Prognostic value of two-dimensional echocardiography and N-terminal proatrial natriuretic peptide following an acute myocardial infarction. Assessment of baseline values (2-7 days) and changes at 3 months in patients with a preserved systolic function.

AIMS: The purpose of this prospective, observational study was to evaluate the relationship of left ventricular volumes, systolic function and plasma N-terminal proatrial natriuretic peptide (Nt-proANP) to cardiac morbidity and mortality in post-myocardial infarction patients with left ventricular ejection fraction > or =40%. METHODS AND RESULTS: Two-dimensional echocardiographic recordings and Nt-proANP measurements were obtained in 834 patients who survived acute myocardial infarction. Patients were examined at 2-7 days and 3 months after the index infarction and followed up for 24 months. All measurements of left ventricular volumes, ejection fraction and Nt-proANP were performed in core laboratories. During follow-up 102 patients sustained one or more incidents of the combined primary end-point: cardiac death (n=11), recurrent infarction (n=55) or heart failure requiring hospitalization or treatment with an ACE inhibitor and a diuretic (n=52). Using Cox proportional hazards model, baseline Nt-proANP predicted these events (chi-square 25.3, P<0.0001), while baseline echo volumes and ejection fraction did not. During the subsequent 3-24 month period, 51 patients suffered a primary end-point: cardiac death (n=9), recurrent infarction (n=29), heart failure (n=21). An increase in left ventricular end-systolic volume was the strongest predictor for adverse events (chi-square 19.1, P<0.0001), especially for heart failure. Individual changes in Nt-proANP did not predict cardiac events, whereas both echocardiographic variables and Nt-proANP measured at 3 months had a prognostic impact on subsequent cardiac events (3-24 months). CONCLUSIONS: In post-myocardial infarction patients with preserved left ventricular function (left ventricular ejection fraction > or =40%) baseline Nt-proANP, but not echocardiographic left ventricular volumes predicted adverse cardiac events. Early changes in left ventricular volumes and ejection fraction from baseline to 3 months had a further prognostic impact on subsequent events (3-24 months).

Reappearance of myocytes in ovine infarcts produced by six hours of complete ischemia followed by reperfusion.

BACKGROUND: In this study we tested the hypothesis that delayed reperfusion of ischemic myocardium-too late to save myocytes-attenuates infarct expansion and improves collagen synthesis. METHODS: The hypothesis was tested in a sheep model of anteroapical infarction that has no collateral blood flow to the area at risk. After coronary ligation or arterial occlusion for 1 or 6 hours, sheep had serial hemodynamic and quantitative echocardiographic studies before and after infarction and 2, 5, 8, and 12 weeks later. Hearts were examined by light and electron microscopy at 2 and 12 weeks; hydroxyproline and ratios of type I/III collagen were measured at 12 weeks. RESULTS: After coronary occlusion, left ventricular (LV) function progressively decreased and size increased to form an anteroapical aneurysm. After 1 hour of ischemia, neither resting LV size nor function changed; the infarct contained a midmyocardial scar between epicardial and endocardial muscle. After 6 hours of ischemia, LV function was significantly better than that in nonperfused sheep. Two weeks after 6 hours of ischemia, no viable myocytes were visible by light microscopy, but electron micrographs showed rare intact nucleated myocytes with scarce cytoplasmic myofibrils. At the 12th week epicardial and endocardial myocytes reappeared in the infarct. Infarct collagen type I/III ratios were 1.2 in reperfused groups and 0.7 in nonperfused sheep. CONCLUSIONS: Delayed reperfusion causes loss and subsequent reappearance of ovine epicardial myocytes, improves collagen type I/III ratios, and attenuates LV dilatation and loss of function. One hypothesis to explain the reappearance of myocytes is that reperfusion partially reverses an incomplete apoptotic process.

Right ventricular dysplasia in an asymptomatic young man: an uncommon case with biventricular involvement and no known family history.

A 33-year-old man had cardiomegaly on a routine x-ray examination. He was asymptomatic with no history of infarction, syncope, or palpitations. There was no family history of congenital heart disease or sudden death. Two-dimensional transthoracic echocardiography demonstrated marked enlargement of the right atrium and ventricle with severely depressed right and left ventricular function that was consistent with right ventricular dysplasia. The patient was treated with an angiotensin-converting enzyme inhibitor and did well for 6 months, but then developed symptomatic left-sided congestive heart failure. Short-term improvement was obtained with intravenous inotropic therapy, but he continued to have progressive symptoms of heart failure. Approximately 7 months after his initial presentation, the patient underwent orthotopic heart transplantation for intractable congestive heart failure. Pathologic examination of the explanted heart established the diagnosis of right ventricular dysplasia with left ventricular involvement. This is an uncommon presentation of right ventricular dysplasia with biventricular involvement and no known family history.

Restraining acute infarct expansion decreases collagenase activity in borderzone myocardium.

BACKGROUND: After acute myocardial infarction, regional myocardial wall strains and stresses change and a complex cellular and biochemical response is initiated to remodel the ventricle. This study tests the hypothesis that changes in regional ventricular wall strains affect regional collagen accumulation and collagenase activity. METHODS: Fourteen sheep had acute anteroapical infarction that progressively expands into left ventricular aneurysm within 8 weeks. In 7 sheep, infarct expansion was restrained by prior placement of mesh over the area at risk. Fourteen days after infarction, and after hemodynamic and echocardiographic measurements, animals were euthanized for histology, measurements of hydroxyproline, matrix metalloproteinase-1 (MMP-1 or collagenase) and MMP-2 (gelatinase) activity, as well as collagen type I and III in infarcted, borderzone, and remote myocardium. RESULTS: Restraining infarct expansion does not change collagen content or MMP-1 or MMP-2 activity in the infarct, but significantly increases the ratio of collagen I/III. In borderzone and remote myocardium infarct, restraint significantly increases collagen content and significantly reduces MMP-1 activity. MMP-2 activity is reduced (p = 0.059) in borderzone myocardium only. Between groups, the ratio of type I/III fibrillar collagen does not change in borderzone myocardium. CONCLUSIONS: Fourteen days after acute myocardial infarction, restraining infarct expansion increases collagen accumulation in borderzone and remote myocardium, which may prevent expansion of hypocontractile, fully perfused "remodeling myocardium" adjacent to the infarct. This study demonstrates that changes in regional myocardial wall strain alter the cellular and biochemical processes involved in postinfarction ventricular remodeling.

Structural determinants of aortic regurgitation in type A dissection and the role of valvular resuspension as determined by intraoperative transesophageal echocardiography.

Disruption of the aortic root by dissection often produces significant aortic regurgitation (AR). Resuspension of the native valve usually reestablishes competence. The mechanisms of this complex process are poorly understood. We used intraoperative transesophageal echocardiography to characterize the in vivo aortic root structure of type A aortic dissection and the changes brought about by native valve resuspension. Intraoperative transesophageal echocardiograms were obtained from 34 patients with type A dissection and aortic resuspension between January 1990 and April 1997. The severity of AR, aortic root diameter, circumference of the aortic annulus, percentage of the annulus dissected, and presence of leaflet prolapse were assessed in multiple planes. Preoperatively, AR of varying degree was present in 25 patients (73%). Multivariate analysis revealed that preoperative AR was most related to percentage of the annulus dissected (p<0.0001) and less related to root diameter (p<0.01). Leaflet prolapse was predicted by percent aortic annulus dissected (p <0.0001). After resuspension, annular dissection and leaflet prolapse were no longer present. Postoperative AR was significantly decreased from preoperative AR (p<0.0001) and was considered trace to mild. Although postoperative root diameter and annular circumference decreased (p<0.001), individual reductions in AR did not correlate with individual changes in root diameter or annular circumference. The degree of dissection of the valve annulus is the most significant determinant of leaflet prolapse and AR severity. Overall size of the aortic root also contributes to AR. Surgical resuspension significantly decreases root size, but its primary benefit is restoration of the structural integrity of the aortic annulus.

Bicuspid aortic valves are associated with aortic dilatation out of proportion to coexistent valvular lesions.

BACKGROUND: Bicuspid aortic valves (BAVs) are associated with premature valve stenosis, regurgitation, and ascending aortic aneurysms. We compared aortic size in BAV patients with aortic size in control patients with matched valvular lesions (aortic regurgitation, aortic stenosis, or mixed lesions) to determine whether intrinsic aortic abnormalities in BAVs account for aortic dilatation beyond that caused by valvular hemodynamic derangement alone. METHODS AND RESULTS: Diameters of the left ventricular outflow tract, sinus of Valsalva, sinotubular junction, and proximal aorta were measured from transthoracic echocardiograms in 118 consecutive BAV patients. Annular area was measured by planimetry, and BAV eccentricity was expressed as the ratio of the right leaflet area to the total annular area. Seventy-seven control patients with tricuspid aortic valves were matched for sex and for combined severity of regurgitation and stenosis. BAV patients (79 men and 39 women, aged 44.1+/-15.5 years) had varying degrees of regurgitation (84 patients [71%]) and stenosis (48 patients [41%]). Within the bicuspid group, multivariate analysis demonstrated that aortic diameters increased with worsening aortic regurgitation (P:<0.001) and advancing age (P:<0.05) but not with the severity of aortic stenosis. BAV patients had larger aortic diameters than did control patients at all ascending aortic levels measured (P:<0.01), despite advanced age in the control patients. CONCLUSIONS: Aortic dimensions are larger in BAV patients than in control patients with comparable degrees of tricuspid aortic valve disease. Although more severe degrees of aortic regurgitation are associated with aortic dilatation in BAV patients, intrinsic pathology appears to be responsible for aortic enlargement beyond that predicted by hemodynamic factors.

Pheochromocytoma crisis, cardiomyopathy, and hemodynamic collapse.

Pheochromocytoma is a notorious clinical entity. Although suspicion is aroused by severe hypertension in young patients, this sign is often absent. We present a case in which early absence of hypertension and nonspecific signs and symptoms led to failure of prompt diagnosis. The delay proved fatal when the patient developed fulminant pheochromocytoma crisis. This case illustrates a variety of clinical features seen from the vantage of the evolution of the disease as it went unrecognized. The patient's course underscores the importance of familiarity with the gamut of manifestations for timely diagnosis, and the priority of the latter given the looming risk of overwhelming complications.

Effect of systemic sclerosis on left ventricular long-axis motion and left ventricular mass assessed by magnetic resonance.

The aim of this study was to assess the effect of scleroderma on left ventricular mass and subendocardial function using cardiovascular magnetic resonance (CMR) to determine parameters reflecting early dysfunction from fibrosis. Fifteen patients with a history of scleroderma had left ventricular mass measured with standard techniques and regional subendocardial contractile function assessed using myocardial velocity mapping in the basal short-axis plane with long-axis sensitized velocity mapping. Peak myocardial velocities in systole and diastole were measured to reflect systolic and diastolic function. The variance in the regional myocardial velocity, was determined as a parameter of function heterogeneity around the ventricle. The results were compared with 19 healthy volunteers without a history of cardiovascular disease. In 10 patients, pulmonary transfer factor was measured using a single-breath helium dilution technique. The duration of scleroderma correlated with left ventricular mass (r = 0.7, p < 0.05), the coefficient of variation of velocity (r = 0.63, p < 0.05), and inversely with the mean left ventricular diastolic long-axis velocity (r = -0.63, p < 0.05). There was also a correlation between left ventricular diastolic long-axis velocity and the pulmonary transfer factor (r = 0. 7, p < 0.05). Trends suggested differences between control subjects and scleroderma patients for mean systolic (64 vs. 49 mm/sec, p = 0.09) and diastolic (90 vs. 72 mm/sec, p = 0.07) velocities, as well as velocity variance (26 vs. 33, p = 0.09). In conclusion, there is a relationship between duration of scleroderma and both left ventricular mass and diastolic function, which may result from increased myocardial fibrosis. Trends suggest absolute differences in functional values with control subjects that reflect impaired diastolic and systolic function, with greater regional heterogeneity that is consistent with nonuniform collagen deposition, but a larger sample size is required to confirm this. CMR should be explored further as a technique for monitoring myocardial involvement in scleroderma noninvasively.

Left ventricular remodelling in post-myocardial infarction patients with left ventricular ejection fraction 40-50% vs 25-39%. Influence of nisoldipine treatment? An echocardiographic substudy from the DEFIANT II study.

OBJECTIVE: Left ventricular (LV) remodelling following acute myocardial infarction has generally been studied in patients with LV ejection fraction (EF) < 40%, and it has been shown that this process can be attenuated by ACE inhibitors. Little is known regarding LV remodelling in patients with LVEF > or = 40% or the effects of treatment in this patient cohort. The DEFIANT II study (Doppler Flow and Echocardiography in Functional cardiac insufficiency) included 542 post-infarction patients with LVEF 25-50% without overt heart failure within 13 days following acute myocardial infarction (AMI). They were then randomized to nisoldipine coat-core (CC) or placebo and followed up for 6 months. DESIGN: Two-dimensional echoes were obtained after 8 (5-13) days and 6 months following AMI. SETTING: LV end diastolic (ED) and end systolic (ES) volumes (V) were calculated in 503 patients with technically satisfactory paired echoes using the biplabe method of discs in a core laboratory. SUBJECTS: Group A. 217 patients with baseline EF 40-50%, of whom 112 were randomized to nisoldipine and 104 to placebo (one patient was taken off study medication). Group B. 286 patients with EF 25-39%, of whom 145 were randomized to nisoldipine and 141 to placebo. RESULTS: LVEDV was 175 (+/-45) ml in Group A vs 203 (+/-49) ml in Group B (p = 0.001) at baseline and 184 (+/-48) ml vs 213 (+/-56) ml (p = 0.001), respectively, at 6 months. LVESV at baseline was 97 (+/-42) ml in Group A vs 133 (+/-37) ml in Group B (p = 0.001), and 106 (+/-34) ml vs 134 (+/-45) ml (p = 0.001) at 6 months, respectively. The increase of LVESV was 9 (+/-29) ml in Group A vs 2 (+/-35) ml in Group B (p = 0.007). LVEF decreased by 2 (+/-6)% in Group A vs an increase of 3 (+/-6)% in Group B (p = 0.001). Treatment with nisoldipine had no influence on LV volumes in either of the two groups or in the total study group. CONCLUSION: LV dilatation 6 months following AMI in patients with EF 40-50% was similar in end diastole, but more pronounced in end systole vs patients with EF 25-39%. LV remodelling did not change significantly after nisoldipine treatment.

Restraining infarct expansion preserves left ventricular geometry and function after acute anteroapical infarction.

BACKGROUND: Expansion of an acute myocardial infarction predicts progressive left ventricular (LV) dilatation, functional deterioration, and early death. This study tests the hypothesis that restraining expansion of an acute infarction preserves LV geometry and resting function. METHODS AND RESULTS: In 23 sheep, snares were placed around the distal left anterior descending and second diagonal coronary arteries. In 12 sheep, infarct deformation was prevented by Marlex mesh placed over the anticipated myocardial infarct. Snared arteries were occluded 10 to 14 days later. Serial hemodynamic measurements and transdiaphragmatic quantitative echocardiograms were obtained up to 8 weeks after anteroapical infarction of 0.23 of LV mass. In sheep with mesh, circulatory hemodynamics, stroke work, and end-systolic elastance return to preinfarction values 1 week after infarction and do not change subsequently. Ventricular volumes and ejection fraction do not change after the first week postinfarction. Control animals develop large anteroapical ventricular aneurysms, increasing LV dilatation, and progressive deterioration in circulatory hemodynamics and ventricular function. At week 8, differences in LV end-diastolic pressure, cardiac output, end-diastolic and end-systolic volumes, ejection fraction, stroke work, and end-systolic elastance are significant (P<0.01) between groups. CONCLUSIONS: Preventing expansion of acute myocardial infarctions preserves LV geometry and function.

Sustained-release calcium channel antagonists in cardiovascular disease: pharmacology and current therapeutic use.

Calcium channel antagonists are a heterogeneous group of drugs with differing cardiovascular effects, and are effective in the treatment of hypertension and angina pectoris. A number of these agents are available in a sustained-release formulation. These formulations produce a gradual and sustained drop in peripheral vascular resistance, thereby avoiding reflex sympathetic stimulation, and thus may avoid the deleterious effects that have been reported with short-acting preparations. The results of a number of trials with sustained-release calcium channel antagonists have been reported recently, and the results are promising. Currently they can be recommended for use in patients with hypertension or stable angina which cannot be controlled with other agents. They have been shown to be at least safe when used in patients with left ventricular systolic dysfunction, and may be useful in certain subsets of patients with heart failure. The empirical use of calcium channel antagonists in unstable angina and acute myocardial infarction is not supported by the currently available data. Several large trials with sustained-release formulations are ongoing, which may alter treatment recommendations in the future.

The fen-phen finale: a study of weight loss and valvular heart disease.

OBJECTIVE: To assess weight loss, as well as the prevalence of valvular heart disease, in 21 obese women who completed 2 years of treatment by fenfluramine and phentermine (fen-phen) in June 1997. RESEARCH METHODS AND PROCEDURES: Patients were 21 of 22 women who had completed a 1-year, open-label trial of fen-phen combined with lifestyle modification. This study describes the results of a second year of treatment. The presence of valvular heart disease, defined as aortic regurgitation of mild or greater severity and/or mitral regurgitation of moderate or greater severity, was assessed using two-dimensional, color Doppler and pulsed- and continuous-wave Doppler examinations. RESULTS: At 2 years, the 21 patients had a mean reduction in initial weight of 13.9 + 10.0%, which was significantly (p<0.001) smaller than their 1-year loss of 17.1 +/- 8.7%. Nine of 21 patients reported that they took fen-phen irregularly during the last 4 months of the study because of fears of developing health complications. These nine patients had a 2-year weight loss of 8.7 +/- 7.5%, compared with a significantly (p<0.04) larger loss of 17.6 +/- 10.5% for participants who reported taking medication regularly. Six of 20 (30%) patients met criteria for valvular heart disease. None of the six had signs or symptoms of this condition. DISCUSSION: Fenfluramine was withdrawn from the market on September 15, 1997 because of concerns that it was associated with valvular heart disease. The present findings are discussed in terms of the potentially favorable long-term benefits of combining lifestyle modification with weight loss medications that are both safe and effective.

Infarct size and location determine development of mitral regurgitation in the sheep model.

OBJECTIVE: This study tests the hypothesis that neither small nor large myocardial infarctions that include the anterior papillary muscle produce mitral regurgitation in sheep. METHODS: Coronary arterial anatomy to the anterior left ventricle and papillary muscle was determined by dye injection in 41 sheep hearts and by triphenyl tetrazolium chloride in 13. Development of acute or chronic mitral regurgitation and changes in left ventricular dimensions were studied by use of transdiaphragmatic echocardiography in 21 sheep after infarction of 24% and 33% of the anterior left ventricular mass. These data were compared with previous data from large and small posterior left ventricular infarctions. RESULTS: Ligation of two diagonal arteries infarcts 24% of the left ventricular mass and 82% of the anterior papillary muscle. Ligation of both diagonals and the first circumflex branch infarcts 33% of the left ventricle and all of the anterior papillary muscle. Neither infarction causes mitral regurgitation, although left ventricular cavity dimensions increase significantly at end systole. After the smaller infarction, the left ventricular cavity enlarges 150% over 8 weeks without mitral regurgitation. CONCLUSIONS: In sheep small and large infarctions of the anterior wall that include the anterior papillary muscle do not produce either acute or chronic mitral regurgitation despite left ventricular dilatation. In contrast large posterior infarctions produce immediate mitral regurgitation owing to asymmetric annular dilatation and discoordination of papillary muscle relationships to the valve. After small posterior infarctions that include the posterior papillary muscle, mitral regurgitation develops because of annular and ventricular dilatation during remodeling.

Distortions of the mitral valve in acute ischemic mitral regurgitation.

BACKGROUND: In the absence of papillary muscle rupture, the precise deformations that cause acute postinfarction mitral valve regurgitation are not understood and impair reparative efforts. METHODS: In 6 Dorsett hybrid sheep, sonomicrometry transducers were placed around the mitral annulus (n = 6) and at the tips and bases of both papillary muscles (n = 4). Later, specific circumflex coronary arteries were occluded to infarct approximately 32% of the posterior left ventricle and produce acute 2 to 3+ mitral regurgitation. Before and after infarction, distance measurements between sonomicrometry transducers produced three-dimensional coordinates of each transducer every 5 ms. RESULTS: After infarction, the annulus dilated asymmetrically orthogonal to the line of leaflet coaptation, but the annular area increased only 9.2% +/- 6.3% (p = 0.02). At end-systole, posterior papillary muscle length increased 2.3 +/- 0.9 mm (p = 0.005); the posterior papillary muscle tip moved closer to the annular plane and centroid, and the anterior papillary muscle tip moved away. CONCLUSIONS: Small deformations in mitral valvular spatial geometry after large posterior infarctions are sufficient to produce moderate to severe mitral regurgitation. The most important changes are asymmetric annular dilatation, prolapse of leaflet tissue tethered by the posterior papillary muscle, and restriction of leaflet tissue attached to the anterior papillary muscle.

Diagnosis of a persistent coronary fistula after ventricular septal defect patch closure.

Penetrating chest trauma can result in multiple clinical syndromes depending on the structures involved. Tamponade, valvular regurgitation, ventricular septal defect (VSD), conduction system abnormalities, and coronary lacerations have been reported. We report a case of right ventricular free wall laceration, VSD, and coronary artery fistula involving a septal perforator.

Global cardiac function using fast breath-hold MRI: validation of new acquisition and analysis techniques.

Calculation of global cardiac function parameters has been validated using fast, segmented k-space, breath-hold, gradient-echo, magnetic resonance images. Images of phantoms, experimental animals, normal volunteers, and patients were acquired with a 1.5 T clinical scanner. Humans were imaged using two phased-array surface coils in multicoil mode. Myocardial contours were extracted using a new interactive, semi-automated method based on the active contour model method. Images were acquired in the short-axis orientation, and, using a new imaging and analysis strategy, in rotating plane long-axis orientations, to provide better definition of the valve planes and the apex, and also to reduce the number of slices (compared with the short-axis method) required to sample the whole heart. Validation was accomplished through calculation of the volumes of phantoms and left and right ventricular masses of animal hearts. Functional parameters from MRI were compared with those from echocardiograms and radionuclide angiograms in normal volunteers and patients, respectively.

Venous thromboembolism: detection by duplex scanning.

PURPOSE: The usefulness of transcranial Doppler monitoring in identifying emboli in the arterial circulation has been established. We attempted to extend this technique to identify embolism in the venous circulation and to note any changes in embolism rate with anticoagulation. METHODS: From March to July 1993, 218 patients were evaluated by duplex scan for deep venous thrombosis. RESULTS: Sixty patients had positive study results; 26 scans (43%) demonstrated embolism. In five patients (19%) the emboli were also seen on a B-mode image, enabling us to estimate embolus size, which ranged from 200 to 5000 micrometer. Embolus counts varied from 5 to 800 per minute. Deep venous thrombosis was located in the iliofemoral vein in 2 patients, superficial femoral/profunda vein in 8, saphenofemoraal junction in 1, popliteal vein in 1, and the calf in 10. Concomitantly, studies in 158 patients were negative for deep venous thrombosis; embolism was detected in 4 patients (3%) in this group. In patients taking heparin, the embolus counts decreased 50% or more within 24 hours, and all embolism was abolished within 72 hours. Two patients died of pulmonary embolus. CONCLUSIONS: Patients with duplex scans that are positive for deep venous thrombosis have a high incidence of ongoing embolism. Heparin appears effective in eliminating the microemboli detected. The relationship among microembolism, deep venous thrombosis, and clinically significant pulmonary embolism remains to be elucidated.