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Background— Regression of left ventricular (LV) hypertrophy with normalization of diastolic function has been reported in patients with aortic stenosis late after aortic valve replacement (AVR). The purpose of the present study was to evaluate the effect of AVR on LV function and structure in chronic aortic regurgitation early and late after AVR. Methods and Results— Twenty-six patients were included in the present analysis. Eleven patients with severe aortic regurgitation were studied before, early (21 months) and late (89 months) after AVR through the use of LV biplane angiograms, high-fidelity pressure measurements, and LV endomyocardial biopsies. Fifteen healthy subjects were used as controls. LV systolic function was determined from biplane ejection fraction and midwall fractional shortening. LV diastolic function was calculated from the time constant of LV relaxation, peak filling rates, and myocardial stiffness constant. LV structure was assessed from muscle fiber diameter, interstitial fibrosis, and fibrous content. LV muscle mass decreased significantly by 38% early and 55% late after surgery. Ejection fraction was significantly reduced preoperatively and did not change after AVR ( P =NS). LV relaxation was significantly prolonged before surgery (89±28 ms) but was normalized late after AVR (42±14 ms). Early and late peak filling rates were increased preoperatively but normalized postoperatively. Diastolic stiffness constant was increased before surgery (22±6 versus 9±3 in control subjects; P =0.0003) and remained elevated early and late after AVR (23±4; P =0.002). Muscle fiber diameter decreased significantly after AVR but remained increased at late follow-up. Interstitial fibrosis was increased preoperatively and increased even further early but decreased late after AVR. Fibrosis was positively linearly correlated to myocardial stiffness and inversely correlated to LV ejection fraction. Conclusions— Patients with aortic regurgitation show normalization of macroscopic LV hypertrophy late after AVR, although fiber hypertrophy persists. These changes in LV myocardial structure late after AVR are accompanied by a change in passive elastic properties with persistent diastolic dysfunction. Clinical Trial Registration— URL: http://www.clinicaltrial.gov. Unique identifier: NCT00976625.

Background— Stent coating with titanium-nitride-oxide has been shown to reduce neointimal hyperplasia in the porcine restenosis model. We designed a prospective, randomized, clinical study to investigate the safety and efficacy of titanium-nitride-oxide–coated stents compared with stainless steel stents. Methods and Results— Ninety-two patients with de novo lesions were randomly assigned to treatment with titanium-nitride-oxide–coated stents (n=45) or stainless steel stents of otherwise identical design (n=47; control). Baseline characteristics were similar in both groups. At 30 days, no stent thromboses or other adverse events had occurred in either group. Quantitative coronary angiography at 6 months revealed lower late loss (0.55±0.63 versus 0.90±0.76 mm, P =0.03) and percent diameter stenosis (26±17% versus 36±24%, P =0.04) in lesions treated with titanium-nitride oxide–coated than in control stents. Binary restenosis was reduced from 33% in the control group to 15% in the titanium-nitride oxide–coated stent group ( P =0.07). Intravascular ultrasound studies at 6 months showed smaller neointimal volume in titanium-nitride-oxide–coated stents than in control stents (18±21 versus 48±28 mm 3 , P P =0.02), largely driven by a reduced need for target-lesion revascularization (7% versus 23%, P =0.07). Conclusions— Revascularization with titanium-nitride-oxide–coated stents is safe and effective in patients with de novo native coronary artery lesions. Titanium-nitride-oxide–coated stents reduce restenosis and major adverse cardiac events compared with stainless steel stents of otherwise identical design.

Abstract —The use of quantitative coronary angiography, combined with Doppler and PET, has recently been directed at the study of α-adrenergic coronary vasomotion in humans. Confirming prior animal experiments, there is no evidence of α-adrenergic coronary constrictor tone at rest. Again confirming prior experiments, responses to α-adrenoceptor activation are augmented in the presence of coronary endothelial dysfunction and atherosclerosis, involving both α 1 - and α 2 -adrenoceptors in epicardial conduit arteries and microvessels. Such augmented α-adrenergic coronary constriction is observed during exercise and coronary interventions, and it is powerful enough to induce myocardial ischemia and limit myocardial function. Recent studies indicate a genetic determination of α 2 -adrenergic coronary constriction.

Background —Previous experimental studies have shown that nitric oxide (NO) modulates cardiac function by an abbreviation of systolic contraction and an enhancement of diastolic relaxation. However, the response to NO donors of patients with severe pressure-overload hypertrophy and diastolic dysfunction is unknown. Methods and Results —Intracoronary NO donors were given to 17 patients with severe aortic stenosis. A dose-response curve was obtained with nitroglycerin (30, 90, and 150 μg) in 11 patients and sodium nitroprusside (1, 2, and 4 μg/min) in 6. Left ventricular (LV) high-fidelity pressure measurements with simultaneous LV angiograms were performed at baseline and after the maximal dose of NO. The dose-response curve for intracoronary NO donors showed a marked fall in LV end-diastolic pressure, from 23 to 14 mm Hg (−39%; P P P P Conclusions —In patients with severe pressure-overload hypertrophy, intracoronary NO donors exert a marked decrease in LV end-diastolic pressure without affecting LV systolic pump function. Thus, the hypertrophied myocardium appears to be particularly susceptible to NO donors, with a marked improvement in diastolic function.

Background —It has been shown that exercise-induced coronary vasodilation of angiographically normal coronary vessels is reduced in hypercholesterolemic patients. The purpose of this study was to evaluate the effect of calcium channel blockers on coronary vasomotion of angiographically smooth coronary arteries in hypercholesterolemic patients. Methods and Results —A total of 57 patients were included in the present analysis. Vasomotion of angiographically normal coronary arteries was evaluated in 37 control subjects (group 1) without and 20 patients (group 2) with calcium blocker administration before physical exercise. Both groups were subdivided into subgroup A (normal cholesterol values: ≤5.5 mmol/L or 212 mg%) and subgroup B (elevated cholesterol values: >5.5 mmol/L or 212 mg%). Coronary luminal area at rest and during exercise was assessed by biplane quantitative coronary angiography. The normal vessels showed a significant increase in coronary luminal area during exercise in subgroup A (n=13) with normal cholesterol values (31%; P P =NS). In contrast, all patients in group 2 showed similar vasodilation during exercise, namely, 22% ( P P Conclusions —Coronary vasomotor response to exercise is inversely related to actual serum cholesterol level in angiographically normal vessels. Administration of calcium antagonists normalizes exercise-induced vasodilation and thus eliminates cholesterol-induced abnormal vasomotion, probably by a direct effect on the smooth muscles of the vasculature.

Background Coronary flow reserve (CFR) is reduced in a majority of patients after heart transplantation (HTx). Pharmacological interventions, however, provide only limited information on CFR under physiological conditions. Thus, CFR during exercise was evaluated in the present study. Methods and Results Coronary angiography was performed at rest and during supine bicycle exercise in 35 patients early (2 to 3 months; n=10) or late (1 to 6 years; mean, 2.5 years; n=25) after HTx and in 8 controls (C). CFR was determined by parametric imaging after administration of 10 mg intracoronary papaverine, during exercise, and after 1.6 mg sublingual nitroglycerin. Epicardial coronary artery size was measured by quantitative coronary angiography. CFR after papaverine was normal early (3.6±0.5 versus C, 3.6±0.7; P =NS) and late (3.8±1.3; P =NS) after HTx. During exercise, CFR was normal early (3.1±0.6 versus C, 3.9±0.9; P =NS) but decreased late (2.3±0.6; P P r =−.39, P r =−.44, P Conclusions CFR during exercise is normal early but reduced late after HTx, whereas CFR after papaverine administration is maintained. This difference between physiological and pharmacological vasodilation suggests progressive endothelial dysfunction after HTx.

Background Endothelial dysfunction with a loss of endothelium-dependent vasodilation has been reported in patients with arterial hypertension. The purpose of the present study was to evaluate coronary vasomotor response to dynamic exercise in patients with coronary artery disease with and without arterial hypertension and to determine the effect of calcium antagonists on coronary vasomotion. Methods and Results Cross-sectional areas of a normal and a stenotic coronary vessel segment were examined in 79 patients with coronary artery disease at rest and during supine bicycle exercise (Ex). Change in luminal area after acute administration of a calcium antagonist (diltiazem or nicardipine), during exercise, and after sublingual nitroglycerin (percent change compared with rest=100%) was assessed by biplane quantitative coronary arteriography. Patients were divided into two groups: Group 1 (control) consisted of 48 patients without (normotensive subjects, n=30; hypertensive subjects, n=18) and group 2 of 31 patients with (normotensive subjects, n=15; hypertensive subjects, n=16) pretreatment with a calcium antagonist immediately before exercise. The groups did not differ with regard to clinical characteristics or hemodynamic data measured during exercise. Mean aortic pressure at rest, however, was significantly increased in hypertensive patients compared with normotensive subjects in group 1 (103 mm Hg versus 92 mm Hg, P P P P P =NS) and stenotic vessel segments (+24% versus +26%, P =NS). Conclusions Abnormal coronary vasomotion during exercise can be observed in hypertensive patients with reduced vasodilator response in normal arteries and enhanced vasoconstrictor response in stenotic arteries. Calcium antagonists prevent the abnormal response of normal and stenotic coronary arteries to exercise in hypertensive patients and thus may compensate for endothelial dysfunction with reduced vasodilator response to exercise.

Introduction: Regression of left ventricular (LV) hypertrophy with normalization of diastolic function has been reported in patients with aortic stenosis. The purpose of the present study was to evaluate the effect of aortic valve replacement (AVR) on LV systolic and diastolic function an LV structure in chronic aortic regurgitation (AR) early and late after AVR. Methods: 25 patients were included in the present analysis. Ten patients with severe AR were studied before, early (21 months) and late (89 months) after AVR using LV biplane angiograms, high-fidelity pressure measurements, and endomyocardial biopsies. Fifteen healthy subjects were used as controls. LV systolic function was determined from biplane ejection fraction (EF) and midwall fractional shortening, LV diastolic function from the time constant of LV relaxation, peak filling rates, and myocardial stiffness constant. LV structure was assessed from muscle fiber diameter, interstitial fibrosis and volume fraction of myofibrils. Results : LV muscle mass was significantly increased preoperatively but decreased by 38% early and 55% late after surgery, but remained (ns) elevated compared to controls. LV EF and midwall fractional shortening did not change after AVR. LV relaxation was significantly prolonged before (89±28 ms vs. controls 47±11 ms, p Conclusions : Patients with AR show normalization of macroscopic LV hypertrophy late after AVR, altough fiber hypertrophy persists. These changes in LV myocardial structure late after AVR are accompanied by a change in passive elastic properties with persistent diastolic dysfunction due to the increased interstitial fibrosis.

Background— Stent thrombosis may occur late after drug-eluting stent (DES) implantation, and its cause remains unknown. The present study investigated differences of the stented segment between patients with and without very late stent thrombosis with the use of intravascular ultrasound. Methods and Results— Since January 2004, patients presenting with very late stent thrombosis (>1 year) after DES implantation underwent intravascular ultrasound. Findings in patients with very late stent thrombosis were compared with intravascular ultrasound routinely obtained 8 months after DES implantation in 144 control patients, who did not experience stent thrombosis for ≥2 years. Very late stent thrombosis was encountered in 13 patients at a mean of 630±166 days after DES implantation. Compared with DES controls, patients with very late stent thrombosis had longer lesions (23.9±16.0 versus 13.3±7.9 mm; P P P P 2 ; P =0.46) but significantly larger for the in-stent segment (28.6±11.9 versus 20.1±6.7 mm 2 ; P =0.03) in very late stent thrombosis patients compared with DES controls. Incomplete stent apposition was more frequent (77% versus 12%; P 2 ; P =0.03) in patients with very late stent thrombosis compared with controls. Conclusions— Incomplete stent apposition is highly prevalent in patients with very late stent thrombosis after DES implantation, suggesting a role in the pathogenesis of this adverse event.

A report by Virmani et al1 described a localized hypersensitivity and late coronary thrombosis secondary to a sirolimus-eluting stent in a 58-year-old man who died 18 months after stent implantation. The authors discussed a localized hypersensitivity vasculitis in response to the Cypher stents, resulting in an acute myocardial infarction, secondary to late in-stent thrombosis at 18 months. The hypersensitivity reaction was thought to be either due to the metallic stent, the polymer, or the sirolimus coating. The exact mechanism, however, remained unclear, and it was postulated that polymers, like those used for coating of the metallic stent, may have been responsible for the hypersensitivity vasculitis. In October 2003, the US Food and Drug administration notified physicians of …

Background— Intracoronary radiotherapy (brachytherapy) has been proposed as treatment option for in-stent restenosis. Long-term results of brachytherapy with regard to vascular integrity and vasomotor responsiveness are unknown. The purpose of the present study was to determine the vasomotor response after brachytherapy and to assess its influence on vasomotion during exercise. Methods and Results— Biplane quantitative coronary angiography was performed at rest and during bicycle exercise in 27 patients with coronary artery disease. Fourteen patients underwent coronary stenting and were studied 10±3 months after intervention (control group). Thirteen patients were treated with brachytherapy (Guidant Galileo System) for in-stent restenosis with a mean dosis of 20 Gy at 1 mm into the vessel wall and were studied 9±1 months after radiation (brachytherapy group). Minimal luminal area, stent area, and proximal, distal, and a reference vessel area were determined. The reference vessel showed exercise-induced vasodilation (26±4%, P P P Conclusions— Normal vessel segments elicit flow-mediated vasodilation during exercise. Stent implantation does not affect physiological response to exercise proximal and distal to the stent. Brachytherapy eliminates exercise-induced vasodilation, although dilatory response to nitroglycerin is maintained, suggesting endothelial dysfunction as the underlying mechanism.

Background— The role of pro-brain natriuretic peptide (proBNP) for the prediction of clinical outcome has not been examined in patients with acute pulmonary embolism (PE). Methods and Results— ProBNP levels were measured in 73 patients with acute PE within 4 hours of admission. Adverse clinical outcome was defined as in-hospital death or the need for at least 1 of the following: cardiopulmonary resuscitation, mechanical ventilation, pressors, thrombolysis, catheter fragmentation, or surgical embolectomy. In the 53 patients with a benign clinical outcome, proBNP (median 121, range 16 to 34 802 pg/mL) was lower than in 20 patients with adverse clinical outcome (median 4250, range 92 to 49 607 pg/mL; P P =0.02) after adjusting for severity of PE (submassive/massive), troponin T levels >0.01ng/mL, age >70 years, gender, and history of congestive heart failure. Conclusions— Low proBNP levels predict an uneventful hospital course in patients with acute PE. A proBNP level

Background — Stenting has proved beneficial for treating threatened closure and reducing restenosis after balloon angioplasty. However, the implantation of a coronary metallic prosthesis has been related to impaired vasomotion distal to the stent as assessed by acetylcholine infusion. Thus, the purpose of the present study was to determine the vasomotion of stented coronary arteries and to assess its influence on the vasomotion of adjacent vessel segments during bicycle exercise. Methods and Results — Biplane quantitative coronary angiography was performed at rest and during bicycle exercise in 26 patients with coronary artery disease. Twelve patients had single vessel disease with stable angina pectoris (controls; group 1). Fourteen patients underwent coronary stenting for therapeutic reasons and were studied 10±3 months after the intervention (group 2). Minimal luminal area, stent area, and proximal and distal vessel areas were determined. In controls (group 1), vasoconstriction of the stenotic artery (− 29±4%; P P P P Conclusions — In contrast to the vasoconstriction of vessels in control patients, normal vasodilation of proximal and distal segments occurred during the physiological stress of exercise in patients with coronary stent placement. As expected, vasomotion was abolished in the stented region.

Background — Coronary stents prevent constrictive arterial remodeling but stimulate neointimal hyperplasia. Stainless steel induces a metallic foreign body reaction, which is absent for titanium. The hypothesis of the present study was that titanium renders the stent surface biologically inert, with reduced platelet and fibrinogen binding. Methods and Results — Twelve pigs were instrumented with a stainless steel and 2 titanium-nitride-oxide–coated stents (TiNOX 1, ceramic; TiNOX 2, metallic). Animals were restudied after 6 weeks. Histological specimens of stented segments were analyzed by digital morphometry. Platelet adhesion and fibrinogen binding studies were performed in the perfusion chamber. Under in vitro conditions, TiNOX 1 showed reduced platelet adhesion (65±3%) compared with TiNOX 2 (72±5%; P P P P P 2 ) than in TiNOX 1–coated (1.47±0.84 mm 2 , P 2 , P Conclusions — TiNOX coating significantly reduces neointimal hyperplasia in stainless steel stents. The antiproliferative effect was similar for both TiNOX coatings, suggesting that the electrochemical properties are more important for attenuation of neointimal proliferation than the observed differences in platelet adhesion and fibrinogen binding.

Background —Endothelial dysfunction of coronary arteries with impaired vasodilation has been reported in patients with arterial hypertension. However, the effect of dynamic exercise on coronary vasomotion of a stenotic vessel segment before and after PTCA has not yet been evaluated in these patients. Methods and Results —Coronary vasomotion of a normal and a stenotic vessel segment was studied in 39 patients with coronary artery disease during supine bicycle exercise before and 9±3 months after PTCA. Luminal area changes were determined by biplane quantitative coronary arteriography. There were 21 normotensive and 18 hypertensive patients who did not differ with regard to clinical characteristics. Percent area stenosis decreased after PTCA from 90% to 39% ( P P P P P =NS), which was reversed after PTCA (+3% versus +2%, P =NS). Conclusions —Normal coronary arteries show reduced vasodilation during exercise in hypertensive patients that may be explained by the presence of endothelial dysfunction. Stenotic vessels demonstrate paradoxical vasoconstriction during exercise in both normotensive and hypertensive patients. PTCA reverses vasoconstriction by elimination of the flow-limiting stenosis and prevention of coronary stenosis narrowing during exercise in normotensive and hypertensive patients.

Background The incidence of angina pectoris (AP) in patients with severe aortic stenosis (AS) and normal coronary arteries has been reported to be 30% to 40%. The exact pathophysiological mechanism, however, is not known. The purpose of this work was to evaluate the various hemodynamic and angiographic determinants of myocardial perfusion in 61 patients with severe AS. Methods and Results In a retrospective analysis, 61 patients with severe AS and without significant coronary artery disease were studied. Thirty-three patients with atypical chest pain and angiographically normal arteries served as control subjects. Patients were divided into two groups: 32 with AP and 29 without AP. Quantitative coronary angiography was performed in 59 patients and 22 control subjects. Coronary flow reserve was determined in 29 patients and 7 control subjects by use of coronary sinus thermodilution technique. Patients with AP had a lower left ventricular (LV) muscle mass, an increased LV peak systolic pressure, and increased wall stress than those without AP. Vessels of the left coronary artery were smaller and coronary flow reserve was lower in patients with AP than in those without. Inadequate LV hypertrophy with an increased wall stress was found in patients with AP but not in patients without AP. Conclusions Myocardial ischemia in patients with severe AS can occur in the absence of coronary artery disease and appears to be due to inadequate LV hypertrophy with high systolic and diastolic wall stresses and a reduced coronary flow reserve. The cause of inadequate LV hypertrophy, however, remains unclear.

Background Enlargement of the epicardial coronary arteries occurs in left ventricular (LV) hypertrophy as an adaptation to the increased coronary blood flow. Methods and Results Vasodilator capacity of the epicardial coronary arteries was determined in 44 patients. The dose-response relation of intracoronary nitroglycerin was assessed in 14 patients (7 control subjects and 7 patients with aortic stenosis [study A]) using quantitative coronary angiography. In a second study (B), vasodilator capacity of the epicardial coronary arteries was determined in 15 control subjects and 15 patients with valvular heart disease. In study A, a curvilinear dose-response relation with maximal vasodilation after 90 μg intracoronary nitroglycerin was found in both control subjects and patients with aortic stenosis. Vasodilator capacity was reduced in those with aortic stenosis, although sensitivity to nitroglycerin was similar in both groups. In study B, coronary circumferential length at baseline was larger in those with LV hypertrophy (12.2±2.2 mm) than in control subjects (8.6±1.5 mm; P P r =−.71, P Conclusions Vasodilator capacity of the epicardial coronary arteries is reduced in patients with LV hypertrophy, although sensitivity to nitroglycerin is normal. This may be due to a flow-mediated decrease in coronary vasomotor tone and/or the occurrence of vascular remodeling with an enlargement of the coronary arteries.

Background The remodeling of the left ventricle in patients with aortic stenosis after aortic valve replacement (AVR) is a complex process involving structural and functional changes. Methods and Results Twenty-two patients were included in the present analysis. Twelve patients with severe aortic stenosis were studied before surgery, early (22±8 months) and late (81±22 months) after AVR using left ventricular biplane angiograms, high-fidelity pressure measurements, and endomyocardial biopsies. Ten healthy subjects were used as controls. Left ventricular systolic function was assessed from biplane ejection fraction, and diastolic function from the time constant of relaxation, the peak filling rate, and the myocardial stiffness constant. Left ventricular structure was evaluated from interstitial fibrosis, fibrous content, and muscle fiber diameter. Left ventricular muscle mass was significantly increased before surgery in patients with aortic stenosis and remained increased early after surgery, although there was a 35% decrease. Late after AVR, muscle mass decreased significantly but remained slightly ( P =NS) elevated. Left ventricular ejection fraction increased slightly after AVR. Left ventricular relaxation was significantly prolonged before surgery and returned toward normal early and late after AVR. Peak filling rates remained unchanged before and after surgery. Myocardial stiffness constant was increased before surgery in patients with aortic stenosis compared with controls and increased even further early after AVR but was normalized late after surgery. Muscle fiber diameter was elevated in patients with aortic stenosis before and after surgery compared with controls; however, it decreased significantly early and late after AVR with respect to preoperative data but remained hypertrophied even late after surgery. Interstitial fibrosis and fibrous contents were larger before surgery than in control subjects and increased even more early but decreased significantly late after AVR. Conclusions Diastolic stiffness increases in aortic stenosis early after AVR parallel to the increase in interstitial fibrosis, whereas relaxation rate decreases with a reduction in left ventricular muscle mass. Late after AVR, both diastolic stiffness and relaxation are normalized due to the regression of both muscular and nonmuscular tissue. Thus, reversal of diastolic dysfunction in aortic stenosis takes years and is accompanied by a slow regression of interstitial fibrosis.

BACKGROUND It has been shown that there is impairment of the vasodilatory response to acetylcholine in patients with hypercholesterolemia and angiographically normal coronary arteries. Moreover, in patients with angiographically smooth coronary arteries, the number of coronary risk factors is associated with a loss of endothelium-dependent vasodilation. The purpose of the present analysis was to evaluate in patients with and without coronary artery disease coronary vasomotor response to dynamic exercise in angiographically normal and stenosed coronary arteries and to relate the response to serum cholesterol levels as well as to other coronary risk factors. METHODS AND RESULTS Luminal area change during exercise (delta-ex, percent change compared with rest = 100%) was determined by biplane quantitative coronary arteriography in three groups: Group 1 consisted of 14 patients with normal total serum cholesterol of < 200 mg/100 mL; mean, 173 mg/100 mL (mean age, 51 years). Group 2 comprised 23 patients with a slightly elevated cholesterol of 200 to 250 mg/100 mL; mean, 223 mg/100 mL (mean age, 53 years). Group 3 had 24 patients with markedly elevated cholesterol of > 250 mg/100 mL; mean, 288 mg/100 mL (mean age, 54 years). Serum cholesterol levels and categorical risk factors such as positive family history, history of hypertension, smoking, obesity, and diabetes were related to exercise-induced vasomotor response. The three groups did not differ with regard to clinical characteristics, exercise work load, and hemodynamic data measured during exercise. However, delta-ex in normal vessels was significantly different between all three groups (ANOVA, P < .01): +31% (group 1), +18% (group 2), and +4% (group 3). Delta-ex in stenotic vessels did not differ between the groups: -5% (group 1), -13% (group 2), and -12% (group 3). Delta-ex of the nonstenosed vessel correlated significantly and inversely with total cholesterol, with low-density lipoprotein cholesterol, with the ratio of total to high-density lipoprotein cholesterol, and with the number of coronary risk factors present in a patient. High total cholesterol and a history of hypertension were independent risk factors for impaired coronary vasomotion. CONCLUSIONS In patients with and without coronary artery disease, hypercholesterolemia and a history of hypertension independently impair exercise-induced coronary vasodilation in angiographically normal coronary arteries. In the stenotic vessel, vasomotion during exercise does not appear to be influenced by the actual serum cholesterol. The precise mechanism by which the impaired vasomotion of the angiographically normal coronary arteries is mediated is unknown, but a direct negative effect of hypercholesterolemia on endothelial function or early undetected atherosclerosis appears to be the most likely explanation.

BACKGROUND Segmental wall motion was assessed noninvasively in eight patients with hypertrophic cardiomyopathy and six healthy volunteers by magnetic resonance myocardial tagging. METHODS AND RESULTS Localization scans were performed for determination of the true short-axis views of the left ventricle (double-angulated view). Spatial modulation of magnetization was used to produce a rectangular grid of landmarks. Distortion of the grid was assessed at end diastole, mid systole, and end systole with multiphase gradient echoes. Image sets were acquired at three different planes, namely, the base, the equator, and the apex. Quantitative evaluation was carried out by computer-assisted image analysis. Each individual grid crossing point was identified automatically and the displacement calculated. A polar coordinate system with the center of gravity as motion reference point was chosen to assess fractional rotation and radial displacement at the endocardial, midwall, and epicardial layers of the septal, anterior, posterior, and inferior regions. A wringing motion of the left ventricle with a clockwise rotation of 5.0 +/- 2.4 degrees at the base and a counterclockwise rotation of -9.6 +/- 2.9 degrees at the apex was observed in control subjects. An equal rotation of 5.0 +/- 2.5 degrees at the base and a slightly reduced rotation of -7.3 +/- 5.2 degrees at the apex was found in patients with hypertrophic cardiomyopathy. A transmural gradient in fractional rotation and radial displacement was observed, with the highest values in the endocardial layer. Rotation in patients with hypertrophic cardiomyopathy was significantly less than in normal volunteers in the posterior region of the equatorial and apical planes. Furthermore, radial displacement was significantly reduced in the septum and inferior wall. In the anterior and posterior wall segments, a reduction of the radial displacement was observed only in the epicardium and midwall layers. CONCLUSIONS Magnetic resonance myocardial tagging allows the noninvasive assessment of regional wall motion. Both in normal volunteers and in patients with hypertrophic cardiomyopathies, cardiac motion occurs in a complex mode, with the base and the apex rotating in opposite directions and the equatorial plane as a transitional zone (wringing motion). A reduced cardiac rotation can be observed in patients with hypertrophic cardiomyopathy mainly in the posterior region, whereas a reduced radial displacement is found in the inferior septal zone.

BACKGROUND The effect of regression of myocardial hypertrophy on coronary artery dimensions was evaluated in patients with aortic valve disease who underwent valve replacement. METHODS AND RESULTS Cross-sectional area (CSA) of the three major coronary arteries (left anterior descending [LAD], left circumflex [LCx], and right coronary artery) was determined by quantitative coronary arteriography in 15 patients with aortic valve disease before and 38 months (range, 14-113 months) after successful aortic valve replacement. Twelve normal subjects served as controls. Left ventricular (LV) angiographic mass was calculated according to the method of Rackley. CSA of the left coronary artery was larger in aortic valve disease than in controls (LAD, 15 versus 8 mm2, p less than 0.001; LCx, 14 versus 6 mm2, p less than 0.001). After valve replacement, CSA of the left coronary artery decreased (LAD, 12 mm2, p less than 0.05 versus before surgery; LCx, 11 mm2, p less than 0.05 versus before surgery) but remained significantly larger than in controls. CSA of the right coronary artery in patients with aortic valve disease was not different from controls. LV muscle mass was significantly increased in aortic valve disease patients before (364 g) and after (250 g) valve replacement compared with controls (135 g). The appropriateness of coronary artery size with respect to muscle mass was evaluated by normalizing CSA of the left coronary artery (LAD + LCx) per 100 g of LV muscle mass (mm2/100 g). This index amounted to 11 mm2/100 g in controls, to 8 mm2/100 g in preoperative patients (p less than 0.05 versus controls), and to 10 mm2/100 g in postoperative patients with aortic valve disease (p = NS versus controls). CONCLUSIONS In patients with aortic valve disease, CSA of the proximal LAD and LCx is increased, but this increase is not sufficient to keep CSA per 100 g of LV mass within normal limits. The postoperative decrease in muscle mass is associated with a decrease in the size of LAD and LCx, whereas the size of the right coronary artery remains unchanged. In contrast to the preoperative state, the residually hypertrophied LV myocardium after aortic valve replacement is supplied by an enlarged but adequately sized LAD and LCx.

BACKGROUND Coronary vasomotion was evaluated at rest and during bicycle exercise in 33 patients (age, 53 +/- 7 years) with coronary artery disease. In a first group of patients (n = 15), vasomotion was studied before and 4.3 +/- 2.3 months (early) after percutaneous transluminal coronary angioplasty (PTCA), whereas in a second group (n = 18), exercise coronary arteriography was performed 30 +/- 11 months (late) after successful PTCA. Patients with restenosis (percent area stenosis greater than or equal to 75% or percent diameter stenosis greater than or equal to 50%) were excluded. METHODS AND RESULTS Luminal areas of a normal segment and the stenotic segment were determined at rest, during supine bicycle exercise, and 5 minutes after sublingual nitrate administration by using biplane quantitative coronary arteriography. Work loads before and early after PTCA were identical in group 1 and similar late after PTCA in group 2. Percent area stenosis decreased from 86% to 36% (p less than 0.001) in group 1 and from 93% to 46% (p less than 0.001) in group 2. Normal coronary arteries showed mild vasodilation during exercise before (+3%, NS versus rest), early (+7%, NS versus rest), and late after (+10%, p less than 0.05 versus rest) PTCA. Administration of sublingual nitrate was associated with significant vasodilation of the normal vessel segment before (+27%, p less than 0.001 versus rest), early (+31%, p less than 0.001 versus rest), and late (+21%, p less than 0.001 versus rest) after PTCA. In contrast, the stenotic vessel segments showed coronary vasoconstriction during exercise before PTCA (-25%, p less than 0.001 versus rest), whereas minimal vasomotion was observed early (+2%; NS versus rest) as well as late (+5%; NS versus rest) after PTCA. Individual post-PTCA (early and late) exercise data elicited vasodilation in 19, no vasomotion in four, and vasoconstriction in 10 instances. Sublingual administration of nitrate was associated with a significant increase in minimal luminal area before (+18%, p less than 0.05 versus rest), early (+24%, p less than 0.01 versus rest), and late (+16%, p less than 0.001 versus rest) after PTCA. An inverse linear correlation was found between the percent change in minimal luminal area during peak exercise and percent area stenosis at rest (r = 0.77, p less than 0.001). CONCLUSIONS Exercise-induced stenosis narrowing is observed before PTCA but normal vasomotion is reestablished in two thirds of all patients early and late after PTCA. In one third, an abnormal reaction to exercise (i.e., vasoconstriction) persisted after PTCA, mainly in those patients with a residual area stenosis of 50% (percent diameter stenosis of 30%) or more. Thus, PTCA appears to have a salutary effect on coronary vasomotion during exercise, which, however, remains dependent on the severity of the residual stenosis.

BACKGROUND In chronic mitral regurgitation, the myocardium responds to the increased filling volume by geometric alteration and eccentric hypertrophy. This study was designed to evaluate the effects of a pure volume overload on left ventricular diastolic chamber and myocardial properties and to assess the relation of passive diastolic function to systolic ejection performance. METHODS AND RESULTS By use of simultaneous cineangiography and left ventricular micromanometry, left ventricular passive diastolic stiffness was evaluated in nine normal controls (group 1), 14 patients with chronic mitral regurgitation and a normal ejection fraction (greater than or equal to 57%, group 2), and 13 patients with mitral regurgitation and a reduced ejection fraction (less than 57%, group 3). Passive diastolic function was evaluated by using a three-constant elastic model. Left ventricular chamber properties were represented by the relation of pressure to volume; myocardial properties were evaluated by relating myocardial midwall stress to midwall strain. The constant of left ventricular chamber stiffness was decreased in group 2 compared with controls (p less than 0.05) but it was normal in group 3. The constant of myocardial stiffness was increased in group 3 compared with groups 1 and 2 (p less than 0.01). Among patients with mitral regurgitation, there was a significant inverse relation between ejection fraction and the constant of myocardial stiffness (r = -0.83). CONCLUSIONS The chronic adaptation to volume overload in chronic mitral regurgitation tends to decrease left ventricular chamber stiffness. Patients with mitral regurgitation and a depressed ejection fraction demonstrated diastolic myocardial dysfunction. Compromised diastolic function in patients with chronic mitral regurgitation and reduced systolic performance may contribute to the clinical manifestations of congestive heart failure.

To study the vasomotility of normal and diseased coronary arteries during dynamic exercise, symptom-limited supine bicycle exercise during cardiac catheterization was performed by 18 patients with classic angina pectoris. The cardiovascular response was assessed by hemodynamic measurements and computer-assisted determination of normal and stenotic coronary artery luminal areas from biplane coronary angiograms made before, during, and after exercise. After baseline measurements were recorded, 12 patients (group 1) performed bicycle exercise for 3.4 min (mean), reaching a maximum workload of 81 W (mean); at the end of exercise they received 1.6 mg sublingual nitroglycerin. After measurements at rest in six other patients (group 2), 0.1 mg intracoronary nitroglycerin was given, followed by exercise (3.8 min, 96 W; NS) and sublingual nitroglycerin as in group 1. During exercise in group 1, luminal area of the coronary stenosis decreased to 71% of resting levels (p less than .001), while area of the normal coronary artery increased to 123% of control (p less than .001). After sublingual nitroglycerin at the end of exercise, area of the normal vessel further increased to 140% of control (p less than .001), while luminal area of the stenosis dilated to 112% of resting levels (p less than .001 vs exercise, NS vs rest). Pretreatment with intracoronary nitroglycerin increased both normal (121%; p less than .05) and stenotic (122%; p less than .05) luminal areas, while preventing the previously observed narrowing of stenosis during exercise (114%; NS). Exercise resulted in a similar heart rate-systolic pressure product and caused angina pectoris in two-thirds of the patients in each group. However, patients pretreated with intracoronary nitroglycerin (group 2) had a lower mean pulmonary arterial pressure during maximum exercise (35 mm Hg) than those patients (group 1) not receiving pretreatment (47 mm Hg; p less than .001). Group 2 patients reached a percentage of their predicted work capacity (65%) that was about the same as that during previous upright bicycle exercise (71%; NS), while group 1 patients had a significantly lower work capacity (51% of predicted) than that before catheterization (82%; p less than .001). Hence, narrowing of coronary artery stenosis during dynamic exercise is attributable to active vasoconstriction due to its reversibility by preexercise intracoronary nitroglycerin. Patients who did not experience narrowing of stenosis during exercise (group 2) had less evidence of myocardial ischemia (lower mean pulmonary arterial pressure) and maintained their work capacity.(ABSTRACT TRUNCATED AT 400 WORDS)

Passive diastolic properties were determined in 10 control patients and 21 patients with aortic valve disease before and 17.5 months after successful valve replacement. Ten patients had severe aortic stenoses (AS), five had combined aortic valve lesions (AS + aortic insufficiency [AI]), and six patients had severe AI. Left ventricular endomyocardial biopsies were obtained before and after surgery in patients with AS, AS + AI, and AI. Simultaneous echocardiographic and high-fidelity pressure measurements were made in all patients, and left ventricular chamber stiffness was calculated from a viscoelastic pressure-circumference relationship and left ventricular myocardial stiffness from a viscoelastic stress-strain relationship. The constant of chamber stiffness, beta', was slightly although not significantly increased in patients with AS (0.27 before and 0.24 after surgery), but was normal in those with AS + AI (0.22 before and 0.17 after surgery) and slightly decreased in those with AI (0.18 before and 0.16 after surgery) when compared with in control subjects (0.21). The constant of myocardial stiffness beta was normal in patients with AS (13.2), AS + AI (11.5), and AI (11.7) before surgery compared with in the control group (12.5). beta increased, however, significantly in those with AS (25.2; p less than .02), but not in those with AS + AI (16.3; NS) and AI (12.8; NS) after surgery. Myocardial morphologic characteristics showed a significant decrease in muscle fiber diameter in patients with AS, AS + AI, and AI, as well as a significant increase in interstitial fibrosis from 15% to 26% (p less than .05) in those with AS and a slight increase from 15% to 22% (NS) in those with AS + AI and from 19% to 24% (NS) in those with AI. Left ventricular fibrous content (left ventricular muscle mass index multiplied by interstitial fibrosis) remained, however, unchanged in all three groups after aortic valve replacement. In conclusion, left ventricular chamber stiffness is increased in AS but decreased in AI, whereas LV myocardial stiffness is normal in patients with aortic valve disease before surgery. After surgery, left ventricular myocardial stiffness increased significantly in AS patients but remained unchanged in those with AI. Postoperative changes in myocardial structure were characterized by a decrease in muscle fiber diameter and a relative increase in interstitial fibrosis, whereas fibrous content remained unchanged. Thus, regression of myocardial hypertrophy in aortic valve disease is accompanied by an increase of myocardial stiffness in concentric hypertrophy that is not seen in eccentric hypertrophy.

Left ventricular pressure (LVP) decay and early diastolic pressures were studied at rest and during exercise in three groups of patients. Patients in the ischemia group (n = 15) had coronary artery disease and developed new regional wall motion abnormalities documented by biplane LV cineangiography during exercise. Patients in the control group (n = 4) had a normal exercise response. Patients in the scar group (n = 5) had prior infarction, akinetic scars and no ischemia with exercise. Isovolumic pressure data were used to compute the time constant (T) of LVP decay (from the linear relation of LVP and negative dP/dt) and an extrapolated baseline pressure (PB) at dP/dt = 0. During exercise in the ischemia group, minimal LV diastolic pressure (PL) increased from 9 +/- 3 to 21 +/- 5 mm Hg (p less than 0.001), end-systolic volume increased from 38 +/- 7 to 55 +/- 8 ml/m2 (p less than 0.001) and PB rose from -10 +/- 7 to 11 +/- 8 mm Hg (p less than 0.001); T decreased (from 55 +/- 9 to 37 +/- 8 msec, p less than 0.001), although inadequately, compared with the decrease in the control group (from 49 +/- 15 to 22 +/- 2 msec, p less than 0.01). Relaxation at PL during exercise was incomplete in the ischemia group (2.2 +/- 0.4 T) and complete in the control group (3.8 +/- 0.7 T, p less than 0.05). The time course of LVP fall was extrapolated from the isovolumic period into the passive LV filling phase. The extrapolated pressure at the time PL occurred (PE) rose from 0 +/- 4 to 20 +/- 7 mm Hg with ischemia (p less than 0.001). Thus, the characteristics of LVP decay can account for the elevated early diastolic pressures during ischemia. In contrast, the scar group maintained a low PL during exercise (11 +/- 3 to 8 +/- 3 mm Hg), even though T decreased inadequately (from 66 +/- 10 to 36 +/- 5 msec, p less than 0.01), because PB did not shift upward. Ischemia-related pressure elevations involve both delayed relaxation and a pressure baseline shift. During exercise, LVP decay is normally adjusted to maintain low diastolic pressures; with exercise-induced ischemia, LVP decay is abnormal and early diastolic pressures are severely elevated.

We studied the hemodynamic response to supine bicycle exercise in 20 patients late (10 +/- 2 years) after aortic valve replacement (for aortic stenosis in 12 patients, aortic insufficiency in six patients, and for combined stenosis and insufficiency in two patients). The pulmonary artery wedge pressure was obtained with a pulmonary artery balloon catheter, and left ventriculography was performed by digital-subtraction angiography after injection of radiographic contrast into the pulmonary artery. These patients were compared with 11 control subjects with no or minimal cardiac disease studied routinely for evaluation of chest pain in whom left ventricular end-diastolic pressure and a direct contrast ventriculogram were obtained. Compared with the control population, the study population had similar left heart filling pressures (7 +/- 3 vs 9 +/- 3 mm Hg, NS), but higher left ventricular ejection fractions (75 +/- 7% vs 67 +/- 7%, p less than .02) and higher left ventricular muscle mass indexes (106 +/- 28 vs 85 +/- 9 g/m2, p less than .01). Elevated myocardial muscle mass led to lower systolic wall stress in the study population than in the control subjects (254 +/- 65 vs 320 +/- 49 10(3).dynes/cm2, p less than .01) and might explain the higher ejection fraction observed. Fourteen patients had a normal response to exercise (with left heart filling pressures of 16 +/- 4 vs 18 +/- 2 mm Hg for control subjects, NS; and left ventricular ejection fraction of 77 +/- 8% vs 73 +/- 5% for control subjects, NS). However, while the remaining six patients had a normal exercise left ventricular ejection fraction (72 +/- 9%, NS), they had an abnormal rise in left heart filling pressure (33 +/- 8 mm Hg, p less than .01). Preoperatively these patients also had higher left ventricular mid- and end-diastolic pressures at similar diastolic volumes, suggesting a decrease in chamber compliance. Thus, late after aortic valve replacement there is a subgroup of patients who, despite normal hemodynamics and normal left ventricular systolic function as assessed by the left ventricular ejection fraction at rest, have an abnormal response to exercise characterized primarily by a substantial rise in left heart filling pressures. Preoperatively this group also has a decrease in diastolic chamber compliance despite nearly normal left ventricular ejection fractions. This abnormality appears to result from a primary derangement of diastolic function that is not evident at rest.

The intrapatient comparison of the simple elastic and viscoelastic stress-strain relationship showed a significantly better curve fitting (r = 0.93 vs 0.96) for the viscoelastic model. The correction by the viscoelastic model occurred mainly during the highly filling-rate dependent early diastole, whereas the correction during atrial filling was low. Early diastolic deviations from the simple elastic stress-strain relationship were especially pronounced in the patients with myocardial hypertrophy. The viscoelastic constants of myocardial stiffness, B and K, were significantly different from the corresponding simple elastic constants, b and k, indicating that the simple elastic stiffness constants include both elastic and viscous forces.

We have developed a model for assessing the influence of the decaying contractile systolic tension on diastolic wall dynamics and the passive properties of left ventricular muscle. Total measured left ventricular diastolic pressure and stress (sigma T) are determined by two overlapping processes: the decay of actively developed pressure and stress (sigma A) and the buildup of passive filling pressure and stress (sigma*). The decaying contractile stress sigma A is formulated in terms of a relaxation pressure with a time constant (T) assessed during the isovolumic relaxation interval. By subtracting the contribution of sigma A from sigma T we obtain sigma*. With micromanometry, echocardiography, and cineangiography, total and passive stress-strain relations and strain rates were evaluated over the entire filling period in six normal control subjects and in seven patients with aortic stenosis. Elastic stiffness constants (k), the slopes of the linear passive stiffness vs sigma* relations, did not differ in the two groups over a common lower stress range (6/6 normal, k = 9.37 +/- 1.23; 7/7 aortic stenosis, k = 9.34 +/- 1.08). Over a higher sigma* range, transition into a much steeper linear region occurred, and k values were much larger (4/7 aortic stenosis, k = 28.76 +/- 2.02). When diastolic stress levels are elevated, passive stiffness-stress relations can be better described as bilinear, with a much greater wall stiffness constant in the higher than in the lower stress range. Dynamic effects of decaying systolic contractile wall stress components are important in the rapid filling phase in normal hearts as well as in those with aortic stenosis.

Simultaneous left ventricular micromanometry and biplane cineangiography were performed in nine control subjects (group 1), 14 patients with chronic mitral regurgitation and an ejection fraction of 57% or greater (group 2), and 13 patients with mitral regurgitation and an ejection fraction of less than 57% (group 3). End-diastolic volume index was increased in both groups with mitral regurgitation (p less than .001) compared with the control group. Left ventricular end-diastolic wall thickness did not differ among the three groups, but the left ventricular muscle mass index was greater in both groups with mitral regurgitation than in controls (p less than .001). End-diastolic pressure was elevated in both groups 2 and 3 compared with group 1 (p less than .05), but peak systolic, mean systolic, and incisural pressure were not different among the three groups. End-diastolic stress was larger in groups 2 and 3 than in group 1 (p less than .05). Muscle fiber stretch was greater in group 2 than in the control group (p less than .05) but was not different between the controls and group 3. End-systolic stress, determined as the circumferential stress at aortic valve closure, at the maximal pressure/volume ratio, or using a nonsimultaneous method, was larger in group 3 than in groups 1 and 2. Mean systolic stress was evaluated from aortic valve opening to aortic valve closure in all patients; mean stress from end-diastole to aortic valve closure and from end-diastole to minimum volume was assessed in mitral regurgitation alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Left ventricular biplane cineangiography, micromanometry, and endomyocardial biopsies were performed in 27 patients with aortic stenosis (AS) and in 17 patients with aortic insufficiency (AI). Twenty-three patients with AS and 15 with AI were restudied at an intermediate time (18 months after successful valve replacement), and nine patients with AS and six with AI were restudied late (70 and 62 months after surgery). Biopsy samples were evaluated for muscle fiber diameter, percent interstitial fibrosis, and volume fraction of myofibrils. In control biopsy samples obtained from five donor hearts at transplantation, these morphometric variables averaged 21.2 microns, 7.0%, and 57.2%, respectively. After surgery, mass determined by cineangiography decreased from 186 to 115 and 94 g/m2 in patients with AS and from 201 to 131 and 93 g/m2 in patients with AI. At the three studies, muscle fiber diameter was 30.9, 28.0, and 28.7 microns in patients with AS and was 31.4, 27.6, and 26.4 microns in patients with AI. Percent interstitial fibrosis was 18.2, 25.8, and 13.7% in patients with AS and was 20.4, 23.7, and 19.2% in patients with AI. Left ventricular fibrous content decreased from 34.2 to 29.8 and to 12.7 g/m2 in patients with AS and from 42.1 to 28.9 and to 18.9 g/m2 in patients with AI. Volume fraction of myofibrils was 57.7, 56.8, and 49.0% in patients with AS and was 56.8, 56.6 and 48.8% in patients with AI. Thus, the decrease of muscle mass determined by cineangiography at the intermediate time after valve replacement is mediated by regression of myocardial cellular hypertrophy in patients with AS and AI and in addition by a decrease of fibrous content in patients with AI. Late after surgery, left ventricular fibrous content also decreases in patients with AS. This late decrease associated with minor changes of end-diastolic volume may be important for improvement of increased diastolic myocardial stiffness. Even 6-7 years after valve replacement, incomplete regression of structural abnormalities of left ventricular hypertrophy still exists compared with the normal myocardium. The residually increased relative interstitial fibrosis and the small late postoperative decrease of volume fraction of myofibrils, associated with a prosthesis-related slight left ventricular pressure increase, are at the origin of a persistent systolic overload at the myofibrillar level.

Myocardial structure of left ventricular segments with recurrent myocardial ischemia was evaluated by morphometry and compared with that of segments with normal blood supply in 15 patients with exercise-induced myocardial ischemia. Left ventricular high-fidelity pressure measurements and simultaneous biplane angiocardiography were performed in patients at rest and during supine bicycle exercise. Left ventricular transmural biopsy samples were obtained during open heart surgery in a normally contracting region and in a region with exercise-induced de novo wall motion abnormalities. Transmural and endocardial and epicardial left ventricular muscle fiber diameter and interstitial nonmuscular tissue were determined by morphometry. Eight patients were restudied 8 months after successful bypass grafting. Heart rate and left ventricular end-diastolic pressure increased significantly preoperatively and postoperatively during exercise. However, left ventricular end-diastolic pressure was significantly higher preoperatively (33 mm Hg) during exercise than postoperatively (19 mm Hg; p less than .01). Left ventricular ejection fraction dropped significantly during exercise (63% vs 54%; p less than .001) before surgery but remained unchanged (64% vs 66%; NS) after revascularization. Regional axis shortening of the normokinetic region increased slightly during exercise pre- and postoperatively, but decreased in the hypokinetic region from 42% at rest to 25% during exercise (p less than .001) before surgery and from 47% at rest to 41% during exercise (p less than .05) after revascularization. Transmural muscle fiber diameter (normal less than or equal to 23 microns) was significantly larger in regions with exercise-induced ischemia (29.3 microns, p less than .025) than in normally contracting regions (27.3 microns). Interstitial nonmuscular tissue (normal less than or equal to 10%) was significantly increased in regions with exercise-induced wall motion abnormalities (19.8%) compared with normally contracting regions (15.5%; p less than .05). In the endocardial half of left ventricular segments with recurrent myocardial ischemia interstitial tissue was significantly increased (23.7%; p less than .01) compared with that in the epicardial half of the same segment (17.5%). It is concluded that structural alterations of the myocardium (muscle fiber hypertrophy and increased interstitial nonmuscular tissue) develop especially in the endocardial layers of the transiently ischemic myocardium with normal function at rest.(ABSTRACT TRUNCATED AT 400 WORDS)

Left ventricular systolic and diastolic function were studied before and after surgical revascularization in a group of 24 patients with stable angina who all had an excellent clinical response to surgery. With use of micromanometer left ventricular pressure measurements and ventricular volumes, calculated from biplane cineangiograms, left ventricular function at rest and during exercise before and after surgery was compared. Before surgery all patients had exercise-induced ischemia with new asynergy, a fall in ejection fraction from 57% to 49% (p less than .001), and a rise in left ventricular end-diastolic pressure from 23 to 37 mm Hg (p less than .001). Postoperative exercise resulted in no new asynergy and ejection fraction rose from 59% to 61% (p less than .05). Left ventricular end-diastolic pressure still rose from 17 to 25 mm Hg (p less than .01). Left ventricular pressure decay during exercise was greatly improved after revascularization and allowed maintenance of reduced early diastolic pressures. The early diastolic pressure nadir before surgery rose from 9 to 21 mm Hg (p less than .001); the postoperative nadir was 5 mm Hg at rest and 6 mm Hg during exercise. All patients had an upward shift in the diastolic pressure-volume relationship during preoperative exercise. After revascularization there was no upward shift in some patients and a much smaller shift in others. The postoperative increase in left ventricular end-diastolic pressure was due to increased end-diastolic volume, not altered compliance. There was an increase in mean right atrial pressure during exercise either before (6 to 11 mm Hg) or after surgery (4 to 10 mm Hg). These increases were quite variable, suggesting no consistent role of pericardial restraint during exercise. Early diastolic peak filling rate during exercise was greater after surgery (1260 vs 950 ml/sec, p less than .001). In fact, during postoperative exercise early diastolic filling rates were greater than normal, reflecting the persistence of abnormally high atrial pressures for filling. As at preoperative study, late diastolic filling during exercise was restricted after revascularization when compared with that in a control group. Postoperatively patients undergoing bypass procedures with a good clinical result showed significantly improved left ventricular diastolic and systolic function. Persistent elevation of end-diastolic and atrial pressures and other abnormalities of diastolic function may reflect chronic structural changes and need to be taken into account when evaluating patients after bypass surgery.

To assess the time course and extent of regression of myocardial hypertrophy after removal of the inciting hemodynamic stress, 21 patients with either aortic stenosis or aortic insufficiency were studied preoperatively, after an intermediate period (1.6 +/- 0.5 years), and late (8.1 +/- 2.9 years) after aortic valve replacement, and results were compared with those in 11 control patients. After aortic valve replacement there was significant hemodynamic improvement, with a fall in the left ventricular end-diastolic volume index (164 +/- 73 to 105 +/- 35 ml/m2, p less than .01), a fall in left heart filling pressure (19 +/- 9 to 12 +/- 5 mm Hg, p less than .01), and maintenance of the cardiac index (3.3 +/- 0.8 to 3.5 +/- 0.8 liters/min/m2, NS) and left ventricular ejection fraction (60 +/- 13% to 64 +/- 10%, NS). By the late study the cardiac index (4.0 +/- 0.6 liters/min/m2, p less than .01) and left ventricular ejection fraction (66 +/- 15%, p less than .05) had further increased and were significantly greater than before surgery. For the group as a whole, the left ventricular muscle mass index fell 31% after surgery by the time of the intermediate postoperative study (174 +/- 38 vs 120 +/- 29 g/m2, p less than .01), and a further 13% from the intermediate to the late study (105 +/- 32 g/m2, p less than .05). At the preoperative study left ventricular muscle mass index was greatest in those patients with aortic insufficiency (191 +/- 36 g/m2), and greater in those with aortic stenosis (158 +/- 33 g/m2) than in control subjects (85 +/- 9 g/m2, p less than .05). At the intermediate postoperative study left ventricular muscle mass index remained significantly higher in both those with preoperative aortic insufficiency (128 +/- 29 g/m2) and those with stenosis (114 +/- 27 g/m2) than in the control subjects (p less than .01). By the time of the late postoperative study there were no longer any significant differences in left ventricular muscle mass index. Thus, the regression of myocardial hypertrophy is a process that occurs over many years after correction of the primary hemodynamic abnormality. As this process of myocardial remodeling occurs, continued improvement in cardiac function may occur, and the improvement occurring between the intermediate and late postoperative studies at a slight but constant afterload excess (inherent in the relative stenosis of the aortic prosthesis) suggests that the hypertrophied myocardium is operating at a reduced level compared with normal myocardium.