Cardiac and pulmonary toxicity in patients undergoing high-dose chemotherapy for lymphoma and breast cancer: prognostic factors.

We sought to define risk factors predisposing breast cancer and lymphoma patients to cardiac and pulmonary toxicity when undergoing high-dose chemotherapy (HDC) and autologous stem cell rescue (ASCR). Additionally, we evaluated in depth the predictive value of the ejection fraction measured prior to HDC in determining cardiac toxicity. In this retrospective analysis, 24 variables were examined in 138 patients undergoing HDC and ASCR from 1990 until 1995. Logistic regression models were used to model the probability of experiencing cardiac and pulmonary toxicity as a function of the 24 prognostic covariates. Cardiac toxicity occurred in 12% of patients and pulmonary toxicity in 24% of patients. Bivariate analyses showed that patients with lymphoma (as opposed to breast cancer) and those with a higher cardiac risk factor score were more likely to experience cardiac toxicity. Multivariate logistic regression models predicted lymphoma and older age to be risk factors for cardiac toxicity. History of an abnormal ejection fraction and higher doses of anthracyclines prior to HDC may also contribute to cardiac toxicity. Pulmonary toxicity occurred more commonly in lymphoma than breast cancer patients, likely due to the busulfan used in the HDC regimen. No other risk factors for pulmonary toxicity were identified. We conclude that older patients with lymphoma should be carefully evaluated prior to being accepted for HDC programs. Older patients with breast cancer may tolerate this procedure well. There is a trend towards cardiac toxicity in patients with a past history of low ejection fraction, although seemingly poor cardiac risk patients may fare well with HDC if carefully selected with the aid of a thorough cardiac evaluation.

Doppler echocardiographic evaluation of severe rheumatic submitral valve stenosis.

The submitral apparatus may play a predominant role in rheumatic mitral stenosis and should be evaluated aggressively with Doppler echocardiography, especially in patients in whom percutaneous mitral balloon valvotomy is being considered. The following case presents a patient with rheumatic mitral valve stenosis in whom some noninvasive clues alerted us to the presence of predominant submitral stenosis.

Correlates of mitral valve prolapse among patients with panic disorder.

Mitral valve prolapse (MVP) has been observed more frequently than expected among patients who report the current experience of panic attacks. The MVP observed has been generally of a mild variety and has not been associated with clinically meaningful variables in studies to date. In the current study, 82 patients with panic disorder (PD) who were recruited for a study of the drug treatment of PD were assessed for the presence of MVP, and patients with and without MVP were compared on several variables. Statistically significant findings were that patients with MVP were younger and more often female; reported an earlier age of onset of PD and more frequent panic attacks; and had a higher ponderal index, lower weight, and lower levels of triiodothyronine than patients without MVP. Contrary to previous studies, these results suggest that the presence of MVP among patients with PD is associated with potentially meaningful differences. While generalizability may be limited and causal relationships speculative at this time, the variables identified in this study deserve more explicit attention in future studies of PD and MVP.

Contrast echocardiography during coronary arteriography in humans: perfusion and anatomic studies.

In humans, the physiologic relation between myocardial blood flow and epicardial coronary artery anatomy remains poorly defined. With the recent development of sonicated microbubble contrast agents, it is now possible to use contrast echocardiography to assess myocardial perfusion and to correlate blood flow with angiographically identified coronary artery anatomy. The purpose of the current study was to determine myocardial perfusion patterns in patients without significant coronary artery disease. The results may be used as a reference to analyze myocardial blood flow in patients with coronary artery disease. Sonicated meglumine sodium diatrizoate solution (Renografin-76), which contains microbubbles measuring 4.5 +/- 2.8 micrograms in diameter by laser analysis, was used as the echocardiographic contrast agent during elective coronary arterriography in 14 patients without significant coronary artery disease. Patients received intracoronary injections of 1.5 to 2 ml of sonicated Renografin-76 without complications. Perfusion characteristics were studied by visual assessment of the two-dimensional echocardiographic images obtained after individual injections. In patients found to be free of significant coronary artery disease by arteriography, the left coronary system always supplied the anteroseptal, anterior, anterolateral and posterior regions of the left ventricle at the mid-papillary, cross-sectional level. The right coronary artery system perfused the inferior and inferoseptal regions in 89% of the patients identified with a right dominant system. The anterolateral papillary muscle was perfused from the left coronary system in all cases. The posteromedial papillary muscle was perfused from the left coronary system in 58% of the patients and from the right system in 42% of the patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of intracoronary injections of sonicated microbubbles on left ventricular contractility.

Despite the recent interest in contrast-enhanced echocardiography as a means of defining myocardial perfusion, the effects of echo contrast agents on left ventricular (LV) contractility in humans remains poorly defined. This is particularly relevant because intracoronary injection of contrast agents used for angiographic visualization of coronary arteries produces significant alterations in LV hemodynamics. The relation of LV end-systolic wall stress (sigma es) to rate-corrected velocity of fiber shortening (Vcfc), a load-independent index of contractility, was studied in 7 patients undergoing elective coronary arteriography. Two-dimensional and targeted M-mode echocardiographic and central aortic pressure tracings were recorded during injections of standard volumes of angiographic (7 to 9 ml of nonsonicated Renografin-76) and echocardiographic (1.5 to 2.0 ml of sonicated Renografin-76) contrast agents into the left main coronary artery. The order in which agents were injected was randomly determined. Myocardial contractility was assessed under control conditions and 5 and 15 seconds after injection. Alterations in contractility relative to control were measured as the change in Vcfc after elimination of afterload (sigma es) as a confounding variable. An injection of Renografin-76 adequate for angiographic imaging of coronary artery anatomy resulted in a significant depression of LV contractility (p less than 0.001) in conjunction with a tendency toward increased afterload (p = 0.12); recovery occurred by 15 seconds after injection. The smaller amounts of sonicated Renografin-76 required to give adequate contrast enhancement of the myocardium did not alter LV contractile state or afterload.(ABSTRACT TRUNCATED AT 250 WORDS)

Mitral valve prolapse and thyroid abnormalities in patients with panic attacks.

Panic disorder has been associated with mitral valve prolapse and thyroid abnormalities. Mitral valve prolapse has also been associated with thyroid abnormalities. The authors studied a consecutive series of 65 patients self-referred for evaluation of panic attacks, who were examined for cardiac and thyroid abnormalities. Fifty percent of the patients had mitral valve prolapse according to both cardiac auscultation and echocardiography. Twenty-six percent of the women had some thyroid abnormality; 17% had thyroid microsomal antibodies. There was no apparent relationship between mitral valve prolapse and thyroid abnormalities. These observations suggest that panic attacks, mitral valve prolapse, and autoimmune thyroid disorders are associated.

Quantitative effects of osmotic diuresis following angiographic contrast administration.

Osmotic diuresis resulting from the administration of angiographic contrast poses the potential threat of marked volume losses obligated by the renal excretion of non-reabsorbable solute. We prospectively assessed urinary excretion of solute and water following cardiac angiography in 14 euvolemic subjects without preexisting renal disease, by a protocol that allowed each patient to serve as his own control. During the initial 6 h after the beginning of angiography, contrast administration resulted in increased total osmolar excretion from a control rate of 0.79 +/- 0.09 to 1.09 +/- 0.09 mOsm/min (P less than .05) with a return to control values thereafter. Surprisingly, sodium, potassium, and chloride excretion rates did not differ significantly from control values. After subtraction of the molar contribution of electrolytes, urea, and creatinine from the total osmolar excretion rate, it was apparent that the "residual osmolar excretion rate" of 0.48 +/- 0.05 mOsm/min was markedly elevated over the control value of 0.11 +/- 0.05 mOsm/min (P less than .01), reflecting the excretion of contrast agent. Despite the marked osmotic diuresis, urine output during this period (3.9 +/- 0.2 cc/min) did not differ significantly from the control value of 4.0 +/- 0.3 cc/min. We conclude that marked volume losses are not a necessary concomitant of contrast-induced osmotic diuresis in the euvolemic cardiac patient without renal disease.

Methods for evaluating cardiac wall motion in three dimensions using bifurcation points of the coronary arterial tree.

An accurate three-dimensional (3D) representation of heart wall motion would be an important means of evaluating cardiac function. To accomplish this, we have developed an interactive computer graphics system designed to enter the time-dependent 3D positions of bifurcations of the coronary arterial tree. These bifurcations are precise markers of the epicardial surface, and their motions accurately represent the motion of the underlying heart wall. We demonstrate techniques for calculating local wall motion, including displacement and velocity, for determining a time-dependent center-of-contraction point towards which the epicardium tends to move and for tracking the mechanical contraction wave using cross-correlation methods. We have applied these techniques to study seven patients with normal left ventriculograms and coronary arteriograms. We have found these methods to be generally applicable and to provide information not obtainable without 3D analysis.

Drainage of right superior vena cava into both atria. Review of the literature and description of a case presenting with polycythemia and paradoxical embolization.

An unusual cause of polycythemia, cyanosis and paradoxical embolus is described in a 37-year-old man, consisting of a rare congenital anomaly of the superior vena cava (SVC). The right-sided SVC received pulmonary venous drainage from the right lung and drained, through two channels, into both atria with the left atrium receiving the larger of the two channels. The atrial septum was intact. Corrective surgery and postoperative cardiac catheterization are described and the literature concerning anomalies of the right superior vena cava is reviewed.

The angiographic effect of ergonovine and nifedipine in coronary artery spasm.

In a patient with variant angina, we have shown that the calcium-channel blocker nifedipine inhibits both spontaneous and ergonivine-induced coronary artery spasm. It had no effect, however, on the dose-related diffuse vasoconstriction caused by ergonovine, suggesting two distinct responses of coronary arteries to ergonovine provocation. Nifedipine did not cause epicardial coronary artery dilatation, as did nitroglycerin, supporting the rationale of using both therapies together to treat coronary artery spasm.

Detection, prediction, and significance of perioperative myocardial infarction following aorta-coronary bypass.

One hundred consecutive patients undergoing aorta-coronary bypass grafting (ACBG) alone, without ventricular venting, were prospectively studied to determine the incidence and consequence of perioperative myocardial infarction (PMI) and the clinical variables that were predictive of PMI. Incidence was determined by serial electrocardiography (ECG) 100 patients; serum CK, GOT, and LDH (100 patients). CK isoenzymes (qualitative 100 patients, quantitated 50 patients); vectorcardiography (VCG) (78 patients); and 99mtechnetium pyrophosphate scintigraphy (TcPyp) (52 patients). The incidence of PMI by ECG was 9%; an additional 8% of cases was diagnosed by enzymes alone. The incidence of diagnostic change by VCG was 19% and by scintigraphy, 25%. Using at least one changed variable of the remaining three as the reference standard, the relative sensitivity and relative specificity of given variables in the diagnosis of PMI were as follows: ECG 67% and 100%, respectively; VCG 85% and 94%; scintigraphy 92% and 97%; and serum enzymes 86% and 96%. By univariate analysis, unstable angina was the only significant predictor of PMI. The operative mortality rate was 2% and the mortality rate at 12 months was 5%. There was a significantly greater mortality rate in patients with PMI diagnosed by ECG (p less than 0.01), in patients with unstable angina pectoris before operation (p less than 0.05), and in women (p less than 0.05).

Calcific stenosis of the porcine heterograft.

We have encountered two cases of late calcification of the porcine heterograft. A patient in chronic renal failure died of sepsis and endocarditis fifteen months after replacement of the mitral and tricuspid valves. At postmortem examination, both heterograft valves exhibited severe calcification and thrombosis. A second patient with rheumatic heart disease and sickle cell disease underwent mitral valve replacement for severe regurgitation. Thirty months later, cardiac catheterization revealed prosthetic valve stenosis. The valve was replaced successfully, and the excised heterograft exhibited severe calcification with restriction of leaflet motion. Although calcification of the porcine heterograft is known to occur in patients with infection or disorders of calcium metabolism, dysfunction of the heterograft is rare in our experience.

Surgical treatment of recurrent primary malignant tumor of the left atrium.

A young woman presented with a tumor in the left atrium resembling a left atrial myxoma. After simple excision of the tumor the diagnosis of primary malignant fibrous histiocytoma of the heart was made. A course of radiation therapy was given. Four subsequent recurrences were treated by cardiotomy and resection of the left atrial wall. At the third, fourth, and fifth operations fulguration of the left atrial wall was performed. Subsequent chemotherapy failed to control the tumor. The patient was admitted 6 weeks after the last resection and died. Postmortem examination revealed a large recurrent tumor obstructing the left atrium with no metastases. The clinical course, cardiac catherization data, and postmortem examination are presented. Palliation was achieved by repeated resection of a radiation-resistent primary sarcoma of the heart.

Ventriculographic features predictive of surgical outcome for left ventricular aneurysm.

Although clinical and hemodynamic stability predicted outcome very well when left ventricular aneurysm was electively resected in 25 patients (95% survival), more discriminate criteria were essential for 20 patients undergoing urgent operation for severe myocardial decompensation (50% survival). Three methods of ventriculographic analysis primarily sensitive to the function of the non-aneurysmal left ventricle were evaluated. These methods separated patients undergoing urgent operation into a population with high operative risk (less than 18% survival) and a population with low operative risk (greater than 82% survival). These criteria also separated 15 patients undergoing operation within three months of myocardial infarction into a group with excellent prognosis (greater than 85% survival) and a group with poor prognosis (less than 15% survival). The high operative risk in patients undergoing urgent operation or operation within three months of myocardial infarction, when non-aneurysmal ventricular function is poor, may be too high; it should be undertaken only under unusual circumstances.

Right ventricular performance during ischemia: an anatomic and hemodynamic analysis.

This study in the pig was designed to characterize right ventricular (RV) contractile responses during infarction involving three areas of the heart--anteroseptal, anterolateral, and inferoseptal. Porcine coronary architecture was studied from multicolor vinyl casts. Distribution of blood supply to ventricular myocardium and papillary muscles was defined by intra-arterial dye injection. High-fidelity pressure and flow data were measured simultaneously in both ventricles following ligation of approximately equal lengths of the anterior descending, left circumflex, or posterior descending arteries. In the three groups, weight of myocardium involved by the occluded artery was comparable and there was significant depression of left ventricular performance, more pronounced in the two anterior infarcts. However, in anterolateral infarction, despite the obligatory drop in RV flow, there was no significant alteration in RV end-diastolic pressure (EDP), peak rate of rise of RV pressure (dP/dt), or time-to-peak developed dP/dt. In contrast, with both anteroseptal and inferoseptal infarctions there were significant alterations in all RV contractile parameters, at increased levels of RVEDP, signifying a primary depression in RV contractile state. With inferoseptal infarction, further occlusion of the right coronary near its origin produced a more exaggerated and selective RV contractile abnormality and, in half of the animals, varying degrees of acute tricuspid insufficiency.

Mechanical circulatory assistance for the treatment of complications of coronary artery disease.

Surgery has become an accepted method of treatment for coronary artery disease and its complications. Revascularization results in significant improvement in symptoms for patients with angina pectoris. Occasionally, patients requiring surgery for angina pectoris will sustain reversible ischemic damage during operation; such patients can be successfully weaned from cardiopulmonary bypass with full recovery when intra-aortic balloon counterpulsation is used. Arrhythmias associated with ischemic damage to the myocardium also can be controlled when IABCP is used for physiologic assistance. Patients in cardiogenicshock of pulmonary edema after acute myocardial infarction have an ominous prognosis. When decompensation occurs, IABCP may be used to stabilize the patient and to allow study and corrective surgery if possible. The prognosis is better for patients with ventricular septal defect, although selected patients without a mechanical defect of the myocardium can be salvaged if the response to IABCP is favorable. Counterpulsation has also been shown to be useful in achieving pulsatile cardiopulmonary bypass and in assisting high-risk patients through operation. External pressure circulatory assist (EPCA) is less effective than IABCP in assisting the failing myocardium; however, the external device is noninvasive and may be a useful adjunct in situations where IABCP is not feasible.

Expansion of extracellular space in the nonischemic zone of the infarcted heart and concomitant changes in tissue electrolyte contents in the rat.

The alterations in electrolyte content that occur in an infarcted zone of the heart have also been reported to occur in a similar manner, although to a far less degree, in the distant, apparently normal zones of the heart. These alterations in the nonischemic myocardium have usually been tabulated without comment, presumably because their magnitudes approach values of statistical dispersion. Our measurements of electrolyte content in the normal zone of the infarcted rat heart confirmed that all of the electrolyte contents were slightly modified. There was a rise in sodium, calcium, and chloride and a decline in potassium and magnesium. In addition, the extracellular space ([14C]sucrose) in this zone was elevated by nearly 15%. We have postulated a mechanism for this elevation based on an increase in the net filtration rate through myocardial capillaries. The expansion of the extracellular space can account for all of the electrolyte changes in the normal zone with the exception of the alteration in calcium. Therefore, there is no basis for assuming that these myocardial alterations reflect general movements of electrolytes down their electrochemical gradients. We suggest that the increment in the nominal concentration of cellular calcium is related to a compensatory mechanism that allows the reduced mass of functional myocardium to contract more vigorously.

Biventricular dynamics during quantitated anteroseptal infarction in the porcine heart.

The porcine heart has been shown to have close anatomic similarity to the human heart and was used as the experimental model in this study to gain further understanding of the early responses of both ventricles during acute anteroseptal myocardial infarction. High fidelity pressure and flow data were measured and multiple preejection and ejection variables were calculated for both ventricles. Infarct weight and distribution in both ventricles were quantitated. The standard infarction resulted from single stage ligation of the left anterior descending coronary artery just beyond its midpoint and second left ventricular branch. It comprised an average of 15.8 percent of total ventricular myocardium with an infarct/perfused ratio of 0.62 and a periinfarction transition zone of 7.5 mm, and involved significant portions of both ventricles and the interventricular septum. Performance characteristics of both ventricles were altered significantly by anteroseptal infarction and involved all phases of contraction--end-diastole, isovolumic systole and ventricular ejection. Although contractile alterations in the right ventricle were significant, they were somewhat delayed, yielding relatively low correlation coefficients with analogous left ventricular contractile indexes. These correlations became quite distinct during specific ventricular stresses. Comparison of anterolateral and anteroseptal infarction, matched in terms of infarct size, indicated that the right ventricular changes in the latter were related to direct involvement of the right ventricular free wall and septum rather than secondary to left ventricular alterations.