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BackgroundQuantification of cardiac output and pulmonary vascular resistance (PVR) are critical components of invasive hemodynamic assessment, and can be measured concurrently with pressures using phase contrast CMR flow during real-time CMR guided cardiac catheterization.MethodsOne hundred two consecutive patients underwent CMR fluoroscopy guided right heart catheterization (RHC) with simultaneous measurement of pressure, cardiac output and pulmonary vascular resistance using CMR flow and the Fick principle for comparison. Procedural success, catheterization time and adverse events were prospectively collected.ResultsRHC was successfully completed in 97/102 (95.1%) patients without complication. Catheterization time was 20±11min. In patients with and without pulmonary hypertension, baseline mean pulmonary artery pressure was 39±12mmHg vs. 18±4mmHg (p&nbsp

Transcatheter electrosurgery refers to a family of procedures using radiofrequency energy to vaporize and traverse or lacerate tissue despite flowing blood. The authors review theory, simulations, and benchtop demonstrations of how guidewires, insulation, adjunctive catheters, and dielectric medium interact. For tissue traversal, all but the tip of traversing guidewires is insulated to concentrate current. For leaflet laceration, the "Flying V" configuration concentrates current at the inner lacerating surface of a kinked guidewire. Flooding the field with non-ionic dextrose eliminates alternative current paths. Clinical applications include traversing occlusions (pulmonary atresia, arterial and venous occlusion, and iatrogenic graft occlusion), traversing tissue planes (atrial and ventricular septal puncture, radiofrequency valve repair, transcaval access, Potts and Glenn shunts), and leaflet laceration (BASILICA, LAMPOON, ELASTA-Clip, and others). Tips are provided for optimizing these techniques. Transcatheter electrosurgery already enables a range of novel therapeutic procedures for structural heart disease, and represents a promising advance toward transcatheter surgery.

Objectives The authors propose a novel transcatheter transection of the anterior mitral leaflet to prevent iatrogenic left ventricular outflow tract (LVOT) obstruction during transcatheter mitral valve replacement (TMVR). Background LVOT obstruction is a life-threatening complication of TMVR caused by septal displacement of the anterior mitral leaflet. Methods In vivo procedures in swine were guided by biplane x-ray fluoroscopy and intracardiac echocardiography. Retrograde transaortic 6-F guiding catheters straddled the anterior mitral leaflet. A stiff 0.014-inch guidewire with polymer jacket insulation was electrified and advanced from the LVOT, through the A2 leaflet base, into the left atrium. The wire was snared and externalized, forming a loop that was energized and withdrawn to lacerate the anterior mitral leaflet. Results The anterior mitral leaflet was successfully lacerated in 7 live and 1 post-mortem swine under heparinization. Lacerations extended to 89 ± 19% of leaflet length and were located within 0.5 ± 0.4 mm of leaflet centerline. The chordae were preserved and retracted the leaflet halves away from the LVOT. LVOT narrowing after benchtop TMVR was significantly reduced with intentional laceration of the anterior mitral leaflet to prevent LVOT obstruction than without (65 ± 10% vs. 31 ± 18% of pre-implantation diameter, p Conclusions Using simple catheter techniques, the anterior mitral valve leaflet was transected. Cautiously applied in patients, this strategy can prevent anterior mitral leaflet displacement and LVOT obstruction caused by TMVR.

ObjectivesThis study sought to demonstrate transcatheter deployment of a circumferential device within the pericardial space to modify tricuspid annular dimensions interactively and to reduce functional tricuspid regurgitation (TR) in swine.BackgroundFunctional TR is common and is associated with increased morbidity and mortality. There are no reported transcatheter tricuspid valve repairs. We describe a transcatheter extracardiac tricuspid annuloplasty device positioned in the pericardial space and delivered by puncture through the right atrial appendage. We demonstrate acute and chronic feasibility in swine.MethodsTransatrial intrapericardial tricuspid annuloplasty (TRAIPTA) was performed in 16 Yorkshire swine, including 4 with functional TR. Invasive hemodynamics and cardiac magnetic resonance imaging (MRI) were performed at baseline, immediately after annuloplasty and at follow-up.ResultsPericardial access via a right atrial appendage puncture was uncomplicated. In 9 naïve animals, tricuspid septal-lateral and anteroposterior dimensions, the annular area and perimeter, were reduced by 49%, 31%, 59%, and 24% (p < 0.001), respectively. Tricuspid leaflet coaptation length was increased by 53% (p < 0.001). Tricuspid geometric changes were maintained after 9.7 days (range, 7 to 14 days). Small effusions (mean, 46 ml) were observed immediately post-procedure but resolved completely at follow-up. In 4 animals with functional TR, severity of regurgitation by intracardiac echocardiography was reduced.ConclusionsTransatrial intrapericardial tricuspid annuloplasty is a transcatheter extracardiac tricuspid valve repair performed by exiting the heart from within via a transatrial puncture. The geometry of the tricuspid annulus can interactively be modified to reduce severity of functional TR in an animal model.

Objectives: We test the safety of transatrial pericardial access using small catheters, infusion of carbon dioxide (CO2) or iodinated contrast to facilitate sub-xiphoid access, and catheter withdrawal under full anticoagulation. Background: Sub-xiphoid pericardial access is required for electrophysiological and structural heart interventions. If present, an effusion protects the heart from needle injury by separating the myocardium from the pericardium. However, if the pericardium is ‘dry' then there is a significant risk of right ventricle or coronary artery laceration caused by the heart beating against the needle tip. Intentional right atrial exit is an alternative pericardial access route, through which contrast media could be infused to separate pericardial layers. Methods: Transatrial pericardial access was obtained in a total of 30 Yorkshire swine using 4Fr or 2.8Fr catheters. In 16 animals, transatrial catheters were withdrawn under anticoagulation and MRI was performed to monitor for pericardial hemorrhage. In 14 animals, iodinated contrast or CO2 was infused before sub-xiphoid access was obtained. Results: Small effusions (mean 18.5 ml) were observed after 4Fr (1.3 mm outer-diameter) but not after 2.8Fr (0.9 mm outer-diameter) transatrial catheter withdrawal despite full anticoagulation (mean activated clotting time 383 sec), with no hemodynamic compromise. Pericardial CO2 resorbed spontaneously within 15 min. Conclusions: Intentional transatrial exit into the pericardium using small catheters is safe and permits infusion of CO2 or iodinated contrast to separate pericardial layers and facilitate sub-xiphoid access. This reduces the risk of right ventricular or coronary artery laceration. 2.8Fr transatrial catheter withdrawal does not cause any pericardial hemorrhage, even under full anticoagulation. © 2014 Wiley Periodicals, Inc.

INTRODUCTION—Closed-chest access and closure of direct cardiac punctures may enable a range of therapeutic procedures. We evaluate the safety and feasibility of closing percutaneous direct ventricular access sites using a commercial collagen-based femoral artery closure device. METHODS—Yorkshire swine underwent percutaneous transthoracic left ventricular access (n=13). The access port was closed using a commercial collagen-based vascular closure device (Angio-Seal, St Jude Medical) with or without prior separation of the pericardial layers by instillation of fluid into the pericardial space (“permissive pericardial tamponade”). After initial nonsurvival feasibility experiments (n=6); animals underwent one-week (n=3) or six-week follow up (n=4). RESULTS—In naive animals, the collagen plug tended to deploy outside the parietal pericardium, where it failed to accomplish hemostasis. “Permissive pericardial tamponade” was created under MRI, and accomplished early hemostasis by allowing the collagen sponge to seat on the epicardial surface inside the pericardium. After successful closure, six of seven animals accumulated a large pericardial effusion 5±1 days after closure. Despite percutaneous drainage during 6-week follow-up, the large pericardial effusion recurred in half, and was lethal in one. CONCLUSIONS—A commercial collagen based vascular closure device may achieve temporary but not durable hemostasis when closing a direct left ventricular puncture port, but only after intentional pericardial separation. These insights may contribute to development of a superior device solution. Elective clinical application of this device to close apical access ports should be avoided.

Objectives We developed and tested a novel transcatheter circumferential annuloplasty technique to reduce mitral regurgitation in porcine ischemic cardiomyopathy. Background Catheter-based annuloplasty for secondary mitral regurgitation exploits the proximity of the coronary sinus to the mitral annulus, but is limited by anatomic variants and coronary artery entrapment. Methods The procedure, “cerclage annuloplasty,” is guided by magnetic resonance imaging (MRI) roadmaps fused with live X-ray. A coronary sinus guidewire traverses a short segment of the basal septal myocardium to re-enter the right heart where it is exchanged for a suture. Tension is applied interactively during imaging and secured with a locking device. Results We found 2 feasible suture pathways from the great cardiac vein across the interventricular septum to create cerclage. Right ventricular septal re-entry required shorter fluoroscopy times than right atrial re-entry, which entailed a longer intramyocardial traversal but did not cross the tricuspid valve. Graded tension progressively reduced septal-lateral annular diameter, but not end-systolic elastance or regional myocardial function. A simple arch-like device protected entrapped coronary arteries from compression even during supratherapeutic tension. Cerclage reduced mitral regurgitation fraction (from 22.8 ± 12.7% to 7.2 ± 4.4%, p = 0.04) by slice tracking velocity-encoded MRI. Flexible cerclage reduced annular size but preserved annular motion. Cerclage also displaced the posterior annulus toward the papillary muscles. Cerclage introduced reciprocal constraint to the left ventricular outflow tract and mitral annulus that enhanced leaflet coaptation. A sample of human coronary venograms and computed tomography angiograms suggested that most have suitable venous anatomy for cerclage. Conclusions Transcatheter mitral cerclage annuloplasty acutely reduces mitral regurgitation in porcine ischemic cardiomyopathy. Entrapped coronary arteries can be protected. MRI provided insight into the mechanism of cerclage action.

A sedentary workforce may be at increased risk for future cardiovascular disease. Exercise at the work site has been advocated, but effects on endothelium as a biomarker of risk and relation to weight loss, lipid changes, or circulating endothelial progenitor cells (EPCs) have not been reported. Seventy-two office and laboratory employees (58 women; average age 45 years, range 22 to 62; 26 with body mass index values30 kg/m(2)) completed 3 months of participation in the National Heart, Lung, and Blood Institute's Keep the Beat program, with the determination of vital signs, laboratory data, and peak oxygen consumption (VO(2)) during treadmill exercise. Brachial artery endothelium was tested by flow-mediated dilation (FMD), which at baseline was inversely associated with Framingham risk score (r = -0.3689, p0.0001). EPCs were quantified by colony assay. With exercise averaging 98 +/- 47 minutes each workweek, there was improvement in FMD (from 7.8 +/- 3.4% to 8.5 +/- 3.0%, p = 0.0096) and peak VO(2) (+1.2 +/- 3.1 ml O(2)/kg/min, p = 0.0028), with reductions in diastolic blood pressure (-2 +/- 8 mm Hg, p = 0.0478), total cholesterol (-8 +/- 25 mg/dl, p = 0.0131), and low-density lipoprotein cholesterol (-7 +/- 19 mg/dl, p = 0.0044) but with a marginal reduction in weight (-0.5 +/- 2.1 kg, p = 0.0565). By multiple regression modeling, lower baseline FMD, greater age, reductions in total and low-density lipoprotein cholesterol and diastolic blood pressure, and increases in EPC colonies and peak VO(2) were jointly statistically significant predictors of change in FMD and accounted for 47% of the variability in FMD improvement with program participation. Results were similar when modeling was performed for women only. In contrast, neither adiposity at baseline nor change in weight was a predictor of improved endothelial function. In conclusion, daily exercise achievable at their work sites by employees with sedentary occupations improves endothelial function, even with the absence of weight loss, which may decrease cardiovascular risk, if sustained.

Our purpose was to determine predictors of endothelial function and potential association with cardiovascular risk in women with sedentary occupations, in whom obesity-associated risk factors may contribute to excess morbidity and mortality. Ninety consecutive women (age range 22 to 63 years, 22 overweight (body mass index [BMI]or =25 to 29.9 kg/m(2)) and 42 obese (BMIor = 30 kg/m(2)), had vital signs, lipids, insulin, glucose, high-sensitivity C-reactive protein, and sex hormones measured. Endothelial function was determined using brachial artery flow-mediated dilation after 5 minutes of forearm ischemia. Treadmill stress testing was performed with gas exchange analysis at peak exercise (peak oxygen consumption [Vo(2)]) to assess cardiorespiratory fitness. Brachial artery reactivity was negatively associated with Framingham risk score (r = -0.3542, p = 0.0007). Univariate predictors of endothelial function included peak Vo(2) (r = 0.4483, p0.0001), age (r = -0.3420, p = 0.0010), BMI (r = -0.3065, p = 0.0035), and high-sensitivity C-reactive protein (r = -0.2220, p = 0.0400). Using multiple linear regression analysis with stepwise modeling, peak Vo(2) (p = 0.0003) was the best independent predictor of brachial artery reactivity, with age as the only other variable reaching statistical significance (p = 0.0436) in this model. In conclusion, endothelial function was significantly associated with cardiovascular risk in women with sedentary occupations, who were commonly overweight or obese. Even in the absence of routine exercise, cardiorespiratory fitness, rather than conventional risk factors or body mass, is the dominant predictor of endothelial function and suggests a modifiable approach to risk.

Background— Percutaneous access for mitral interventions is currently limited to transapical and transseptal routes, both of which have shortcomings. We hypothesized that the left atrium could be accessed directly through the posterior chest wall under imaging guidance. Methods and Results— We tested percutaneous transthoracic left atrial access in 12 animals (10 pigs and 2 sheep) under real-time magnetic resonance imaging or x-ray fluoroscopy plus C-arm computed tomographic guidance. The pleural space was insufflated with CO 2 to displace the lung, an 18F sheath was delivered to the left atrium, and the left atrial port was closed using an off-the-shelf nitinol cardiac occluder. Animals were survived for a minimum of 7 days. The left atrial was accessed, and the port was closed successfully in 12/12 animals. There was no procedural mortality and only 1 hemodynamically insignificant pericardial effusion was observed at follow-up. We also successfully performed the procedure on 3 human cadavers. A simulated trajectory to the left atrium was present in all of 10 human cardiac computed tomographic angiograms analyzed. Conclusions— Percutaneous transthoracic left atrial access is feasible without instrumenting the left ventricular myocardium. In our experience, magnetic resonance imaging offers superb visualization of anatomic structures with the ability to monitor and address complications in real-time, although x-ray guidance seems feasible. Clinical translation seems realistic based on human cardiac computed tomographic analysis and cadaver testing. This technique could provide a direct nonsurgical access route for future transcatheter mitral implantation.

Background Realtime MR enables radiation free guidance for right heart catheterization (RHC). In addition to catheter navigation for sampling of invasive pressures and blood oxygen saturations, MR permits concomitant assessment of cardiac chamber volumes and cardiac output with phase contrast flow measurements. By performing repeat measurements under different physiological provocations (e.g. saline volume challenge, inhaled nitric oxide, or exercise), diagnostic yield increases by revealing symptoms and pathologic findings not apparent at rest. Herein we present the NIH experience of MR RHC to date.

Fractalkine, a chemokine expressed by inflamed endothelium, induces leukocyte adhesion and migration via the receptor CX3CR1, and the CX3CR1 polymorphism V249I affects receptor expression and function. Here we show that this polymorphism is an independent risk factor for atherosclerotic coronary artery disease (CAD). Genotyping of the CX3CR1-V249I polymorphism was performed in a cohort of 339 white individuals who underwent cardiac catheterization (n=197 with and n=142 without CAD, respectively). In 203 patients, intracoronary acetylcholine 15 μg/min) and sodium nitroprusside (20 μg/min) were administered to test endothelium-dependent and -independent coronary vascular function, respectively. Change in coronary vascular resistance (ΔCVR) was measured as an index of microvascular dilation. An association was observed between presence of the CX3CR1 I249 allele and reduced prevalence of CAD, independent of established CAD risk factors (odds ratio=0.54 [95% confidence interval, 0.30 to 0.96], P =0.03). Angiographic severity of CAD was also lower in these subjects ( P =0.01). Furthermore, endothelium-dependent vasodilation was greater in these individuals compared with individuals homozygous for the CX3CR1-V249 allele (ΔCVR during acetylcholine = −46±3% versus −36±3%, respectively, P =0.02), whereas ΔCVR with sodium nitroprusside was similar in both groups (−55±2% versus −53±2%, P =0.45). The association between CX3CR1 genotype and endothelial function was independent of established risk factors and presence of CAD by multivariate analysis ( P =0.02). Thus, the CX3CR1 I249 allele is associated with decreased risk of CAD and improved endothelium-dependent vasodilation. This suggests that CX3CR1 may be involved in the pathogenesis of CAD.

Objectives. This study sought to compare the circadian variations in transient ischemic activity, mean heart rate and ischemic threshold between women and men with coronary artery disease.Background. There is a circadian variation in ischemic activity, onset of myocardial infarction and sudden cardiac death in patients with coronary artery disease, but studies assessing ischemia have incorporated predominantly male subjects.Methods. Thirty-one women and 45 men underwent at least 48 h of ambulatory ST segment monitoring.Results. There was a similar and significant circadian variation in ischemic activity in both women and men (p < 0.001 and p < 0.0001, respectively), with a trough at night, a surge in the morning and a peak between 1 and 2 pm, corresponding to a similar circadian variation in mean hourly heart rate (p < 0.0001) that was not different between men and women (p = 0.28, power to detect a shift 99.9%). Mean heart rate at onset of ischemia (ischemia threshold) had similar variability in women and men (p = 0.96), and harmonic regression analysis confirmed a significant circadian variation (p < 0.0001), with a trough at night and a peak during activity hours. Heart rate increased significantly in the 5 min before ischemia throughout the 24 h (p < 0.0001), with no gender differences in the pattern of preonset to onset heart rate changes over time (p = 0.52); the smallest differences were recorded in the middle of the night. The majority of ischemic episodes (80%) had a heart rate increase >5 beats/min in the 5 min before ischemia, but there were no gender differences.Conclusions. Women with coronary artery disease have a pattern of ischemic activity and underlying pathophysiologic mechanisms very similar to men. The importance of increase in myocardial oxygen demand in the genesis of ischemia in both men and women is reflected by similar magnitude of heart rate increases before ischemia. The lower ischemic threshold during the nocturnal hours, when blood pressure is also lower, is consistent with a circadian variation is underlying coronary vascular tone.

Background We aim to deliver large appliances into the left ventricle through the right ventricle and across the interventricular septum. This transthoracic access route exploits immediate recoil of the septum, and lower transmyocardial pressure gradient across the right versus left ventricular free wall. The route may enhance safety and allow subxiphoid rather than intercostal traversal. Methods The entire procedure was performed under real-time CMR guidance. An “active” CMR needle crossed the chest, right ventricular free wall, and then the interventricular septum to deliver a guidewire then used to deliver an 18Fr introducer. Afterwards, the right ventricular free wall was closed with a nitinol occluder. Immediate closure and late healing of the unrepaired septum and free wall were assessed by oximetry, angiography, CMR, and necropsy up to four weeks afterwards. Results The procedure was successful in 9 of 11 pigs. One failed because of refractory ventricular fibrillation upon needle entry, and the other because of inadequate guidewire support. In all ten attempts, the right ventricular free wall was closed without hemopericardium. There was neither immediate nor late shunt on oximetry, X-ray angiography, or CMR. The interventricular septal tract fibrosed completely. Transventricular trajectories planned on human CT scans suggest comparable intracavitary working space and less acute entry angles than a conventional atrial transseptal approach. Conclusion Large closed-chest access ports can be introduced across the right ventricular free wall and interventricular septum into the left ventricle. The septum recoils immediately and heals completely without repair. A nitinol occluder immediately seals the right ventricular wall. The entry angle is more favorable to introduce, for example, prosthetic mitral valves than a conventional atrial transseptal approach.

Investigational transcatheter replacement mitral valves are bulky devices requiring large caliber access ports. An access route (Fig 1A) that does not impact left ventricular (LV) function could simplify device engineering and improve patient outcomes. We hypothesized that by deflating a lung, it is

To determine predictors of exercise benefit in patients with hypertrophic cardiomyopathy after operative relief of left ventricular (LV) outflow tract obstruction, 30 patients underwent catheterization and exercise testing before and 6 months after operation, and hemodynamic measurements were obtained. The increase in maximal oxygen consumption (VO2max) during treadmill exercise testing was chosen as an index of exercise benefit. Univariate analysis showed a significant positive correlation of operative change in VO2max with preoperative LV end-diastolic and pulmonary arterial wedge pressures, operative change in exercise duration, and operative reductions in LV end-diastolic and pulmonary arterial wedge pressures and resting LV outflow tract gradient, and a significant negative correlation with preoperative VO2max and percent predicted VO2max. Multivariate analysis by stepwise linear regression of only significant univariate variables selected only preoperative percent predicted VO2max, and operative reduction in LV end-diastolic pressure and resting LV outflow tract gradient as significant predictors of postoperative change in VO2max. Stepwise regression analysis, applied only to preoperative exercise and catheterization hemodynamic variables, selected only preoperative percent predicted VO2max and preoperative LV end-diastolic pressure as predictors of improvement in exercise capacity. Thus, patients with obstructive hypertrophic cardiomyopathy, after failing medical therapy, are most likely to demonstrate improvement in exercise capacity if preoperative exercise testing demonstrates limited exercise capacity and if surgery achieves reduction in elevated resting LV outflow tract gradients and LV filling pressures.

Anginal chest pain in patients with angiographically normal coronary arteries may be caused by a limited coronary flow response to stress because of abnormal function of the coronary microcirculation (microvascular angina). Studies of forearm arterial function suggested that patients with microvascular angina may have a diffuse disorder of smooth muscle tone. Because dyspnea is common in these patients and seems disproportionate to the severity of myocardial ischemia, we studied air flow (forced expiratory volume in 1 second, or FEV1) in the basal state and after methacholine inhalation to determine whether bronchial smooth muscle is affected in this syndrome. Five of 36 patients with microvascular angina had a basal FEV1 of less than 70% of that predicted and did not receive methacholine. Of the remaining 31 patients, 14 (45%) had a more-than-20% reduction in FEV1 after methacholine inhalation (as much as 25 mg/ml), a response significantly greater than that of nine patients with heart disease (0%, p less than 0.025) and 24 normal volunteers of similar age and gender distribution (13%, p less than 0.025). Furthermore, the product of the methacholine dose inhaled and the magnitude of decline in FEV1 from baseline (methacholine response score) was significantly lower in patients with microvascular angina than in normal volunteers (16 +/- 8.6 versus 22.2 +/- 3.7, p = 0.026). We conclude that airway hyperresponsiveness is frequently demonstrable in patients with microvascular angina; these findings are consistent with our hypothesis that this syndrome may represent a more generalized abnormality of vascular and nonvascular smooth muscle function.

Lidoflazine, a piperazine derivative calcium antagonist, was investigated as therapy in 22 patients with microvascular angina (chest pain, angiographically normal coronary arteries and left ventricle, microvascular constrictor response to pacing after ergonovine administration and limited coronary flow response to dipyridamole). Eighteen of 22 patients reported symptom benefit while taking lidoflazine 360 mg daily. Compared to baseline exercise treadmill testing, lidoflazine resulted in significant improvement in exercise duration (812 +/- 337 vs 628 +/- 357 seconds, p less than 0.01) and time to onset of chest pain (530 +/- 343 vs 348 +/- 246 seconds, p less than 0.01). The 5 patients with ischemic ST-segment changes during baseline testing demonstrated an almost 4-minute delay in ST-segment depression (3 patients) or no ST-segment depression (2 patients) while taking lidoflazine. Repeat invasive study of coronary flow in 11 patients taking lidoflazine demonstrated significantly greater coronary vasodilation at rest, during pacing, during pacing after ergonovine and after dipyridamole administration (all p less than 0.03), compared to the initial drug-free study. During the randomized, placebo-controlled phase of the study with 7-week treatment periods, 9 of 11 patients who completed this phase of the study preferred lidoflazine and all demonstrated improved exercise capacity with lidoflazine compared to placebo. However, 3 patients developed malignant ventricular arrhythmias, and 1 died while taking lidoflazine, resulting in termination of the study. Limited coronary vasodilator response in microvascular angina has a reversible vasoconstrictor component and may be due to elevated systolic calcium levels. Despite the hemodynamic, symptom and exercise benefit, lidoflazine may be unsafe for clinical use because of its propensity to cause potentially fatal ventricular arrhythmias.

To ascertain the relative prevalence of abnormalities of coronary flow reserve and esophageal function in patients with chest pain despite angiographically normal coronary arteries, 87 patients underwent invasive study of coronary flow reserve and, during the same week, esophageal testing.Sixty-three of the 87 patients (72%) demonstrated abnormalities of coronary flow reserve, as evidenced by an increase in coronary resistance during the stress of rapid atrial pacing after administration of ergonovine 0.15 mg intravenously (1.33 +/- 0.36 mm Hg.minute/mL), compared with pacing at the same heart rate before ergonovine administration (1.10 +/- 0.33 mm Hg.minute/mL). This higher coronary vascular resistance occurred in the absence of significant epicardial coronary artery luminal narrowing. Fifty-seven of these 63 patients (90%) with a coronary vasoconstrictor response to ergonovine described their typical chest pain during pacing stress, compared with only six of 24 patients (25%) who demonstrated no coronary flow abnormality (p less than 0.001). After administration of dipyridamole 0.5 to 0.75 mg/kg intravenously to 65 patients, the 48 patients with ergonovine-induced vasoconstriction had a significantly higher minimum coronary resistance, compared with the 17 patients without a coronary vasoconstrictor response to ergonovine (0.65 +/- 0.21 versus 0.47 +/- 0.13 mm Hg.minute/mL, p less than 0.03). Twenty of 87 patients (23%) had abnormal esophageal motility [nutcracker esophagus (11), nonspecific motility disorder (seven), and diffuse esophageal spasm (two)], including 16 of the 63 patients (25%) with abnormal coronary flow reserve. Twenty-four (28%) patients experienced their typical chest pain during motility testing, but only five of these patients met criteria for abnormal esophageal motility. Nine of 75 patients tested (12%) had their typical chest pain during Bernstein testing, and 18 of 38 patients (47%) tested had their typical chest pain provoked by intraesophageal balloon distention.Seventy-one of 87 patients (82%) with anginal-like chest pain and normal epicardial vessels in our series had a disorder of either coronary flow reserve, esophageal motility, and/or reproduction of typical chest pain during acid infusion. Of interest, chest pain was commonly encountered during cardiac and esophageal testing (85% of patients), regardless of the ability to demonstrate an abnormality of coronary flow reserve or abnormal esophageal function. This suggests that pain experienced by these patients may be a consequence of myocardial ischemia, esophageal dysfunction, abnormal visceral nociception, or a combination of any or all of these entities.

Background Transcatheter aortic valves have benefitted from device miniaturization and in-situ assembly to reduce delivery system caliber and enable trans-vascular delivery. In contrast, investigational transcatheter mitral prostheses are bulky devices that require large caliber access ports. Trans-apical delivery is undesirable because of increased morbidity associated with rib spreading, closure site bleeding and impact on left ventricle (LV) function. Trans-septal delivery is challenging because of the acute angle required to reach the mitral valve. A ‘straight shot’ to the mitral valve (Fig 1A) that does not violate the LV myocardium is preferable, both in terms of device engineering and patient outcome. We hypothesized that with realtime MR guidance and by deflating a lung, it is possible to access the left atrium (LA) directly through the posterior chest wall, and close the access port using off-the-shelf nitinol devices.

Background — Whether patients at increased risk can be identified from a relatively low-risk population by coronary vascular function testing remains unknown. We investigated the relationship between coronary endothelial function and the occurrence of acute unpredictable cardiovascular events (cardiovascular death, myocardial infarction, stroke, and unstable angina) in patients with and without coronary atherosclerosis (CAD). Methods and Results — We measured the change in coronary vascular resistance (ΔCVR) and epicardial diameter with intracoronary acetylcholine (ACh, 15 μg/min) to test endothelium-dependent function and sodium nitroprusside (20 μg/min) and adenosine (2.2 mg/min) to test endothelium-independent vascular function in 308 patients undergoing cardiac catheterization (132 with and 176 without CAD). Patients underwent clinical follow-up for a mean of 46±3 months. Acute vascular events occurred in 35 patients. After multivariate analysis that included CAD and conventional risk factors for atherosclerosis, ΔCVR with ACh ( P =0.02) and epicardial constriction with ACh ( P =0.003), together with increasing age, CAD, and body mass index, were independent predictors of adverse events. Thus, patients in the tertile with the best microvascular responses with ACh and those with epicardial dilation with ACh had improved survival by Kaplan-Meier analyses in the total population, as did those in the subset without CAD. Similar improvement in survival was also observed when all adverse events, including revascularization, were considered. Endothelium-independent responses were not predictive of outcome. Conclusions — Epicardial and microvascular coronary endothelial dysfunction independently predict acute cardiovascular events in patients with and without CAD, providing both functional and prognostic information that complements angiographic and risk factor assessment.

mined by small vessel tone, which is closely coupled to myocardial oxygen demand and, potentially, by structural narrowings in large and small coronary arteries. We observed that the reduction in coronary blood flow in patients with TAA could not be accounted for solely by arteriosclerosis in epicardial arteries, because the epicardial diameter was not appreciably reduced. This suggests that the reduction in coronary blood flow (increase in TFC) was largely due to structural disease or constriction in the microvascular bed not detectable by angiography and supports the use of TFC as a physiologic adjunct in the diagnosis of TAA. 2 In summary, an increase in TFC (or decrease in resting coronary blood flow) over a 4-year period was observed in cardiac transplant recipients who developed angiographic evidence of coronary arteriosclerosis. The absence of severe structural narrowings in epicardial arteries suggests that TFC was altered by coexisting disease in the microvascular circulation. We suggest that the TFC is a new quantitative approach to assessing transplant-associated arteriosclerosis that is simple, intuitive, and easily acquired. For these reasons, this technique could be widely adapted by many cardiac catheterization laboratories involved in the routine assessment of the cardiac transplant allograft.

Why LVEF impairment ,0.36 is not as good a predictor of survival as NYHA functional class in this study is unclear. LVEF assesses systolic LV function alone, whereas functional class assesses diastolic and systolic function indirectly. LV diastolic dysfunction, in combination with systolic impairment, might predict survival better than systolic impairment alone. In the CABG Patch Trial, functional class represented a composite of symptoms over the 2-month period before CABG, eliminating the possibility that transient changes in preload alone were responsible for the symptoms. Because functional class had longterm predictive value after CABG, it was unlikely

Patients with stable single or 2-vessel coronary artery disease (CAD) and normal, or mildly depressed left ventricular function have a good prognosis. We have investigated the long-term prognostic significance of a positive exercise test (ExTestl in this population to establish whether it is useful in identifying a “high-risk” subgroup within a recognised “low-risk” population. Between 1987–94,162 patients with documented single (n=89) or double (n=73) vessel CAD (exclUding left main and proximal left anterior descending CAD), left ventricular ejection fraction >35% (mean 51%, range 36–72%) on radionuclide ventriculography, and an interpretable ExTest were assigned to receive medical therapy. There were 123 males and 39 females (mean age 60 yrs). A positive ExTest for ischemia was present in 104 (64%) pts. Pts were followed for a mean period of 49 months (range 6–82 months), during which time 34 (21%) had cardiac events (cardiac death n = 3, myocardial infarction (AMI) n = 14, unstable angina n = 6, elective revascularisation n = 11). Similar proportion of pts with a positive ExTest and a negative ExTest suffered cardiac events (all events, including revascularization) during follow-up (21% and 20.7% respectively). Kaplan Meier survival analysis demonstrated no difference between the groups. Survival analysis also failed to demonstrate any difference in the incidence of acute cardiac events (cardiac death and AMI) between positive and negative ExTest groups; of 15 events, 6 (40%) occurred in those with a positive Extest. Pts with 2-vessel disease suffered significantly more events than those with I-vessel disease (29% vs 14.6%, P < 0.05), but there was no difference in acute events (cardiac death and AMI) between the two subsets. Even in pts with 2-vessel disease, there was no difference in survival in those with and without a positive ExTest. The data indicate that although detection of ischemia by exercise testing is useful as an initial diagnostic tool, once the coronary anatomy and left ventricular function are known, the presence of ischemia on treadmill exercise is of limited prognostic value in “low-risk” pts with stable CAD. These findings are consistent with reports demonstrating that acute cardiac events often result from plaque rupture in non-significantly stenosed vessels.

Background Myocardial haemorrhage after myocardial infarction (MI) frequently goes undetected. Since the paramagnetic effects of oxidised iron may result in signal loss on T2* and T2-weighted MRI, we investigated the diagnostic accuracy of T2-weighted MRI in experimental MI. Methods Acute MI was created in swine (43±9.5 kg) by occluding the left anterior descending coronary artery (n=10) or circumflex (n=5) for 90 min followed by reperfusion for ≤3 days (n=2), 10 days (n=7) or 60 days (n=6). Cardiac MRI was performed at 1.5 T using T2-prepared steady-state free-precession (T2P-SSFP) and gadolinium enhanced (CE) MRI. Left ventricular (LV) sections were visually inspected, photographed and stained for histology. Gross images and histology were scored for myocardial haemorrhage by an experienced cardiac pathologist blinded to all other data. Regions of low signal intensity on T2-weighted and CE-MRI were independently determined by three cardiologists blinded to the pathology results. Results Eighty ventricular slices of pathology were matched with MRI (n=68 for first pass CE-CMR). All sections exhibited hyperintense zones consistent with oedema on T2-weighted, scar on CE-MRI and pathologic evidence of MI. Myocardial haemorrhage occurred in 49 LV sections (61%) and corresponded with signal voids on 48 T2-weighted (98%) and 26 CE-MRI (53%). Alternatively, signal voids occurred in the absence of haemorrhage in three T2-weighted (90% specificity) and five CE-MRI (84% specificity). On first pass CE-MRI, 27/43 perfusion defects corresponded with haemorrhage (63% sensitivity) while 5/25 defects occurred in the absence of haemorrhage (80% specificity). The positive and negative predictive values for pathological evidence of haemorrhage were 94% & 96% for T2-weighted, 84% & 53% for CE-MRI, and 84% & 56% for first pass perfusion. Conclusions T2-weighted MRI has high diagnostic accuracy for myocardial haemorrhage. Heterogeneity of signal intensity associated with acute MI on T2-weighted MRI is partially due to intramyocardial haemorrhage.

BACKGROUND Exercise-induced abnormalities during thallium-201 scintigraphy that normalize at rest frequently occur in patients with hypertrophic cardiomyopathy. However, it is not known whether these abnormalities are indicative of myocardial ischemia. METHODS AND RESULTS Fifty patients with hypertrophic cardiomyopathy underwent exercise 201Tl scintigraphy and, during the same week, measurement of myocardial lactate metabolism and hemodynamics during pacing stress. Thirty-seven patients (74%) had one or more 201Tl abnormalities that completely normalized after 3 hours of rest; 26 had regional myocardial 201Tl defects, and 26 had apparent left ventricular cavity dilatation with exercise, with 15 having coexistence of these abnormal findings. Of the 37 patients with reversible 201Tl abnormalities, 27 (73%) had metabolic evidence of myocardial ischemia during rapid atrial pacing (myocardial lactate extraction of 0 mmol/l or less) compared with four of 13 patients (31%) with normal 201Tl scans (p less than 0.01). Eleven patients had apparent cavity dilatation as their only 201Tl abnormality; their mean postpacing left ventricular end-diastolic pressure was significantly higher than that of the 13 patients with normal 201Tl studies (33 +/- 5 versus 21 +/- 10 mm Hg, p less than 0.001). There was no correlation between the angiographic presence of systolic septal or epicardial coronary arterial compression and the presence or distribution of 201Tl abnormalities. Patients with ischemic ST segment responses to exercise had an 80% prevalence rate of reversible 201Tl abnormalities and a 70% prevalence rate of pacing-induced ischemia. However, 69% of patients with nonischemic ST segment responses had reversible 201Tl abnormalities, and 55% had pacing-induced ischemia. CONCLUSIONS Reversible 201Tl abnormalities during exercise stress are markers of myocardial ischemia in hypertrophic cardiomyopathy and most likely identify relatively underperfused myocardium. In contrast, ST segment changes with exercise and systolic compression of coronary arteries on angiography are unreliable markers of inducible myocardial ischemia in hypertrophic cardiomyopathy. Apparent cavity dilatation during 201Tl scintigraphy may indicate ischemia-related changes in left ventricular filling, with elevation in diastolic pressures and endocardial compression.

Objective. —To assess long-term prognostic significance of transient ischemia in patients with documented coronary artery disease and stable symptoms and to examine the relation between transient ischemia and the site of angiographic disease progression following acute cardiac events. Design. —Cohort study with a mean±SD follow-up of 51.5±23.8 months. Setting. —Ambulatory patients with stable coronary artery disease, assigned to medical therapy. Patients. —A total 221 patients (173 men; mean age, 60.8 years) were recruited. Of the 221 patients, 101 (45.7%) had single-vessel, 86 (38.9%) had 2-vessel, and 34 (15.4%) had 3-vessel disease. A total of 135 had a positive exercise test for ischemia, and mean±SD resting left ventricular ejection fraction (LVEF) was 49.8%±11.4%. Using conventional criteria, patients were prospectively stratified as low risk for continued medical therapy (single-vessel disease, 2-vessel disease with negative exercise test, or LVEF≥40%; n=189 [85.5%]) or high risk for continued medical therapy (multivessel disease with ischemia and/or left ventricular dysfunction; n=32 [14.5%]). Interventions. —Ambulatory ST-segment monitoring, treadmill exercise testing, radionuclide ventriculography, and coronary angiography. Main Outcome Measures. —Demographic, clinical, ambulatory monitoring, treadmill exercise, and left ventricular function variables as independent predictors of acute (cardiac death, myocardial infarction, or unstable angina) or all (including revascularization) cardiac events in the overall and the low-risk population. Results. —None of the clinical or noninvasive measures of ischemia were of prognostic significance in the overall or the low-risk group. The only significant independent predictor of outcome in all patients for all events, including revascularization, was the number of diseased vessels (ϰ 2 =13.5 [ df =1]; P 2 =10.3 [ df =1]; P =.001). In the low-risk group, the number of diseased vessels was the only predictor for all events (ϰ 2 =4.6; P =.03). For acute cardiac events, none of the variables tested were of prognostic significance. Based on the frequency of events in the low-risk patients, a 2-fold increase in the rate of cardiac events in patients with transient ischemia compared with those without transient ischemia during ambulatory monitoring could be excluded with greater than 85% power and α of.05. Of 30 patients suffering acute nonfatal cardiac events during follow-up, angiography was performed in 27, revealing significant progression of coronary disease in 24 (88.8%) and the development of new significant lesions at sites remote from previously significant lesions in 20 (74%) cases. These new lesions were equally likely to occur in those with or without transient ischemia at initial assessment. Conclusions. —Acute cardiac events in predominantly low-risk stable angina patients with confirmed coronary disease are unpredictable, and those more likely to suffer such an event cannot be identified by the detection of ambulatory ischemia. Acute nonfatal cardiac events result predominantly from the development of significant new coronary lesions, not initially severe enough to cause ischemia. Patients categorized as high risk for long-term medical therapy have an increased rate of cardiac events (mainly revascularization) when compared with low-risk patients.

To assess the impact of operative reduction of left ventricular outflow obstruction in hypertrophic cardiomyopathy, measurements of great cardiac vein flow, oxygen and lactate content, left ventricular pressures, and cardiac index were measured at rest and during pacing stress in 20 consecutive patients (13, myotomy-myectomy; six, mitral valve replacement; one, both myotomy-myectomy and mitral valve replacement) who underwent both preoperative and postoperative studies. All had angiographically normal epicardial coronary arteries. Operation resulted in reduction in outflow gradient (64 +/- 38 to 4 +/- 7 mm Hg, p less than 0.001) and in left ventricular systolic pressure (186 +/- 32 to 128 +/- 22 mm Hg, p less than 0.001) and was associated with reduction in great cardiac vein flow (101 +/- 26 to 78 +/- 16 ml/min, p less than 0.001) and oxygen consumption in the anterior left ventricle and septum (11.9 +/- 4.1 to 8.4 +/- 1.9 ml O2/min, p less than 0.001) in the basal state. During rapid atrial pacing, 13 of 20 patients experienced chest pain postoperatively, whereas all 20 developed chest pain during preoperative pacing, with an improvement in pacing anginal threshold (or heart rate 150 if no chest pain was experienced) of 16 +/- 18 beats/min (p less than 0.001). The peak great cardiac vein flow (161 +/- 41 to 131 +/- 45 ml/min, p less than 0.025) and myocardial oxygen consumption (19.4 +/- 6.1 to 14.3 +/- 5.5 ml O2/min, p less than 0.005) during pacing, which correlated directly with the severity of the basal left ventricular gradient (p = 0.011 and p = 0.002, respectively), were also reduced by surgery. Lactate metabolism during pacing changed from net production before surgery to net consumption after operation (-17 +/- 47.6 to 4.4 +/- 29.8 mumol/min, p less than 0.01), with six of 20 patients producing lactate after surgery compared with 13 of 20 before surgery (p = 0.06). The six patients with the highest peak great cardiac vein flow (greater than 175 ml/min) during preoperative pacing had greater symptom and metabolic benefit during pacing after surgery compared with the 14 patients with lower peak coronary flow. Postpacing left ventricular end-diastolic pressure (30 +/- 7 to 23 +/- 7 mm Hg, p less than 0.001) and pulmonary artery wedge pressure (24 +/- 6 to 20 +/- 5, p less than 0.001) were reduced after surgery.(ABSTRACT TRUNCATED AT 400 WORDS)

Patients with anginal chest pain despite angiographically normal coronary arteries and left ventricles may have abnormalities of coronary flow reserve. Twenty-five patients were found to have limited flow reserve during rapid atrial pacing after administration of 0.15 to 0.30 mg iv ergonovine, associated with precipitation of chest pain and hemodynamic and metabolic evidence of myocardial ischemia. No significant narrowing occurred in epicardial coronary artery luminal diameter. An additional 15 patients had no chest pain during pacing; because they developed significantly higher great cardiac vein flow and lower coronary resistance they were considered to have normal vasodilator reserve. After administration of dipyridamole (0.5 to 0.75 mg/kg iv), the lowest absolute levels to which coronary resistance fell (0.79 +/- 0.23 vs 0.47 +/- 0.12 mm Hg X min/ml; p less than .001) and the maximal absolute levels to which great cardiac vein flow rose (134 +/- 34 vs 202 +/- 45 ml/min; p less than .001) were impaired in the 25 patients with ergonovine-induced flow limitation compared with the 15 patients without flow limitation after ergonovine. In addition, 18 of the 25 patients with limited flow reserve after dipyridamole experienced chest pain despite an increase in coronary flow. In these patients, dipyridamole-induced increased flow across small prearteriolar coronary arteries, which were narrowed because of abnormal tonus or sensitivity to vasoconstrictor stimuli, could have resulted in a transmural redistribution of blood flow away from the subendocardium, precipitating subendocardial ischemia. These studies suggest that patients with anginal chest pain despite normal epicardial coronary arteries may have exaggerated coronary responses to vasoconstrictor stimuli, which can result in myocardial ischemia during stress, as well as attenuated responses to coronary vasodilator stimuli.

Fifty patients with hypertrophic cardiomyopathy underwent invasive study of coronary and myocardial hemodynamics in the basal state and during the stress of pacing. The 23 patients with basal obstruction (average left ventricular outflow gradient, 77 +/- 33 mm Hg; left ventricular systolic pressure, 196 +/- 33 mm Hg, mean +/- 1 SD) had significantly lower coronary resistance (0.85 +/- 0.18 versus 1.32 +/- 0.44 mm Hg X min/ml, p less than 0.001) and higher basal coronary flow (106 +/- 20 versus 80 +/- 25 ml/min, p less than 0.001) in the anterior left ventricle, associated with higher regional myocardial oxygen consumption (12.4 +/- 3.6 versus 8.9 +/- 3.3 ml oxygen/min, p less than 0.001) compared with the 27 patients without obstruction (mean left ventricular systolic pressure 134 +/- 18 mm Hg, p less than 0.001). Myocardial oxygen consumption and coronary blood flow were also significantly higher at paced heart rates of 100 and 130 beats/min (the anginal threshold for 41 of the 50 patients) in patients with obstruction compared with those without. In patients with obstruction, transmural coronary flow reserve was exhausted at a heart rate of 130 beats/min; higher heart rates resulted in more severe metabolic evidence of ischemia with all patients experiencing chest pain, associated with an actual increase in coronary resistance. Patients without obstruction also demonstrated evidence of ischemia at heart rates of 130 and 150 beats/min, with 25 of 27 patients experiencing chest pain. In this group, myocardial ischemia occurred at significantly lower coronary flow, higher coronary resistance and lower myocardial oxygen consumption, suggesting more severely impaired flow delivery in this group compared with those with obstruction. Abnormalities in myocardial oxygen extraction and marked elevation in filling pressures during stress were noted in both groups. Thus, obstruction to left ventricular outflow is associated with high left ventricular systolic pressure and oxygen consumption and therefore has important pathogenetic importance to the precipitation of ischemia in patients with hypertrophic cardiomyopathy. Patients without obstruction may have greater impairment in coronary flow delivery during stress.

The causes of chest pain in patients found to have angiographically normal coronary arteries during cardiac catheterization remain controversial. Cardiac sensitivity to catheter manipulation, pacing at various stimulus intensities and intracoronary injection of contrast medium was examined in several groups of patients who underwent cardiac catheterization. Right heart (especially right ventricular) catheter manipulation and pacing and intracoronary contrast medium provoked chest pain typical of that previously experienced in 29 (81%) of 36 patients with chest pain and angiographically normal coronary arteries and 15 (46%) of 33 symptomatic patients with hypertrophic cardiomyopathy. In contrast, only 2 (6%) of 33 symptomatic patients with coronary artery disease experienced their typical chest pain with these sensitivity tests (p less than 0.001). None of 10 patients with valvular heart disease but without a chest pain syndrome experienced any sensation with these tests. Cutaneous pain threshold testing demonstrated that patients with chest pain and normal coronary arteries had a higher pain threshold to thermal stimulation compared with patients who had coronary artery disease or hypertrophic cardiomyopathy. No relation existed between cardiac sensitivity and cutaneous sensitivity testing. Thus, patients who have chest pain despite angiographically normal coronary arteries may have abnormal cardiac sensitivity to a variety of stimuli. This increased sensitivity may be of causal importance to their chest pain syndrome or may contribute to their perception of ischemia-induced pain. The same phenomenon was also commonly seen in symptomatic patients with hypertrophic cardiomyopathy. Whether this phenomenon represents abnormal activation of pain receptors within the heart or abnormal processing of visceral afferent neural impulses in the peripheral or central nervous system is unknown.

Left ventricular pulsus alternans (LVPA), a rhythmic beat to beat variation in left ventricular systolic pressure and outflow gradient, was noted in 35 of 200 ventricular systolic pressure and outflow gradient, was noted in 35 of 200 patients with hypertrophic cardiomyopathy undergoing hemodynamic study. LVPA was not associated with significant systemic pulsus alternans nor right ventricular pulsus alternans. All patients with LVPA had severe outflow gradients at rest or during provocation. Of 61 patients with severe basal outflow gradients (greater than 80 mm Hg), 12 demonstrated LVPA at rest. Eight of these patients underwent ventricular septal myotomy-myectomy; all had successful abolition of basal outflow gradient. Of the seven of these eight patients who underwent postoperative hemodynamic study and who were in sinus rhythm, none demonstrated LVPA. Eleven of 60 patients with basal outflow gradients ranging from 10 to 70 mm Hg demonstrated LVPA during maneuvers provocative for outflow gradients (mean gradient 90 +/- 37 mm Hg). Two of these patients underwent ventricular septal myotomy-myectomy; neither had a gradient nor LVPA during provocation postoperatively. Twelve additional patients with basal outflow gradients ranging from 0 to 115 mm Hg had LVPA after ectopic beats, generally occurring during maneuvers provocative for outflow gradients, associated with severe outflow gradients (mean gradient 130 +/- 39 mm Hg) during the postextrasystolic beat. None of the 41 patients without an outflow gradient, basal or during provocation, was found to have LVPA. Thus LVPA is commonly seen in during provocation, was found to have LVPA. Thus LVPA is commonly seen in patients with hypertrophic cardiomyopathy and severe left ventricular outflow gradients and may represent inadequate left ventricular contractile function in the presence of high left ventricular systolic pressures.

When angina occurs in patients with hypertension, it is usually attributed to coronary artery disease or left ventricular hypertrophy. To determine the contribution of coronary microvascular abnormalities to angina in patients with hypertension, we evaluated hypertensive patients without coronary artery disease or left ventricular hypertrophy by measuring the coronary responses to rapid atrial pacing before and after administration of ergonovine. We compared 12 hypertensive patients who had pacing-induced angina with 13 normotensive subjects without such angina. The two groups had similar coronary flow (in the great cardiac vein) at rest; however, pacing increased coronary flow less in hypertensive patients with angina than in normotensive subjects (48 vs. 83 percent; P = 0.05). In the hypertensive patients with angina, pacing after ergonovine increased coronary flow by only 32 percent (as compared with 48 percent before ergonovine; P less than 0.05) and decreased coronary resistance by 15 percent (as compared with 28 percent before ergonovine; P less than 0.05), indicating the presence of ergonovine-induced vasoconstriction. In normotensive subjects, in contrast, cardiac pacing after ergonovine increased coronary flow by 112 percent (P less than 0.001), and its effect on coronary resistance was not different from that of pacing before ergonovine. The hypertensive patients with angina had a significant increase in myocardial oxygen extraction during pacing after ergonovine and less of an increase in myocardial lactate consumption - a response consistent with the presence of myocardial ischemia. Thus, angina in hypertensive patients without epicardial coronary disease may be caused by myocardial ischemia, which appears to be due to an abnormally elevated resistance of the coronary microvasculature.

Twenty-six patients with dilated cardiomyopathy and angiographically normal coronary arteries, 12 of whom gave a history of anginal chest pain, underwent noninvasive and invasive hemodynamic study. During treadmill exercise testing, patients with a history of angina demonstrated worse effort tolerance (7.4 +/- 4.9 versus 13.6 +/- 5.1 minutes, p less than 0.005) and a lower end-exercise systolic blood pressure-heart rate product (17.9 +/- 3.4 versus 23.6 +/- 4.9 mm Hg.beats/min x 10(3), p less than 0.005) compared with patients without a history of angina. During rapid atrial pacing after ergonovine, 0.15 mg intravenously, 11 of the 12 patients with a history of angina experienced their typical chest pain, in contrast to only 1 of 12 patients without a history of angina. The angina group, compared with the nonangina group, had significantly lower great cardiac vein flow (118 +/- 24 versus 160 +/- 43 ml/min, p less than 0.01), and higher coronary resistance (0.87 +/- 0.21 versus 0.66 +/- 0.25 mm Hg.min/ml, p less than 0.05), significant widening of the arterial--great cardiac vein oxygen difference and a significant fall in cardiac index during pacing. Further, ergonovine resulted in higher coronary resistance during pacing in the angina group compared with pacing alone (+0.16 +/- 0.16 mm Hg min/ml, p less than 0.01), in the absence of significant reduction in epicardial coronary artery luminal diameter. After dipyridamole, 0.5 to 0.75 mg/kg intravenously, to 21 patients, the 7 patients with a history of angina had significantly lower flow (149 +/- 37 versus 218 +/- 73 ml/min, p less than 0.05) and higher coronary resistance (0.59 +/- 0.09 versus 0.43 +/- 0.17 mm Hg.min/ml, p less than 0.05) than did the nonangina group. It is concluded that patients with dilated cardiomyopathy and chest pain unrelated to epicardial coronary artery disease exhibit impaired vasodilator responses to both metabolic and pharmacologic stimuli, and an increased sensitivity to the vasoconstrictor effects of ergonovine. Whether these findings are of etiologic or long-term prognostic significance is unknown.

Functional tricuspid regurgitation (TR) is clinically significant. TR predicts mortality independent of LVEF, age or pulmonary artery pressure. Persistent TR after mitral valve surgery is an independent poor prognostic sign. Tricuspid valve repair is usually an adjunct to other surgery. We present

We designed and built a device that is positioned along the atrioventricular groove in the pericardial space and tightened to modify the geometry of the tricuspid annulus to treat functional tricuspid regurgitation. The device is delivered to the pericardial space from within via trans-atrial