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A global multidisciplinary workshop was convened to discuss the multimodality diagnostic evaluation of aortic regurgitation (AR). Specifically, the focus was on assessment tools for AR severity and analyzing evolving data on the optimal timing of aortic valve intervention. The key concepts from this expert panel are summarized as: 1) echocardiography is the primary imaging modality for assessment of AR severity; however, when data is incongruent or incomplete, cardiac magnetic resonance may be helpful; 2) assessment of left ventricular size and function is crucial in determining the timing of intervention; 3) recent evidence suggests current cutpoints for intervention in asymptomatic severe AR patients requires further scrutiny; 4) left ventricular end-systolic volume index has emerged as an additional parameter that has promise in guiding timing of intervention; and 5) the role of additional factors (including global longitudinal strain, regurgitant fraction, and myocardial extracellular volume) is worthy of future investigation., Competing Interests: Funding Support and Author Disclosures Dr Ranard has received institutional funding to Columbia University from Boston Scientific. Dr Bax has received speaker bureau fees from Abbott and Edwards Lifesciences. Dr Delgado has received speaker fees from Abbott Vascular, Edwards Lifesciences, GE Healthcare, Medtronic, Novartis, and Philips; and has received consulting fees from Edwards Lifesciences and Novo Nordisk. Dr Leipsic has received institutional CT core lab contracts with Edwards Lifesciences, Abbott, Boston Scientific, Medtronic, and PI Cardia. Dr Lang is on the Speakers Bureau and has received grants from Philips Medical Systems. Dr Vahl has received institutional funding to Columbia University Irving Medical Center from Boston Scientific, Edwards Lifesciences, JenaValve, Medtronic, and Siemens Healthineers; and has personally received consulting fees from 4C Medical, Abbott Vascular, and Boston Scientific. Dr Leon has received institutional clinical research grants from Abbott, Boston Scientific, Edwards Lifesciences, Medtronic, and JenaValve. Dr Rigolin has stock ownership in Edwards Lifesciences. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Although early reperfusion is the most desirable intervention after ischemic myocardial insult, it may add to damage through oxidative stress., Objectives: This study investigated the cardioprotective effects of a single intravenous dose of heat shock protein-72 (HSP72) coupled to a single-chain variable fragment (Fv) of monoclonal antibody 3E10 (3E10Fv) in a rabbit ischemia-reperfusion model. The Fv facilitates rapid transport of HSP72 into cells, even with intact membranes., Methods: A left coronary artery occlusion (40 min) reperfusion (3 h) model was used in 31 rabbits. Of these, 12 rabbits received the fusion protein (Fv-HSP72) intravenously. The remaining 19 control rabbits received a molar equivalent of 3E10Fv alone (n = 6), HSP72 alone (n = 6), or phosphate-buffered saline (n = 7). Serial echocardiographic examinations were performed to assess left ventricular function before and after reperfusion. Micro-single-photon emission computed tomography imaging of 99m Tc-labeled annexin-V was performed with micro-computed tomography scanning to characterize apoptotic damage in vivo, followed by gamma counting of the excised myocardial specimens to quantify cell death. Histopathological characterization of the myocardial tissue and sequential cardiac troponin I measurements were also undertaken., Results: Myocardial annexin-V uptake was 43% lower in the area at risk (p = 0.0003) in Fv-HSP72-treated rabbits compared with control animals receiving HSP72 or 3E10Fv alone. During reperfusion, troponin I release was 42% lower and the echocardiographic left ventricular ejection fraction 27% higher in the Fv-HSP72-treated group compared with control animals. Histopathological analyses confirmed penetration of 3E10Fv-containing molecules into cardiomyocytes in vivo, and treatment with Fv-HSP72 showed fewer apoptotic nuclei compared with control rabbits., Conclusions: Single-dose administration of Fv-HSP72 fusion protein at the time of reperfusion reduced myocardial apoptosis by almost one-half and improved left ventricular functional recovery after myocardial ischemia-reperfusion injury in rabbits. It might have potential to serve as an adjunct to early reperfusion in the management of myocardial infarction., (Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: The purpose of this study was to compare the treatment effects of septal myectomy with dual-chamber pacing in patients with hypertrophic obstructive cardiomyopathy (HOCM)., Background: The optimal treatment for symptomatic patients with drug-refractory HOCM is unknown. Both dual-chamber pacing and surgical myectomy may result in subjective symptom improvement. However, no direct comparisons with objective end points have been reported., Methods: Thirty-nine patients with symptomatic HOCM were analyzed in this concurrent cohort study. Twenty patients underwent surgical myectomy, and 19 received dual-chamber pacemakers based on patient preference. These patients had prospective baseline and follow-up evaluations including physician assessment, echocardiography and standardized metabolic treadmill exercise testing., Results: Baseline symptom status, left ventricular outflow tract gradients, exercise times and maximal oxygen consumption peak were similar between the two groups. Left ventricular outflow gradient was reduced from 76+/-57 to 9+/-17 mm Hg (p = 0.0001) after myectomy, and from 77+/-61 to 55+/-39 mm Hg (p = 0.07) after pacing (p = 0.02 for comparison with myectomy). Ninety percent of myectomy patients experienced symptomatic improvement as compared with 47% in the pacing group. Exercise duration increased significantly from 6.6+/-2.8 to 8.7+/-3.0 min (p = 0.0003) after myectomy compared with a change from 6.4+/-2.1 to 7.0+/-2.2 min (p = NS) in the pacing group. Maximal oxygen consumption increased from 19.4+/-6.4 to 22.2+/-6.5 ml/kg/min after myectomy (p = 0.004), whereas the pacing group did not experience any significant change (19.6+/-6.5 vs. 20.1+/-6.5 ml/kg/min, p = NS)., Conclusions: Surgical myectomy and dual-chamber pacing improve subjective measures of functional status in patients with symptomatic HOCM. In this nonrandomized study, myectomy offered greater reduction in left ventricular outflow tract gradients and larger improvements in objective measures of patient symptoms and functional status when compared with dual-chamber pacing.

Objectives: This study was designed to determine the usefulness of transthoracic Doppler measurements in detecting increased left ventricular (LV) end-diastolic pressure in patients with coronary artery disease, specifically examining the influence of systolic function on the accuracy of these methods., Background: Studies that have correlated Doppler indexes with LV filling pressures primarily involved patients with LV systolic dysfunction. The reliability of Doppler indexes in estimating filling pressures in patients with coronary artery disease and preserved systolic function is unclear., Methods: Pulsed wave Doppler transmitral and pulmonary venous flow velocity curves and LV pressure were recorded in 83 patients with coronary artery disease., Results: Conventional Doppler indexes (deceleration time of mitral E wave velocity, ratio of peak mitral E to A wave velocities and pulmonary venous systolic fraction) correlated with LV filling pressure in patients with an ejection fraction (EF) < or = 50% but not in those with an EF > 50%. Previously published regression analysis for prediction of LV filling pressure was accurate in patients with an EF < or = 50% but not in those with an EF > 50%. The difference between flow duration with atrial contraction in the pulmonary veins and transmitral flow duration with atrial contraction correlated with LV filling pressure in both groups., Conclusions: Analysis of the early diastolic portion of the transmitral or pulmonary venous flow velocity curves can be used to predict LV filling pressures in patients with systolic dysfunction, but are inaccurate in patients with preserved systolic function. The combined analysis of both flow velocity curves at atrial contraction is a reliable, feasible predictor of increased LV filling pressure, irrespective of systolic function.

Objectives: The aim of this study was to demonstrate the usefulness of preload alterations in assessing left ventricular filling pressures with transmitral Doppler velocity curves., Background: Doppler mitral inflow velocities, used to estimate left ventricular filling pressures noninvasively, are limited in predicting left ventricular filling pressures, especially in patients with normal systolic function and a "pseudonormal" mitral filling pattern., Methods: Forty-nine patients were studied in the cardiac catheterization laboratory with simultaneous Doppler echocardiography using high fidelity catheters to compare left ventricular diastolic filling pressures (pre-A wave left ventricular pressure) and Doppler mitral inflow at baseline and during reduction of preload during the strain phase of the Valsalva maneuver (n = 27) or sublingual nitroglycerin (n = 36), or both (n = 14). Doppler measurements consisted of E (initial peak velocity), A (velocity at atrial contraction), deceleration time (time from E velocity to deceleration of flow extrapolated to baseline) and absolute A wave velocity (A' [peak A wave velocity minus velocity at onset of atrial contraction])., Results: In patients with high pre-A wave pressure (> or 15 mm Hg), there was a greater change in the E/A' ratio during the Valsalva maneuver than in patients with a normal pre-A wave pressure (-1.22 +/- 1.1 vs. -0.35 +/- 0.17; p = 0.02). A similar change was seen when comparing the change in the E/A' ratio after administration of nitroglycerin in patients with a high versus a normal pre-A wave pressure (0.81 +/- 0.49 vs. 0.18 +/- 0.17; p < 0.001). These differences were present in patients with a normal E/A ratio at baseline., Conclusions: Alterations in preload during assessment of Doppler echocardiographic indexes may be useful in noninvasively assessing left ventricular filling pressures.

Abnormalities of diastolic function have a major role in producing the signs and symptoms of heart failure. However, diastolic function of the heart is a complex sequence of multiple interrelated events, and it has been difficult to understand, diagnose and treat the various abnormalities of diastolic filling that occur in patients with heart disease. Recently, Doppler echocardiography has been used to examine the different diastolic filling patterns of the left ventricle in health and disease, but confusion about diagnosis and treatment options has arisen because of the misinterpretation of these flow velocity curves. This review presents a simplified approach to understanding the process of diastolic filling of the left ventricle and interpreting the Doppler flow velocity curves as they relate to this process. It has been hypothesized that transmitral flow velocity curves show a progression over time with diseases involving the myocardium. This concept can be applied clinically to estimate left ventricular filling pressures and to predict prognosis in selected groups of patients. Specific therapy for diastolic dysfunction based on Doppler flow velocity curves is discussed.

Objectives: In a double-blind, randomized, crossover trial we sought to evaluate the effect of dual-chamber pacing in patients with severe symptoms of hypertrophic obstructive cardiomyopathy., Background: Recently, several cohort trials showed that implantation of a dual-chamber pacemaker in patients with severely symptomatic hypertrophic obstructive cardiomyopathy can relieve symptoms and decrease the severity of the left ventricular outflow tract gradient. However, the outcome of dual-chamber pacing has not been compared with that of standard therapy in a randomized, double-blind trial., Methods: Twenty-one patients with severely symptomatic hypertrophic obstructive cardiomyopathy were entered into this trial after baseline studies consisting of Minnesota quality-of-life assessment, two-dimensional and Doppler echocardiography and cardiopulmonary exercise tests. Nineteen patients completed the protocol and underwent double-blind randomization to either DDD pacing for 3 months followed by backup AAI pacing for 3 months, or the same study arms in reverse order., Results: Left ventricular outflow tract gradient decreased significantly to 55 +/- 38 mm Hg after DDD pacing compared with the baseline gradient of 76 +/- 61 mm Hg (p < 0.05) and the gradient of 83 +/- 59 mm Hg after AAI pacing (p < 0.05). Quality-of-life score and exercise duration were significantly improved from the baseline state after the DDD arm but were not significantly different between the DDD arm and the backup AAI arm. Peak oxygen consumption did not significantly differ among the three periods. Overall, 63% of patients had symptomatic improvement during the DDD arm, but 42% also had symptomatic improvement during the AAI backup arm. In addition, 31% had no change and 5% had deterioration of symptoms during the DDD pacing arm., Conclusions: Dual-chamber pacing may relieve symptoms and decrease gradient in patients with hypertrophic obstructive cardiomyopathy. In some patients, however, symptoms do not change or even become worse with dual-chamber pacing. Subjective symptomatic improvement can also occur from implantation of the pacemaker without its hemodynamic benefit, suggesting the role of a placebo effect. Long-term follow-up of a large number of patients in randomized trials is necessary before dual-chamber pacing can be recommended for all patients with severely symptomatic hypertrophic obstructive cardiomyopathy.

Objectives: This study was undertaken to determine whether the presence of calcium in the mitral valve commissures, as demonstrated echocardiographically, could predict outcome and to compare this with an established echocardiographic scoring system., Background: Percutaneous mitral balloon valvotomy is an effective form of treatment for mitral valve stenosis. It is important to identify patients who would benefit from this procedure. Commissural splitting is the dominant mechanism by which mitral valve stenosis is relieved by this technique, and thus commissural morphology may predict outcome., Methods: One hundred forty-nine consecutive patients who underwent percutaneous mitral balloon valvotomy at the Mayo Clinic were evaluated retrospectively. The morphology of the mitral valve apparatus on the baseline echocardiograms was scored in blinded manner using a semiquantitative grading system of leaflet thickening, mobility, calcification and subvalvular thickening (Abascal score). Additionally, each of the medial and lateral commissures was graded for the presence or absence of calcification. End points were death, New York Heart Association functional class, repeat percutaneous mitral balloon valvotomy and mitral valve replacement at follow-up., Results: The mean follow-up period was 1.8 years (maximum 7.9 years). Univariate predictors of death and all events combined included age, the use of a double-balloon technique, the presence of calcium in a commissure and the Abascal score, as continuous variables. Patients with an Abascal score < or = 8 showed a trend toward improved survival at 36 months free of death, repeat percutaneous mitral balloon valvotomy or mitral valve replacement (78 +/- 6% vs. 67 +/- 8%, p = 0.07) and free of all events combined (75 +/- 6% vs. 64 +/- 8%, p = 0.07) versus those patients with a score > 8. However, survival at 36 months free of death, repeat percutaneous mitral balloon valvotomy or mitral valve replacement (86 +/- 4% vs. 40 +/- 4%) and free of all events combined (82 +/- 5% vs. 38 +/- 10%) at follow-up was significantly different between patients without commissural calcium and those with commissural calcium (p < 0.001). In a Cox regression model with Abascal score and commissural calcium and their interaction, calcification emerged as the only significant variable (p < 0.01)., Conclusions: The presence of commissural calcium is a strong predictor of outcome after percutaneous mitral balloon valvotomy. Patients with evidence of calcium in a commissure have a lower survival rate and a higher incidence of mitral valve replacement and all end points combined. Thus, the simple presence or absence of commissural calcification assessed by two-dimensional echocardiography can be used to predict outcome.

Objectives: The purpose of this study was to examine the relation of the mitral flow velocity curves to left ventricular filling pressures in patients with two different types of myocardial problems: hypertrophic cardiomyopathy and severe left ventricular systolic dysfunction., Background: Previous studies have suggested that assessment of Doppler-derived mitral flow velocity curves can be used to predict left ventricular filling pressures in specific disease entities. However, it is unclear whether information derived from specific mitral flow velocity curves obtained from one disease entity can be valid in other disease states., Methods: The study group consisted of 42 patients with left ventricular systolic dysfunction (group A) and 55 patients with hypertrophic cardiomyopathy (group B); both groups underwent simultaneous cardiac catheterization and were studied by Doppler echocardiography. High fidelity measures of left atrial and left ventricular pressures were obtained simultaneously with mitral flow velocity curves., Results: There was a significant relation between the Doppler echocardiographic variables and mean left atrial pressure in group A patients. The left atrial pressure was directly related to the E/A ratio (r = 0.49, p = 0.004) and inversely related to the deceleration time (r = 0.73, p < 0.001). The sensitivity and specificity of the deceleration time, < 180 m/s, which indicated a mean left atrial pressure > or = 20 mm Hg, were both 100%. In group B patients, there was no significant relation between mean left atrial pressure and deceleration time., Conclusions: Doppler echocardiographic mitral flow velocity curves are useful in predicting and estimating left ventricular filling pressures in patients with left ventricular dysfunction. However, because of the complexity of the multiple interrelated factors that determine diastolic filling of the left ventricle, these flow velocity curves cannot be used in patients with other disease entities, such as hypertrophic cardiomyopathy. Future studies of different disease states are necessary to fully understand the role of Doppler echocardiography in the assessment of diastolic filling.

Objectives: This study sought to examine the value of analyzing Doppler echocardiographically derived tricuspid regurgitation signals during respiration in relation to the diagnosis of constrictive pericarditis., Background: A physiologic hallmark of constrictive pericarditis is enhanced ventricular interdependence, which produces reciprocal changes in right and left ventricular filling and ejection dynamics during the respiratory cycle. It was hypothesized that these changes could be detected noninvasively by analyzing Doppler echocardiographically derived tricuspid regurgitation signals and that this information could assist in noninvasively diagnosing constrictive pericarditis., Methods: Simultaneous Doppler echocardiography and catheterization studies of the right and left sides of the heart with high fidelity pressure manometers were performed in 5 patients with surgically confirmed constrictive pericarditis and 12 patients (control subjects) with heart failure due to other causes., Results: Changes observed in tricuspid regurgitation Doppler echocardiographic variables from onset to peak inspiration in patients with constrictive pericarditis were significantly different from those in control subjects. Mean (+/- SD) percent change in maximal tricuspid regurgitation velocity was 13% +/- 6% and -8% +/- 7% in the constrictive pericarditis and control groups, respectively (p < 0.0001); mean percent change in tricuspid regurgitation signal duration was 18% +/- 2% and -2% +/- 7%, respectively (p < 0.0001); mean percent change in tricuspid regurgitation time velocity integral was 27% +/- 15% and -10% +/- 12%, respectively (p < 0.0001)., Conclusions: Respiratory changes in Doppler echocardiographically derived tricuspid regurgitation peak velocity and velocity duration are increased in patients with constrictive pericarditis and may be helpful in diagnosing this condition noninvasively.

Objectives: The purpose of this study was to determine whether two-dimensional and Doppler echocardiography are predictive of clinical outcome in patients with hypertrophic obstructive cardiomyopathy who undergo septal myectomy., Background: Surgical myectomy provides excellent relief of symptoms in most patients with hypertrophic obstructive cardiomyopathy who are severely symptomatic despite medical therapy. There is a subset of patients who will remain symptomatic even after operation. Because comprehensive two-dimensional and Doppler echocardiography can define the range of anatomic and associated pathophysiologic abnormalities, it was hypothesized that preoperative echocardiographic variables may be predictive of clinical outcome after septal myectomy., Methods: The clinical, electrocardiographic (ECG), echocardiographic and surgical data of 47 adult patients with hypertrophic cardiomyopathy who underwent isolated septal myectomy from 1986 to 1992 were analyzed. Specific symptoms were evaluated both preoperatively and at 1 year postoperatively. Electrocardiography and echocardiography were performed preoperatively and postoperatively. The ECG and echocardiographic variables were analyzed to determine whether any were predictive of residual symptoms 1 year postoperatively., Results: The mean [+/-SD] age of the patients was 47 +/- 15 years. All were New York Heart Association functional class III or IV. Dyspnea was present in all 47 patients and was severe in 70%. Most patients experienced symptomatic improvement at 1 year; dyspnea persisted in 26 patients (55%). The preoperative echocardiographic variables of asymmetric hypertrophy, severe systolic anterior motion of the mitral leaflet(s) and prolonged isovolumetric relaxation time were independent predictors of mild or no residual dyspnea postoperatively., Conclusions: This initial study shows that the preoperative echocardiographic variables of asymmetric hypertrophy, severe systolic anterior motion of the mitral leaflet(s) and prolonged isovolumetric relaxation time can identify patients who are most likely to benefit from septal myectomy.

Objectives: This study sought to evaluate prospectively the acute hemodynamic effect of dual-chamber pacing by using a combined hemodynamic approach of high fidelity pressure and Doppler velocity measurements., Background: Dual-chamber pacing has been proposed recently as an alternative in the symptomatic treatment of patients with hypertrophic obstructive cardiomyopathy. Although early reports documented a decrease in left ventricular outflow tract gradient and symptomatic improvement, questions remain about the hemodynamic effects of dual-chamber pacing on systolic and diastolic function., Methods: Twenty-nine patients with hypertrophic cardiomyopathy underwent a combined cardiac catheterization and Doppler echocardiographic study during normal sinus rhythm and P-synchronous pacing at various atrioventricular (AV) intervals. High fidelity pressure measurements of left ventricular inflow and left atrial pressures, ascending aortic pressure, thermodilution cardiac output and Doppler mitral flow velocity curves were obtained to evaluate both systolic and diastolic left ventricular function., Results: During AV pacing at the shortest delay of 60 ms, there was a significant decrease in cardiac output (p < 0.05) and peak positive dP/dt (p < 0.05), an increase in mean left atrial pressure (p < 0.05) and a prolongation of tau, the time constant of relaxation (p < 0.05), compared with that during normal sinus rhythm. During pacing at the optimal AV delay (longest AV interval with pre-excitation), there was a similar trend, with deterioration in both systolic and diastolic function variables but of lesser magnitude than that during pacing at the shortest AV intervals. The deterioration in both systolic and diastolic function was present in 21 patients with and 8 without left ventricular outflow obstruction. There was a modest decrease in left ventricular outflow tract gradient from 73.3 +/- 45.0 (mean +/- SD) to 61.3 +/- 40.5 mm Hg (p = 0.03) during dual-chamber pacing at the optimal AV delay compared with that during normal sinus rhythm., Conclusions: The acute effect of pacing the right atrium and ventricle may be detrimental to both systolic and diastolic function of the left ventricle, particularly at the short AV intervals. Further studies of the long-term effects of dual-chamber pacing in carefully performed randomized studies are needed.

Objectives: The purpose of this study was to use intravascular ultrasound to determine the morphologic appearance of the coronary arteries, relating the absence, presence and extent of atherosclerosis to the response of the coronary arteries to acetylcholine infusion., Background: Endothelial function plays a major role in the pathophysiology of myocardial ischemia and angina pectoris. The response of the coronary arteries to selective infusion of acetylcholine has been used to examine endothelial function, with vasoconstriction occurring in the absence of intact endothelial function. Vasoconstriction to acetylcholine infusion in humans without overt coronary artery disease has been attributed to early atherosclerosis not detected by coronary angiography., Methods: Twenty-nine patients without overt coronary artery disease underwent selective coronary angiography and selective intracoronary infusion of increasing concentrations of acetylcholine (10(-6), 10(-5) and 10(-4) mol/liter), followed by intravascular ultrasound imaging., Results: The response of the coronary arteries to acetylcholine infusion was not dependent on the absence or presence of atherosclerotic plaque, as detected by intravascular ultrasound. The percent change in epicardial coronary artery diameter during acetylcholine infusion versus baseline was -14 +/- 28% (mean +/- SD) in the seven patients with no visible atherosclerosis on intravascular ultrasound versus -9 +/- 20% in the 22 patients with visible atherosclerosis on intravascular ultrasound (p = NS, confidence interval -14% to 25%). There was a greater vasoconstrictive response to acetylcholine infusion in patients with risk factors for coronary artery disease than in those without risk factors (p = 0.003)., Conclusions: The vasoreactive response to acetylcholine is not necessarily dependent on ultrasound detection of the presence or absence of atherosclerosis.

Objectives: This study was undertaken to determine the mechanism by which improvement in hemodynamic variables may occur with dual-chamber pacing in patients with severe left ventricular dysfunction., Background: Dual-chamber pacing has recently been proposed as a therapeutic alternative for the relief of symptoms in patients with dilated cardiomyopathy., Methods: Fifteen patients with severe left ventricular systolic dysfunction were studied acutely during atrioventricular (AV) sequential pacing at various AV intervals (60, 100, 120, 140, 180 and 240 ms) with use of combined Doppler velocity curves and pressures obtained by high fidelity manometer-tipped catheters and thermodilution cardiac output., Results: Neither cardiac output nor mean left atrial pressure was significantly different when hemodynamic variables in the baseline state were compared with those during AV sequential pacing at the various AV intervals in all patients. The patients were classified into two groups. In group I (eight patients with PR intervals > 200 ms on the rest 12-lead electrocardiogram), cardiac output was significantly increased when AV sequential pacing at the optimal AV interval to output was compared with that at the baseline state (3.0 +/- 1.0 vs. 3.9 +/- 0.43 liters/min, p = 0.005) because timing of mechanical atrial and ventricular synchrony was optimized. In addition, left ventricular end-diastolic pressure and duration of diastolic filling were increased, and diastolic mitral regurgitation was abolished. In group II (seven patients who had normal AV conduction at rest), cardiac output during AV pacing decreased from the baseline value without change in the diastolic filling period., Conclusions: Dual-chamber pacing may improve acute hemodynamic variables in selected patients with dilated cardiomyopathy, mainly by optimization of the timing of mechanical atrial and ventricular synchrony. Reestablishment of the optimal diastolic filling period and abolition of diastolic mitral regurgitation may also contribute to hemodynamic improvement.

Objectives: The hypothesis was that cardiac surgery for symptomatic carcinoid heart disease in conjunction with adjunctive therapy could improve the long-term outlook of patients with carcinoid heart disease., Background: Patients with carcinoid heart disease have a dismal prognosis; most die of progressive right heart failure within 1 year after onset of symptoms. Improved therapies for the systemic manifestations of the carcinoid syndrome have resulted in symptomatic improvement and prolonged survival in patients without heart disease., Methods: Twenty-six patients with symptomatic carcinoid heart disease underwent valvular surgery. Preoperative clinical, laboratory, Doppler echocardiographic and hemodynamic factors were evaluated. The survival of the surgical group was compared with that of a control group of 40 medically treated patients., Results: There were nine perioperative deaths (35%), primarily from postoperative bleeding and right ventricular failure. Of the 17 surgical survivors, 8 were alive at a mean of 28 months of follow-up. The postoperative functional class of the eight surviving patients was substantially improved. Late deaths were primarily due to hepatic dysfunction caused by metastatic disease. The only predictor of operative mortality (p = 0.03) was low voltage on preoperative electrocardiography (limb lead voltage < or = 5 mm). Predictors of late survival included a lower preoperative somatostatin requirement and a lower preoperative urinary 5-hydroxy-indoleacetic acid level. There was a trend toward increased survival for the surgical group compared with the control group., Conclusions: Because new therapies have improved survival in patients with the malignant carcinoid syndrome, cardiac involvement has become a major cause of morbidity and mortality. Valve surgery is the only definitive treatment. Although cardiac surgery carries a high perioperative mortality, marked symptomatic improvement occurs in survivors. Surgical intervention should therefore be considered when cardiac symptoms become severe.

Objectives: This study compared the accuracy of Doppler echocardiography with that of conventional cardiac catheterization in the measurement of transmitral gradients in patients with mitral stenosis., Background: Simultaneous measurement of left atrial and left ventricular pressures is the most accurate method for determination of the mean mitral valve gradient in patients with mitral stenosis. Because of the inherent risks of transseptal catheterization, pulmonary capillary wedge pressure has been used in many invasive laboratories for determination of the mean mitral valve gradient. Recent studies have observed significant errors when pulmonary capillary wedge pressure was used for these measurements. Doppler echocardiography provides a noninvasive alternative for measurement of the transmitral gradient, but its relative accuracy has remained unclear., Methods: Seventeen patients with mitral stenosis who underwent transseptal cardiac catheterization had simultaneous measurement of 1) transmitral gradient by direct left atrial and left ventricular pressures, 2) transmitral gradient by pulmonary capillary wedge and left ventricular pressures, and 3) transmitral gradient by Doppler echocardiography., Results: Transmitral gradient measured by pulmonary capillary wedge and left ventricular pressures significantly overestimated the gradient obtained by direct measurement of left atrial pressure, with a mean (+/- SD) difference of 3.3 +/- 3.5 mm Hg (or 53%). Correcting the pulmonary capillary wedge pressure for the phase shift resulted in better correlation, but a consistent overestimation still remained, with a mean difference of 2.5 +/- 2.9 mm Hg (or 43%). The best correlation with the smallest variability was comparison of the Doppler-derived mean gradient with the gradient from direct measurement of left atrial and left ventricular pressures, with a mean difference of 0.2 +/- 1.2 mm Hg., Conclusions: Compared with the transmitral gradient obtained by direct measurement of left atrial and left ventricular pressures, the Doppler-derived gradient is more accurate than that obtained by conventional cardiac catheterization and should be considered the reference standard.

Objectives: The objective of this study was to ascertain whether the reversal of low peak filling rates after administration of calcium channel blockers in patients with diastolic dysfunction indicates true improvement in the rate of ventricular relaxation and left ventricular end-diastolic pressure measured by invasive indexes., Background: Depressed filling rates measured noninvasively have been associated with diastolic dysfunction, specifically abnormal relaxation of the left ventricle. There is a reversal of these low peak filling rates after administration of calcium channel blockers., Methods: Doppler echocardiographic measurements of peak filling rates were made and invasive high fidelity manometer-tipped pressures were measured before and after administration of verapamil (0.1 mg/kg body weight) in 20 patients with coronary artery disease who had an ejection fraction > 40% and decreased peak filling rates., Results: Verapamil caused significant increases in the peak filling rate, as measured by early transmitral (E) flow velocity, from 0.57 +/- 0.16 m/s to 0.77 +/- 0.15 m/s (p < 0.01), indicating reversal of decreased peak filling rates. Concomitantly, left ventricular end-diastolic pressure increased from 18.0 +/- 7.7 mm Hg to 24.1 +/- 9.0 mm Hg (p < 0.001). The time constant of relaxation was variable, with an overall significant increase from 45.8 +/- 10.4 ms to 53.2 +/- 14.6 ms (p = 0.01)., Conclusions: Verapamil administered intravenously produced reversal of decreased peak filling rates in patients with coronary artery disease and normal ventricular function. However, there was an increase in left ventricular end-diastolic pressure as well as an overall prolongation of the time constant of relaxation. Therefore, changes in peak filling rates do not accurately reflect the response of ventricular relaxation to drug interactions. Thus, calcium channel blockers should be used cautiously in the empiric treatment of patients with diastolic dysfunction.

Patients enrolled in the Mansfield Scientific Aortic Valvuloplasty Registry were followed up a mean of 7 months after balloon aortic valvuloplasty. Results were compared for patients less than 70, 70 to 79 and greater than or equal to 80 years of age at time of valvuloplasty. As assessed by aortic valve area indexed to body surface area, stenosis was more severe in the older patients and the incidence of congestive heart failure was also greater in those aged greater than or equal to 80 years. The results of valvuloplasty were comparable in all three age groups, and indexed final valve area was not significantly different among the groups. In-hospital mortality ranged from 4.2% to 9.4%, but this and other complications were not significantly different among the groups. Total 7 month mortality was 23%. As performed in this registry study, balloon aortic valvuloplasty produced similar results in older and younger patients, despite initially more severe disease in the older patients.

Symptomatic patients with a low cardiac output and low aortic valve gradient have a poor prognosis but are at high risk for aortic valve surgery. The outcome of percutaneous balloon aortic valvuloplasty in this subgroup of patients is unclear. Therefore, 67 patients (group 1) underwent percutaneous balloon aortic valvuloplasty between December 1, 1986 and November 1, 1987 who had a low cardiac index (less than 2.5 liters/min per m2) and a low aortic valve gradient (less than or equal to 40 mm Hg) before the procedure. The results were compared with 200 patients (group 2) who had a low cardiac index but not a low aortic valve gradient (greater than 40 mm Hg) before the procedure and who had similar baseline presenting symptoms. After balloon aortic valvuloplasty, there was a greater decrease in aortic valve gradient in patients in group 2 than in patients in group 1 (mean +/- SD -33.0 +/- 16.7 mm Hg and -14.6 +/- 6.9 mm Hg, respectively; p less than 0.001) although there was no significant difference in improvement in estimated aortic valve area (0.31 +/- 0.21 and 0.31 +/- 0.22 cm2, respectively; p = NS). In-hospital mortality was 11.9% for patients in group 1 which was not significantly different from the 7.5% mortality for patients in group 2. However, the actuarial probability of survival at 12 months for patients who survived the initial hospitalization was 46% in group 1 and 64% in group 2 (p less than 0.05). Moreover, at follow-up (mean 8.8 months) 64% of surviving group 1 patients displayed clinical improvement, compared with 70% of surviving group 2 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

The natural history of severe, symptomatic aortic stenosis has been well documented. However, the natural history of moderate aortic stenosis remains poorly understood. Therefore, a group of 66 patients was identified who had a diagnosis of moderate aortic stenosis at the time of cardiac catheterization (aortic valve area 0.7 to 1.2 cm2) and who did not have surgical therapy during the 1st 180 days after cardiac catheterization. During a mean follow-up period of 35 months, 14 patients died of causes attributed to aortic stenosis and 21 underwent aortic valve replacement. The estimated probability for remaining free of any complication of aortic stenosis at the end of the first 4 years was 59%. Symptomatic patients with decreased ejection fraction or hemodynamic evidence of left ventricular decompensation were at greater risk for these complications. It is concluded that patients with moderate aortic stenosis are at significant risk for the development of complications.

Percutaneous balloon aortic valvuloplasty has been accompanied by significant early periprocedural morbidity and mortality. Identification of factors associated with increased mortality might allow for improved selection of patients. The Mansfield Scientific Balloon Aortic Valvuloplasty Registry was analyzed to identify the frequency of in-hospital death and the factors associated with it. Of 492 patients undergoing the procedure, 37 (7.5%) died during the hospital stay in which valvuloplasty was performed. Twenty-four of these patients died within the first 24 h and the remainder died within 7 days after the procedure. There were significant differences in baseline clinical and hemodynamic characteristics as well as procedural and postprocedural variables between patients dying and those surviving the in-hospital period. Multivariate analysis identified four factors associated with increased mortality: 1) the occurrence of a procedure-related complication, 2) a lower initial left ventricular systolic pressure, 3) a smaller final aortic valve area, and 4) a lower baseline cardiac output. Thus, baseline hemodynamic, procedural and postprocedural variables and complications can be identified that are associated with increased mortality.

Distal intracoronary infusion of the perfluorochemical Fluosol-DA 20% has been shown to prevent systolic dysfunction during coronary artery balloon occlusion in coronary angioplasty. To assess its effect on global diastolic dysfunction, a randomized, single-blind, crossover protocol comparing intracoronary infusion of Fluosol or no infusion (control) was performed during 60 s balloon inflations in 10 patients (mean age 67 years) undergoing coronary angioplasty. Assessment of global systolic and diastolic function was obtained with high fidelity micromanometer measurements of left ventricular pressure. Eighteen pairs of balloon inflations (Fluosol versus control) were analyzed. Patients reported significantly less severe chest pain during inflations accompanied by Fluosol compared with control. However, during coronary balloon occlusion, no significant differences in the changes from baseline values were observed between Fluosol and control with regard to ventricular relaxation, including the time constant of early ventricular relaxation (tau) and maximal rate of fall in left ventricular pressure (maximal negative dP/dt). No differences between Fluosol and control were observed in terms of the increase in end-diastolic pressure or minimal diastolic pressure during balloon inflation. Mean systolic pressure decrease from baseline values was greater during control than during Fluosol inflations (-9.0 +/- 3.3 mm Hg, p = 0.013), but no significant difference was observed in the change in maximal rate of rise in left ventricular pressure (maximal positive dP/dt). These results suggest that Fluosol does not preserve global left ventricular diastolic function during coronary balloon occlusion, possibly because of its limited oxygen delivery capability relative to arterial blood.

Intravascular ultrasound imaging is a new method in which high resolution images of the arterial wall are obtained with use of a catheter placed within an artery. An in vitro Plexiglas well model was used to validate measurements of the luminal area, and an excellent correlation was obtained. One hundred thirty segments of fresh peripheral arteries underwent ultrasound imaging and the findings were compared with the corresponding histopathologic sections. Luminal areas determined with ultrasound imaging correlated well with those calculated from microscopic slides (r = 0.98). Three patterns were identified on the ultrasound images: 1) distinct interface between media and adventitia, 2) indistinct interface between media and adventitia but different echo density layers, and 3) diffuse homogeneous appearance. The types of patterns depended on the relative composition of the media and adventitia. Calcification of intimal plaque obscured underlying structures. Atherosclerotic plaque was readily visualized but could not always be differentiated from the underlying media.

The natural history of asymptomatic, hemodynamically significant, valvular aortic stenosis in adults was documented. Of 471 patients with aortic stenosis identified by Doppler echocardiography (peak systolic flow velocity greater than or equal to 4 m/s) from January 1984 through August 1987, 143 were asymptomatic and had isolated valvular aortic stenosis. Thirty patients underwent aortic valve intervention within 3 months (group 1); the remaining 113 patients did not have an intervention within 3 months (group 2). Follow-up information was available for all patients; the mean duration of follow-up study was 20 months (range 6 to 48). Three cardiac events occurred in the 30 group 1 patients after operation (two deaths, one reoperation). Among the 113 group 2 patients, three had cardiac death presumed to be a result of the aortic stenosis; all three developed symptoms at least 3 months before death. The actuarial probability of remaining free of symptoms of angina, dyspnea or syncope for group 2 was 86% at 1 year and 62% at 2 years. For this group, the 1 and 2 year probabilities of remaining free of cardiac events, including aortic valve intervention or cardiac death, were 93% and 74%, respectively. Of all clinical and echocardiographic variables (group 2), only Doppler flow velocity (p = 0.004) and ejection fraction (p = 0.01) were independent predictors of subsequent cardiac events. Among the 44 patients (groups 1 and 2) with a flow velocity greater than or equal to 4.5 m/s, the relative risk of sustaining a cardiac event (by Cox regression analysis) was 4.9 (p = 0.004).(ABSTRACT TRUNCATED AT 250 WORDS)

Assessment of the functional severity of coronary stenoses has become increasingly important as the intrinsic limitations of coronary angiography have been documented. Videodensitometric coronary flow reserve has been proposed as a means to assess the physiologic significance of a coronary stenosis in humans. This study compared videodensitometric assessment of coronary flow with microsphere quantitation in the closed chest canine model. In five dogs, flow rates were assessed at baseline, after vasodilation with adenosine, after vasoconstriction with vasopressin and during rapid cardiac pacing. The videodensitometric peak density, time to one-half peak density and washout time (time from peak to one-half peak density) were compared at each flow state with flow assessed by microsphere injection. Reproducibility of videodensitometric measurements from two different coronary injections during the same flow state was best with peak density (r = 0.94). Videodensitometric flow ratios (flow state under study to flow at rest) using peak density demonstrated a fair correlation with flow ratios by microsphere (r = 0.81). There was poor correlation between flow ratios when time to one-half peak or washout time was used. Videodensitometric flow measurements used in vivo to assess a wide range of drug-induced coronary flows may not accurately reflect coronary flow measured by microsphere.

Two-dimensional echocardiography has become the diagnostic method of choice for identifying intracardiac masses. However, adjacent extracardiac structures may closely mimic intracardiac masses on the two-dimensional echocardiogram. Five cases of a previously unrecognized phenomenon in which a diaphragmatic hernia mimicked an intraatrial mass are reported. Techniques to identify a diaphragmatic hernia properly on two-dimensional echocardiographic examination and distinguish it from intracardiac masses are discussed.

To evaluate the hemodynamic changes occurring with percutaneous aortic balloon valvuloplasty for aortic stenosis, Doppler echocardiography was performed during the procedure in 16 patients. During balloon inflation, peak velocity and ejection time of the aortic valve systolic signals increased (26 and 30%, respectively; p less than 0.001). Aortic regurgitation deceleration time decreased from 1,337 to 625 ms (p less than 0.001). In three patients, aortic regurgitation stopped before end-diastole; in four patients, end-diastole forward flow across the aortic valve was documented. The deceleration time of the mitral valve inflow signal decreased from 303 to 194 ms (p less than 0.001) during balloon inflation, concurrently with an increase in left ventricular diastolic pressure. Mitral regurgitation signals became more prominent during inflation in 10 patients. Changes that occur during balloon inflation in the aortic valve include progressive left ventricular outflow obstruction, equalization of diastolic aortic and left ventricular pressures and changes in diastolic compliance.

Simultaneous continuous wave Doppler echocardiography and right-sided cardiac pressure measurements were performed during cardiac catheterization in 127 patients. Tricuspid regurgitation was detected by the Doppler method in 117 patients and was of adequate quality to analyze in 111 patients. Maximal systolic pressure gradient between the right ventricle and right atrium was 11 to 136 mm Hg (mean 53 +/- 29) and simultaneously measured Doppler gradient was 9 to 127 mm Hg (mean 49 +/- 26); for these two measurements, r = 0.96 and SEE = 7 mm Hg. Right ventricular systolic pressure was estimated by three methods from the Doppler gradient. These were 1) Doppler gradient + mean jugular venous pressure; 2) using a regression equation derived from the first 63 patients (Group 1); and 3) Doppler gradient + 10. These methods were tested on the remaining 48 patients with Doppler-analyzable tricuspid regurgitation (Group 2). The correlation between Doppler-estimated and catheter-measured right ventricular systolic pressure was similar using all three methods; however, the regression equation produced a significantly better estimate (p less than 0.05). Use of continuous wave Doppler blood flow velocity of tricuspid regurgitation permitted determination of the systolic pressure gradient across the tricuspid valve and the right ventricular systolic pressure. This noninvasive technique yielded information comparable with that obtained at catheterization. Approximately 80% of patients with increased and 57% with normal right ventricular pressure had analyzable Doppler tricuspid regurgitant velocities that could be used to accurately predict right ventricular systolic pressure.

To evaluate prospectively the prognostic value of two-dimensional echocardiography after acute myocardial infarction, two-dimensional echocardiography was performed on 61 consecutive patients who were admitted to the hospital with this condition. A left ventricular wall motion score index was derived from analysis of regional wall motion; an index of 2.0 or more within 12 hours of admission identified patients at high risk for pump failure, malignant ventricular arrhythmia or death. These complications occurred in 24 of 27 patients with an initial wall motion score index of 2.0 or more, but in only 6 of 34 with an initial index of less than 2.0 (p less than 0.0005). Of the 47 patients who were in Killip class I on admission, complications developed in 11 (79%) of the 14 with an initial index of 2.0 or more, but in only 6 (18%) of the 33 with an initial index of less than 2.0. After acute myocardial infarction, early determination of the wall motion score index by two-dimensional echocardiography is useful for identifying patients at high risk for complications and is especially valuable in the subset of patients who initially seem to be in stable condition as judged from clinical variables.

Continuous wave Doppler echocardiography is an accurate and reproducible method for determination of intracardiac pressure gradients in stenotic valve lesions and right-sided regurgitant lesions. Twenty-three patients with either mitral or aortic regurgitation underwent simultaneous continuous wave Doppler and dual catheter pressure recordings to determine if instantaneous pressure gradients can be accurately determined by Doppler ultrasound in left-sided regurgitant valve lesions. Using the modified Bernoulli equation, the maximal and mean pressure gradients between the left ventricle and left atrium were determined by continuous wave Doppler ultrasound in patients with mitral regurgitation and compared with simultaneous catheter-derived pressures. The mean and end-diastolic pressure gradients between the aorta and left ventricle were determined by continuous wave Doppler ultrasound in patients with aortic regurgitation and compared with simultaneous catheter-derived pressures. Diastolic half-times by both continuous wave Doppler ultrasound and catheter pressures were compared in patients with aortic regurgitation. There was a linear correlation between the mean gradients in all patients (r = 0.94; SEE = 6 mm Hg) with a similar correlation between the instantaneous gradients (r = 0.98; SEE = 8 mm Hg). There was a linear correlation between diastolic half-times by catheter and Doppler ultrasound (r = 0.95; SEE = 39 ms). As with other valvular lesions, continuous wave Doppler echocardiography can be used in patients with mitral or aortic regurgitation to accurately determine intracardiac pressure gradients.