Otto Kamp

EAE/ASE recommendations for image acquisition and display using three-dimensional echocardiography.

Roberto M. Lang, MD, FASE*‡, Luigi P. Badano, MD, FESC†‡, Wendy Tsang, MD*, David H. Adams, MD*, Eustachio Agricola, MD†, Thomas Buck, MD, FESC†, Francesco F. Faletra, MD†, Andreas Franke, MD, FESC†, Judy Hung, MD, FASE*, Leopoldo Pérez de Isla, MD, PhD, FESC†, Otto Kamp, MD, PhD, FESC†, Jaroslaw D. Kasprzak, MD, FESC†, Patrizio Lancellotti, MD, PhD, FESC†, Thomas H. Marwick, MBBS, PhD*, Marti L. McCulloch, RDCS, FASE*, Mark J. Monaghan, PhD, FESC†, Petros Nihoyannopoulos, MD, FESC†, Natesa G. Pandian, MD*, Patricia A. Pellikka, MD, FASE*, Mauro Pepi, MD, FESC†, David A. Roberson, MD, FASE*, Stanton K. Shernan, MD, FASE*, Girish S. Shirali, MBBS, FASE*, Lissa Sugeng, MD*, Folkert J. Ten Cate, MD†, Mani A. Vannan, MBBS, FASE*, Jose Luis Zamorano, MD, FESC, FASE†, and William A. Zoghbi, MD, FASE*

Lenient versus Strict Rate Control in Patients with Atrial Fibrillation

BACKGROUND Rate control is often the therapy of choice for atrial fibrillation. Guidelines recommend strict rate control, but this is not based on clinical evidence. We hypothesized that lenient rate control is not inferior to strict rate control for preventing cardiovascular morbidity and mortality in patients with permanent atrial fibrillation. METHODS We randomly assigned 614 patients with permanent atrial fibrillation to undergo a lenient rate-control strategy (resting heart rate <110 beats per minute) or a strict rate-control strategy (resting heart rate <80 beats per minute and heart rate during moderate exercise <110 beats per minute). The primary outcome was a composite of death from cardiovascular causes, hospitalization for heart failure, and stroke, systemic embolism, bleeding, and life-threatening arrhythmic events. The duration of follow-up was at least 2 years, with a maximum of 3 years. RESULTS The estimated cumulative incidence of the primary outcome at 3 years was 12.9% in the lenient-control group and 14.9% in the strict-control group, with an absolute difference with respect to the lenient-control group of -2.0 percentage points (90% confidence interval, -7.6 to 3.5; P<0.001 for the prespecified noninferiority margin). The frequencies of the components of the primary outcome were similar in the two groups. More patients in the lenient-control group met the heart-rate target or targets (304 [97.7%], vs. 203 [67.0%] in the strict-control group; P<0.001) with fewer total visits (75 [median, 0], vs. 684 [median, 2]; P<0.001). The frequencies of symptoms and adverse events were similar in the two groups. CONCLUSIONS In patients with permanent atrial fibrillation, lenient rate control is as effective as strict rate control and is easier to achieve. (ClinicalTrials.gov number, NCT00392613.)

Arterial Stiffness Increases With Deteriorating Glucose Tolerance Status The Hoorn Study

Background—Type 2 diabetes (DM-2) and impaired glucose metabolism (IGM) are associated with an increased cardiovascular disease risk. In nondiabetic individuals, increased arterial stiffness is an important cause of cardiovascular disease. Associations between DM-2 and IGM and arterial stiffness have not been systematically investigated. Methods and Results—In a population-based cohort (n=747; 278 with normal glucose metabolism, 168 with IGM, and 301 with DM-2; mean age, 68.5 years), arterial stiffness was ultrasonically estimated by distensibility and compliance of the carotid, femoral, and brachial arteries and by the carotid elastic modulus. After adjustment for age, sex, and mean arterial pressure, DM-2 was associated with increased carotid, femoral, and brachial stiffness, whereas IGM was associated only with increased femoral and brachial stiffness. Carotid but not femoral or brachial stiffness increased from IGM to DM-2. Standardized &bgr;s (95% CI) for IGM and DM-2, compared with normal glucose metabolism, were −0.06 (−0.23 to 0.10) and −0.37 (−0.51 to −0.23) for carotid distensibility; −0.02 (−0.18 to 0.18) and −0.25 (−0.40 to −0.09) for carotid compliance; −0.05 (−0.23 to 0.13) and 0.25 (0.10 to 0.40) for carotid elastic modulus; −0.70 (−0.89 to −0.51) and −0.67 (−0.83 to −0.52) for femoral distensibility; and −0.62 (−0.80 to −0.44) and −0.79 (−0.94 to −0.63) for femoral compliance. The brachial artery followed a pattern similar to that of the femoral artery. Increases in stiffness indices were explained by decreases in distension, increases in pulse pressure, an increase in carotid intima-media thickness, and, for the femoral artery, a decrease in diameter. Hyperglycemia or hyperinsulinemia explained only 30% of the arterial changes associated with glucose tolerance. Adjustment for conventional cardiovascular risk factors did not affect these findings. Conclusions—IGM and DM-2 are associated with increased arterial stiffness. An important part of the increased stiffness occurs before the onset of DM-2 and is explained neither by conventional cardiovascular risk factors nor by hyperglycemia or hyperinsulinemia.

Automatic segmentation of echocardiographic sequences by active appearance motion models

A novel extension of active appearance models (AAMs) for automated border detection in echocardiographic image sequences is reported. The active appearance motion model (AAMM) technique allows fully automated robust and time-continuous delineation of left ventricular (LV) endocardial contours over the full heart cycle with good results. Nonlinear intensity normalization was developed and employed to accommodate ultrasound-specific intensity distributions. The method was trained and tested on 16-frame phase-normalized transthoracic four-chamber sequences of 129 unselected infarct patients, split randomly into a training set (n=65) and a test set (n=64). Borders were compared to expert drawn endocardial contours. On the test set, fully automated AAMM performed well in 97% of the cases (average distance between manual and automatic landmark points was 3.3 mm, comparable to human interobserver variabilities). The ultrasound-specific intensity normalization proved to be of great value for good results in echocardiograms. The AAMM was significantly more accurate than an equivalent set of two-dimensional AAMs.

Ultrasound and Microbubble-Targeted Delivery of Macromolecules Is Regulated by Induction of Endocytosis and Pore Formation

Contrast microbubbles in combination with ultrasound (US) are promising vehicles for local drug and gene delivery. However, the exact mechanisms behind intracellular delivery of therapeutic compounds remain to be resolved. We hypothesized that endocytosis and pore formation are involved during US and microbubble targeted delivery (UMTD) of therapeutic compounds. Therefore, primary endothelial cells were subjected to UMTD of fluorescent dextrans (4.4 to 500 kDa) using 1 MHz pulsed US with 0.22-MPa peak-negative pressure, during 30 seconds. Fluorescence microscopy showed homogeneous distribution of 4.4- and 70-kDa dextrans through the cytosol, and localization of 155- and 500-kDa dextrans in distinct vesicles after UMTD. After ATP depletion, reduced uptake of 4.4-kDa dextran and no uptake of 500-kDa dextran was observed after UMTD. Independently inhibiting clathrin- and caveolae-mediated endocytosis, as well as macropinocytosis significantly decreased intracellular delivery of 4.4- to 500-kDa dextrans. Furthermore, 3D fluorescence microscopy demonstrated dextran vesicles (500 kDa) to colocalize with caveolin-1 and especially clathrin. Finally, after UMTD of dextran (500 kDa) into rat femoral artery endothelium in vivo, dextran molecules were again localized in vesicles that partially colocalized with caveolin-1 and clathrin. Together, these data indicated uptake of molecules via endocytosis after UMTD. In addition to triggering endocytosis, UMTD also evoked transient pore formation, as demonstrated by the influx of calcium ions and cellular release of preloaded dextrans after US and microbubble exposure. In conclusion, these data demonstrate that endocytosis is a key mechanism in UMTD besides transient pore formation, with the contribution of endocytosis being dependent on molecular size.

Assessment of Myocardial Reperfusion by Intravenous Myocardial Contrast Echocardiography and Coronary Flow Reserve After Primary Percutaneous Transluminal Coronary Angiography in Patients With Acute Myocardial Infarction

Background—This study investigated whether the extent of perfusion defect determined by intravenous myocardial contrast echocardiography (MCE) in patients with acute myocardial infarction (AMI) treated by primary percutaneous transluminal coronary angioplasty (PTCA) relates to coronary flow reserve (CRF) for assessment of myocardial reperfusion and is predictive for left ventricular recovery. Methods and Results—Twenty-five patients with first AMI underwent intravenous MCE with NC100100 with intermittent harmonic imaging before PTCA and after 24 hours. MCE before PTCA defined the risk region and MCE at 24 hours the “no-reflow” region. The no-reflow region divided by the risk region determined the ratio to the risk region. CFR was assessed immediately after PTCA and 24 hours later. Left ventricular wall motion score indexes were calculated before PTCA and after 4 weeks. CFR at 24 hours defined a recovery (CFR ≥1.6; n=17) and a nonrecovery group (CFR <1.6; n=8). Baseline CFR did not differ between groups. M...

Prognostic Implications of Restrictive Left Ventricular Filling in Acute Myocardial Infarction: A Serial Doppler Echocardiographic Study

OBJECTIVES This study was designed to evaluate the relative prognostic significance of restrictive left ventricular (LV) filling after acute myocardial infarction. BACKGROUND Data regarding the contribution of diastolic dysfunction to prognosis after myocardial infarction are limited, and the additional value over the assessment of systolic dysfunction is not known. METHODS Serial Doppler echocardiography was performed in 95 patients on days 1, 3 and 7 and 3 months after acute myocardial infarction. Patients were classified into two groups: a restrictive group (n = 12) with a peak velocity of early diastolic filling wave (E)/peak velocity of late filling wave (A) ratio > or = 2 or between 1 and 2 and a deceleration time (DT) < or = 140 ms during at least one echocardiographic study; and a nonrestrictive group (n = 83) with an E/A ratio < or = 1 or between 1 and 2 and a DT > 140 ms at all examinations. RESULTS Cardiac death occurred in 10 patients during a mean follow-up interval of 32 +/- 17 months. The survival rate at 1 year was 100% in the nonrestrictive group and only 50% in the restrictive group. After 1 year there was a continuing divergence of mortality, resulting in a 3-year survival rate of 100% and 22%, respectively. Univariate Cox analysis revealed that restrictive LV filling, wall motion score index, ejection fraction and end-systolic and end-diastolic volume indexes, as well as peak creatine kinase, peak MB fraction and heart failure during the hospital course were significant predictors of cardiac death, although restrictive filling was the single best predictor (p < 0.0001). Multivariate analysis showed that restrictive filling adds prognostic information to clinical and echocardiographic variables of systolic dysfunction. CONCLUSIONS Restrictive LV filling after acute myocardial infarction is the single best predictor of cardiac death and adds significantly to clinical and echocardiographic markers of systolic dysfunction.

Pioglitazone Improves Cardiac Function and Alters Myocardial Substrate Metabolism Without Affecting Cardiac Triglyceride Accumulation and High-Energy Phosphate Metabolism in Patients With Well-Controlled Type 2 Diabetes Mellitus

Background— Cardiac disease is the leading cause of mortality in type 2 diabetes mellitus (T2DM). Pioglitazone has been associated with improved cardiac outcome but also with an elevated risk of heart failure. We determined the effects of pioglitazone on myocardial function in relation to cardiac high-energy phosphate, glucose, and fatty acid metabolism and triglyceride content in T2DM patients. Methods and Results— Seventy-eight T2DM men without structural heart disease or inducible ischemia as assessed by dobutamine stress echocardiography were assigned to pioglitazone (30 mg/d) or metformin (2000 mg/d) and matching placebo for 24 weeks. The primary end point was change in cardiac diastolic function from baseline relative to myocardial metabolic changes, measured by magnetic resonance imaging, proton and phosphorus magnetic resonance spectroscopy, and [18F]-2-fluoro-2-deoxy-d-glucose and [11C]palmitate positron emission tomography. No patient developed heart failure. Both therapies similarly improved glycemic control, whole-body insulin sensitivity, and blood pressure. Pioglitazone versus metformin improved the early peak flow rate (P=0.047) and left ventricular compliance. Pioglitazone versus metformin increased myocardial glucose uptake (P<0.001), but pioglitazone-related diastolic improvement was not associated with changes in myocardial substrate metabolism. Metformin did not affect myocardial function but decreased cardiac work relative to pioglitazone (P=0.006), a change that was paralleled by a reduced myocardial glucose uptake and fatty acid oxidation. Neither treatment affected cardiac high-energy phosphate metabolism or triglyceride content. Only pioglitazone reduced hepatic triglyceride content (P<0.001). Conclusions— In T2DM patients, pioglitazone was associated with improvement in some measures of left ventricular diastolic function, myocardial glucose uptake, and whole-body insulin sensitivity. The functional changes, however, were not associated with myocardial substrate and high-energy phosphate metabolism.

Improved clinical outcome after invasive management of patients with recent myocardial infarction and proven myocardial viability: primary results of a randomized controlled trial (VIAMI-trial)

BackgroundPatients with ST-elevation myocardial infarction (STEMI) not treated with primary or rescue percutaneous coronary intervention (PCI) are at risk for recurrent ischemia, especially when viability in the infarct-area is present. Therefore, an invasive strategy with PCI of the infarct-related coronary artery in patients with viability would reduce the occurrence of a composite end point of death, reinfarction, or unstable angina (UA).MethodsPatients admitted with an (sub)acute myocardial infarction, who were not treated by primary or rescue PCI, and who were stable during the first 48 hours after the acute event, were screened for the study. Eventually, we randomly assigned 216 patients with viability (demonstrated with low-dose dobutamine echocardiography) to an invasive or a conservative strategy. In the invasive strategy stenting of the infarct-related coronary artery was intended with abciximab as adjunct treatment. Seventy-five (75) patients without viability served as registry group. The primary endpoint was the composite of death from any cause, recurrent myocardial infarction (MI) and unstable angina at one year. As secondary endpoint the need for (repeat) revascularization procedures and anginal status were recorded.ResultsThe primary combined endpoint of death, recurrent MI and unstable angina was 7.5% (8/106) in the invasive group and 17.3% (19/110) in the conservative group (Hazard ratio 0.42; 95% confidence interval [CI] 0.18-0.96; p = 0.032). During follow up revascularization-procedures were performed in 6.6% (7/106) in the invasive group and 31.8% (35/110) in the conservative group (Hazard ratio 0.18; 95% CI 0.13-0.43; p < 0.0001). A low rate of recurrent ischemia was found in the non-viable group (5.4%) in comparison to the viable-conservative group (14.5%). (Hazard-ratio 0.35; 95% CI 0.17-1.00; p = 0.051).ConclusionWe demonstrated that after acute MI (treated with thrombolysis or without reperfusion therapy) patients with viability in the infarct-area benefit from a strategy of early in-hospital stenting of the infarct-related coronary artery. This treatment results in a long-term uneventful clinical course. The study confirmed the low risk of recurrent ischemia in patients without viability.Trial registrationClinicalTrials.gov: NCT00149591.

Hemodynamic Benefits of Right Ventricular Outflow Tract Pacing: Comparison with Right Ventricular Apex Pacing

To assess optimal hemodynamics in relation to stimulation site during right ventricular pacing, 17 consecutive patients who underwent cardiac catheterization were studied. In all patients, right ventricular apex and right ventricular outflow tract stimulation was performed at 85, 100, and 120 beats/min. Cardiac index at both pacing sites was compared using the left ventricular outflow tract continuous wave Doppler technique. Comparison of the two stimulation sites demonstrated that right ventricular outflow tract pacing resulted in a higher cardiac index at 85 beats/min (2.42 ± 1.2 vs 2.04 ±1.0 L/min per m2, P < 0.002) at 100 beats/min (2.78 ± 1.4 vs 2.35 ± 1.1 L/min perm2, P < 0.001) and 120 beats/min (3.00 ± 1.5 vs 2.61 ± 0.9 L/min perm2, P < 0.001). From a total of 51 paired observations, 45 showed an increase in cardiac index during outflow tract pacing as compared to apex pacing. Right ventricular outflow tract pacing at 120 beats/min resulted in a lower cardiac index than right ventricular apex pacing in patients with significant coronary artery disease and/or impaired left ventricular function (ejection fraction ≤ 50%), whereas right ventricular outflow tract pacing produced higher cardiac indices in the absence of these abnormalities. Right ventricular outflow tract pacing resulted in higher cardiac indices as compared to apex pacing in all other subgroups at all other pacing sites tested. It is concluded that stimulation of the right ventricular outflow tract offers a significant hemodynamic benefit during single chamber pacing as compared to conventional apex pacing, particularly in the absence of significant coronary artery disease and/or left ventricular dysfunction.