMI. LV ejection fraction (LVEF), and LV end-systolic and end-diastolic volumes were assessed. RESULTS: Absolute differences for LVEF and LV end-diastolic volume between CMR and CE were significantly smaller than that between CMR and SPECT. CE estimate of LVEF more accurately classified patients into LVEF less than 35%, 35% to 45%, and greater than 45% (agreement = 83%, kappa = 0.66 with CMR) compared with SPECT (agreement = 61%, kappa = 0.36 with CMR). CONCLUSION: CE is more accurate than gated SPECT for the estimation of LV remodeling after AMI.

Stress echocardiography is superior to exercise ECG in the risk stratification of patients presenting with acute chest pain with negative Troponin.

OBJECTIVE: To compare exercise electrocardiography (ExECG) and stress echocardiography (SE) in the risk stratification of patients presenting to hospital with cardiac-sounding chest pain, non-diagnostic ECGs and negative cardiac Troponin. METHODS: Patients presenting with acute chest pain were prospectively randomised to early ExECG or SE. A post-test likelihood of CAD was determined by the pre-test likelihood and the result of the stress test. Patients with a low post-test likelihood of CAD were discharged; those with a high post-test probability were considered for coronary angiography. All others were managed according to standard hospital protocols. RESULTS: A total of 302 patients underwent either ExECG or SE. SE identified significantly more patients with a low post-test probability of CAD (80% vs 31%, p<0.0001) and significantly fewer patients with an intermediate post-test likelihood of CAD compared to ExECG (3% vs 47%; p<0.0001). Significantly fewer patients undergoing SE were referred for further tests to exclude or refute the diagnosis of CAD (16% vs 52%; p<0.0001). In total, 36 (12%) had flow limiting CAD demonstrated by coronary angiography. Significant CAD was seen in fewer patients with a positive ExECG than with a positive SE (56% vs 84% (p=0.12)). Event rates were low for both modalities in patients with low post-test probability (3.5% for SE vs 5.1% for ExECG; p=ns) though the number of patients identified as low risk was higher if SE was performed. CONCLUSION: Despite negative cardiac Troponin, 12% of patients with acute chest pain had significant CAD. SE is superior to ExECG in discriminating between those patients with a low and intermediate risk of CAD and correctly identified patients with significant CAD, as well as conferring an excellent prognosis in those considered low risk. SE significantly reduces the requirement for further tests to diagnose CAD compared to ExECG.

Improved accuracy of low-power contrast echocardiography for the assessment of left ventricular remodeling compared with unenhanced harmonic echocardiography after acute myocardial infarction: comparison with cardiovascular magnetic resonance imaging.

BACKGROUND: Assessment of left ventricular (LV) remodeling after acute myocardial infarction (AMI) has both therapeutic and prognostic implications. Low-power contrast echocardiography (CE) has the advantage of simultaneously assessing myocardial perfusion and LV remodeling. OBJECTIVE: This study aimed to evaluate the accuracy of low-power CE to assess LV remodeling after AMI compared with unenhanced harmonic echocardiography (HE). METHODS: A total of 36 consecutive patients underwent HE, CE (SonoVue), and cardiovascular magnetic resonance (CMR) imaging 7 to 10 days after AMI. Left ventricular ejection fraction (LVEF), end-systolic volume (LVESV), and end-diastolic volume (LVEDV) were assessed. RESULTS: Absolute differences for LVESV and LVEDV between CMR and CE were significantly smaller than those between CMR and HE. CE estimate of LVEF more accurately classified patients into LVEF < 35%, 35% to 45%, and > 45% (agreement, 83%; kappa = 0.66 with CMR) compared with HE (agreement, 69%; kappa = 0.33 with CMR). CONCLUSIONS: Low-power CE is more accurate than HE for estimating LV remodeling after AMI.

Myocardial contrast echocardiography for distinguishing ischemic from nonischemic first-onset acute heart failure: insights into the mechanism of acute heart failure.

BACKGROUND: Distinguishing ischemic from nonischemic origin in patients presenting with acute heart failure (AHF) not resulting from acute myocardial infarction has both therapeutic and prognostic implications. The aim of the study was to assess whether myocardial contrast echocardiography (MCE) can identify underlying coronary artery disease (CAD) as the cause of AHF. METHODS AND RESULTS: Fifty-two consecutive patients with AHF with no prior clinical history of CAD and no clinical evidence of acute myocardial infarction underwent resting echocardiography and MCE both at rest and after dipyridamole stress at a mean of 9+/-2 days after admission. All patients underwent coronary arteriography before discharge. Of the 52 patients, 22 demonstrated flow-limiting CAD (>50% luminal diameter narrowing). Sensitivity, specificity, and positive and negative predictive values of MCE for the detection of CAD were 82%, 97%, 95%, and 88%, respectively. Among clinical, ECG, biochemical, resting echocardiographic, and MCE markers of CAD, MCE was the only independent predictor of CAD (P<0.0001). Quantitative MCE demonstrated significantly (P<0.0001) lower myocardial blood flow velocity reserve in vascular territories subtended by >50% CAD (0.59+/-0.46) compared with patients with normal coronary arteries (1.99+/-1.00). However, myocardial blood flow velocity reserve in patients with no significant CAD was significantly (P=0.03) lower compared with control (2.91+/-0.41). Myocardial blood flow velocity reserve correlated significantly (P<0.0001) with increasing severity of CAD. CONCLUSIONS: MCE, which is a bedside technique, may be used to detect CAD in patients presenting with AHF without a prior history of CAD or evidence of acute myocardial infarction. Quantitative MCE may further risk-stratify patients with AHF but no CAD.

Usefulness of myocardial contrast echocardiography in predicting collateral blood flow in the presence of a persistently occluded acute myocardial infarction-related coronary artery.

Adequate collateral blood flow at rest can sustain myocardial viability despite persistent occlusion of the infarct-related artery (IRA) in acute myocardial infarction (AMI). This has therapeutic and prognostic implications. Studies addressing the value of intravenous myocardial contrast echocardiography (MCE) to detect collateral blood flow after AMI in humans are limited. Accordingly, 70 consecutive patients with AMI underwent low-power intravenous MCE using a Sonovue infusion 7 to 10 days after thrombolysis. Myocardial perfusion detected by MCE was analyzed (qualitatively and quantitatively) in the akinetic segments in 20 patients (29%) with an occluded IRA who subsequently underwent revascularization. Contractile reserve, which is a marker of myocardial viability, was assessed with low-dose dobutamine 12 weeks after mechanical revascularization. Of the 102 akinetic segments (32%), 37 (36%) showed contractile reserve. Contractile reserve was present in 24 of the 29 segments (83%) with homogenous contrast opacification and absent in 60 of the 73 segments (82%) with reduced/absent opacification. Quantitative peak contrast intensity, microbubble velocity, and myocardial blood flow were significantly higher (p <0.0001) in the segments with contractile reserve than in those without contractile reserve. Multiple logistic regression analysis using electrocardiographic, biochemical, and myocardial contrast echocardiographic markers of collateral blood flow showed that MCE (odds ratio 26.0, 95% confidence interval 6.3 to 108.0, p <0.001) was the only independent predictor of collateral blood flow as demonstrated by the presence of contractile reserve. MCE may thus be used as a reliable bedside technique for the accurate evaluation of collateral blood flow in the presence of an occluded IRA after AMI.