Low Frequency Electromagnetic Field Conditioning Protects against I/R Injury and Contractile Dysfunction in the Isolated Rat Heart.

Low frequency electromagnetic field (LF-EMF) decreases the formation of reactive oxygen species, which are key mediators of ischemia/reperfusion (I/R) injury. Therefore, we hypothesized that the LF-EMF protects contractility of hearts subjected to I/R injury. Isolated rat hearts were subjected to 20 min of global no-flow ischemia, followed by 30 min reperfusion, in the presence or absence of LF-EMF. Coronary flow, heart rate, left ventricular developed pressure (LVDP), and rate pressure product (RPP) were determined for evaluation of heart mechanical function. The activity of cardiac matrix metalloproteinase-2 (MMP-2) and the contents of coronary effluent troponin I (TnI) and interleukin-6 (IL-6) were measured as markers of heart injury. LF-EMF prevented decreased RPP in I/R hearts, while having no effect on coronary flow. In addition, hearts subjected to I/R exhibited significantly increased LVDP when subjected to LF-EMF. Although TnI and IL-6 levels were increased in I/R hearts, their levels returned to baseline aerobic levels in I/R hearts subjected to LF-EMF. The reduced activity of MMP-2 in I/R hearts was reversed in hearts subjected to LF-EMF. The data presented here indicate that acute exposure to LF-EMF protects mechanical function of I/R hearts and reduces I/R injury.

Late inflammatory and thrombotic changes in irradiated hearts of C57BL/6 wild-type and atherosclerosis-prone ApoE-deficient mice.

BACKGROUND AND PURPOSE: Radiation-induced heart disease represents a late complication of thoracic radiotherapy. We investigated the inflammatory and thrombotic response after local heart irradiation in wild-type and atherosclerosis-prone mice. MATERIAL AND METHODS: Atherosclerosis-prone ApoE(-/-) and C57BL/6 wild-type mice were sacrificed 20, 40, and 60 weeks after irradiation with 0.2, 2, 8, or 16 Gy. The expression of CD31, vascular cell adhesion molecule-1 (VCAM-1), thrombomodulin (TM), and CD45 were quantified by immunofluorescence staining of heart tissue sections. RESULTS: Microvascular density decreased at 40 weeks after 16 Gy in C57BL/6 but not in ApoE(-/-) mice. CD31 expression declined in C57BL/6 mice at 40 weeks (8 Gy), but increased in ApoE(-/-) mice at 20 (2/8/16 Gy) and 60 weeks (16 Gy). Capillary area decreased in C57BL/6 at 40 weeks (8/16 Gy) but increased in ApoE(-/-) mice at 20 weeks (16 Gy). Endocardial VCAM-1 expression remained unchanged. TM-positive capillaries decreased at 40 weeks (8/16 Gy) in C57BL/6 and at 60 weeks (2/16 Gy) in ApoE(-/-) mice. Leukocyte infiltration transiently rose 40 weeks after 8 Gy (only ApoE(-/-)) and 16 Gy. After receiving a low irradiation dose of 0.2 Gy, no significant changes were observed in any of the mouse models. CONCLUSION: This study demonstrated that local heart irradiation affects microvascular structure and induces inflammatory/thrombotic responses in mice in a dose- and time-dependent manner. Thereby, significant prothrombotic changes were found in both strains, although they were progressive in ApoE(-/-) mice only. Proinflammatory responses, like the increase of adhesion molecules and leukocyte infiltration, were more pronounced and occurred at lower doses in ApoE(-/-) vs. C57BL/6 mice. These findings indicate that metabolic risk factors, such as decreased ApoE lipoproteins, may lead to an enhanced proinflammatory and prothrombotic late response in locally irradiated hearts.

No association between left-breast radiation therapy or breast arterial calcification and long-term cardiac events in patients with breast cancer.

BACKGROUND: Recent studies have suggested an association between radiation therapy (RT) of the left breast and increased incidence of coronary artery disease. However, the increased sparing afforded with modern RT may decrease long-term cardiac risk. The aims of our study were to evaluate the association between the RT and cardiac events in breast cancer patients who underwent contemporary RT and to examine whether breast arterial calcification (BAC) seen on mammogram predicts for cardiac events. METHODS AND MATERIALS: In our observational, descriptive pilot study, 2,439 patients with breast cancer between 1986 and 2007 and a minimum of 3 years since completing RT were asked to complete a questionnaire regarding cardiac events since RT completion. The preoperative and follow-up mammograms were coded for presence/absence of BAC by an experienced radiologist blinded to questionnaire results. Cardiac events were compared between patients who received left- and right-sided adjuvant radiation. RESULTS: At a mean follow-up of 7.5 years (range 3-24), 687 patients completed the questionnaire, with 602 eligible for analysis. Baseline characteristics (age, body mass index [BMI], surgery type, cardiovascular risk factors, and time since RT) were similar in patients who received left- versus right-sided RT. Hypertension before RT and during follow-up, baseline cardiovascular disease, age >50, BMI >30 kg/m², and subsequent development of diabetes were significantly associated with posttreatment cardiac events. BACs were associated with cardiac events reported before breast cancer diagnosis; however, no association was found between left-sided breast RT or BAC and subsequent cardiac events. CONCLUSION: In a large single-institutional observational study, no association was found between left-sided breast RT or BAC and subsequent cardiac events.

SPECT analysis of cardiac perfusion changes after whole-breast/chest wall radiation therapy with or without active breathing coordinator: results of a randomized phase 3 trial.

PURPOSE: Cardiac muscle perfusion, as determined by single-photon emission computed tomography (SPECT), decreases after breast and/or chest wall (BCW) irradiation. The active breathing coordinator (ABC) enables radiation delivery when the BCW is farther from the heart, thereby decreasing cardiac exposure. We hypothesized that ABC would prevent radiation-induced cardiac toxicity and conducted a randomized controlled trial evaluating myocardial perfusion changes after radiation for left-sided breast cancer with or without ABC. METHODS AND MATERIALS: Stages I to III left breast cancer patients requiring adjuvant radiation therapy (XRT) were randomized to ABC or No-ABC. Myocardial perfusion was evaluated by SPECT scans (before and 6 months after BCW radiation) using 2 methods: (1) fully automated quantitative polar mapping; and (2) semiquantitative visual assessment. The left ventricle was divided into 20 segments for the polar map and 17 segments for the visual method. Segments were grouped by anatomical rings (apical, mid, basal) or by coronary artery distribution. For the visual method, 2 nuclear medicine physicians, blinded to treatment groups, scored each segment's perfusion. Scores were analyzed with nonparametric tests and linear regression. RESULTS: Between 2006 and 2010, 57 patients were enrolled and 43 were available for analysis. The cohorts were well matched. The apical and left anterior descending coronary artery segments had significant decreases in perfusion on SPECT scans in both ABC and No-ABC cohorts. In unadjusted and adjusted analyses, controlling for pretreatment perfusion score, age, and chemotherapy, ABC was not significantly associated with prevention of perfusion deficits. CONCLUSIONS: In this randomized controlled trial, ABC does not appear to prevent radiation-induced cardiac perfusion deficits.

Patterns of cardiac perfusion abnormalities after chemoradiotherapy in patients with lung cancer.

OBJECTIVE: We evaluated the prevalence of myocardial perfusion defects using myocardial perfusion imaging (MPI) after chemoradiation or radiation therapy (CRT/RT) in lung cancer patients and described their patterns in relation to tumor location. METHODS: MPI in 44 patients who received RT for lung cancer and 44 control patients were compared. The two groups were comparable in risk factors for coronary artery disease. Data regarding tumor stage and location, interval between CRT/RT and MPI, and mean radiation dose to the heart was collected. The level of radiation delivered to the affected segments of the left ventricle versus the normal segments was compared using the isodose lines on the simulation computed tomography. RESULTS: Considering all tumor locations, 8 patients (18%) demonstrated MPI defects after CRT/RT versus 9 (20%) in the controls. However, 7 of 18 patients (39%) with centrally located tumors in the CRT/RT group versus only 1 of 15 patients (7%) in the control group demonstrated MPI defect (p= 0.04). The defects in the CRT/RT group were in the anterior and septal segments while the defects were in different segments in the controls. The median interval between end of RT and MPI was 12.3 months. The affected segments in the CRT/RT group received a mean radiation dose of 39.6 versus 11.4 Gy (p = 0.003) to the normal segments. CONCLUSIONS: CRT/RT to centrally located lung tumors tends to cause anterior/septal MPI defects. Abnormal MPI segments in the CRT/RT group have received significantly higher radiation than normal segments.

[Photon radiation-induced structural and functional changes in the myocardium of hypertensive SHR rats].

Male rats were irradiated by a Korobkov photon light-emitting diode matrix with a maximum irradiation at 612 nm every day 1 h per day for 13 days. After a course of irradiation, the rhythmoinotropic characteristics of the cardiac muscle significantly improved. Exposure to photon radiation initiated an active rearrangement in myocytes as shown by a morphological analysis. Considerable changes were found in the structure of sarcoplasmic reticulum (SR); the area of SR profiles increased more than twofold compared to control. This suggests a proportional increase in the ability of SR to absorb calcium, due to both an increase in its buffer capacity and possibly, an improved functioning of Ca2+ ATPase of the reticulum. Probably, the photon therapy leads to the normalization of calcium homeostasis in myocytes and improvement of the characteristics of the cardiac muscle contraction-relaxation cycle. Furthermore, changes in the proportions of the myocardium capillaries (increased by 75% compared to control; p < 0.001) and the area of mitochondrial profiles of myocytes (increased by 13%; p < 0.05) were observed, which lead to more active metabolic processes and a rise in energy potential in myocardial cells after photon radiation treatment.

The effect of continuous light exposure of rats on cardiac response to ischemia-reperfusion and NO-synthase activity.

Factors modulating cardiac susceptibility to ischemia-reperfusion (I/R) are permanently attracting the attention of experimental cardiology research. We investigated, whether continuous 24 h/day light exposure of rats can modify cardiac response to I/R, NO-synthase (NOS) activity and the level of oxidative load represented by conjugated dienes (CD) concentration. Two groups of male adult Wistar rats were studied: controls exposed to normal light/dark cycle (12 h/day light, 12 h/day dark) and rats exposed to continuous light for 4 weeks. Perfused isolated hearts (Langendorff technique) were exposed to 25 min global ischemia and subsequent 30 min reperfusion. The recovery of functional parameters (coronary flow, left ventricular developed pressure, contractility and relaxation index) during reperfusion as well as the incidence, severity and duration of arrhythmias during first 10 min of reperfusion were determined. The hearts from rats exposed to continuous light showed more rapid recovery of functional parameters but higher incidence, duration and severity of reperfusion arrhythmias compared to controls. In the left ventricle, the NOS activity was attenuated, but the CD concentration was not significantly changed. We conclude that the exposure of rats to continuous light modified cardiac response to I/R. This effect could be at least partially mediated by attenuated NO production.

The incidence and functional consequences of RT-associated cardiac perfusion defects.

PURPOSE: Radiation therapy (RT) for left-sided breast cancer has been associated with cardiac dysfunction. We herein assess the temporal nature and volume dependence of RT-induced left ventricular perfusion defects and whether these perfusion defects are related to changes in cardiac wall motion or alterations in ejection fraction. METHODS: From 1998 to 2001, 114 patients were enrolled onto an IRB-approved prospective clinical study to assess changes in regional and global cardiac function after RT for left-sided breast cancer. Patients were imaged 30 to 60 minutes after injection of technetium 99m sestamibi or tetrofosmin. Post-RT perfusion scans were compared with the pre-RT studies to assess for RT-induced perfusion defects as well as functional changes in wall motion and ejection fraction. Two-tailed Fisher's exact test and the Cochran-Armitage test for linear trends were used for statistical analysis. RESULTS: The incidence of new perfusion defects 6, 12, 18, and 24 months after RT was 27%, 29%, 38%, and 42%, respectively. New defects occurred in approximately 10% to 20% and 50% to 60% of patients with less than 5%, and greater than 5%, of their left ventricle included within the RT fields, respectively (p = 0.33 to 0.00008). The rates of wall motion abnormalities in patients with and without perfusion defects were 12% to 40% versus 0% to 9%, respectively; p values were 0.007 to 0.16, depending on the post-RT interval. CONCLUSIONS: Radiation therapy causes volume-dependent perfusion defects in approximately 40% of patients within 2 years of RT. These perfusion defects are associated with corresponding wall-motion abnormalities. Additional study is necessary to better define the long-term functional consequences of RT-induced perfusion defects.

Brachytherapy: potential therapy for refractory coronary spasm.

OBJECTIVES: We sought to demonstrate that brachytherapy reduces coronary spasm in refractory and highly symptomatic variant angina. BACKGROUND: In some patients with variant angina due to extensive vasoconstriction, intensive drug therapy fails to sufficiently relieve symptoms. METHODS: In 18 patients with frequent angina episodes despite triple anti-anginal therapy, coronary spasm was induced by intracoronary acetylcholine (ACh) infusion. Five patients had spasm in a second vessel. Intracoronary radiation (20 Gy) was applied to vasospastic segments using a beta-emitting ((32)P) wire source centered within a Galileo balloon. Parameters of vessel function before and after brachytherapy were investigated. RESULTS: Before brachytherapy, artery diameters decreased (p < 0.0001) from 2.8 +/- 0.4 mm to 1.0 +/- 0.4 mm for the first vessels and from 3.1 +/- 0.3 mm to 1.0 +/- 0.2 mm for the second vessels. After brachytherapy (143 +/- 106 and 80 +/- 52 days for first and second vessels, respectively), ACh-induced vasoconstriction was significantly reduced. The ACh-induced changes in artery diameter before and after brachytherapy were -1.5 +/- 0.5 mm and -0.5 +/- 0.3 mm (p < 0.0001) for the first vessels and -1.4 +/- 0.3 mm and -0.4 +/- 0.2 mm (p < 0.01) for the second vessels, respectively. In non-irradiated spastic vessels, ACh-induced vasoconstriction remained unchanged (e.g., -1.7 +/- 0.6 mm, -1.6 +/- 0.3 mm, and -1.5 +/- 0.5 mm for second vessels, at first investigation, first follow-up, and immediately before brachytherapy, respectively). Angina frequency decreased from 15.6 +/- 6.0 to 2.2 +/- 2.4 angina episodes/week (p < 0.001) in treated patients. CONCLUSIONS: Brachytherapy is a potential therapy in patients with highly symptomatic variant angina.

Evaluation of myocardial perfusion and left ventricular function six months after percutaneous transmyocardial laser revascularization: comparison of two Ho-YAG laser systems with the same wavelength, but different energy delivery and navigation systems.

BACKGROUND AND OBJECTIVES: Myocardial perfusion and left ventricular function (LVF) were assessed after percutaneous transmyocardial laser revascularization (PTMR) in patients not amenable to conventional revascularization, with a comparison of two laser systems. STUDY DESIGN/MATERIALS AND METHODS: PTMR was performed with an Eclipse laser in 15 patients, and with a Biosense DMR in 10 patients. (201)Thallium scintigraphy, coronary angiography, and ventriculography were performed at baseline and at the 7.5+/-4.3-month follow-up. All patients in the Biosense DMR group and 10 in the Eclipse group underwent NOGA mapping before PTMR and after follow-up. RESULTS: The event-free survival rates were comparable, and the angina scores of all patients improved significantly, but more so in the Biosense DMR group than in the Eclipse group (1.2+/-1.1 vs. 2.3+/-0.9, P < 0.05). Both, the electrical activity assessed by NOGA mapping and the normalized (201)thallium uptake at redistribution improved significantly in the treated segments after Biosense DMR, while the global LVF decreased insignificantly in the Eclipse group. CONCLUSIONS: PTMR resulted in significant improvements in the clinical symptoms, but the electrical activity improved only in the Biosense DMR group, without transforming to a better LVF.

Symptomatic cardiac events following radiation therapy for left-sided breast cancer: possible association with radiation therapy-induced changes in regional perfusion.

Our group has demonstrated that tangential radiation therapy (RT) to the left breast or chest wall can cause perfusion changes in the anterior myocardium. We assess if RT-induced perfusion changes are associated with the development of symptoms consistent with cardiac dysfunction. Between 1998 and 2001, 114 patients were enrolled into an institutional review board-approved prospective study and had pre-RT and serial post-RT (range, 6-24 months) single photon emission computed tomography (SPECT) scans to assess changes in regional cardiac perfusion. Thirty-one patients were excluded. The incidence of cardiac symptoms in patients with and without RT-induced perfusion defects was compared using a 2-tailed Fisher's exact test. With a median follow-up of 16 months (range, 6-24 months), 10 of 83 evaluable patients had > or = 1 episode of transient chest pain, occurring 0-14 months after RT (median, 6 months). The rates of chest pain in the patients with and without new perfusion defects were 9 of 31 and 1 of 52, respectively (P = 0.0004). A similar result was found when patients were segregated based on the use of chemotherapy. Two of these 10 cases were diagnosed as pericarditis. No patient had myocardial infarction or congestive heart failure. Cardiac symptoms occur more frequently in patients with perfusion abnormalities by SPECT after RT than in patients with normal SPECT scans, suggesting that such perfusion defects may be clinically significant. One confounding factor is that women who know they have RT-induced perfusion defects may be more likely to report episode of chest pain. Long-term follow-up will be necessary to better assess the clinical significance of RT-induced perfusion defects.

Effects of amifostine on radiation-induced cardiac damage.

The purpose of this study was to investigate whether administration of amifostine prior to irradiation could reduce radiation damage of the rat heart. Female Spraque-Dawley rats were randomized to receive single-dose irradiation (0-22.5 Gy) locally to the heart. Fifteen to twenty minutes before radiation exposure, the animals received either intraperitoneally administered amifostine (160 mg/kg) or buffered saline solution. At 6 months post-irradiation, cardiac function was assessed by the in vitro working rat heart preparation. The severity of interstitial and/or perivascular fibrosis in different anatomical regions of the rat heart was assessed using a semi-quantitative scoring system. Radiation exposure to doses > or = 20 Gy markedly reduced coronary flow, aortic flow and cardiac output. Administration of amifostine prior to radiotherapy afforded protection against these effects and normal cardiac output was maintained, even after 22.5 Gy. A small, non-significant, reduction in histological damage (i.e. perivascular fibrosis and interstitial fibrosis) was also apparent in animals treated with amifostine. There was a clear protective effect of amifostine on the severity and extent of macroscopic damage in lung tissue included in the cardiac irradiation field. The findings of this study suggest that a single dose of amifostine administered prior to irradiation is effective in reducing cardiac damage.

Myocardial perfusion changes in patients irradiated for left-sided breast cancer and correlation with coronary artery distribution.

PURPOSE: To evaluate postradiation regional heart perfusion changes with single photon emission tomography (SPECT) myocardial perfusion imaging in 69 patients treated with tangential photon beams radiation therapy (RT) for left-sided breast cancer. To correlate SPECT changes with percent irradiated left ventricle (LV) volume and risk factors for coronary artery disease (CAD). METHODS AND MATERIALS: Rest SPECT of the LV was acquired pre-RT and at 6-month intervals post-RT. The extent of defects (%) with a severity > 1.5 standard deviations below the mean was quantitatively analyzed for the distributions of the left anterior descending (LAD) artery, left circumflex (LCX) artery, and right coronary artery (RCA) based on computer assisted polar map reconstruction (i.e., bull's-eye-view). Changes in perfusion were correlated with percent irradiated LV receiving > 25 Gy (range 0-32%). Data on patient- and treatment-related factors were collected prospectively (e.g., cardiac premorbidity, risk factors for CAD, chemotherapy, and hormonal treatment). RESULTS: In the LAD distribution, there were increased perfusion defects at 6 months (median 11%; interquartile range 2-23) compared with baseline (median 5%; interquartile range 1-14) (p < 0.001). There were no increases in perfusion defects in the LCX or RCA distributions. In multivariate analysis, the SPECT perfusion changes in the LAD distribution at 6 months were independently associated with percent irradiated LV (p < 0.001), hormonal therapy (p = 0.005), and pre-RT hypercholesterolemia (p = 0.006). The SPECT defects in the LAD distribution at 12 and 18 months were not statistically different from those at 6 months. The perfusion defects in the LAD distribution were limited essentially to the regions of irradiated myocardium. CONCLUSION: Tangential photon beam RT in patients with left-sided breast cancer was associated with short-term SPECT defects in the vascular distribution corresponding to the radiation portals. Factors related to the extent of perfusion defects included the percent irradiated LV, hormonal treatment, and pre-RT hypercholesterolemia.

Effect of in vivo heart irradiation on coronary reactivity in the rat.

The frequent exposure of the heart to radiation during thoracic tumor radiotherapy often results in chronic impairment of myocardial function. The aim of the present investigation was to evaluate the effect of irradiation on coronary vascular tone in rat hearts exposed in vivo to a single dose of 20 Gy gamma rays. The ability of rat hearts to respond to changes in coronary reactivity was analyzed 1, 15, 30 and 60 days following cardiac irradiation, using the Langendorff model, after perfusion of either L-nitro-arginine (LNA), an inhibitor of nitric oxide synthetase or SIN 1, a nitric oxide donor drug. LNA-induced vasoconstriction and SIN 1-induced vasodilation were lost respectively 15 days and 30 days after irradiation, and associated with smooth muscle cell alterations observed in microscopy, but without any changes in myocardial MDA levels. Thus, our results suggest that 1) endothelium may represent an early and specific radiation target, characterized by radiation-induced vascular tone dysfunctions, with no detectable microscopical changes; 2) alterations are progressive, resulting first from endothelial damage, followed by smooth muscle cell injuries. In conclusion, a local cardiac irradiation induced cellular dysfunction, characterized by a loss of coronary reactivity without changes of the lipid peroxidation index in the hearts.

[Effect of the He-Ne laser irradiation on resistance of the isolated heart to the ischemic and reperfusion injury]. / Vliianie izlucheniia He-Ne lazera na ustoichivost' izolirovannogo serdtsa k ishemicheskomu i reperfuzionnomu povrezhdeniiu.

The aim of this work was to investigate the myocardial protection against ischemia/reperfusion using low level laser irradiation (LLLI). It has been shown that pulse pressure was higher in the period of post-ischemic reperfusion as compared with the control group. It provided a better restoration of myocardial contractility as well as increasing of coronary flow in the reperfusion period. The amount of ventricular rhythm disorder episodes decreased. These effects of laser application were registered in conditions of coronary flow reduction less than 50%. One of the suggested mechanisms of laser effect is an ATP-sensitive channel activation.

Cardiac perfusion changes in patients treated for breast cancer with radiation therapy and doxorubicin: preliminary results.

PURPOSE: To determine the incidence and dose dependence of regional cardiac perfusion abnormalities in patients with left-sided breast cancer treated with radiation therapy (RT) with and without doxorubicin (Dox). METHODS: Twenty patients with left-sided breast cancer underwent cardiac perfusion imaging using single photon emission computed tomography (SPECT) prechemotherapy, pre-RT, and 6 months post-RT. SPECT perfusion images were registered onto 3-dimensional (3D) RT dose distributions. The volume of heart in the RT field was quantified, and the regional RT dose was calculated. A decrease in regional cardiac perfusion was assessed subjectively by visual inspection and objectively using image fusion software. Ten patients received Dox-based chemotherapy (total dose 120-300 mg/m(2)), and 10 patients had no chemotherapy. RT was delivered by tangent beams in all patients to a total dose of 46-50 Gy. RESULTS: Overall, 60% of the patients had new visible perfusion defects 6 months post-RT. A dose-dependent perfusion defect was seen at 6 months with minimal defect appreciated at 0-10 Gy, and a 20% decrease in regional perfusion at 41-50 Gy. One of 20 patients had a decrease in left ventricle ejection fraction (LVEF) of greater than 10% at 6 months; 2/20 patients had developed transient pericarditis. No instances of myocardial infarction or congestive heart failure (CHF) have occurred. CONCLUSIONS: RT causes cardiac perfusion defects 6 months post-RT in most patients. Long-term follow-up is needed to assess whether these perfusion changes are transient or permanent and to determine if these findings are associated with changes in overall cardiac function and clinical outcome.

Thallium-201 scintigraphy is not predictive of late cardiac complications in patients with Hodgkin's disease treated with mediastinal radiation.

PURPOSE: To assess whether abnormalities depicted by Thallium-201 scintigraphy can predict the occurrence of late cardiac complications in patients with Hodgkin's disease treated with mantle field radiation therapy. METHODS AND MATERIALS: Thallium scintigraphy was performed in 49 patients at a median of 75 months after initial treatment (range 28-208 months). Initial treatment consisted in chemotherapy, given to two-thirds of the patients and mantle field radiation, delivered to all patients, using a 25-MV linear accelerator. Myocardial perfusion defects were observed in 78% of patients on thallium scintigraphy. These patients had their cardiac status reassessed at a median follow-up of 13.5 years after treatment. RESULTS: Forty-two patients were assessable, as data on the cardiac status were missing in 7 patients. The majority of patients received at least 40 Gy, and 75% of them were treated with one field per day. The median follow-up of patients is 13.5 years (range 9-24.5). Eleven cardiac complications were observed in 9 patients (coronary artery disease [n = 2], conduction-system abnormalities [n = 3], valvular defects [n = 5], and congestive heart disease [n = 1]). The median 15-year actuarial incidence of cardiac complications was 21% (95% confidence interval of 9-40%). The positive and negative predictive value of thallium scintigraphy was 19% and 77%, respectively. The univariate analysis showed that the extent of left ventricle exposure to irradiation was an adverse prognostic factor, and chemotherapy administered before mantle field irradiation was of borderline significance. CONCLUSION: Thallium scintigraphy is not predictive of late cardiac complications. The extent of left ventricle exposure to radiation and possibly chemotherapy given before radiation treatment are adverse prognostic factors.