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.

Hemodynamic effects of vasodilator therapy in severe left heart failure combined with large atrial septal defects.

Two patients presented with severe left heart failure and large secundum atrial septal defects without severe pulmonary hypertension. The acute hemodynamic effects of two commonly used vasodilator agents, isosorbide dinitrate and hydralazine, are described. Although isosorbide dinitrate improved systemic forward cardiac output, it also increased left-to-right intracardiac shunting in both patients. On the other hand, hydralazine dramatically improved systemic toward output and concomitantly diminished left-to-right shunt flow in each patient (43 and 21 percent). The complexities of combined severe left ventricular failure and a large atrial septal defect with left-to-right shunting, and the importance of extensive hemodynamic monitoring at the time of pharmacologic intervention, are discussed.

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.

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.

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.

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.

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.

Extensive myocardial blood flow distribution through individual coronary artery bypass grafts.

The regional myocardial perfusion distribution of coronary artery bypass grafts were studied in 61 patients who received 162 grafts. Selective intragraft instillations of radioactive-labeled macroaggregated albumin particles were used to study perfusion. The extent of individual graft perfusion was assessed in 100 patent grafts. Regional myocardial blood flow distribution was similar to the blood flow distribution of the native vessel receiving the graft in 64 of 100 grafts and less than that expected of the native vessel in 12 grafts. However, 24 grafts demonstrated a blood flow distribution pattern which extended beyond the normal distribution expected of the native vessel receiving the graft. This extensive perfusion could be attributed to collateral vessels or retrograde flow. A high incidence of both graft and native vessel occlusion was found in areas receiving blood from these distant grafts with extensive distributions (16/24), and left ventricular wall motion was preserved or significantly improved postoperatively in 28/31 segments in such areas. When comparing angiographic and scintigraphic methods of evaluating myocardial perfusion, the angiogram underestimated the full extent of graft blood flow distribution in 13 of 24 instances (54 percent).

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.

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.

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.

Assessment of ventricular function by combined noninvasive measures: factors accounting for methodologic disparities.

We studied the predictive accuracy and disparities among cineventriculographic ejection fraction, pre-ejection period over left ventricular ejection time (PEP/LVET) obtained from the systolic time intervals and the percent shortening of the internal echocardiographic diameter (% delta D) in assessing left ventricular performance in 453 consecutive patients without valvular heart disease. In 308 patients all three tests were normal, and in 78 patients all three tests were abnormal. Overall agreement (predictive accuracy) among ejection fraction (normal greater than or equal to 57), % delta D (normal greater than or equal to 28%) and PEP/LVET (normal less than or equal to 0.42) was 85%. In 67 patients disparities among the tests as measures of global left ventricular performance were found. The major mechanisms accounting for such disparities were: (a) large segmental contraction abnormalities which selectively distort the % delta D and ejection fraction and (b) diminished isovolumic pressure (less than 45 mmHg) which distorts PEP/LVET. When patients with segmental contraction abnormalities and low isovolumic pressure were excluded the agreement between PEP/LVET and ejection fraction was 97%, ejection fraction and % delta D 98% and PEP/LVET and % delta D 97%. The combined uses of systolic time intervals and echocardiogram minimizes error due to segmental contraction abnormalities and isovolumic pressure. If both PEP/LVET and % delta D are concordant the agreement with ejection fraction is 94% for normal and 99% for abnormal left ventricular function.

Biochemical and histologic correlates of ventricular end-diastolic pressure.

The associations of elevated left ventricular (LV) and right ventricular (RV) end-diastolic pressure (EDP) were evaluated in 28 patients with non-ischemic congestive cardiomyopathy. Right-sided endomyocardial biopsies from each patient were evaluated for ATP content, percent fibrosis and myocardial fiber diameter. The resting RVEDP and LVEDP and the post-angiographic LVEDP were correlated with the results from the biopsies. There was a correlation of the LVEDP with the RVEDP (r = 0.67, P less than 0.001) by a linear plot. There was no correlation of any EDP measurement with the percent fibrosis. There was, however, a rough correlation of the myocardial fiber diameter with RVEDP (r = 0.40, P less than 0.05). Myocardial ATP content correlated with the RVEDP (r = -0.53, P less than 0.005), the LVEDP (r = -0.65, P less than 0.001) and the post-angiographic LVEDP (r = -0.72, P less than 0.001). These data demonstrate that an elevated ventricular EDP correlates most closely with depressed levels of myocardial ATP. The myocardial cell diameter correlated less well and there was no correlation of EDP with fibrosis. Metabolic factors may be more important than histologic parameters in the elevated ventricular EDP of non-ischemic congestive cardiomyopathy.

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.

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.

Methacholine provocation of Prinzmetal's variant angina pectoris: a revised perspective.

We report 13 patient with unequivocal Prinzmetal's variant angina pectoris as the entire experience with this syndrome during a 7-year period in a single institution. The clinical diagnosis of this relatively uncommon disorder is emphasized. Five patients were given 10 mg of methacholine subcutaneously. Three demonstrated subsequent delayed appearance of chest pain, ECG change, and coronary vasospasm following early appearance of muscarinic effects. Two Prinzmetal patients had no provocation of variant angina following methacholine, though they did experience significantly less blood pressure fall in response to muscarinic provocation. Another 23 subjects with incompletely explained chest pain given methacholine had neither ECG change nor spasm. Methacholine provocation of variant angina need not necessarily implicated a parasympathomimetic mechanism for otherwise spontaneous episodes. Rather, provocation would appear to occur via the customary reflex adrenergic response to drug-induced hypotension. Methacholine is probably safe though unreliable as an agent to be used for spasm provocation.