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.

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.

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.

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.

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.

Microvascular response to metabolic and pressure challenge in the human coronary circulation.

In vivo observations of microcirculatory behavior during autoregulation and adaptation to varying myocardial oxygen demand are scarce in the human coronary system. This study assessed microvascular reactions to controlled metabolic and pressure provocation [bicycle exercise and external counterpulsation (ECP)]. In 20 healthy subjects, quantitative myocardial contrast echocardiography and arterial applanation tonometry were performed during increasing ECP levels, as well as before and during bicycle exercise. Myocardial blood flow (MBF; ml·min(-1)·g(-1)), the relative blood volume (rBV; ml/ml), the coronary vascular resistance index (CVRI; dyn·s·cm(-5)/g), the pressure-work index (PWI), and the pressure-rate product (mmHg/min) were assessed. MBF remained unchanged during ECP (1.08 ± 0.44 at baseline to 0.92 ± 0.38 at high-level ECP). Bicycle exercise led to an increase in MBF from 1.03 ± 0.39 to 3.42 ± 1.11 (P < 0.001). The rBV remained unchanged during ECP, whereas it increased under exercise from 0.13 ± 0.033 to 0.22 ± 0.07 (P < 0.001). The CVRI showed a marked increase under ECP from 7.40 ± 3.38 to 11.05 ± 5.43 and significantly dropped under exercise from 7.40 ± 2.78 to 2.21 ± 0.87 (both P < 0.001). There was a significant correlation between PWI and MBF in the pooled exercise data (slope: +0.162). During ECP, the relationship remained similar (slope: +0.153). Whereas physical exercise decreases coronary vascular resistance and induces considerable functional capillary recruitment, diastolic pressure transients up to 140 mmHg trigger arteriolar vasoconstriction, keeping MBF and functional capillary density constant. Demand-supply matching was maintained over the entire ECP pressure range.

Figulla PFO occluder versus Amplatzer PFO occluder for percutaneous closure of patent foramen ovale.

BACKGROUND: Percutaneous closure of patent foramen ovale (PFO) has been shown safe and feasible using several devices. The Occlutech Figulla single layer PFO Occluder (FPO) constitutes an alternative to the Amplatzer PFO Occluder (APFO). OBJECTIVES: We report our experience with both devices in a single-center case-control study. METHODS: Twenty patients undergoing percutaneous PFO closure using an FPO for secondary prevention of paradoxical embolism or diving were blindly matched with 20 patients receiving an APFO during the same time period. Contrast transesophageal echocardiography (TEE) was performed 6 months after device implantation to assess for residual shunting and device-associated thrombus. RESULTS: Patient baseline characteristics were well matched by study design. Procedural success was 95% with FPO vs. 100% for APFO (P = 1.0), with 3 (15%) peri-procedural complications with FPO vs. none with APFO (P = 0.24). These comprised one asymptomatic device embolization in the descending aorta with percutaneous retrieval, one transient ischemic attacks, and one suspected device endocarditis. Contrast TEE at 6 months showed significantly more residual shunts in the FPO-group (39% vs. 0%; P = 0.01). Two FPO patients with a moderate residual shunt underwent implantation of a second device (APFO 25 mm) vs. none in the APFO group (P = 0.48). No thrombi were observed in either group. During 1.7 ± 0.7 years of follow-up, no death or recurrent embolic event occurred. CONCLUSIONS: According to this single-center case-control study, PFO closure with the FPO appears less efficacious than with the APFO.

Determinants of preformed collateral vessels in the human heart without coronary artery disease.

BACKGROUND: Coronary collaterals protect myocardium jeopardized by coronary artery disease (CAD). Promotion of collateral circulation is desirable before myocardial damage occurs. Therefore, determinants of collateral preformation in patients without CAD should be elucidated. METHODS: In 106 patients undergoing coronary angiography who were free of coronary stenoses, a total of 39 clinical test variables were collected. The coronary collateral flow index (CFI) was measured. Stepwise multiple linear regression analysis was performed after choosing a restricted number of candidates emerging from univariate testing. Separate multiple regression analyses were performed in patients with and without beta-blocker therapy. RESULTS: Nine parameters were found to be possible determinants of CFI by univariate analysis: arterial hypertension (aHT), dyslipidemia, statins, diuretics, age, height, heart rate (HR), pulse pressure amplitude, and left ventricular end-diastolic pressure (LVEDP). After multiple regression analysis, a low HR, absence of aHT, and elevated LVEDP were significantly related to CFI (F = 5.31, p = 0.002, adjusted r(2) = 0.12). In patients without beta-blockers, a low HR and absence of aHT were independent predictors of CFI (F = 8.03, p < 0.001, n = 50, adjusted r(2) = 0.30). CONCLUSIONS: A low HR and absence of aHT are both related to collateral preformation in humans. We suppose that bradycardia favors fluid shear stress in coronary arteries, thus triggering collateral growth.

Right ventricular systolic function assessment: rank of echocardiographic methods vs. cardiac magnetic resonance imaging.

AIMS: Right ventricular (RV) systolic function is prognostically important, but its assessment by echocardiography remains challenging, in part because of the multitude of available measurement methods. The purpose of this prospective study was to rank these methods against the reference of RV ejection fraction (EF) as obtained in a broad clinical population by magnetic resonance imaging (MRI). METHODS AND RESULTS: Two hundred and twenty-three individuals were included in the study. The following seven Doppler echocardiographic parameters were tested using receiver operating characteristic (ROC) analysis for their accuracy to distinguish between normal and moderately impaired RVEF by MRI (RVEF cut-off 50%), respectively, between moderately and severely reduced RVEF (cut-off 30%): RV fractional area and fractional long-axis change (FLC), RV myocardial performance index (MPI), tricuspid annular peak systolic excursion, Doppler tissue imaging-derived isovolumic acceleration and peak systolic velocity (S') at the lateral tricuspid annulus, and strain at the lateral free wall as obtained by speckle-tracking echocardiography. Survival analysis was performed. All seven Doppler echocardiographic parameters correlated significantly with RVEF by MRI (range between 5 and 85%). RVEF <50% was best detected by S' < 11 cm/s: area under the ROC curve 0.779 (95% confidence interval 0.716-0.843), sensitivity 0.740, and specificity 0.753. RVEF ≤30% was best detected by MPI > 0.50: area under the ROC curve 0.948 (95% confidence interval 0.906-0.991), sensitivity 0.947, and specificity 0.852. The Kaplan-Meier analysis revealed reduced cumulative survival among patients with RVEF ≤30% (P = 0.0003). CONCLUSION: A systolic long-axis peak velocity of <11 cm/s at the lateral tricuspid annulus most accurately detects moderately impaired RVEF as obtained by MRI; severely reduced RVEF ≤30% is best detected by RV MPI at a value of >0.50.

An indicator of sudden cardiac death during brief coronary occlusion: electrocardiogram QT time and the role of collaterals.

AIMS: The coronary collateral circulation has a beneficial role regarding all-cause and cardiac mortality. Hitherto, the underlying mechanism has not been clarified. The aim of this prospective study was to assess the effect of the coronary collateral circulation on electrocardiogram (ECG) QTc time change during short-term myocardial ischaemia. METHODS AND RESULTS: A total of 150 patients (mean age 63 +/- 11 years, 38 women) were prospectively included in this study. An ECG was recorded at baseline and during a standardized 1 min coronary balloon occlusion. QT interval was measured before, during, and after balloon occlusion and was corrected for heart rate (QTc). Simultaneously obtained collateral flow index (CFI), expressing collateral flow relative to normal anterograde flow, was determined based on intracoronary pressure measurements. During occlusion of the left anterior descending coronary artery mean QTc interval increased from 422 +/- 33 to 439 +/- 36 ms (P < 0.001), left circumflex occlusion led to an increase from 414 +/- 32 to 427 +/- 27 ms (P < 0.001). QTc was not influenced by occlusion of the right coronary artery (RCA) (417 +/- 35 and 415 +/- 34 ms, respectively; P = 0.863). QTc change during occlusion of the left coronary artery was inversely correlated with CFI (R(2) = 0.122, P = 0.0002). CONCLUSION: Myocardial ischaemia leads to QT prolongation during a controlled 1 min occlusion of the left, but not the RCA. QT prolongation is inversely related to collateral function indicating a protective mechanism of human coronary collaterals against cardiac death.

Instantaneous coronary collateral function during supine bicycle exercise.

AIMS: The instantaneous response of the collateral circulation to isometric physical exercise in patients with non-occlusive coronary artery disease (CAD) is not known. METHODS AND RESULTS: Thirty patients (age 59 +/- 9 years) undergoing percutaneous coronary intervention because of stable CAD were included in the study. Collateral function was determined before and during the last minute of a 6 min protocol of supine bicycle exercise during radial artery access coronary angiography. Collateral flow index (CFI, no unit) was determined as the ratio of mean distal coronary occlusive to mean aortic pressure both subtracted by central venous pressure. To avoid confounding due to recruitment of coronary collaterals by repetitive balloon occlusions, patients were randomly assigned to a group 'rest first' with CFI measurement during rest followed by CFI during exercise, and to a group 'exercise first' with antecedent CFI measurement during exercise before CFI at rest. Simultaneously, coronary collateral conductance (occlusive myocardial blood flow per aorto-coronary pressure drop) was determined by myocardial contrast echocardiography in the last 10 consecutive patients. Overall, CFI increased from 0.168 +/- 0.118 at rest to 0.262 +/- 0.166 during exercise (P = 0.0002). The exercise-induced change in CFI did not differ statistically in the two study groups. Exercise-induced CFI reserve (CFI during exercise divided by CFI at rest) was 2.2 +/- 1.8. Overall, rest to peak bicycle exercise change of coronary collateral conductance was from 0.010 +/- 0.010 to 1.109 +/- 0.139 mL/min/100 mmHg (P < 0.0001); the respective change was similar in both groups. CONCLUSION: In patients with non-occlusive CAD, collateral flow instantaneously doubles during supine bicycle exercise as compared with the resting state. ClinicalTrials.gov Identifier: NCT00947050.