Factors influencing lesion formation during radiofrequency catheter ablation

In radiofrequency (RF) ablation, the heating of cardiac tissue is mainly resistive. RF current heats cardiac tissue and in turn the catheter electrode is being heated. Consequently, the catheter tip temperature is always lower--or ideally equal--than the superficial tissue temperature. The lesion size is influenced by many parameters such as delivered RF power, electrode length, electrode orientation, blood flow and tissue contact. This review describes the influence of these different parameters on lesion formation and provides recommendations for different catheter types on selectable parameters such as target temperatures, power limits and RF durations.     

Reversal of ventricular premature beat induced cardiomyopathy by radiofrequency catheter ablation

Frequent monomorphic ventricular premature beats (VPBs) may lead to left ventricular dysfunction. We describe two patients with frequent monomorphic VPBs and dilated cardiomyopathy in whom left ventricular function normalised after elimination of the VPBs by radiofrequency catheter ablation. The recent literature on this topic is summarised and potential candidates for catheter ablation are discussed. (Neth Heart J 2010;18:493-8.)     

Determination of lesion size by ultrasound during radiofrequency catheter ablation.

The catheter tip temperature that is used to control the radiofrequency generator output poorly correlates to lesion size. We, therefore, evaluated lesions created in vitro using a B-mode ultrasound imaging device as a potential means to assess lesion generation during RF applications non-invasively. Porcine ventricular tissue was immersed in saline solution at 37 degrees C. The catheter was fixed in a holder and positioned in a parallel orientation to the tissue with an array transducer (7.5 MHz) app. 3 cm above the tissue. Lesions were produced either in a temperature controlled mode with a 4-mm tip catheter with different target temperatures (50, 60, 70 and 80 degrees C, 80 W maximum output) or in a power controlled mode (25, 50 and 75 W, 20 ml/min irrigation flow) using an irrigated tip catheter. Different contact forces (0.5 N, 1.0 N) were tested, and RF was delivered for 60 s. A total of 138 lesions was produced. Out of these, 128 could be identified on the ultrasound image. The lesion depth and volume was on average 4.1 +/- 1.6 mm and 52 +/- 53 mm3 as determined by ultrasound and 3.9 +/- 1.7 mm and 52 +/- 55 mm3 as measured thereafter, respectively. A linear correlation between the lesion size determined by ultrasound and that measured thereafter was demonstrated with a correlation coefficient of r = 0.87 for lesion depth and r = 0.93 for lesion volume. We conclude that lesions can be assessed by B-mode ultrasound imaging.     

抗血小板制剂对射频消融术前后vWF、血小板和凝血纤溶活性的影响

目的：探讨消融技术后血栓栓塞的机制和预防的方法,为临床提供血栓栓塞并发症的防治方法。方法：在我科行射频消融术的室上速患者158名,年龄15-61岁,其中右侧旁道12例,双径路62例,左侧旁道84例。随机分为五组,组Ⅰ（n=31）术前未服抗血小板制剂,术后立即服用阿斯匹林0.3g,1／日;组Ⅱ（n=32）术前3天始服用阿斯匹林0.3g,1／日;组Ⅲ（n=30）术前3天始服用氯吡格雷75mg1／日;组Ⅳ（n=32）术前3天服用阿斯匹林0．3g＋氯吡格雷75mg 1／日;组V（n=33）术前3天始服用阿斯匹林0.3g,1／日,术后皮下注射速避凝0．4ml 1／日。分别于入院后、电生理检查前即成功放置鞘管后、消融前即静推肝素前、消融后即刻、消融后24h采血。测定血浆血小板仪颗粒膜蛋白（GMP-140）水平、D-二聚体、血管性假血友病因子（vWF）。结果：①组IGMP-140水平自穿刺后即开始上升,射频消融术后24小时仍处于较高水平,血管穿刺后电生理检查前明显升高为30．41±5．67ng／ml（P〈0．05）,而射频消融术后升高为60．4±12．79ng／ml（P〈0．05）,但组Ⅱ、Ⅲ、Ⅳ、Ⅴ尤其是组IVGMP-140水平始终处于相对较低的水平（P〈0．05）。②组ID-二聚体水平自穿刺后即开始上升,射频消融术后24小时仍处于较高水平,血管穿刺后电生理检查前明显升高为0．58±0．22mg／L（P〈0．05）,而射频消融术后升高为1．50±0．56mg／L（P〈0．05）。组Ⅱ、Ⅲ、Ⅳ、Ⅴ尤其是组ⅣD-二聚体水平与组Ⅰ相比始终处于较低水平（P〈0．05）。③血浆vWF的水平：各组vWF水平自血管穿刺结束后即明显升高（P〈0．05）,射频消融术后组Ⅰ、Ⅲ升高明显,而组Ⅱ、Ⅳ、VvWF水平只有轻度升高（P〈0．05）,各组vWF水平在术后24小时仍维持相对较高的水平。④血浆GMP-140、D-二聚体、vWF在射频消融前后的改变与累及放电量、放电时间、放电次数、消融时间及肌钙蛋白Ⅰ等无关（P〈0．05）。结论：射频消融对内皮细胞有损伤作用,可导致GMP-140、D-二聚体的明显升高呈血栓前状态。不同的抗血小板制剂对其有改善作用。阿斯匹林可能降低血浆中vWF水平。     

Importance of physical parameters for the effectiveness of radiofrequency catheter ablation]

Radiofrequency catheter ablation has been shown to be an effective form of treatment of accessory pathways in patients with WPW-syndrome and other supraventricular tachycardias. However, the biophysical parameters so far used in vivo neither correlated with the size of the myocardial lesion nor did they provide any information about contact of the electrode with the myocardial wall. In this study, 104 radiofrequency energy applications were performed on excised pig myocardium in circulating heparinized pig blood, and in blood alone, and root mean square (rms) voltage, current and phase angle were measured using a specially developed device. The calculated effective power and output power differed by only 2-7% measured at the point of maximum current during coagulation. A progressive drop in current following a rise in impedance led to a phase shift of more than 80 degrees with a decrease in effective power to 17% of the output power. Hence, apparent output power was mainly ineffective power. The time-dependent variations of phase angle, impedance and current were found to be useful for distinguishing between the coagulated media. These results show that physical parameters measured during radio-frequency catheter ablation may help to monitor electrode position in the clinical situation and reduce the number of ineffective energy applications.     

Benchmark solution for the prediction of temperature distributions during radiofrequency ablation of cardiac tissue

Several studies on radiofrequency (RF) ablation are aimed at accurately predicting tissue temperature distributions by numerical solution of the bioheat equation. This paper describes the development of a solution that can serve as a benchmark for subsequent numerical solutions. The solution was obtained using integral transforms and evaluated using a C program. Temperature profiles were generated at various times and for different convection coefficients. In addition, a numerical model was developed using the same assumptions made in obtaining the benchmark solution. Comparison of surface and axial temperature profiles shows that the two solutions match very closely, cross validating the numerical methods used in evaluating both solutions.     

Thermal modeling of lesion growth with radiofrequency ablation devices

Background  

Temperature is a frequently used parameter to describe the predicted size of lesions computed by computational models. In many cases, however, temperature correlates poorly with lesion size. Although many studies have been conducted to characterize the relationship between time-temperature exposure of tissue heating to cell damage, to date these relationships have not been employed in a finite element model.     

In vitro assessment of a combined radiofrequency ablation and cryo-anchoring catheter for treatment of mitral valve prolapse

Percutaneous approaches to mitral valve repair are an attractive alternative to surgical repair or replacement. Radiofrequency ablation has the potential to approximate surgical leaflet resection by using resistive heating to reduce leaflet size, and cryogenic temperatures on a percutaneous catheter can potentially be used to reversibly adhere to moving mitral valve leaflets for reliable application of radiofrequency energy. We tested a combined cryo-anchoring and radiofrequency ablation catheter using excised porcine mitral valves placed in a left heart flow loop capable of reproducing physiologic pressure and flow waveforms. Transmitral flow and pressure were monitored during the cryo-anchoring procedure and compared to baseline flow conditions, and the extent of radiofrequency energy delivery to the mitral valve was assessed post-treatment. Long term durability of radiofrequency ablation treatment was assessed using statically treated leaflets placed in a stretch bioreactor for four weeks. Transmitral flow and pressure waveforms were largely unaltered during cryo-anchoring. Parameter fitting to mechanical data from leaflets treated with radiofrequency ablation and cryo-anchoring revealed significant mechanical differences from untreated leaflets, demonstrating successful ablation of mitral valves in a hemodynamic environment. Picrosirius red staining showed clear differences in morphology and collagen birefringence between treated and untreated leaflets. The durability study indicated that statically treated leaflets did not significantly change size or mechanics over four weeks. A cryo-anchoring and radiofrequency ablation catheter can adhere to and ablate mitral valve leaflets in a physiologic hemodynamic environment, providing a possible percutaneous alternative to surgical leaflet resection of mitral valve tissue.     

Platelet-derived growth factor blockade on cardiac remodeling following infarction

Cardiac repair and remodeling occur following myocardial infarction (MI). Our previous study demonstrated that platelet-derived growth factor (PDGF)-A/-D and PDGF receptors (PDGFR) are increased in the infarcted heart, with cells expressing PDGFR primarily endothelial and fibroblast-like cells. In the present study, we tested the hypothesis that PDGF contributes to cardiac angiogenesis and fibrogenesis post-MI. Rats with experimental MI were treated with either a PDGFR antagonist (Imatinib, 40 mg/kg/day) or vehicle by gavage, and sham-operated rats served as the controls. Cardiac fibrogenesis, angiogenesis, and ventricular function were detected at weeks 1 and 4 post-MI. We found that (1) transforming growth factor (TGF)-β1, tissue inhibitors of metalloproteinases (TIMP)-1/-2, and type I collagen mRNA were all significantly increased in the infarcted heart at week 1 post-MI, while PDGFR blockade significantly reduced these fibrogenic mediators in the noninfarcted myocardium as compared to controls; (2) fibrosis developed in both the infarcted and noninfarcted myocardium at week 4 with PDGFR blockade significantly suppressing collagen volume in the noninfarcted myocardium; (3) angiogenesis was activated in the infarcted myocardium, particularly at week 1, and was not altered by treatment with imatinib; and (4) ventricular dysfunction was evident in MI rats at week 4, and mildly improved with imatinib treatment. These observations indicated that PDGF can contribute to the development of cardiac interstitial fibrosis in the noninfarcted myocardium, but does not alter scar formation in the infarcted myocardium. Further, this study suggests the potential therapeutic effects of PDGFR blockade on interstitial fibrosis of the infarcted heart.     

Sex-related changes in cardiac function following myocardial infarction in mice

Recent awareness of cardiovascular diseases as a number one killer of the middle-aged women has prompted interest in sex differences leading to heart failure (HF). Therefore, we evaluated cardiac function in female and male mice following myocardial infarction (MI) using the Millar pressure-volume (P-V) conductance system in vivo, at time points corresponding to early (2 wk), late compensatory hypertrophy (4 wk), and decompensation (10 wk) to HF. A significant deterioration of the load dependent and independent hemodynamic measurements occurred in both female and male mice during the early phase of hypertrophy. Later, compensatory hypertrophy was marked by a normalization of volumes to control levels in females compared with males. The most notable differences between sexes occurred in the measurements of cardiac contractility during the decompensation to HF. In females, there was a significant improvement in contractility compared with males, which was apparent in the load-independent measurements of preload recruitable stroke work (10 wk post-MI, female=48.7+/-8.0 vs. male=25.2+/-1.8 mmHg, P<0.05) and maximum dP/dt vs. maximum end-diastolic volume (10 wk post-MI, female=359+/-58 vs. male=149+/-28 mmHg.s(-1).microl(-1), P<0.05). Despite these differences, there were no differences in the heart weight to body weight ratio and infarct size between the sexes. These data demonstrate that compensatory hypertrophy is associated with an improvement in contractility and a delayed decompensation to HF in females. However, compensatory hypertrophy in males appears to be undermined by a steady decline in contractility associated with decompensation to HF.     

Successful catheter ablation of persistent electrical storm late post myocardial infarction by targeting purkinje arborization triggers

Drug refractory ventricular tachycardia (VT) occurring as a storm after acute myocardial infarction has grave prognosis. We report a case of a middle-aged lady who presented with drug refractory VT that lead to persistent electrical storm two weeks after an anterior wall myocardial infarction. She underwent a successful catheter ablation of VT followed a few days later by implantation of an AICD. Catheter ablation of the VT could control the persistent electrical storm and the patient was free from a recurrence of VT at three month follow up.     

Assessment of cardiac function with the pressure-volume conductance system following myocardial infarction in mice

Myocardial infarction (MI) is a major cause of heart failure (HF) with the progressive worsening of cardiac performance due to structural and functional alterations. Therefore, we studied cardiac function in adult mice following MI using the Millar pressure-volume (P-V) conductance catheter system in vivo during the later phase of compensatory remodeling and decompensation to HF. We evaluated load-dependent and -independent parameters in control and 2-, 4-, 6-, and 10-wk post-MI mice and integrated changes in function with changes in gene expression. Our results indicated a significant deterioration of cardiac function in post-MI mice over time, reflected first by systolic dysfunction, followed by a transient improvement before further decline in both systolic and diastolic function. Associated with the function and adaptive remodeling were transient changes in fetal gene and extracellular matrix gene expression. However, undermining the compensatory remodeling response was a continual decline in cardiac contractility, which promoted the transition into failure. Our study provided a scheme of integrated cardiac function and gene expression changes occurring during the adaptive and maladaptive response of the heart independent of systemic vascular properties during the transition to HF following MI in mice. P-V loop analysis was used to quantitatively evaluate the gradual deterioration in cardiac function post-MI. P-V loop analysis was found to be an appropriate method for assessment of global cardiac function under varying load-dependent and -independent conditions in the murine model with many similarities to data obtained from larger animals and humans.     

Interleukin-2 enhances angiogenesis and preserves cardiac function following myocardial infarction

We previously demonstrated that injection of IL-2-activated natural killer (NK) cells contribute to vascular remodeling via a4b7 integrin and killer cell lectin-like receptor (KLRG) 1 and promote cardiac repair following myocardial infarction (MI). The aim of the present study is to test the hypothesis that injection of recombinant human interleukin (rhIL)-2 improves angiogenesis and preserves heart function after MI. A single IV injection of rhIL-2 two days following MI improved by 27.7% the left ventricular (LV) fractional shortening of immune competent (C57Bl6) mice, but had no effect on cardiac function of immune-deficient (NOD-SCID IL2Rγnull) mice. Immunohistochemical analysis of C57Bl6 cross sections of heart revealed that collagen deposition was reduced by 23.1% and that capillary density was enhanced in the scar area and the border zone of the infarct respectively by 22.4% and 33.6% following rhIL-2 injection. In addition, rhIL-2 enhanced 1.6-fold the in vivo endothelial cell proliferation index and 1.8-fold the number of NK cell infiltrating the infarcted heart, but had no effect on the number of cardiac CD4 and CD8 cells. In vitro, rhIL-2 activated NK cells enhanced cardiac endothelial cell proliferation by 17.2%. Here we show that a single IV injection of rhIL-2 positively impacted cardiac function by improving angiogenesis through a process involving NK cells.     

Paradoxical loss of excitation with high intensity pulses during electric field stimulation of single cardiac cells

Transmembrane potential responses of single cardiac cells stimulated at rest were studied with uniform rectangular field pulses having durations of 0.5-10 ms. Cells were enzymatically isolated from guinea pig ventricles, stained with voltage sensitive dye di-8-ANEPPS, and stimulated along their long axes. Fluorescence signals were recorded with spatial resolution of 17 microm for up to 11 sites along the cell. With 5 and 10 ms pulses, all cells (n = 10) fired an action potential over a broad range of field amplitudes (approximately 3-65 V/cm). With 0.5 and 1 ms pulses, all cells (n = 7) fired an action potential for field amplitudes ranging from the threshold value (approximately 4-8 V/cm) to 50-60 V/cm. However, when the field amplitude was further increased, five of seven cells failed to fire an action potential. We postulated that this paradoxical loss of excitation for higher amplitude field pulses is the result of nonuniform polarization of the cell membrane under conditions of electric field stimulation, and a counterbalancing interplay between sodium current and inwardly rectifying potassium current with increasing field strength. This hypothesis was verified using computer simulations of a field-stimulated guinea pig ventricular cell. In conclusion, we show that for stimulation with short-duration pulses, cells can be excited for fields ranging between a low amplitude excitation threshold and a high amplitude threshold above which the excitation is suppressed. These results can have implications for the mechanistic understanding of defibrillation outcome, especially in the setting of diseased myocardium.     

Treatment of pathologic spinal fractures with combined radiofrequency ablation and balloon kyphoplasty

Background

A current paradigm in the treatment of cervical cancer with radiation therapy is that intracavitary brachytherapy is an essential component of radical treatment. This is a matched retrospective comparison of the results of treatment in patients treated with external beam chemoradiation (EBRT-CT) and radical hysterectomy versus those treated with identical chemoradiation followed by brachytherapy.

Methods

In this non-randomized comparison EBRT-CT protocol was the same in both groups of 40 patients. In the standard treated patients, EBRT-CT was followed by one or two intracavitary Cesium (low-dose rate) applications within 2 weeks of finishing external radiation to reach a point A dose of at least 85 Gy. In the surgically treated patients, radical hysterectomy with bilateral pelvic lymph node dissection and para-aortic lymph node sampling were performed within 7 weeks after EBRT-CT. Response, toxicity and survival were evaluated.

Results

A total of 80 patients were analyzed. The patients receiving EBRT-CT and surgery were matched with the standard treated cases. There were no differences in the clinicopathological characteristics between groups or in the delivery of EBRT-CT. The pattern of acute and late toxicity differed. Standard treated patients had more chronic proctitis while the surgically treated had acute complications of surgery and hydronephrosis. At a maximum follow-up of 60 months, median follow-up 26 (2–31) and 22 (3–27) months for the surgery and standard therapy respectively, eight patients per group have recurred and died. The progression free and overall survival are the same in both groups.

Conclusion

The results of this study suggest that radical hysterectomy can be used after EBRT-CT without compromising survival in FIGO stage IB2-IIB cervical cancer patients in settings were brachytherapy is not available. A randomized study is needed to uncover the value of surgery after EBRT-CT.