Multimodality Imaging in the Management of Tricuspid Valve Regurgitation.

Approximately 5% of elderly patients suffer from moderate or severe tricuspid valve regurgitation, which is an independent predictor of high morbidity and mortality. Surgical treatment of isolated tricuspid valve regurgitation has been associated with elevated fatality rate, leading to a growing interest in minimal invasive, transcatheter-based therapies such as transcatheter edge-to-edge repair and transcatheter valve replacement. Nevertheless, despite high procedural efficacy and safety of transcatheter-based therapies, a number of challenges limit their rapid adoption in routine clinical practice. In particular, the wide range of transcatheter approaches to address the significant variability in tricuspid valve pathology challenges the reproducibility of clinical outcomes. Multimodality imaging is pivotal for grading the regurgitation severity, determining the underlying pathology, assessing RV function and pulmonary pressures, identifying concomitant cardiac disease, and selecting the most beneficial treatment modality and access. This article reviews the role of different imaging modalities in guiding the management of patients with significant tricuspid valve regurgitation.

Clinical outcomes of Watchman vs. Amplatzer occluders for left atrial appendage closure (WATCH at LAAC).

AIMS: This study compares clinical outcomes of Watchman vs. Amplatzer devices for left atrial appendage closure (LAAC). METHODS AND RESULTS: Of two real-world registries, the Watchman registry Lichtenfels, Germany, and the Amplatzer registry Bern-Zurich, Switzerland, 303 and 333 consecutive patients, respectively, were included. After a 1:1 propensity score matching, 266 vs. 266 patients were compared by use of the predefined primary efficacy endpoint of stroke, systemic embolism and cardiovascular/unexplained death, the primary safety endpoint of major peri-procedural complications and major bleeding events at follow-up, and the combined hazard endpoint, a composite of all above-mentioned hazards. Mean age was 75.3 ± 7.8 (Watchman) vs. 75.1 ± 9.9 (Amplatzer) years, CHA2DS2-VASc score 4.5 ± 1.7 vs. 4.5 ± 1.5, and HAS-BLED score 3.2 ± 1.0 vs. 3.2 ± 1.0. At a mean follow-up of 2.4 ± 1.3 vs. 2.5 ± 1.5 years and 1.322 patient-years, the primary endpoints of efficacy [40/646, 6.2% [Watchman] vs. 43/676, 6.4% [Amplatzer]; hazard ratio (HR), 1.02; 95% confidence interval (CI), 0.66-1.58; P = 0.92] and safety (33/646, 5.1% vs. 30/676, 4.4%; HR, 0.57; 95% CI, 0.29-1.11; P = 0.10), as well as the combined hazard endpoint (69/646, 10.7% vs. 66/676, 9.8%; HR, 0.80; 95% CI, 0.55-1.12; P = 0.26) were similar for both groups. CONCLUSION: This study suggests comparable efficacy and safety of the Watchman and Amplatzer devices.

Myocardial Microvascular Responsiveness During Acute Cardiac Sympathectomy Induced by Thoracic Epidural Anesthesia.

OBJECTIVE: To evaluate the effect of acute cardiac sympathectomy by thoracic epidural anesthesia on myocardial blood flow and microvascular function. DESIGN: A prospective observational study. SETTING: The study was conducted in a tertiary teaching hospital. PARTICIPANTS: Ten patients with a mean age of 48 years (range 22-63 years) scheduled for thoracic surgery. INTERVENTIONS: Myocardial contrast echocardiography was used to study myocardial blood flow and microvascular responsiveness at rest, during adenosine-induced hyperemia, and after sympathetic stimulation by the cold pressor test. Repeated measurements were performed without and with thoracic epidural anesthesia. MEASUREMENTS AND MAIN RESULTS: An increased myocardial blood volume was observed with thoracic epidural anesthesia compared to baseline (from 0.08±0.02 to 0.10±0.03 mL/mL; p = 0.02). No difference existed in resting myocardial blood flow between baseline conditions and epidural anesthesia (0.85±0.24 v 1.03±0.27 mL/min/g, respectively). Hyperemia during thoracic epidural anesthesia increased myocardial blood flow to 4.31±1.07 mL/min/g (p = 0.0008 v baseline) and blood volume to 0.17±0.04 mL/mL (p = 0.005 baseline). After sympathetic stimulation, no difference in myocardial blood flow parameters was observed CONCLUSIONS: Acute cardiac sympathectomy by thoracic epidural anesthesia increased the blood volume in the myocardial capillary system. Also, thoracic epidural anesthesia increased hyperemic myocardial blood flow, indicating augmented endothelial-independent vasodilator capacity of the myocardium.

Function of natural internal mammary-to-coronary artery bypasses and its effect on myocardial ischemia.

BACKGROUND: The function of naturally existing internal mammary (IMA)-to-coronary artery bypasses and their quantitative effect on myocardial ischemia are unknown. METHODS AND RESULTS: The primary end point of this study was collateral flow index (CFI) obtained during two 1-minute coronary artery balloon occlusions, the first with and the second without simultaneous distal IMA occlusion. The secondary study end point was the quantitatively determined intracoronary ECG ST-segment elevation. CFI is the ratio of simultaneously recorded mean coronary occlusive pressure divided by mean aortic pressure both subtracted by mean central venous pressure. A total of 180 pairs of CFI measurements were performed among 120 patients. With and without IMA occlusion, CFI was 0.110±0.074 and 0.096±0.072, respectively (P<0.0001). The difference of CFI obtained in the presence minus CFI obtained in the absence of IMA occlusion was highest and most consistently positive during left IMA with left anterior descending artery occlusion and during right IMA with right coronary artery occlusion (ipsilateral occlusions): 0.033±0.044 and 0.025±0.027, respectively. This CFI difference was absent during right IMA with left anterior descending artery occlusion and during left IMA with right coronary artery occlusion (contralateral occlusions): -0.007±0.034 and 0.001±0.023, respectively (P=0.0002 versus ipsilateral occlusions). The respective CFI differences during either IMA with left circumflex artery occlusion were inconsistently positive. Intracoronary ECG ST-segment elevations were significantly reduced during ipsilateral IMA occlusions but not during contralateral or left circumflex artery occlusions. CONCLUSION: There is a functional, ischemia-reducing extracardiac coronary artery supply via ipsilateral but not via contralateral natural IMA bypasses. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCTO1676207.

Direct quantitative assessment of the peripheral artery collateral circulation in patients undergoing angiography.

BACKGROUND: Despite the fact that numerous studies have pursued the strategy of improving collateral function in patients with peripheral artery disease, there is currently no method available to quantify collateral arterial function of the lower limb. METHODS AND RESULTS: Pressure-derived collateral flow index (CFIp, calculated as (occlusive pressure-central venous pressure)/(aortic pressure-central venous pressure); pressure values in mm Hg) of the left superficial femoral artery was obtained in patients undergoing elective coronary angiography using a combined pressure/Doppler wire (n=30). Distal occlusive pressure and toe oxygen saturation (Sao2) were measured for 5 minutes under resting conditions, followed by an exercise protocol (repetitive plantar-flexion movements in supine position; n=28). In all patients, balloon occlusion of the superficial femoral artery over 5 minutes was painless under resting conditions. CFIp increased during the first 3 minutes from 0.451±0.168 to 0.551±0.172 (P=0.0003), whereas Sao2 decreased from 98±2% to 93±7% (P=0.004). Maximal changes of Sao2 were inversely related to maximal CFIp (r(2)=0.33, P=0.003). During exercise, CFIp declined within 1 minute from 0.560±0.178 to 0.393±0.168 (P<0.0001) and reached its minimum after 2 minutes of exercise (0.347±0.176), whereas Sao2 declined to a minimum of 86±6% (P=0.002). Twenty-five patients (89%) experienced pain or cramps/tired muscles, whereas 3 (11%) remained symptom-free for an occlusion time of 10 minutes. CFIp values were positively related to the pain-free time span (r(2)=0.50, P=0.002). CONCLUSIONS: Quantitatively assessed collateral arterial function at rest determined in the nonstenotic superficial femoral artery is sufficient to prevent ischemic symptoms during a total occlusion of 5 minutes. During exercise, there is a decline in CFIp that indicates a supply-demand mismatch via collaterals or, alternatively, a steal phenomenon. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. UNIQUE IDENTIFIER: NCT01742455.

Effects of Thoratec pulsatile ventricular assist device timing on the abdominal aortic wave intensity pattern.

Arterial waves are seen as possible independent mediators of cardiovascular risks, and the wave intensity analysis (WIA) has therefore been proposed as a method for patient selection for ventricular assist device (VAD) implantation. Interpreting measured wave intensity (WI) is challenging, and complexity is increased by the implantation of a VAD. The waves generated by the VAD interact with the waves generated by the native heart, and this interaction varies with changing VAD settings. Eight sheep were implanted with a pulsatile VAD (PVAD) through ventriculoaortic cannulation. The start of PVAD ejection was synchronized to the native R wave and delayed between 0 and 90% of the cardiac cycle in 10% steps or phase shifts (PS). Pressure and velocity signals were registered, with the use of a combined Doppler and pressure wire positioned in the abdominal aorta, and used to calculate the WI. Depending on the PS, different wave interference phenomena occurred. Maximum unloading of the left ventricle (LV) coincided with constructive interference and maximum blood flow pulsatility, and maximum loading of the LV coincided with destructive interference and minimum blood flow pulsatility. We believe that noninvasive WIA could potentially be used clinically to assess the mechanical load of the LV and to monitor the peripheral hemodynamics such as blood flow pulsatility and risk of intestinal bleeding.

Aortic Valve Planimetry in Aortic Stenosis Quantification: Reliability of Three-Dimensional-Multiplane Reconstruction and Comparison With Established Methods.

We aim to evaluate the reliability and consistency of measuring the aortic valve area (AVA) using 3-dimensional (3D) transesophageal echocardiography and compare it with invasive and noninvasive methods using a continuity equation (CE). Measurements were taken from 119 patients with different severity of aortic stenosis and with normal aortic valve who underwent elective transesophageal echocardiography encompassing the whole spectrum of aortic opening. Three methods were compared to determine AVA. First, the effective AVA was calculated with the standard CE, where the left ventricular outflow tract area was calculated from its 2-dimensional diameter (AVA-CEstd). Second, a modified CE method (AVA-CEmod) was used, in which the left ventricular outflow tract area was measured using 3D-multiplane reconstruction. Third, the geometric AVA was directly measured using 3D-multiplane reconstruction planimetry (AVA-3D). Interobserver and intraobserver variability were analyzed using intraclass correlation coefficients (ICCs). The values were measured by two blinded readers for interobserver variability and by one observer on the same dataset. AVA-3D was significantly larger than AVA-CEmod and AVA-CEstd (1.87 ± 1.00 cm2 vs 1.81 ± 0.92 cm2 p = 0.03 and 1.87 ± 1.00 cm2 vs 1.71 ± 0.85 cm2 p <0.001). However, in the subset of patients with AVA-3D <1.5 cm2, there was no significant difference between AVA-3D and AVA-CEmod (1.06 ± 0.24 vs 1.08 ± 0.26 cm2, paired t test: t = 0.77, degree of freedom = 58, p = 0.44). The ICC between the measurements of AVA-3D and AVA-CEmod (ICC 0.979), and AVA-3D and AVA- CEstd (ICC 0.940), were excellent. AVA-3D delivers very similar results as compared with more established echocardiographic parameters. The difference between effective and geometric AVA did not appear to be clinically relevant in patients with a higher degree of stenosis.

Myocardial analysis from routine 4D cardiac-CT to predict reverse remodeling and clinical outcomes after transcatheter aortic valve implantation.

PURPOSE: Our study aimed to determine whether 4D cardiac computed tomography (4DCCT) based quantitative myocardial analysis may improve risk stratification and can predict reverse remodeling (RRM) and mortality after transcatheter aortic valve implantation (TAVI). METHODS: Consecutive patients undergoing clinically indicated 4DCCT prior to TAVI were prospectively enrolled. 4DCCT-derived left- (LV) and right ventricular (RV), and left atrial (LA) dimensions, mass, ejection fraction (EF) and myocardial strain were evaluated to predict RRM and survival. RRM was defined by either relative increase in LVEF by 5% or relative decline in LV end diastolic diameter (LVEDD) by 5% assessed by transthoracic echocardiography prior TAVI, at discharge, and at 12-month follow-up compared to baseline prior to TAVI. RESULTS: Among 608 patients included in this study (55 % males, age 81 ± 6.6 years), RRM was observed in 279 (54 %) of 519 patients at discharge and in 218 (48 %) of 453 patients at 12-month echocardiography. While no CCT based measurements predicted RRM at discharge, CCT based LV mass index and LVEF independently predicted RRM at 12-month (ORadj = 1.012; 95 %CI:1.001-1.024; p = 0.046 and ORadj = 0.969; 95 %CI:0.943-0.996; p = 0.024, respectively). The most pronounced changes in LVEF and LVEDD were observed in patients with impaired LV function at baseline. In multivariable analysis age (HRadj = 1.037; 95 %CI:1.005-1.070; p = 0.022) and CCT-based LVEF (HRadj = 0.972; 95 %CI:0.945-0.999; p = 0.048) and LAEF (HRadj = 0.982; 95 %CI:0.968-0.996; p = 0.011) independently predicted survival. CONCLUSION: Comprehensive myocardial functional information derived from routine 4DCCT in patients with severe aortic stenosis undergoing TAVI could predict reverse remodeling and clinical outcomes at 12-month following TAVI.

Systemic and pulmonary vascular dysfunction in children conceived by assisted reproductive technologies.

BACKGROUND: Assisted reproductive technology (ART) involves the manipulation of early embryos at a time when they may be particularly vulnerable to external disturbances. Environmental influences during the embryonic and fetal development influence the individual's susceptibility to cardiovascular disease, raising concerns about the potential consequences of ART on the long-term health of the offspring. METHODS AND RESULTS: We assessed systemic (flow-mediated dilation of the brachial artery, pulse-wave velocity, and carotid intima-media thickness) and pulmonary (pulmonary artery pressure at high altitude by Doppler echocardiography) vascular function in 65 healthy children born after ART and 57 control children. Flow-mediated dilation of the brachial artery was 25% smaller in ART than in control children (6.7 ± 1.6% versus 8.6 ± 1.7%; P<0.0001), whereas endothelium-independent vasodilation was similar in the 2 groups. Carotid-femoral pulse-wave velocity was significantly (P<0.001) faster and carotid intima-media thickness was significantly (P<0.0001) greater in children conceived by ART than in control children. The systolic pulmonary artery pressure at high altitude (3450 m) was 30% higher (P<0.001) in ART than in control children. Vascular function was normal in children conceived naturally during hormonal stimulation of ovulation and in siblings of ART children who were conceived naturally. CONCLUSIONS: Healthy children conceived by ART display generalized vascular dysfunction. This problem does not appear to be related to parental factors but to the ART procedure itself. CLINICAL TRIAL REGISTRATION: URL: www.clinicaltrials.gov. Unique identifier: NCT00837642.

General anesthesia with sevoflurane decreases myocardial blood volume and hyperemic blood flow in healthy humans.

BACKGROUND: Preservation of myocardial perfusion during general anesthesia is likely important in patients at risk for perioperative cardiac complications. Data related to the influence of general anesthesia on the normal myocardial circulation are limited. In this study, we investigated myocardial microcirculatory responses to pharmacological vasodilation and sympathetic stimulation during general anesthesia with sevoflurane in healthy humans immediately before surgical stimulation. METHODS: Six female and 7 male subjects (mean age 43 years, range 28-61) were studied at baseline while awake and during the administration of 1 minimum alveolar concentration sevoflurane. Using myocardial contrast echocardiography, myocardial blood flow (MBF) and microcirculatory variables were assessed at rest, during adenosine-induced hyperemia, and after cold pressor test-induced sympathetic stimulation. MBF was calculated from the relative myocardial blood volume multiplied by its exchange frequency (ß) divided by myocardial tissue density (ρT), which was set at 1.05 g·mL(-1). RESULTS: During sevoflurane anesthesia, MBF at rest was similar to baseline values (1.05 ± 0.28 vs 1.05 ± 0.32 mL·min(-1)·g(-1); P = 0.98; 95% confidence interval [CI], -0.18 to 0.18). Myocardial blood volume decreased (P = 0.0044; 95% CI, 0.01-0.04) while its exchange frequency (ß) increased under sevoflurane anesthesia when compared with baseline. In contrast, hyperemic MBF was reduced during anesthesia compared with baseline (2.25 ± 0.5 vs 3.53 ± 0.7 mL·min(-1)·g(-1); P = 0.0003; 95% CI, 0.72-1.84). Sympathetic stimulation during sevoflurane anesthesia resulted in a similar MBF compared to baseline (1.53 ± 0.53 and 1.55 ± 0.49 mL·min(-1)·g(-1); P = 0.74; 95% CI, -0.47 to 0.35). CONCLUSIONS: In otherwise healthy subjects who are not subjected to surgical stimulation, MBF at rest and after sympathetic stimulation is preserved during sevoflurane anesthesia despite a decrease in myocardial blood volume. However, sevoflurane anesthesia reduces hyperemic MBF, and thus MBF reserve, in these subjects.

Evidence for a sigmoidal flow-to-valve opening relation in low-flow low-gradient aortic stenosis.

We analyzed the relationship between flow (Q) and aortic valve opening area (AVA) using a sequence of echocardiographic stress tests of increasing strength. Low-dose dobutamine stress echocardiography (DSE) has been used to differentiate pseudo-severe from true severe aortic stenoses. Because the Q-response to DSE is so variable between individuals, AVA has been projected to a standardized flow (AVAproj) using linear interpolation. A linear Q-to-AVA relation implies that AVA shows an unconstrained increase. We applied three stress maneuvers of increasing strength to investigate whether AVA shows signs of saturation. We performed an echocardiographic examination at rest, during the passive leg raise maneuver ("PLR"), maximal dobutamine infusion ("Dmax"), and their combination ("Dmax + PLR") in 45 patients with severe low-flow, low-gradient aortic stenosis. We analyzed the effect of the stress maneuver on Q, AVA, valve compliance (VC), and AVAproj. We also compared the proportion of patients with nonconclusive test (ΔQ < 20%) between stress maneuvers. We computed the Akaike information criterion (AIC) to compare a linear with a saturating function for the Q-AVA relation. Q gradually increased from "PLR" to "Dmax" to "Dmax + PLR" (P < 0.0001), whereas the number of nonconclusive tests concomitantly diminished from n = 35 to n = 3. The stress sequence increased AVA (P < 0.001) but decreased AVAproj (P = 0.006) and VC (P = 0.005). In the pooled Q-AVA data, the AIC value was lower for the saturating (sigmoidal) model compared with the linear model fitting (-1,593 vs. -1,504). "Dmax + PLR" is capable of reducing the number of nonconclusive DSE tests. With increasing stress strength, the Q-AVA relation progressively flattens, indicating saturation.NEW & NOTEWORTHY The relation between transaortic flow (Q) and aortic valve opening area (AVA) shows a saturation when three different stress maneuvers are used to increase Q as much as possible. This has implications for the assessment of aortic stenosis severity.

Imaging of Bioprosthetic Valve Dysfunction after Transcatheter Aortic Valve Implantation.

Transcatheter aortic valve implantation (TAVI) has become the standard of care in elderly high-risk patients with symptomatic severe aortic stenosis. Recently, TAVI has been increasingly performed in younger-, intermediate- and lower-risk populations, which underlines the need to investigate the long-term durability of bioprosthetic aortic valves. However, diagnosing bioprosthetic valve dysfunction after TAVI is challenging and only limited evidence-based criteria exist to guide therapy. Bioprosthetic valve dysfunction encompasses structural valve deterioration (SVD) resulting from degenerative changes in the valve structure and function, non-SVD resulting from intrinsic paravalvular regurgitation or patient-prosthesis mismatch, valve thrombosis, and infective endocarditis. Overlapping phenotypes, confluent pathologies, and their shared end-stage bioprosthetic valve failure complicate the differentiation of these entities. In this review, we focus on the contemporary and future roles, advantages, and limitations of imaging modalities such as echocardiography, cardiac computed tomography angiography, cardiac magnetic resonance imaging, and positron emission tomography to monitor the integrity of transcatheter heart valves.

Pulmonary artery pressure and cardiac function in children and adolescents after rapid ascent to 3,450 m.

High-altitude destinations are visited by increasing numbers of children and adolescents. High-altitude hypoxia triggers pulmonary hypertension that in turn may have adverse effects on cardiac function and may induce life-threatening high-altitude pulmonary edema (HAPE), but there are limited data in this young population. We, therefore, assessed in 118 nonacclimatized healthy children and adolescents (mean ± SD; age: 11 ± 2 yr) the effects of rapid ascent to high altitude on pulmonary artery pressure and right and left ventricular function by echocardiography. Pulmonary artery pressure was estimated by measuring the systolic right ventricular to right atrial pressure gradient. The echocardiography was performed at low altitude and 40 h after rapid ascent to 3,450 m. Pulmonary artery pressure was more than twofold higher at high than at low altitude (35 ± 11 vs. 16 ± 3 mmHg; P < 0.0001), and there existed a wide variability of pulmonary artery pressure at high altitude with an estimated upper 95% limit of 52 mmHg. Moreover, pulmonary artery pressure and its altitude-induced increase were inversely related to age, resulting in an almost twofold larger increase in the 6- to 9- than in the 14- to 16-yr-old participants (24 ± 12 vs. 13 ± 8 mmHg; P = 0.004). Even in children with the most severe altitude-induced pulmonary hypertension, right ventricular systolic function did not decrease, but increased, and none of the children developed HAPE. HAPE appears to be a rare event in this young population after rapid ascent to this altitude at which major tourist destinations are located.

Coronary collaterals and risk for restenosis after percutaneous coronary interventions: a meta-analysis.

BACKGROUND: The benefit of the coronary collateral circulation (natural bypass network) on survival is well established. However, data derived from smaller studies indicates that coronary collaterals may increase the risk for restenosis after percutaneous coronary interventions. The purpose of this systematic review and meta-analysis of observational studies was to explore the impact of the collateral circulation on the risk for restenosis. METHODS: We searched the MEDLINE, EMBASE and ISI Web of Science databases (2001 to 15 July 2011). Random effects models were used to calculate summary risk ratios (RR) for restenosis. The primary endpoint was angiographic restenosis > 50%. RESULTS: A total of 7 studies enrolling 1,425 subjects were integrated in this analysis. On average across studies, the presence of a good collateralization was predictive for restenosis (risk ratio (RR) 1.40 (95% CI 1.09 to 1.80); P = 0.009). This risk ratio was consistent in the subgroup analyses where collateralization was assessed with intracoronary pressure measurements (RR 1.37 (95% CI 1.03 to 1.83); P = 0.038) versus visual assessment (RR 1.41 (95% CI 1.00 to 1.99); P = 0.049). For the subgroup of patients with stable coronary artery disease (CAD), the RR for restenosis with 'good collaterals' was 1.64 (95% CI 1.14 to 2.35) compared to 'poor collaterals' (P = 0.008). For patients with acute myocardial infarction, however, the RR for restenosis with 'good collateralization' was only 1.23 (95% CI 0.89 to 1.69); P = 0.212. CONCLUSIONS: The risk of restenosis after percutaneous coronary intervention (PCI) is increased in patients with good coronary collateralization. Assessment of the coronary collateral circulation before PCI may be useful for risk stratification and for the choice of antiproliferative measures (drug-eluting stent instead bare-metal stent, cilostazol).

Contrast-enhanced ultrasound for myocardial perfusion imaging.

Ultrasound contrast agents are gas-filled microbubbles that enhance visualization of cardiac structures, function and blood flow during contrast-enhanced ultrasound (CEUS). An interesting cardiovascular application of CEUS is myocardial contrast echocardiography, which allows real-time myocardial perfusion imaging. The intraoperative use of this technically challenging imaging method is limited at present, although several studies have examined its clinical utility during cardiac surgery in the past. In the present review we provide general information on the basic principles of CEUS and discuss the methodology and technical aspects of myocardial perfusion imaging.

Predicting progression of aortic stenosis by measuring serum calcification propensity.

BACKGROUND: The aim of this prospective, double-blinded study in patients with aortic sclerosis was to determine whether a new calcification propensity measure in the serum could predict disease progression. METHODS: We included 129 consecutive patients with aortic sclerosis as assessed during a routine clinical echocardiographic exam. Clinical, echocardiographic, and serum laboratory parameters were collected, including a new blood test providing an overall measure of calcification propensity by monitoring the maturation time of calciprotein particles (T50 test). The echocardiographic exam was repeated after 1 year. Multiple regression analysis was performed to identify independent predictors of the annual increase of peak transvalvular Doppler velocity (∆vmax). Furthermore, the accuracy of the T50 test to detect patients with the most marked stenosis progression was assessed by receiver operating characteristic (ROC)-analysis. RESULTS: Mean age was 75 ± 9 years, 79% were men. The T50 was 271 ± 58 min. Overall, there was no significant stenosis progression between baseline and follow-up (∆vmax 3.8 ± 29.8 cm/s, p = ns). The T50 test was not found to be an independent linear predictor in multivariate testing. By ROC-analysis, however, a T50-value ≤ 242 min was able to significantly detect a ∆vmax above the 90th percentile (∆vmax ≥ 43 cm/s, AUC = 0.67, p = .04, Sensitivity = 69%, Specificity = 70%). CONCLUSIONS: The T50 test showed a modest but significant ability to identify a pronounced aortic stenosis progression in patients with aortic sclerosis. The test could not be established as an independent linear predictor of disease progression, possibly due to the low valvular disease burden and short follow-up interval.

Sigmoid isostiffness-lines: An in-vitro model for the assessment of aortic stenosis severity.

Introduction: The aortic valve opening area (AVA), used to quantify aortic stenosis severity, depends on the transvalvular flow rate (Q). The currently accepted clinical echocardiographic method assumes a linear relation between AVA and Q. We studied whether a sigmoid model better describes this relation and determined "isostiffness-lines" across a wide flow spectrum, thus allowing building a nomogram for the non-invasive estimation of valve stiffness. Methods: Both AVA and instantaneous Q (Qinst) were measured at 10 different mean cardiac outputs of porcine aortic valves mounted in a pulsatile flow loop. The valves' cusps were chemically stiffened to obtain three stiffness grades and the procedure was repeated for each grade. The relative stiffness was defined as the ratio between LV work at grade with the added stiffness and at native stiffness grade. AVA peak ¯ corresponding to the selected Q peak ¯ of the highest 3 and 5 cardiac output values was predicted in K-fold cross-validation using sequentially a linear and a sigmoid model. The accuracy of each model was assessed with the Akaike information criterion (AIC). Results: The sigmoid model predicted more accurately AVA peak ¯ (AIC for prediction of AVA with Q peak ¯ of the 3 highest cardiac output values: -1,743 vs. -1,048; 5 highest cardiac output values: -1,471 vs. -878) than the linear model. Conclusion: This study suggests that the relation between AVA and Q can be better described by a sigmoid than a linear model. This construction of "isostiffness-lines" may be a useful method for the assessment of aortic stenosis in clinical echocardiography.

Passive Leg Raise Stress Echocardiography in Severe Paradoxical Low-Flow, Low-Gradient Aortic Stenosis.

BACKGROUND: Dobutamine stress echocardiography is used to increase transvalvular flow in patients with low-flow, low-gradient aortic stenosis (AS). Dobutamine fails to increase the stroke volume index (SVI) in one third of patients. The aim of this study was to test whether passive leg raise (PLR) added to dobutamine could increase SVI and transvalvular flow in patients with severe paradoxical low-flow, low-gradient AS. METHODS: Forty-five patients with apparent severe low-flow, low-gradient AS on the basis of traditional measurements were included. Twenty-five were categorized as belonging to the paradox group (left ventricular ejection fraction [EF] ≥ 50%) and 20 to the low EF group (left ventricular EF < 50% or "classical" low-flow, low-gradient AS) for comparison. A four-step stress echocardiographic examination was performed: resting conditions (rest), PLR alone (PLR), maximal dobutamine infusion rate (Dmax), and a combination of Dmax and PLR (Dmax+PLR). Aortic valve area, SVI, and mean transvalvular flow were calculated using both the velocity-time integral (VTI) of left ventricular outflow tract and the Simpson method. Changes compared with rest and between the stress maneuvers were analyzed. RESULTS: In the paradox group, compared with rest, left ventricular end-diastolic volume was significantly decreased with Dmax but was completely restored with Dmax+PLR (rest vs Dmax vs Dmax+PLR: 61 ± 15 vs 49 ± 18 mL [P < .001] vs 61 ± 18 mL [P = NS]). The smallest increase in SVI in the paradox group was observed during Dmax (PLR vs Dmax vs Dmax+PLR: VTI, 38 ± 4 mL/m2 [P < .001] vs 36 ± 7 mL/m2 [P = .019] vs 41 ± 7 mL/m2 [P < .001]; Simpson, 28 ± 6 mL/m2 [P < .001], 21 ± 7 mL/m2 [P = NS], 27 ± 7 mL/m2 [P = NS]). Compared with Dmax, Dmax+PLR was able to achieve a higher SVI (VTI, 36 ± 7 vs 41 ± 7 mL/m2 [P < .001]; Simpson, 21 ± 7 vs 27 ± 7 mL/m2 [P < .001]) and transvalvular flow with the Simpson method only (179 ± 56 vs 219 ± 56 mL/sec, P < .001), as well as a higher mean gradient (34 ± 10 vs 39 ± 12 mm Hg, P = .003) and AVA with the Simpson method (0.64 ± 0.21 vs 0.73 ± 0.21 cm2, P = .026). In the low EF group, only SVI VTI (31 ± 8 vs 35 ± 7 mL/m2, P = .034) and mean gradient (29 ± 12 vs 34 ± 14 mm Hg, P = .003) were higher with Dmax+PLR. The proportion of patients with SVI VTI ≥ 35 mL/m2 and increases of SVI VTI of >20% compared with rest was highest with Dmax+PLR in both groups. CONCLUSIONS: Dobutamine decreases preload in paradoxical low-flow, low-gradient AS. Adding PLR counteracts this effect, resulting in increased SVI and flow (in one method). The combined stress maneuver allowed reclassification of some patients from severe to moderate AS and may therefore be useful in selected cases in this population in which severity is uncertain.

Short- and Long-Term Effects of High-Intensity Interval Training vs. Moderate-Intensity Continuous Training on Left Ventricular Remodeling in Patients Early After ST-Segment Elevation Myocardial Infarction-The HIIT-EARLY Randomized Controlled Trial.

Aim: Due to insufficient evidence on the safety and effectiveness of high-intensity interval training (HIIT) in patients early after ST-segment elevation myocardial infarction (STEMI), we aimed to compare short- and long-term effects of randomized HIIT or moderate-intensity continuous training (MICT) on markers of left ventricular (LV) remodeling in STEMI patients receiving optimal guideline-directed medical therapy (GDMT). Materials and Methods: Patients after STEMI (<4 weeks) enrolled in a 12-week cardiac rehabilitation (CR) program were recruited for this randomized controlled trial (NCT02627586). During a 3-week run-in period with three weekly MICT sessions, GDMT was up-titrated. Then, the patients were randomized to HIIT or isocaloric MICT for 9 weeks. Echocardiography and cardiopulmonary exercise tests were performed after run-in (3 weeks), end of CR (12 weeks), and at 1-year follow-up. The primary outcome was LV end-diastolic volume index (LVEDVi) at the end of CR. Secondary outcomes were LV global longitudinal strain (GLS) and cardiopulmonary fitness. Results: Seventy-three male patients were included, with the time between STEMI and start of CR and randomization being 12.5 ± 6.3 and 45.8 ± 10.8 days, respectively. Mixed models revealed no significant group × time interaction for LVEDVi at the end of CR (p = 0.557). However, there was a significantly smaller improvement in GLS at 1-year follow-up in the HIIT compared to the MICT group (p = 0.031 for group × time interaction). Cardiorespiratory fitness improved significantly from a median value of 26.5 (1st quartile 24.4; 3rd quartile 1.1) ml/kg/min at randomization in the HIIT and 27.7 (23.9; 31.6) ml/kg/min in the MICT group to 29.6 (25.3; 32.2) and 29.9 (26.1; 34.9) ml/kg/min at the end of CR and to 29.0 (26.6; 33.3) and 30.6 (26.0; 33.8) ml/kg/min at 1 year follow-up in HIIT and MICT patients, respectively, with no significant group × time interactions (p = 0.138 and 0.317). Conclusion: In optimally treated patients early after STEMI, HIIT was not different from isocaloric MICT with regard to short-term effects on LVEDVi and cardiorespiratory fitness. The worsening in GLS at 1 year in the HIIT group deserves further investigation, as early HIIT may offset the beneficial effects of GDMT on LV remodeling in the long term.