Mitral valve prolapse: left ventricular hemodynamics in patients with chest pain, dyspnea or both.

Patients with mitral valve prolapse may present with chest pain and dyspnea. Left ventricular hemodynamics as a cause for these symptoms have not been completely evaluated in these patients. The present study was undertaken to investigate left ventricular hemodynamics in symptomatic patients with mitral valve prolapse. One hundred and three patients with mitral valve prolapse (female 72, male 31, age 56 +/- 11 years) had diagnostic cardiac catheterization for evaluation of chest pain (n = 44), dyspnea (n = 10) and for chest pain plus dyspnea (n = 49). All patients had diagnostic auscultatory findings and angiographic documentation of mitral valve prolapse. Patients with coronary artery disease and mitral regurgitation greater than mild were excluded from the study. Left ventricular end diastolic pressures before (chest pain 9.3 +/- 3.7 mmHg; dyspnea 8.2 +/- 4.2 mmHg; chest pain plus dyspnea 9.3 +/- 4.1 mmHg) and after left ventriculography (chest pain 11.6 +/- 5.5 mmHg; dyspnea 10.2 +/- 2.3 mmHg; chest pain plus dyspnea 11.7 +/- 5.6 mmHg) were normal in the majority of patients and similar in all three groups. Likewise, the left ventricular end diastolic volume index (chest pain 72.0 +/- 16 cm3, dyspnea 69.1 +/- 20 cm3, chest pain plus dyspnea 70.0 +/- 16 cm3) and ejection fraction (chest pain 64.0 +/- 8.4%, dyspnea 64.1 +/- 6.1%, chest pain plus dyspnea 64.3 +/- 6.1%) were normal in the majority of patients and similar in the three groups. Symptomatic patients with mitral valve prolapse without significant mitral regurgitation had normal left ventricular hemodynamics, and their symptoms cannot be explained on the basis of hemodynamic abnormalities alone.

Cardiac catheterization and coronary angiography using 5 French preformed (Judkins) catheters from the percutaneous right brachial approach: a comparative analysis with the femoral approach.

This study describes a method for the performance of cardiac catheterization using 5 French preformed Judkins catheters from a percutaneous right brachial approach, and compares that technique to the more traditional percutaneous right femoral approach with 6 French catheters. One hundred consecutive patients requiring diagnostic left heart catheterization and selective coronary angiography were randomized according to femoral versus brachial arterial technique. Procedural efficiency, radiation exposure, and diagnostic film quality favored the femoral approach, while patient comfort, hemostasis time, time to ambulation, and decreased need for post-procedure nursing care favored the brachial approach. No differences were identified in complications. Cardiac catheterization from a right brachial artery percutaneous approach with 5 French preformed catheters has both advantages and disadvantages when compared with a more traditional femoral approach with 6 French catheters. Multiple factors should be considered before selecting an approach to diagnostic cardiac catheterization and each patient should be individually evaluated for determination of the optimal technique.

Mitral valve prolapse: cardiac arrest with long-term survival.

Cardiac arrest has been reported in patients with mitral valve prolapse; however, clinical characteristics and survival information are limited since most of the cases reported include autopsy data. Nine patients (2 male, 7 female) with mitral valve prolapse were identified who had cardiac arrest; ventricular fibrillation was documented in 8 patients; resuscitation was unsuccessful in 2. Eight had a history of palpitations (months to 15 years duration) and ventricular arrhythmias, 3 had a history (5-15 years) of recurrent syncope, and 1 was totally asymptomatic. Cardiac catheterization-angiographic studies in 8 patients demonstrated normal coronary artery anatomy and mitral valve prolapse. All 9 patients had auscultatory and echocardiographic evidence of mitral valve prolapse. Seven survivors (6 still alive) were followed from 3 to 14 years after cardiac arrest. A subset of patients with mitral valve prolapse and cardiac arrest is described in whom past medical history is compatible with cardiac arrhythmias or syncope, and whose long-term prognosis appears better than patients with other causes of cardiac arrest.

Segmental analysis of the ascending aorta: definition of normality and classification of aortic dilatation.

To better define and classify ascending aortic abnormalities, we adapted the left ventricular dynamic segmental analysis concept to the ascending aorta. Ascending aortic diameters were measured from contrast aortography in 18 normal subjects at the aortic valve (level 1), and 2, 4, and 6 cm above the aortic valve (levels 2, 3, and 4). Diameters greater than two standard deviations (SD) above the mean normal values at any levels were considered abnormal. Aortograms of 102 consecutive patients with abnormal aorta were analyzed. Three patterns of aortic dilatation were identified: I (n = 55), the largest aortic diameter was at level 2 (normal pattern); II (n = 39), the aortic diameters increased from levels 1 to 4; III (n = 8), all aortic diameters were greater than 2 SD above the mean normal values and increased from levels 1 to 4. Segmental analysis of the aorta provides an objective comparative basis for definition and classification of aortic dilatation and aneurysm.

Extension of the serum digoxin concentration--response relationship to patient management.

The purposes of this investigation were to demonstrate how computer simulations may be employed to extrapolate data obtained from a single intravenous digoxin dose to multiple oral dosing patterns and how these simulations may apply to clinical situations. The intravenous data were obtained from a previous study of the pharmacokinetics of serum digoxin and its inotropic response (derived from systolic intervals) in 12 normal male volunteers. The simulations were applied to various clinical situations including variations in oral dosing, alternate loading doses, no loading versus loading dose, and intravenous versus oral dosing. A nonlinear relationship was found between response and the post-distribution serum digoxin concentration in the therapeutic range. Thus, the increase in inotropic response is less than proportional to the increase in digoxin concentration in serum. This nonlinear relationship has several important clinical implications for loading and maintenance dosing protocols. Such concepts may be important relative to more rational clinical use of digoxin and to decreasing digoxin toxicity.

Progression of mitral regurgitation in patients with mitral valve prolapse.

Mitral valve prolapse (MVP) is a very common clinical entity which is frequently associated with mild mitral regurgitation (MR) and which most commonly becomes clinically manifest in the third and fourth decades of life. Severe MR associated with MVP, occurs much less frequently and is most commonly seen in patients above the age of 50 years. Relatively little information is available regarding the progression of mild to severe MR in patients with MVP. This report reviews a recent study which investigated the progression from mild to severe MR in patients with MVP. The study included 86 patients, average age 60 years, who presented with cardiac symptoms and severe MR. A high incidence of MVP was seen on echocardiograms (57 of 75 [75%]) and on left ventriculography (61 of 84 [73%]). Mitral valve replacement was performed in 75 patients. Pathologically all valves appeared grossly enlarged, severely floppy and had extensive myxomatous changes with collagen dissolution. 80 patients had a pre-existing heart murmur first detected at average age 34. Patients remained asymptomatic for an average of 25 years at which time clinical symptoms first appeared. After symptoms developed mitral valve surgery was necessary in most patients within one year. This rapid deterioration could partially be attributed to ruptured chordae in 39 of 76 patients (51%) or atrial fibrillation in 48 of 86 patients (56%). 28 patients had one or more serial clinical evaluations including auscultation, chest x-ray, echocardiography, and cardiac catheterization.(ABSTRACT TRUNCATED AT 250 WORDS)

Floppy mitral valve chordae tendineae: histopathologic alterations.

Pathologic studies of floppy or myxomatous mitral valves have focused primarily on changes in the valve cusps, with little attention given to the chordae tendineae. In a systematic study of the histopathology of floppy mitral valve chordae tendineae, 128 nonruptured chordae from 8 severely regurgitant floppy mitral valves were compared to 152 chordae from 10 normal control mitral valves and to 152 chordae from 8 control mitral valves with severe regurgitation due to ischemic heart disease. Collagen alterations were observed in 2% of normal mitral valve chordae and 3% of control regurgitant mitral valve chordae compared to 38% of floppy mitral valve chordae. Moderate or severe acid mucopolysaccharide accumulation was observed in 2% of normal mitral valve chordae and 3% of control regurgitant mitral valve chordae compared to 39% of floppy mitral valve chordae. Nonuniform histopathologic alterations, rare in normal and control regurgitant mitral valve chordae tendineae, were frequent in floppy mitral valve chordae tendineae (p less than 0.001). Histopathologic alterations provide the basis for abnormal physical properties previously demonstrated in floppy mitral valve chordae tendineae and may predispose to chordal elongation and rupture.

Aortic distensibility in post-stenotic aortic dilatation: the effect of co-existing coronary artery disease.

Aortic distensibility is decreased in patients with coronary artery disease (CAD) and the angiographically normal aorta. To determine if the same is true in patients with aortic stenosis and post-stenotic dilatation, two groups were studied. Group A consisted of 15 patients with post-stenotic aortic dilatation and normal coronary arteries, and group B, 14 patients with post-stenotic aortic dilatation and CAD. The patients were compared to 18 normal subjects. The area of the first 6 cm of the aorta above the valve obtained by aortography was planimetered and the mean diameters were calculated. Distensibility was calculated using the formula: (formula; see text) Distensibility was greater in group A (2.5 +- .4 cm2.dynes-1) compared to group B (1.0 +- 8 cm2.dynes-1, p less than 0.001). Distensibility in normal subjects reported recently from this laboratory (3.4 +- .4 cm2.dynes-1) was greater compared to both groups A and B (p less than 0.001). Thus, distensibility was decreased in patients with post-stenotic aortic dilatation. The further decrease in distensibility in patients with co-existing coronary artery disease may be partially related to abnormal nutrition of the arterial wall since the vasa vasorum of the ascending aorta are derived from the coronary arteries.

Aortic distensibility abnormalities in coronary artery disease.

Vasodilatory capacity of nonstenotic arteries in experimental animals with atherosclerosis is decreased. It was postulated that aortic distensibility may be abnormal in patients with coronary artery disease (CAD). Aortic distensibility was determined in 24 normotensive patients with CAD and an angiographically normal aorta and values were compared with those in 18 age-matched normal subjects. Aortic diameters were measured at 3 levels--2, 4 and 6 cm above the aortic valve--by angiographic techniques. The area of the first 6 cm of the aorta above the aortic valve was planimetered and mean aortic diameters were calculated. Distensibility was calculated using the formula: [2 X (changes of the aortic diameter)/(diastolic aortic diameter) X (changes of the aortic pressure)]. CAD patients had similar aortic pressures but markedly lower distensibility than normal subjects: 0.7 +/- 0.2 vs 1.7 +/- 0.3 (p less than 0.02); 1.5 +/- 0.3 vs 4.0 +/- 0.6 (p less than 0.02); and 1.2 +/- 0.2 vs 5.3 +/- 0.6 (p less than 0.001) at 2, 4 and 6 cm above the aortic valve, respectively. Distensibility was also calculated from the mean aortic diameters and was greater in normal subjects than in CAD patients (3.4 +/- 0.4 vs 1.6 +/- 0.1, p less than 0.001). Decreased aortic distensibility in CAD may be related to the common atherosclerotic process or to reduced ascending aorta vasa vasorum flow from coronary arteries.

Safety and efficacy of inferior vena caval occlusion to rapidly alter ventricular loading conditions in idiopathic dilated cardiomyopathy.

To investigate the safety and efficacy of inferior vena caval (IVC) balloon occlusion for preload alteration in humans, 13 patients with dilated cardiomyopathy were studied before and during repeated (total of 78) IVC occlusions. Left and right ventricular (LV and RV) micromanometer pressures were simultaneously measured and M-mode and 2-D echocardiograms were recorded at end expiration. Complications were limited to abdominal discomfort in 2 patients. With IVC occlusion, RV collapse fluoroscopically shifted the heart toward midline and ventricular septal motion was frequently disordered. Significant (p = 0.001) changes occurred in RV and LV systolic peak pressures (from 19 +/- 6 to 12 +/- 5 mm Hg and from 129 +/- 34 to 109 +/- 25 mm Hg, respectively). LV and RV end-diastolic pressures also decreased significantly (from 18 +/- 7 to 6 +/- 6 mm Hg and from 5 +/- 3 to 2 +/- 2 mm Hg, respectively) (both p less than or equal to 0.0055). Similarly, LV end-diastolic diameter decreased 13% (from 61 +/- 11 to 53 +/- 12 mm, p = 0.0002). Mean heart rate did not change significantly (from 76 +/- 19 to 78 +/- 21 beats/min). Thus, IVC balloon occlusion provides a safe method of repeatedly altering loading conditions in humans. This approach allows for acquisition of important information regarding cardiac chamber dynamics while minimizing the effects of reflex mechanisms and avoiding use of pharmacologic agents.

The mitral valve prolapse epidemic: fact or fiction.

In spite of two decades of research, the precise relationship of anatomic mitral valve prolapse (floppy valve) to the neuroendocrine disorder (MVP syndrome) remains unclear. In all likelihood they are two separate genetic disorders which travel together in some fashion. Mitral valve prolapse is a common disorder but progressive mitral regurgitation usually occurs late in life and in only a few patients. Other complications such as bacterial endocarditis, stroke, and sudden death are far less common but can occur at younger ages. The neuroendocrine syndrome in civilian life is mainly seen in young females (interestingly the peak incidence years correspond to peak female sex hormone output) but can be seen in males when subjected to unusual stress such as military service. More recent echocardiographic studies have questioned whether all prolapsing valves are truly abnormal. It has been shown that echographic prolapse can be produced in normal subjects by reducing venous return and impaired venous return may be present in some patients with the MVP syndrome. However, clicks and murmurs are apparently not heard when normal valves prolapse. It is our opinion that the presence of a click or typical murmur requires some anatomic abnormality of the mitral valve. One wonders if minimal valve abnormality (noted and dismissed by Davies) is the valve abnormality present in many young females with MVP syndrome, and that it may remain a mild abnormality throughout life. Recent psychiatric studies suggest that MVP is present in 30% of patients with Panic Disorder. It is not clear that this psychiatric syndrome is the same thing as the MVP syndrome. In Devereux's study, anxiety proneness was no different in the MVP cohort than in relatives without MVP. It is possible that diagnostic mixing of two similar but separate disorders has occurred, as has been the case since World War I. Perhaps the most important question is whether young patients with MVP syndrome and no echocardiographic criteria for "floppiness" will develop progressive mitral regurgitation or other complications in later life. In other words, how often is MVP syndrome in a young individual without echocardiographic evidence of a floppy valve a precourser to eventual progressive mitral regurgitation? Are there two different populations? Because of the long course of the disorder, several more years of observation (and, it is hoped, prospective longitudinal study) will be required to answer this question.

Evidence for progression from mild to severe mitral regurgitation in mitral valve prolapse.

Little information is available concerning the progression of mild to severe mitral regurgitation (MR) in patients with mitral valve prolapse (MVP). This study reports 86 patients, average age 60 years, who presented with cardiac symptoms, precordial systolic murmur, severe MR and a high incidence of MVP on echocardiography (57 of 75 [75%] ) and left ventriculography (61 of 84 [73%] ). Seventy-five surgically excised mitral valves appeared grossly enlarged and floppy. Histologic studies showed extensive myxomatous changes throughout the leaflets and chordae. Eighty patients had had precordial murmurs first described at average age 34 years, but the average age at which symptoms of cardiac dysfunction appeared was 59. However, once symptoms developed, mitral valve surgery was required within 1 year in 67 of 76 patients who had undergone surgery. Atrial fibrillation, present in 48 of 86 patients (56%), or ruptured chordae tendineae, present in 39 of 76 patients (51%), may have contributed to this rapid progression and deterioration. Additionally, 13 patients had a remote history of documented infective endocarditis. Twenty-eight patients had at least 1 type of serial clinical evaluation that indicated progressive MR in all 28 patients on the basis of changing auscultatory findings (24 of 26), progressive radiographic cardiomegaly (24 of 25), echocardiographic left atrial enlargement (4.3 to 5 cm in 11 patients) and angiographically worsening MR (14 of 15). Twenty-four of these patients had evidence of MVP on at least 1 of their initial studies. Thus, mild MR due to MVP and myxomatous mitral valves is a progressive disease in some patients with MVP.

Giant cell myocarditis.

The present report describes a 45-year-old man with giant cell myocarditis who died of heart failure eight months after the onset of symptoms. On postmortem examination, the heart showed extensive myocardial fibrosis with numerous multinucleated giant cells. The lungs and a series of 20 lymph nodes showed no evidence of granulomatous disease, thereby excluding a diagnosis of sarcoidosis. Circumstantial evidence supports the view that giant cell myocarditis may have an autoimmune origin, and the histopathology suggests that cellular immune mechanisms might have a role in the pathogenesis of this disease. On this basis, it is suggested that cyclosporine, a selective inhibitor of T lymphocyte-mediated immune responses, may be useful for the treatment of this presently fatal disease.

Failure of percutaneous transluminal coronary angioplasty to stimulate platelet and prostaglandin activity.

Platelet function and prostaglandin activity were evaluated in nine patients with coronary artery disease undergoing percutaneous left anterior descending coronary artery angioplasty (PTCA) and compared to nine normal controls. Transcoronary measurements (arterial-coronary sinus) of platelet counts, mean platelet volume, platelet factor 4 (PF4), beta thromboglobulin, thromboxane (B2), and 6-keto-PGF 1 alpha were made. When compared to normal controls, the patients with coronary artery disease had higher circulating baseline levels of PF4 in the coronary sinus. There was no transcardiac production of any factor at baseline or immediately after infusion of nitroglycerin or performance of PTCA. These results suggest that PTCA does not grossly alter arachidonic acid metabolism or platelet activity.

Beneficial effects of nifedipine on rest and exercise myocardial energetics in patients with congestive heart failure.

Rest and exercise systemic hemodynamic parameters, coronary blood flow, and myocardial energetics were assessed before and 15 min after the sublingual administration of 20 mg of nifedipine in 10 patients with idiopathic congestive cardiomyopathy. When compared with control, nifedipine increased rest and exercise cardiac index by 37% and 28%, respectively (p less than .001). Peripheral vasodilation was demonstrated with a drop in systemic arterial pressure, exercise pulmonary capillary wedge pressure, and systemic vascular resistance (p less than .05). The calcium-channel blocker did not alter myocardial oxygen consumption; however, coronary blood flow increased by 32% at rest (p less than .01) while coronary vascular resistance diminished both at rest and after exercise compared with control (p less than .05). Nifedipine elicited a decrease in the rest and exercise aortocoronary sinus oxygen difference while the coronary sinus oxygen saturation increased (p less than .01). In this group of patients with idiopathic congestive cardiomyopathy, nifedipine enhanced myocardial performance while increasing coronary blood flow and favorably altering the myocardial oxygen supply-demand balance.

Reperfusion of the human myocardium by saphenous vein bypass grafts. Biochemical considerations.

The adenine nucleotide content of the human myocardium in the distribution of the left anterior descending coronary artery (LAD) was measured before and after saphenous vein bypass grafting. The purpose of the study were twofold: (1) to relate the level of adenosine triphosphate (ATP) before bypass grafting to the percent stenoses of the LAD and (2) to determine the benefit or lack of benefit of bypass grafting on ATP content. Eighteen patients with angiographically determined LAD lesions of 40% to 100% underwent bypass grafting with standard cardiopulmonary bypass and cardioplegia. Transmural needle biopsy specimens were obtained from the center of the area perfused by the LAD immediately before cross-clamping of the aorta and 30 minutes after reperfusion of the myocardium via the native LAD and the graft. The tissue was divided into thirds: The endocardial and epicardial thirds were analyzed for ATP by high-pressure liquid chromatography and the middle third was viewed by light microscopy. The percent narrowing of the LAD correlated well (r = -0.71) with the ratio of ATP to total adenine nucleotides (TAN) in the endocardium. Epicardial ATP did not correlate with the percent stenoses of the LAD. The endocardial ATP/TAN ratio increased in the group as a whole from 0.51 +/- 0.27 (mean +/- SD) to 0.64 +/- 0.26 (p less than 0.01) after bypass grafting, and this was most impressive in those eight patients with LAD lesions greater than 90% (0.32 +/- 0.20 before grafting to 0.60 +/- 0.29 after grafting, p less than 0.005). However, the epicardial ATP/TAN ratio decreased from 0.75 +/- 0.15 before grafting to 0.64 +/- 0.17 after grafting (p less than 0.05), and this decrease occurred regardless of the percent narrowing of the LAD. There was no difference in vacuolization between the pre-grafting and post-grafting biopsy specimens, and intramyocardial hemorrhage was not observed. This study has demonstrated a close relationship between the degree of LAD stenosis and endocardial ATP content. Also, the endocardium supplied by arteries with greater than 90% lesions had significantly increased ATP while the epicardium had decreased ATP content after bypass grafting.

Hemodynamic correlates for timing intervals, ejection rate and filling rate derived from the radionuclide angiographic volume curve.

This study was designed to more clearly define the relation between various invasive hemodynamic measurements and left ventricular (LV) timing intervals, ejection rate and filling rate derived from the radionuclide angiographic volume curve. Twenty-eight patients were studied with simultaneous intracardiac micromanometer pressure and dP/dt recordings, gated radionuclide angiography and M-mode echocardiography. These techniques permitted multiple variables of systolic and diastolic function to be measured at a constant atrial paced rate of 100 beats/min. There was a strong correlation between peak ejection rate and ejection fraction (r = -0.97) and between peak ejection rate and maximum positive dP/dt (r = -0.85). There also was a strong correlation between peak filling rate and maximum negative dP/dt (r = -0.85). A weaker correlation existed between the time constant of LV relaxation and the peak filling rate (r = -0.49) and between the LV end-diastolic pressure and the peak filling rate (r = -0.62). There was no correlation between the modulus of chamber stiffness and filling rates, and no association was observed between the time to peak filling rate and the hemodynamic variables. Thus, under the conditions studied, the measured peak ejection and filling rate, determined from the radionuclide angiographic volume curve, correlated well with accepted invasive hemodynamic measurements.

Mitral valve prolapse syndrome: analysis of 62 patients aged 60 years and older.

Sixty-two patients diagnosed as having mitral valve prolapse, 60 to 81 years old, presented with disabling chest pain (20), symptoms of arrhythmias including palpitations and syncope (16), or mitral regurgitation (MR) with symptoms of congestive heart failure (26). The diagnosis of MVP was made on the basis of a combination of classic auscultatory, echocardiographic and angiographic findings. Thirteen of the 20 patients with chest pain had normal coronary angiograms and 7 had significant coronary artery disease (CAD). Patients with CAD could not be differentiated by clinical presentation alone. Furthermore, the incidence and types of arrhythmias, the presence of a positive stress test, and hemodynamic findings were similar in all patients in this group whether or not CAD was present. The 16 patients with palpitations had a broad spectrum of rhythm disorders, including both supraventricular and ventricular arrhythmias. Two patients had prehospital "sudden death" and 2 others had systemic emboli. Twenty-one of the 26 patients with MR had valve surgery. Intraoperatively the valves were described as enlarged, floppy and with redundant leaflets. Histologic examination showed extensive "myxomatous" changes throughout the valve leaflets. Thus, mitral valve prolapse is a cause of symptomatic heart disease in the elderly. It has a predictable pattern of clinical presentation and should be considered in the differential diagnosis of older patients with disabling chest pain and arrhythmias and as the cause of progressive or severe MR.