Influence of mRNA expression of epiregulin and amphiregulin on outcome of patients with metastatic colorectal cancer treated with 5-FU/LV plus irinotecan or irinotecan plus oxaliplatin as first-line treatment (FIRE 1-trial).

Our aim was to investigate the impact of EREG and AREG mRNA expression (by RT-qPCR) in patients with metastatic colorectal cancer (mCRC). In addition, epidermal growth factor receptor (EGFR) expression (by immunohistochemistry) as well as RAS-and PIK3CA-mutations (by pyrosequencing) were assessed. Tumors of 208 mCRC patients receiving 5-fluorouracil/leucovorin plus irinotecan (FUFIRI) or irinotecan plus oxaliplatin (mIROX) within the FIRE-1 trial were analyzed for mutations. Molecular characteristics were correlated with response, progression-free survival (PFS), overall survival (OS). mRNA expression was evaluated using ROC-analysis in 192 tumors (AREG high n = 31 vs. low n = 161; EREG high n = 89 vs. low n = 103). High versus low AREG expression was associated with PFS of 10.0 versus 8.0 months (HR = 0.62, 95% CI: 0.402-0.940, p = 0.03) and OS of 24.6 versus 18.7 months (HR = 0.72, 95% CI: 0.476-1.078, p = 0.11). High versus low EREG expression correlated with prolonged PFS (9.4 vs. 6.8 months, HR = 0.62, 95% CI: 0.460-0.846, p = 0.002) and OS (25.8 vs. 15.5 months, HR = 0.48, 95% CI: 0.351-0.657, p < 0.001). The positive prognostic effect of high EREG expression was confirmed in a multivariate analysis and was neither affected by EGFR expression nor by mutations of RAS- and PIK3CA-genes. EREG expression appears as an independent prognostic marker in patients with mCRC receiving first-line irinotecan-based chemotherapy.

CEA response is associated with tumor response and survival in patients with KRAS exon 2 wild-type and extended RAS wild-type metastatic colorectal cancer receiving first-line FOLFIRI plus cetuximab or bevacizumab (FIRE-3 trial).

BACKGROUND: To examine the relation of carcinoembryonic antigen (CEA) response with tumor response and survival in patients with (K)RAS wild-type metastatic colorectal cancer receiving first-line chemotherapy in the FIRE-3 trial comparing FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab. PATIENTS AND METHODS: CEA response assessed as the percentage of CEA decrease from baseline to nadir was evaluated for its association with tumor response and survival. Receiver operating characteristic analysis revealed an optimal cut-off value of 75% using the maximum of sensitivity and specificity for CEA response to discriminate CEA responders from non-responders. In addition, the time to CEA nadir was calculated. RESULTS: Of 592 patients in the intent-to-treat population, 472 were eligible for analysis of CEA (cetuximab arm: 230 and bevacizumab arm: 242). Maximal relative CEA decrease (%) significantly (P = 0.003) differed between the cetuximab arm (median 83.0%; IQR 40.9%-94.7%) and the bevacizumab arm (median 72.3%; IQR 26.3%-91.0%). In a longitudinal analysis, the CEA decrease occurred faster in the cetuximab arm and was greater than in the bevacizumab arm at all evaluated time points until 56 weeks after treatment start. CEA nadir occurred after 3.3 months (cetuximab arm) and 3.5 months (bevacizumab arm), (P = 0.49). In the cetuximab arm, CEA responders showed a significantly longer progression-free survival [11.8 versus 7.4 months; hazard ratio (HR) 1.53; 95% Cl, 1.15-2.04; P = 0.004] and longer overall survival (36.6 versus 21.3 months; HR 1.73; 95% Cl, 1.24-2.43; P = 0.001) than CEA non-responders. Analysis of extended RAS wild-type patients revealed similar results. CONCLUSION: In the FIRE-3 trial, CEA decrease was significantly faster and greater in the cetuximab arm than in the bevacizumab arm and correlated with the prolonged survival observed in patients receiving FOLFIRI plus cetuximab. CLINICAL TRIALS NUMBER: NCT00433927 (ClinicalTrials.gov); AIO KRK0306 FIRE-3.

Correlation of capecitabine-induced skin toxicity with treatment efficacy in patients with metastatic colorectal cancer: results from the German AIO KRK-0104 trial.

BACKGROUND: The AIO KRK-0104 randomised phase II trial investigated the efficacy and safety of two capecitabine-based regimens: combination of capecitabine and irinotecan (CAPIRI) plus cetuximab (CAPIRI-C) and combination of capecitabine with oxaliplatin (CAPOX) plus cetuximab (CAPOX-C) in the first-line treatment of metastatic colorectal cancer (mCRC). Treatment-related skin toxicity (ST) was evaluated separately for capecitabine and cetuximab. The present analysis investigates the correlation of capecitabine-attributed ST (Cape-ST) and parameters of treatment efficacy. METHODS: Patients with mCRC were randomised to cetuximab (400 mg m(-2), day 1, followed by 250 mg m(-2) weekly) plus CAPIRI (irinotecan 200 mg m(-2), day 1; capecitabine 800 mg m(-2), twice daily, days 1-14, every 3 weeks), or cetuximab plus CAPOX (oxaliplatin 130 mg m(-2), day 1; capecitabine 1000 mg m(-2), twice daily, days 1-14, every 3 weeks). RESULTS: Of 185 recruited patients, 149 (CAPIRI-C, n=78; CAPOX-C, n=71) received study treatment beyond the first tumour assessment and were evaluable for efficacy. Capecitabine-attributed ST, predominantly hand-foot syndrome, was observed in 32.2% of patients. Capecitabine-attributed ST grade 1-3 was associated with a significantly higher disease control rate (DCR) (97.9 vs 86.1%, P=0.038) compared with grade 0 toxicity. Moreover, Cape-ST grade 1-3 related to a markedly longer progression-free survival (PFS) (9.9 vs 5.6 months, P<0.001) and overall survival (OS) (32.8 vs 22.4 months, P=0.008). Separate analyses of treatment arms indicated that the effect of Cape-ST on PFS remained significant for both arms, whereas the effect on OS remained apparent as a strong trend. CONCLUSION: This analysis supports the hypothesis that for the evaluated regimens, a correlation exists between Cape-ST and treatment efficacy regarding DCR, PFS, and OS.

Capecitabine plus oxaliplatin (CapOx) versus capecitabine plus gemcitabine (CapGem) versus gemcitabine plus oxaliplatin (mGemOx): final results of a multicenter randomized phase II trial in advanced pancreatic cancer.

BACKGROUND: To compare the efficacy and safety of three different chemotherapy doublets in the treatment of advanced pancreatic cancer (PC). PATIENTS AND METHODS: At total of 190 patients were randomly assigned to receive capecitabine 1000 mg/m(2) twice daily on days 1-14 plus oxaliplatin 130 mg/m(2) on day 1 (CapOx), capecitabine 825 mg/m(2) twice daily on days 1-14 plus gemcitabine 1000 mg/m(2) on days 1 and 8 (CapGem) or gemcitabine 1000 mg/m(2) on days 1 and 8 plus oxaliplatin 130 mg/m(2) on day 8 (mGemOx). Treatment cycles were repeated every three weeks. The primary end point was progression-free survival (PFS) rate at 3 months; secondary end points included objective response rate, carbohydrate antigen 19-9 response, clinical benefit response, overall survival and toxicity. RESULTS: The PFS rate after 3 months was 51% in the CapOx arm, 64% in the CapGem arm and 60% in the mGemOx arm. Median PFS was estimated with 4.2 months, 5.7 months and 3.9 months, respectively (P = 0.67). Corresponding median survival times were: 8.1 months (CapOx), 9.0 months (CapGem) and 6.9 months (mGemOx) (P = 0.56). Grade 3/4 hematological toxicities were more frequent in the two Gem-containing arms; grade 3/4 non-hematological toxicity rates did not exceed 15% in any arm. CONCLUSION: CapOx, CapGem and mGemOx have similar clinical efficacy in advanced PC. Each regimen has a distinct but manageable tolerability profile.

Gemcitabine and carboplatin in intensively pretreated patients with metastatic breast cancer.

BACKGROUND: Patients with metastatic breast cancer (MBC) are increasingly exposed to anthracyclines and taxanes either during treatment of primary breast cancer or during initial therapy of metastatic disease. The combination of gemcitabine and carboplatin was therefore investigated as an anthracycline- and taxane-free treatment option. PATIENTS AND METHODS: MBC patients previously treated with chemotherapy were enrolled in a multicenter phase II study. Treatment consisted of gemcitabine (1,000 mg/m(2) i.v. on days 1 and 8) and carboplatin (AUC 4 i.v. on day 1) applied every 3 weeks. RESULTS: Thirty-nine patients were recruited, and a total of 207 treatment cycles were applied with a median of 5 cycles per patient. One complete response and 11 partial responses were observed for an overall response rate of 31% (95% CI: 17-48%). Twelve patients (31%) had stable disease. Median time to progression was 5.3 months (95% CI: 2.6-6.7 months) and median overall survival from start of treatment was 13.2 months (95% CI: 8.7-16.7 months). Grade 3/4 hematological toxicity included leukopenia (59%/5%), thrombocytopenia (26%/23%) and anemia (10%/0%). Nonhematological toxicity was rarely severe. CONCLUSION: Combination chemotherapy with gemcitabine and carboplatin is an effective and generally well-tolerated treatment option for intensively pretreated patients with MBC. Due to a considerable incidence of severe thrombocytopenia it would be reasonable to consider starting gemcitabine at the lower dose level of 800 mg/m(2).

Impact of BRAF and RAS mutations on first-line efficacy of FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab: analysis of the FIRE-3 (AIO KRK-0306) study.

BACKGROUND: RAS and BRAF mutations have been identified as negative prognostic factors in metastatic colorectal cancer. Efficacy of 5-fluorouracil, leucovorin, irinotecan (FOLFIRI) plus bevacizumab in patients with RAS-mutant tumours needs to be further evaluated. Whether to treat patients with BRAF-mutant tumours with either bevacizumab or anti-epidermal growth factor receptor (EGFR) antibodies remains unclear. METHODS: Patients treated within the FIRE-3 trial were retrospectively tested for BRAF and RAS mutations using formalin fixated paraffin embedded (FFPE) tumour material applying pyrosequencing for KRAS and NRAS exon 2, 3 and 4 mutations as far as for BRAF mutations. Survival analysis was done using Kaplan-Meier estimation and differences were expressed using the log-rank test. Overall response rate (ORR) was compared using Fisher's exact test. Data from a central independent radiological response evaluation were used to calculate early tumour shrinkage (ETS) and depth of response (DpR). RESULTS: Overall, 188 patients with RAS-mutant tumours and 48 with BRAF-mutant tumours were identified. In BRAF-mutant patients, ORR was numerically higher in the cetuximab versus the bevacizumab arm (52% versus 40%), while comparable results were achieved for progression-free survival (PFS; hazard ratio [HR] = 0.84, p = 0.56) and overall survival (OS; HR 0.79, p = 0.45). RAS mutation was associated with a trend towards lower ORR (37% versus 50.5%, p = 0.11) and shorter PFS (7.4 versus 9.7 months; HR 1.25; p = 0.14) in patients receiving FOLFIRI plus cetuximab versus bevacizumab, but OS was comparable (19.1 versus 20.1 months; HR 1.05; p = 0.73), respectively. ETS identified subgroups sensitive to cetuximab-based treatment in both BRAF- (9/17) and RAS-mutant (18/48) patients and was associated with significantly longer OS. DpR was comparable between both treatment arms in RAS- and BRAF-mutant patients, respectively. CONCLUSIONS: In BRAF- and RAS-mutant patients, cetuximab- and bevacizumab-based treatment had comparable survival times. ETS represents an early parameter associated with the benefit from anti-EGFR, while this was not the case with vascular endothelial growth factor A blockade.

Specification of regional wall motion abnormalities by phase analysis of radionuclide angiograms in coronary artery disease and non-coronary artery disease patients.

Fourier transform of gated radionuclide ventriculograms (RNV) permits the quantitative evaluation of regional wall motion abnormalities (RWMA) regarding both regional magnitude (amplitude display) and regional time sequence of contraction (phase display). In this study, an attempt was made to further specify coronary artery disease (CAD) and non-CAD RWMA detected on consecutive exercise RNV in 17 patients (pts) with proven severe CAD; or on resting RNV in 24 pts with transmural myocardial infarction (MI) compared with 27 pts after treatment with daunorubicin (DAU). RWMA were defined objectively from parametric images by a decrease of the sectorial amplitude by more than 2 s.d.s of normal as determined by quantification of RNV studies of 20 normal individuals. In 15 out of 17 CAD pts (88%) and in 19 out of 24 MI pts (79%), a significantly decreased regional amplitude was found. Importantly, in all abnormal CAD and MI amplitude scans (100%), a significantly abnormal phase delay in the same region could be noted. In five out of 27 pts on DAU (18%) an apical hypokinesis could be verified. In comparison with CAD pts, however, the phase distribution was normal in all these DAU pts. Thus, standardized phase analysis of RNV data provides a powerful tool for specifying RWMA. It allows a highly specific separation of RWMA caused by exercise-induced ischemia, MI, or DAU.

Color Doppler echocardiographic determination of mitral regurgitant flow from the proximal velocity profile of the flow convergence region.

Flow rate across an orifice can be determined from color Doppler echocardiographic maps of the flow convergence region proximal to the orifice. Different methods have been developed in vitro. The proximal velocity profile method was prospectively evaluated in patients with mitral regurgitation. Color Doppler echocardiography was performed in 74 patients before cardiac catheterization. The increasing velocities within the flow convergence region were determined in an apical plane on the straight line from the transducer to the leak; thus the proximal velocity profile was established and plotted on a nomogram. Instantaneous regurgitant flow rate was derived from the position of the resulting curve in relation to the nomogram's reference curves, which were derived from in vitro measurements. Regurgitant stroke volume was calculated as regurgitant flow rate.regurgitant velocity-time integral/regurgitant peak velocity, using additional continuous-wave Doppler. The 55 patients with angiographic regurgitation had a close association between regurgitant flow rate (0 to 600 ml/s) and angiographic grade (Spearman's rank correlation coefficient = 0.91; p < 0.0001). Regurgitant flow rate did not overlap between grades < or = 2+, 3+ and 4+. In 16 patients, regurgitant stroke volume by echocardiography correlated well with that by the angiography/Fick method (r = 0.88; SEE = 17.1 ml), with a regression line close to identity (y = 0.89x + 12.7 ml). The proximal velocity profile method enables determination of mitral regurgitant flow and estimation of regurgitant volume.

Impaired granulocytic function in patients with acute leukaemia: only partial normalisation after successful remission-inducing treatment.

In vivo chemotaxis and phagocytic activity of polymorphonuclear neutrophils (PMN) were evaluated in 20 patients with acute myeloid leukaemia (AML), and in 10 patients with acute lymphoblastic leukaemia (ALL). For comparison, 20 healthy individuals were investigated. A skin-chamber technique and a phagocytosis test were used to quantify the neutrophil functions. The local leucocyte mobilisation in the skin-chamber was significantly lower in untreated patients with AML and ALL than in healthy individuals (P < 0.05). Patients with acute leukaemia in remission showed an increase in chemotactic parameters though they remained below normal levels. The phagocytosis index (PI) of peripheral blood PMN was lower than 30% (normal individuals: 60%) in untreated AML and ALL; this difference was significant (P < 0.05). The PI of peripheral blood PMN in patients with acute leukaemia in remission returned to the normal level. Investigation of granulocytic function in patients with acute leukaemia in remission may reveal evidence for reduced protection by these cells against infections and lead to adequate therapy.

[Camera-cinematography of the heart (author's transl)]. / Kamera-Kinematographie des Herzens

By "camera-cinematography" of the heart, we mean an isotope method which permits detailed observation of cardiac mechanics without the use of a catheter. All that is necessary is an intravenous injection of 10 to 15 mCi 99mTc human serum albumen followed after ten minutes by a five to ten minute period of observation with a scintilation camera. At this time the isotope has become distributed in the blood. Variations in the precordial impulses correspond with intra-cardiac changes of blood volume during a cardiac cycle. Analysis of the R-wave provides adequate information of cyclical volume changes in limited portions of the heart. This is achieved by a monitor with a pseudo-3-dimensional display; contraction and relaxation of the myocardium can be shown for any chosen longitudinal or horizontal diameter of the heart. Our programme allows simultaneous presentation of the movement of any point on the myocardium as a time-activity curve. The method is recommended as an addition to chest radiography, heart screening or cardiac kymography before carrying out cardiac catheterisation.

[Radionuclide ventriculography. I. Fundamentals and methods (author's transl)]. / Radionuklid- Ventrikulographie. I. Grundlagen und Methoden.

Using local time activity curves parameters are calculated which depend on the local wall motion of the heart cavities. These functional parameters allow the determination of the contours of the heart cavities and the assessment of segmental wall motion disorders. The left ventricular ejection fraction has been calculated by enddiastolic and endsystolic counts using a method which takes into account background inhomogeneity.

[Radionuclide ventriculography. III. Clinical results--parameters of regional wall motility (author's transl)]. / Radionuklid- Ventrikulographie. III. Klinische Ergebnisse: Parameter der regionalen Wandbewegung.

Radionuclide ventriculography and cineangiography were performed in 62 patients with suspected coronary artery disease. Regional wall motility irregularities could be demonstrated in 97% of those patients who revealed an irregularity in the cineangiogram. Two small scars of the posterior myocardial wall escaped detection. The sensitivity of the radionuclide ventriculography was 97%, the specificity was 80%, 4 patients with normal cineangiography showed small irregularities in the radionuclide ventriculogram. 70 patients with infarction revealed wall motility irregularities in 90%, whereas perfusion defects could be detected by thallium scintigraphy in 66% (young and old infarctions).

[Radionuclide ventriculography. II. Clinical results--parameters of global ventricular function (author's transl)]. / Radionuklid- Ventrikulographie. II. Klinische Ergebnisse: Parameter der globalen Ventrikelfunktion.

The ejection fraction as determined by gated blood pool studies was compared with the ejection fraction as evaluated by the following conventional methods: 1) biplane cineangiography employing the Simpson rule. Correlation was r = 0.805 (n = 25); 2) the same patients using the area-length method (r = 0.88, n = 25); 3) monoplane cineangiography using the method of Greene et al. (5) (r = 0.86, n = 35). In 20 patients the maximal contraction velocity as evaluated by radionuclide ventriculography was compared with the mean systolic ejection rate. The observed correlation was weak (r = 0.62, n = 20); however, it should be noted that the radionuclide method determines the maximum contraction velocity whereas cinceangiography measures an average value over the whole systole.

[Assessment of left ventricular regional function by means of radioactive isotopes (author's transl)]. / Bestimmung der Regionalfunktion des linken Ventrikels mit Hilfe von radioaktiven Isotopen.

Extensive analysis of heart function by scintigraphy yields global parameters of ventricular volumes and their changes during the heart cycle (ejection fraction, enddiastolic and endsystolic volumes, velocity of contraction and relaxation). Additionally, information regarding localized disorders of wall motion may be obtained in a qualitative and quantitative manner by the parameters "phase" and "amplitude". These parameters can be computed from regional time-activity curves by Fourier analysis. The radionuclide ventriculogram at rest is suitable for the detection and follow-up of asynergies caused by acute and chronic infarction. In can also be used as a method of distinguishing between reversible and irreversible asynergy by therapeutical intervention (intervention ventriculography). Abnormalities of regional wall motion which develop during exercise may indicate hemodynamically relevant coronary artery stenoses.

[The role of radionuclide ventriculograms in determining the indications for valve replacement in chronic aortic valve insufficiency]. / Die Rolle des Radionuklid-ventrikulogramms für die Indikationsstellung zum Klappenersatz bei der chronischen Aortenklappeninsuffizienz.

Timing of aortic valve replacement (AVR) in chronic aortic regurgitation (AR) remains a difficult problem in clinical practice. Radionuclide ventriculography (RNV) yields information on the extent of valvular regurgitation, the enlargement and the systolic function of the left ventricle. A "well-timed" AVR is defined by 1) postoperative improvement of clinical symptoms, decrease in left ventricular end-diastolic volume (EDV) and normalization of ejection fraction (EF) as well as by 2) greater improvement under surgical therapy as compared to conservative management. In "too early" AVR the latter condition is not fulfilled, while in "too late" AVR the first condition is not accomplished. In this study 54 patients with chronic aortic incompetence were evaluated by RNV to see whether these three groups ("too early", "well timed", "too late" AVR, resp.) can be separated by the relation between EDV and regurgitant volume (RV), the level of the EDV and the clinical status. The examination was based on pre- and postoperative RNV studies as well as on follow-up studies. A good postoperative result can be expected in cases with a preoperative EDV/RV-ratio similar to that observed in 30 patients with AR in whom AVR was not indicated. In contrast, in the majority of those cases with an EDV/RV-ratio exceeding this normal range the postoperative outcome will be unsatisfactory. If the EDV/RV-ratio is normal, AVR should be performed in cases with an EDV exceeding 400 ml, while in cases with an EDV between 300-400 ml AVR is only indicated in the presence of additional symptoms (NYHA greater than or equal to II).(ABSTRACT TRUNCATED AT 250 WORDS)

[Radionuclide ventriculography--a noninvasive method of diagnosis and quantification of tricuspid valve insufficiency]. / Die Radionuklidventrikulographie--eine nichtinvasive Methode zur Diagnose und Quantifizierung der Trikuspidalklappeninsuffizienz.

The diagnosis of tricuspid regurgitation (TR) is difficult to make by simple clinical methods or by invasive techniques. Contrast echocardiography and Doppler echocardiography have improved diagnostic results, but a golden standard is still not available. Radionuclide ventriculography (RNV) is a well-established method for the detection and quantification of a volume load on the left ventricle: the regurgitation fraction can simply be derived from the regurgitant index as the ratio of enddiastolic-endsystolic count-rate differences between the left and right ventricle. In left heart valvular regurgitation a regurgitant index exceeding the upper normal limit can be expected. This study was performed to evaluate the diagnostic accuracy of an abnormally low regurgitant index in detecting TR, which is accompanied by an isolated volume load on the right ventricle. A series of 33 patients with TR on physical examination and cardiac catheterization underwent RNV and was compared with 48 patients with right ventricular enlargement or pressure load on the right ventricle. In addition, the specificity of the method was evaluated in 470 consecutive patients with various forms of heart disease. In 18 out of 20 subjects with isolated TR a regurgitant index below the lower normal limit was found. The remaining 2 cases with minor TR had a regurgitant index within the normal range, which is 0.89 to 1.97 in this laboratory. In patients with additional volume load on the left ventricle, the sensitivity of the method was found to be low, as could be expected from the principle of the method. The time-activity curve over the liver was usually in phase with that recorded over the atria in subjects with TR. Therefore, the additional examination of a region of interest over the liver was particularly useful in these patients with concomitant aortic or mitral valve regurgitation. None of the 48 patients with right ventricular enlargement or pressure load on the right ventricle had a falsely positive result. A total of 17 out of 470 consecutive patients had a regurgitant index below the normal range; left ventricular function was severely impaired in 9 of these patients. The remaining subjects had a regurgitant index slightly below the lower normal limit. In conclusion, RNV has a high sensitivity in the diagnosis of TR in patients without left heart valvular regurgitation and a high specificity in patients without severely impaired left ventricular function and without left-to-right shunt through an atrial septal defect.(ABSTRACT TRUNCATED AT 400 WORDS)

Efficacy and safety of intravenous amiodarone in acute refractory arrhythmias.

Few data are available on intravenous amiodarone therapy in refractory arrhythmias. This retrospective study in 50 patients (14 with supraventricular and 36 with ventricular tachyarrhythmias) revealed a favorable effect of intravenous amiodarone in the treatment of life-threatening arrhythmias with an overall success rate of 76%. In the subgroup of patients with ventricular fibrillation and concomitant severe congestive heart failure success rate was low (25%, 2/8), whereas effectiveness in patients with ventricular tachycardias was high (greater than 90%) and proved to be independent of left ventricular function. If patients with recurrent ventricular fibrillation were excluded from the analysis, successful treatment with intravenous amiodarone was achieved in 90%, even in those patients with severely compromised myocardium.

Evaluation of aortic and mitral valve regurgitation by radionuclide ventriculography: comparison with the method of Sandler and Dodge.

The present investigation was undertaken to introduce a quantitative scintigraphic method for evaluation of regurgitation and to compare it with the generally accepted quantitative method of Sandler and Dodge (Sandler et al., 1963). Radionuclide ventriculography was carried out after injection of 20 mCi 99mtechnetium-labeled red blood cells. Time-activity curves were obtained from the left and right ventricular regions. The ratio (A) of end-diastolic-end-systolic count-rate differences for the left and right ventricles was calculated. The ratio (A) was compared with a hemodynamic ratio (Ah) determined after the method of Sandler and Dodge (1963) with the stroke volume of the left ventricle measured angiographically, and the stroke volume of the right ventricle measured by thermodilution. In 33 patients with aortic and mitral valve regurgitation we found a correlation of r = 0.75 between (A) and Ah). Due to a broad range of normal values of (A) the sensitivity of the scintigraphic method is low. The specificity seems to be high, however, since in 64 patients with all types of heart diseases there were no false positive results. Comparing the described scintigraphic method with other modern or generally accepted methods, the principal advantages are noninvasiveness, good practicability, and the fact that important additional information about the functional state of the heart is gained. This is important in follow-up studies in patients with chronic valvular incompetence. It seems that this method will become a valuable supplement to heart catheterization in the diagnosis of valvular heart disease and may partially replace invasive methods for measuring the regurgitation fraction.