Strain Imaging Detects Dose-Dependent Segmental Cardiac Dysfunction in the Acute Phase After Breast Irradiation.

PURPOSE: We examined the utility of echocardiographic 2-dimensional speckle tracking strain imaging (SI) for the evaluation of segmental myocardial dysfunction before and after radiation therapy (RT) and the relationship to dose exposure. METHODS AND MATERIALS: We prospectively recruited 40 women with left-sided breast cancer, undergoing only adjuvant RT to the left chest. Comparisons of traditional echocardiographic parameters and SI parameters at baseline and 6 weeks after RT were analyzed. Regional strain and strain rate (SR) parameters were obtained from all 18 left ventricular segments. The correlation of change in strain parameters with segmental radiation dose was examined. RESULTS: We observed a significant reduction in global and segmental systolic strain parameters at 6 weeks after RT compared with baseline, with the largest decrement in the apical segments; this corresponded with the segments receiving the highest radiation dose exposure (apical peak systolic strain of -21.21% ± 3.49% before RT vs -18.69% ± 3.34% after RT, percentage change of 11.88%, P=.002; apical peak systolic SR of -1.17 ± 0.24 s-1 before RT vs -1.04 ± 0.19 s-1 after RT, percentage change of 11.11%, P=.008). There was a modest correlation between the apical segment systolic strain reduction and radiation dose exposure (apical segment Δ change and apical radiation dose, r=0.345, P=.031; apical segment percentage change and apical radiation dose, r=0.346, P=.031). A significant reduction in early diastolic SR was observed in the apical segments after treatment compared with baseline (apical early diastolic SR, 1.54 ± 0.45 s-1 before RT vs 1.35 ± 0.33 after RT s-1; percentage change, 12.34%; P=.034). CONCLUSIONS: Two-dimensional SI detected dose-related regional myocardial dysfunction in the acute phase after RT in chemotherapy-naive left-sided breast cancer patients. Although the long-term effects remain unknown, this imaging modality may have a potential role in the evaluation of irradiation-related cardiotoxicity.

Design of an ultrasonic physiotherapy system with pulse wave feedback control.

BACKGROUND: Due to different physical and biological mechanisms behind ultrasound hyperthermia and phonophoresis, the requirement for ultrasound power, frequency and control modes varies. OBJECTIVE: This paper introduces an adaptive ultrasonic physiotherapy system based on real-time surveillance over physiological characteristics of the patients, which in turn assists the individual treatment and dose limitation in auxiliary rehabilitation. METHODS: The method essentially takes advantage of distinctive characteristics of two different phases (systole and diastole) of the human cardiac cycle as a medium for modulation. The abundance of blood flow during systole enables energy exchange for hyperthermia while blood flow insufficiency caused by diastole assists in drug penetration. Said method could improve the adjuvant therapy as it provides partial drug penetration and therapeutic dosage control. RESULTS: By adjusting time window and intensity of multi-frequency ultrasound, it is possible to reduce the irradiation dosage to around 22% of that during continuous irradiation at 1 MHz. The method shows high potential in clinical practice. CONCLUSION: Frequency-tuning ultrasound therapy would be more efficient regarding drug penetration and improve the therapeutic efficacy of hyperthermia.

Long-term Risk of Heart Failure and Myocardial Dysfunction After Thoracic Radiotherapy: A Systematic Review.

BACKGROUND: Chest irradiation is a commonly used treatment for malignancy, with demonstrated symptomatic and survival benefit. The frequency and presentation of cardiovascular complications of radiotherapy remains unclear. METHODS: We performed a systematic review to evaluate the prevalence and manifestations of myocardial dysfunction (asymptomatic and symptomatic) in long-term cancer survivors treated with radiotherapy. RESULTS: Thoracic radiotherapy is associated with increased risk of heart failure in long-term follow-up, with hazard ratios ranging from 2.7 to 7.4 for Hodgkin lymphoma, and 1.5-2.4 for breast cancer. Although ejection fraction is often normal, systolic dysfunction has been more widely reported with modern techniques including 2-dimensional speckle strain and cardiac magnetic resonance. This might have implications for the selection of patients for cardioprotection. Despite common emphasis, diastolic functional abnormalities were infrequent in the long term. A limited amount of data suggest that right ventricular dysfunction is important in this population. CONCLUSIONS: The reports were heterogeneous, used different treatments, end points, and definitions of myocardial dysfunction, and most studies on the cardiac consequences of radiotherapy involved small numbers of patients and were published decades ago, making it difficult to formulate definitive conclusions for the current era.

Nueva causa de arrastre presistólico: extrasistolia-PR largo / New cause of presystolic drag: long PR extrasystoles

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Subclinical cardiac dysfunction detected by strain imaging during breast irradiation with persistent changes 6 weeks after treatment.

PURPOSE: To evaluate 2-dimensional strain imaging (SI) for the detection of subclinical myocardial dysfunction during and after radiation therapy (RT). METHODS AND MATERIALS: Forty women with left-sided breast cancer, undergoing only adjuvant RT to the left chest, were prospectively recruited. Standard echocardiography and SI were performed at baseline, during RT, and 6 weeks after RT. Strain (S) and strain rate (Sr) parameters were measured in the longitudinal, circumferential, and radial planes. Correlation of change in global longitudinal strain (GLS % and Δ change) and the volume of heart receiving 30 Gy (V30) and mean heart dose (MHD) were examined. RESULTS: Left ventricular ejection fraction was unchanged; however, longitudinal systolic S and Sr and radial S were significantly reduced during RT and remained reduced at 6 weeks after treatment [longitudinal S (%) -20.44 ± 2.66 baseline vs -18.60 ± 2.70* during RT vs -18.34 ± 2.86* at 6 weeks after RT; longitudinal Sr (s(-1)) -1.19 ± 0.21 vs -1.06 ± 0.18* vs -1.06 ± 0.16*; radial S (%) 56.66 ± 18.57 vs 46.93 ± 14.56* vs 49.22 ± 15.81*; *P<.05 vs baseline]. Diastolic Sr were only reduced 6 weeks after RT [longitudinal E Sr (s(-1)) 1.47 ± 0.32 vs 1.29 ± 0.27*; longitudinal A Sr (s(-1)) 1.19 ± 0.31 vs 1.03 ± 0.24*; *P<.05 vs baseline], whereas circumferential strain was preserved throughout. A modest correlation between S and Sr and V30 and MHD was observed (GLS Δ change and V30 ρ = 0.314, P=.05; GLS % change and V30 ρ = 0.288, P=.076; GLS Δ change and MHD ρ = 0.348, P=.03; GLS % change and MHD ρ = 0.346, P=.031). CONCLUSIONS: Subclinical myocardial dysfunction was detected by 2-dimensional SI during RT, with changes persisting 6 weeks after treatment, though long-term effects remain unknown. Additionally, a modest correlation between strain reduction and radiation dose was observed.

Pudendal nerve and internal pudendal artery damage may contribute to radiation-induced erectile dysfunction.

PURPOSE/OBJECTIVES: Erectile dysfunction is common after radiation therapy for prostate cancer; yet, the etiopathology of radiation-induced erectile dysfunction (RI-ED) remains poorly understood. A novel animal model was developed to study RI-ED, wherein stereotactic body radiation therapy (SBRT) was used to irradiate the prostate, neurovascular bundles (NVB), and penile bulb (PB) of dogs. The purpose was to describe vascular and neurogenic injuries after the irradiation of only the NVB or the PB, and after irradiation of all 3 sites (prostate, NVB, and PB) with varying doses of radiation. METHODS AND MATERIALS: Dogs were treated with 50, 40, or 30 Gy to the prostate, NVB, and PB, or 50 Gy to either the NVB or the PB, by 5-fraction SBRT. Electrophysiologic studies of the pudendal nerve and bulbospongiosus muscles and ultrasound studies of pelvic perfusion were performed before and after SBRT. The results of these bioassays were correlated with histopathologic changes. RESULTS: SBRT caused slowing of the systolic rise time, which corresponded to decreased arterial patency. Alterations in the response of the internal pudendal artery to vasoactive drugs were observed, wherein SBRT caused a paradoxical response to papaverine, slowing the systolic rise time after 40 and 50 Gy; these changes appeared to have some dose dependency. The neurofilament content of penile nerves was also decreased at high doses and was more profound when the PB was irradiated than when the NVB was irradiated. These findings are coincident with slowing of motor nerve conduction velocities in the pudendal nerve after SBRT. CONCLUSIONS: This is the first report in which prostatic irradiation was shown to cause morphologic arterial damage that was coincident with altered internal pudendal arterial tone, and in which decreased motor function in the pudendal nerve was attributed to axonal degeneration and loss. Further investigation of the role played by damage to these structures in RI-ED is warranted.

p53 functions in endothelial cells to prevent radiation-induced myocardial injury in mice.

Radiation therapy, which is used for the treatment of some cancers, can cause delayed heart damage. In the heart, p53 influences myocardial injury that occurs after multiple types of stress. Here, we demonstrated that p53 functioned in endothelial cells to protect mice from myocardial injury after whole-heart irradiation. Mice with an endothelial cell-specific deletion of p53 succumbed to heart failure after whole-heart irradiation as a result of myocardial necrosis, systolic dysfunction, and cardiac hypertrophy. Moreover, the onset of cardiac dysfunction was preceded by alterations in myocardial vascular permeability and density, which resulted in cardiac ischemia and myocardial hypoxia. Mechanistic studies with primary cardiac endothelial cells irradiated in vitro indicated that p53 signaling caused mitotic arrest and protected cardiac endothelial cells from cell death resulting from abnormal mitosis or mitotic catastrophe. Furthermore, mice lacking the cyclin-dependent kinase inhibitor p21, which is a transcriptional target of p53, were also sensitized to myocardial injury after whole-heart irradiation. Together, our results demonstrate that the p53-p21 axis functions to prevent radiation-induced myocardial injury in mice.

The effect of radiotherapy on cardiac function.

BACKGROUND: Radiation-induced heart disease is a complication that may be encountered after radiotherapy (RT) of tumors in the vicinity of the heart. In this study, we aimed to evaluate the effect of RT on the heart, by comparing conventional and tissue Doppler echocardiography parameters obtained before and after RT. METHODS: Forty patients who had undergone RT for either lung or left breast cancer were included in the study. ECG, conventional, and tissue Doppler echocardiography were performed before and 4-6 weeks after RT. RESULTS: The mean value of the radiation dose applied to all regions of the heart was calculated as 13.1±2.2 Gy (maximum 41.7 Gy). The value for the left ventricle was 10.2±2.0 Gy (maximum 43.6 Gy). A decrease in early transmitral diastolic velocity (E), E/A ratio, EF, Em, and Em/Am, and an increase in E-wave deceleration time, isovolumic relaxation time, isovolumic contraction time, ejection time, and QTc were found after RT. CONCLUSION: We found detrimental effects of RT on systolic and diastolic cardiac functions and the electrical conduction system of the heart. Maximal prevention should be provided for the patients during RT.

Subclinical late cardiac toxicity in childhood cancer survivors: impact on self-reported health.

BACKGROUND: The authors analyzed how self-reported health and self-reported modified New York Heart Association (NYHA) cardiac function scores were related to cardiac systolic function, cardiac risk factors, and cancer treatment history in childhood cancer survivors who reported no symptoms of cardiac disease. METHODS: Long-term survivors of pediatric cancer who were treated between 1971 and 1995 (current ages, 16-39.7 years) underwent noninvasive clinical and laboratory cardiac risk evaluation and responded to selected subscales of the Medical Outcomes Study 36-item Short Form Health Survey. Results were compared with survivor history of anthracycline therapy alone or with radiotherapy (n=127 patients; mean, 10 years after diagnosis) versus no anthracycline therapy (n=32 patients; mean, 11 years after diagnosis). RESULTS: Sex, current age, highest school grade completed, race, age at diagnosis, diagnostic group, years off therapy, fractional shortening (FS), heart rate, and smoking status were found to be independently predictive of self-reported health. Interaction between female sex and higher low-density lipoprotein values and between diagnosis and abnormal FS variably predicted low reported vitality and low reported modified New York Heart Association (NYHA) scores. Echocardiographic findings, cardiac risk factors, and treatment history explained 13% to 28% of the variance in perceived health and self-reported modified NYHA scores. CONCLUSIONS: Systolic function and cardiac risk factors were linked to lower self-reported health and NYHA scores even in the absence of clinically evident cardiotoxicity.

¿Cuál es el momento idóneo para la medición por ultrasonidos de la dilatación braquial mediada por flujo? / What is the ideal moment for ultrasound measurement of brachial artery flow-mediated dilation?

Introducción y objetivo. Las guías técnicas de medición de la dilatación braquial mediada por flujo (DBMF) recomiendan su medida en diástole para evitar la influencia de la distensibilidad (complianza) arterial en los resultados. Sin embargo, no existen estudios que corroboren esta hipótesis, por lo que éste es el objetivo primordial de nuestro trabajo. Sujetos y métodos. Se reclutaron dos grupos de sujetos con estos criterios: grupo I, sujetos sanos con índice tobillo/brazo (ITB) > 0,9 y menores de 30 años, y grupo II, pacientes con arteriopatía periférica sintomática definida por un ITB < 0,9. Se les realizó la medición de la dilatación de la arteria braquial mediada por flujo (DBMF) en el brazo derecho en sístole (S) y diástole (D). Se midió en el mismo acto el ITB y se recogieron los factores de riesgo y los tratamientos. Además, se determinó la dilatación mediada por flujo en ambas arterias femorales (DFMF). Resultados. Se reclutaron 36 y 33 sujetos de los grupos I y II, respectivamente. Se compararon los valores de dilatación en S y D y se representaron como grupo: S / D (valor p). DBMF: I + II: 8,1 ± 4,6% / 7,6 ± 4,9% (p = 0,3); I: 10,8 ± 2,9% / 9,9 ± 3,8% (p = 0,055); II: 5,2 ± 4,3% / 5,16 ± 4,8% (p = 0,3). DFMF: I + II: 3,13 ± 3,6% / 2,8 ± 3,6% (p = 0,35); I: 5,3 ± 2,9% / 4,8 ± 2,6% (p = 0,02); II: 0,6 ± 2,5% / 0,6 ± 3,4% (p = 0,9). Conclusiones. Si se asume la influencia de la complianza en la dilatación arterial, se observa que la dilatación mediada por flujo en sístole es superior a la diastólica en los sujetos sanos, mientras que en los enfermos esta diferencia es prácticamente inexistente. Aunque la diferencia en la arteria braquial de sujetos sanos no llega a la significación (p = 0,055), sí que lo hace en la femoral (p = 0,02), por lo que, al valorar los datos en conjunto, recomendamos utilizar la medición en diástole para evitar sesgos a la hora de realizar comparaciones entre sanos y enfermos

Introduction and aims. The technical guides to measuring the brachial artery flow-mediated dilation (BFMD) recommend that it should be measured in the diastolic phase in order to prevent results from being influenced by arterial distensibility (compliance). No studies have been conducted, however, to confirm this hypothesis and this is therefore the main purpose of our research. Subjects and methods. Two groups of subjects were recruited on the basis of the following criteria: group I, healthy subjects with an ankle-brachial index (ABI) > 0.9 and below 30 years of age, and group II, composed of patients with symptomatic peripheral arterial disease that was defined by an ABI < 0.9. Brachial artery flow-mediated dilation was measured in the right arm in both the systolic (S) and diastolic (D) phases. The ABI was measured at the same time and the risk factors and treatments were collected. Flow-mediated dilation was also determined in both femoral arteries (FFMD). Results. Groups I and II consisted of 36 and 33 subjects respectively. The dilation values in the S and D phases were compared and represented as a group: S / D (value p). BFMD: I + II: 8.1 ± 4.6% / 7.6 ± 4.9% (p = 0.3); I: 10.8 ± 2.9% / 9.9 ± 3.8% (p = 0.055); II: 5.2 ± 4.3% / 5.16 ± 4.8% (p = 0.3). FFMD: I + II: 3.13 ± 3.6% / 2.8 ± 3.6% (p = 0.35); I: 5.3 ± 2.9% / 4.8 ± 2.6% (p = 0.02); II: 0.6 ± 2.5% / 0.6 ± 3.4% (p = 0.9). Conclusions. If it is assumed that compliance influences arterial dilation, systolic flow-mediated dilation is seen to be higher than in the diastolic phase in healthy subjects, whereas this difference is practically inexistent in patients. Although the difference in the brachial artery of healthy subjects does not reach significance (p = 0.055), it does in the femoral artery (p = 0.02). Therefore, on appraising the data as a whole, we recommend measurement in the diastolic phase in order to avoid the occurrence of biases when comparing between healthy and sick subject

[Effects of gamma-irradiation on the cardiovascular system of sheep]. / Vliianie vozdeistviia gamma-oblucheniia na serdechno-sosudistuiu sistemu ovets.

In experiments with sheep, the response of the vascular system of the mammals to the total exposure dose was studied. A dose increase resulted in a more pronounced impairment of contraction of the cardiac muscle. In response, a compensatory reaction of the peripheral vessels was intensified up to LD50/30. Higher doses led to a complete disorder in the regulatory apparatus of the circulatory system.

Influence of a radiofrequency electromagnetic field on cardiovascular and hormonal parameters of the autonomic nervous system in healthy individuals.

The potential health risks of radiofrequency electromagnetic fields (EMFs) emitted by mobile phones are of considerable public interest. The present study investigated the hypothesis, based on the results of our previous study, that exposure to EMFs can increase sympathetic vasoconstrictor activity. Forty healthy young males and females underwent a single-blind, placebo-controlled protocol once on each of two different days. Each investigation included successive periods of placebo and EMF exposure, given in a randomized order. The exposure was implemented by a GSM-like signal (900 MHz, pulsed with 217 Hz, 2 W) using a mobile phone mounted on the right-hand side of the head in a typical telephoning position. Each period of placebo exposure and of EMF exposure consisted of 20 min of supine rest, 10 min of 70 degrees upright tilt on a tilt table, and another 20 min of supine rest. Blood pressure, heart rate and cutaneous capillary perfusion were measured continuously. In addition, serum levels of norepinephrine, epinephrine, cortisol and endothelin were analyzed in venous blood samples taken every 10 min. Similar to the previous study, systolic and diastolic blood pressure each showed slow, continuous, statistically significant increases of about 5 mmHg during the course of the protocol. All other parameters either decreased in parallel or remained constant. However, analysis of variance showed that the changes in blood pressure and in all other parameters were independent of the EMF exposure. These findings do not support the assumption of a nonthermal influence of EMFs emitted by mobile phones on the cardiovascular autonomic nervous system in healthy humans.

Right heart catheterization in rats with pulmonary hypertension and right ventricular hypertrophy.

Using a special Millar ultraminiature catheter pressure transducer, right ventricular functional parameters were measured in anesthetized, closed-chest rats under control conditions, during acute pulmonary hypertension and after induction of right ventricular hypertrophy. Acute i.v. infusion of noradrenaline and a brief period of hypoxia in female Sprague-Dawley rats elicited a marked increase in right ventricular systolic pressure (RVSP) and in the maximal rate of rise in right ventricular pressure (RV dp/dtmax). After 3 and 16 days of daily administrations of triiodothyronine in female Sprague-Dawley rats, all right ventricular hemodynamic parameters were enhanced along with the increase in left ventricular function. The right and left ventricles were hypertrophied, and cardiac output was increased. After 40 and 45 days subsequent to bilateral thorax irradiation of male Brown-Norway rats, RVSP and RV dp/dtmax were increased, the right ventricle was hypertrophied, while the left ventricle did not exhibit appreciable hemodynamic or morphologic alterations. Cardiac output was depressed. Thus, these two experimental models differ considerably as to the mechanism and time course of the development of right ventricular hypertrophy as well as to the participation of the left ventricle and the involvement of volume overload.