Proton or photon radiosurgery for cardiac ablation of ventricular tachycardia? Breath and ECG gated robust optimization

PurposeVentricular tachycardia (VT) is a life-threatening heart disorder. The aim of this preliminary study is to assess the feasibility of stereotactic body radiation therapy (SBRT) photon and proton therapy (PT) plans for the treatment of VT, adopting robust optimization technique for both irradiation techniques.MethodsECG gated CT images (in breath hold) were acquired for one patient. Conventional planning target volume (PTV) and robust optimized plans (25GyE in single fraction) were simulated for both photon (IMRT, 5 and 9 beams) and proton (SFO, 2 beams) plans. Robust optimized plans were obtained both for protons and photons considering in the optimization setup errors (5 mm in the three orthogonal directions), range (±3.5%) and the clinical target volume (CTV) motion due to heartbeat and breath-hold variability.ResultsThe photon robust optimization method, compared to PTV-based plans, showed a reduction in the average dose to the heart by about 25%; robust optimization allowed also reducing the mean dose to the left lung from 3.4. to 2.8 Gy for 9-beams configuration and from 4.1 to 2.9 Gy for 5-beams configuration. Robust optimization with protons, allowed further reducing the OAR doses: average dose to the heart and to the left lung decreased from 7.3 Gy to 5.2 GyE and from 2.9 Gy to 2.2 GyE, respectively.ConclusionsOur study demonstrates the importance of the optimization technique adopted in the treatment planning system for VT treatment. It has been shown that robust optimization can significantly reduce the dose to healthy cardiac tissues and that PT further increases this gain.     

The effects of right ventricular apical pacing on left ventricular function. Stimulation of the right ventricular apex: should it still be the gold standard?

Current pacing practice is undergoing continuous and substantial changes. Initially pacing had an exclusively palliative role, since it was reserved for patients developing complete heart block or severe symptomatic bradycardia. With the appearance of novel pacing indications such as pacing for heart failure and atrial fibrillation, the effect of pacing site on cardiac function has become a critically important issue and a subject for consideration. It seems that the classical pacing site in the right ventricular apex is no longer the gold standard because of possible disadvantageous effects on cardiac function. The aim of this review article is to discuss the effect of right ventricular apical pacing on cardiac function including cellular and hemodynamic changes. We also aim to discuss the role of alternative pacing sites in the light of cardiac function.     

Premature ventricular contractions of the right ventricular outflow tract: is there an incipient underlying disease? New insights from a speckle tracking echocardiography study

ContextPremature ventricular contractions (PVCs) originating in the right ventricular outflow tract (RVOT) are traditionally considered idiopathic and benign. Echocardiographic conventional measurements are typically normal.AimsTo assess whether right ventricle longitudinal strain, determined by two-dimensional speckle tracking echocardiography, differ between RVOT PVCs patients (treated with catheter ablation) and healthy controls.MethodsWe retrospectively selected patients with PVCs from the RVOT who underwent electrophysiological study and catheter ablation between 2016 and 2019. Patients with documented structural heart disease were excluded. Transthoracic echocardiography was performed and right ventricle global longitudinal strain (RV-GLS), free wall longitudinal strain (RVFW-LS) and left ventricle global longitudinal strain (LV-GLS) were determined as well as conventional ultrasound measurements of RV and LV function.ResultsWe studied 21 patients with RVOT PVCs and 13 controls. Patients with PVCs from the RVOT had lower values of RV-GLS and RVFW-LS compared with the control group (?19.4% versus ?22.5%, P = 0.015 and ?22.1% versus ?25.5, P = 0.041, respectively). They also had lower values of LV-GLS, although still within the normal range (?19.1% versus ?20.9%, P = 0.047). Regarding RVOT PVCs patients only, RV-GLS and RVFW-LS had no correlation with the PVCs burden prior to catheter ablation and they did not differ between the patients in whom the catheter ablation was successful and those in whom it was not. RV-GLS also had a positive correlation with RVOT proximal diameter (r = 0.487, P = 0.025).ConclusionsIn this group of RVOT PVCs patients, we found worse RV longitudinal strain values (and therefore sub-clinical myocardial dysfunction) when compared to healthy controls.     

Incessant tachycardia in a patient with advanced heart failure and left ventricular assist device: What is the mechanism?

We present a case of incessant wide-complex tachycardia in a patient with left-ventricular assist device, and discuss the differential diagnosis with an in-depth analysis of the intracardiac tracings during the invasive electrophysiologic study, including interpretation of the relative timing of the fascicular signals during tachycardia and in sinus rhythm, and interpretation of pacing and entrainment maneuvers.     

Morgan's Canon: Is it still a useful rule of thumb?

For over 100 years, Morgan's Canon has served as the criterion for distinguishing what appears to be complex cognitive processes shown by animals from simpler associative learning processes (Pavlovian and instrumental conditioning). Morgan's ( 1894 ) canon states “In no case is an animal activity to be interpreted in terms of higher psychological processes if it can be fairly interpreted in terms of processes which stand lower in the scale of psychological evolution and development.” In the present article, several examples are provided in which complex human‐like processes are proposed to have been demonstrated but the judicious use of Morgan's Canon suggests that simpler mechanisms may be sufficient to account for the behavior. The use of Morgan's Canon is not meant to reduce behavior to its lowest common denominator but rather to challenge investigators to develop procedures that can distinguish between simple behavioral principles and the more complex processes that cannot be explained in terms of genetics or simple conditioning. Whatever the results of these experiments, they should help identify the underlying processes and mechanisms involved.     

Prevention of ischemic ventricular tachycardia of Purkinje origin: role for alpha(2)-adrenoceptors in Purkinje?

Recent studies have shown the presence of postjunctional alpha(2)-adrenergic receptors on canine Purkinje fibers but not muscle cells. Stimulation of these receptors results in prolongation of the action potential duration and the Purkinje relative refractory period. We studied the effect of alpha(2)-adrenergic agonists on inducible ischemic ventricular tachycardia (VT) of both Purkinje fiber and myocardial origin. Open-chest dogs in whom VT was induced with extrastimuli after occlusion of the anterior descending coronary artery were studied. A mapping system, incorporating Purkinje signals, characterized the mechanisms of VT. The alpha(2)-adrenergic agonists clonidine (0.5-4.0 microg/kg) or UK 14,304 (4-5 microg/kg) versus saline were given intravenously after reproducibility of inducible sustained monomorphic VT had been demonstrated. Eighteen dogs were given clonidine, eleven of which had focal Purkinje VT. Of these 11 dogs, clonidine blocked VT induction in 9 (81.9%) and rendered VT nonsustained in 1 (9.1%), and VT remained inducible in 1 dog (9.1%), although this was focal midmyocardial VT only. In the seven dogs with VT of myocardial origin, six (85.6%) remained inducible with clonidine, whereas one dog (14.4%) had only nonsustained VT after clonidine. Of the six dogs, UK 14,304 blocked VT induction in four (66.6%) and rendered VT nonsustained in one (16.7%), and VT remained inducible in one dog (16.7%). In four dogs with VT of myocardial origin, VT remained inducible. In the eight control dogs that were given saline, focal Purkinje VT was repeatedly inducible. Pharmacological stimulation of postjunctional alpha(2)-adrenoceptors on Purkinje fibers may selectively prevent induction of VT of Purkinje fiber origin in the ischemic canine ventricle.     

Successful ablation of biatrial tachycardia with preserved electrical activation of left atrial appendage by unidirectional connection via Bachmann’s bundle: A case report

A 57-year-old man underwent his seventh ablation session for atrial tachycardia (AT). His previous ablations involved several regions of the right atrium (RA) and left atrium (LA). The AT was characterized as biatrial tachycardia with a circuit involving the mitral annulus and septal RA. The AT was terminated by ablation through the insertion site of Bachmann’s bundle (BB) in both atria. After 3 months, the patient underwent his eighth ablation session because of AT recurrence. Activation maps showed that the connection from the RA to LA and vice versa was maintained via BB and the coronary sinus, respectively. The ablation target to interrupt the AT circuit was the mitral isthmus (MI), not BB, because BB supplied the electrical activation of the left atrial appendage (LAA) via a unidirectional electrical connection from the RA to LA. Ablation attempts from within the coronary sinus were performed to target the epicardial connection in the MI and led to complete blockage of the connection from the LA to RA. Otherwise, the connection from the RA to LA was preserved via BB. The patient was free of symptoms and anti-arrhythmic drugs at the 4-month follow-up. However, he had a high risk of electrical isolation of the LAA because extensive ablations had been performed; the strategy of targeting the MI contributed to the balance between preserving the electrical activation of the LAA and treating the biatrial tachycardia. Verification of the connective pathway between the two atria might be helpful to determine the optimal target.     

Neurological evaluation of chronic headache patients: Is laboratory testing always necessary?

A review of records was conducted to examine the utility of doing routine laboratory testing (EEG and skull X rays) versus testing at the discretion of the attending neurologist on patients presenting for the nonpharmacological treatment of chronic headache. A total of 278 patients underwent neurological evaluation as part of a routine assessment prior to beginning self-regulatory treatment for headache. The first 112 subjects received routine laboratory tests of EEG and skull X-ray films. The second set of 166 subjects received laboratory tests only when deemed necessary by the neurologist. The rate of abnormal EEG in chronic headache sufferers was no greater than that found in the normal population, and only one or two potentially serious abnormalities were found on any laboratory test. A higher rate of abnormality was found when the CT scan was used in conjunction with clinical judgment. The majority of clients with abnormal laboratory tests (most of which were mildly abnormal) still saw substantial headache reduction with self-regulatory treatment for chronic headache. The authors suggest that routine laboratory testing may not be necessary and should be left to the discretion of a qualified neurologist.This research was supported in part by grants from NINCDS, NS-15235 and NS-23440.     

The evolution of comparative cognition: Is the snark still a boojum?

In “The Snark is a Boojum”, Beach [Beach, F.A., 1950. The snark was a boojum. American Psychologist. 5, 115–124] famously asserted that animal psychology embraced too few species and too few problems to deserve the name comparative. Later in the 20th century, others [e.g. Kamil, A.C., 1988. A synthetic approach to the study of animal intelligence. In: Leger, D.W. (Ed.), Comparative Perspectives in Modern Psychology. Nebraska Symposium on Motivation, vol. 35. University of Nebraska Press, Lincoln, NE, pp. 230–257; Shettleworth, S.J., 1993. Where is the comparison in comparative cognition? Alternative research programs. Psychological Science. 4, 179–184] expressed similar concerns about the new subfield of comparative cognition, suggesting that a more biological approach to choice of species and problems was needed to balance a dominant anthropocentrism. The last 10–15 years have seen many new developments, and a recent survey like Beach’s reveals a very different picture. Not only are many more species being studied, contributions by researchers from different backgrounds are increasing, and research on comparative cognition is better connected with developmental psychology, behavioral neuroscience, primatology, behavioral ecology, and other fields. Contemporary research addresses three major aspects of cognition about equally: basic processes, physical cognition, and social cognition. This article describes a selected research program from each area, chosen to exemplify current trends and challenges for the field.     

Practice Research: Is the serological diagnosis of infectious mononucleosis always necessary?

Clinical and serological data from 100 patients who had a Downey lymphocytosis of ≥ 40% of all white cells were assessed over three years. All had clinical evidence of infectious mononucleosis, suggesting that Downey lymphocytosis of ≥ 40% is specific for the illness.     

PVCs with multiple exits and single site of origin in the outflow tract: What is the mechanism?

A 40 year old man with frequent PVCs with two different morphologies was referred for catheter ablation. Although initial mapping in the RVOT revealed fragmented potentials 20ms earlier than PVC2 onset with a good pace map score, ablation at this site was unsuccessful. Subsequent mapping in the LCC/NCC junction revealed that local ventricular activation preceded QRS onset by 30 and 28 ms for PVC1 and PVC2, respectively. Altering the pacing output at this site produced QRS morphologies similar to PVC1(low output,6mA) and PVC2(high output,15mA) with better pace map scores compared to RVOT. During high-output pacing, there was an increase in stim-QRS latency with decremental conduction. Ablation at this site was successful and suppressed both PVCs.     

Is there a correlation between ventricular fibrillation cycle length and electrophysiological and anatomic properties of the canine left ventricle?

We hypothesized that myocardial infarction-related alterations in ventricular fibrillation (VF) cycle length (VFCL) would correlate with changes in local cardiac electrophysiological and anatomic properties. An electrophysiological study was performed in normal, subacute, and chronic infarction mongrel dogs. VF was induced by programmed electrical stimulation and mean and minimum early and late VFCL was determined and correlated with local electrophysiological and anatomic properties. Effective refractory period (ERP), activation recovery time (ART), ERP/ART ratio, threshold, and ERP and ART dispersion were determined at 112 sites on the anterior left ventricle. Wave front progression was analyzed over a 2-s period. The extent of local tissue necrosis and of myocardial fiber disarray was also evaluated. The early mean VFCL was significantly longer in the subacute infarction (149 +/- 35 ms) and chronic infarction dogs (129 +/- 18 ms) compared with control dogs (102 +/- 15 ms; P < 0.0001 for both comparisons) as was the early minimum VFCL with similar trends seen during late VF. Complete epicardial reentrant circuits were significantly more common in normal dogs (4.3 +/- 2.4, 22.4% of cycles) than in subacute (0.75 +/- 0.96, 5.3% of cycles, P < 0.05 vs. normal) and chronic infarction dogs (1.3 +/- 1.3, 7.5% of cycles, P < 0.05 vs. normal). There was a poor correlation between the mean and minimum early and late VFCL and local electrophysiological and anatomic properties (R(2) < 0.2 for all comparisons) with a much better correlation between average mean and minimum VFCL (over the entire plaque) and global ERP and ART dispersion during early and late VF. In conclusion, VFCL in normal and infarcted myocardium shows a poor correlation with local ventricular electrophysiological and anatomic properties measured in sinus rhythm. However, there was a much better correlation between the average VFCL with global dispersion of repolarization. The lack of correlation between local VFCL and refractoriness and the infrequent occurrence of epicardial reentry suggests that intramural reentry may be the primary mechanism of VF in this model.     

Establishing bioequivalence of racemic venlafaxine formulations using stereoselective assay method: Is it necessary?

A bioequivalence study for venlafaxine generic formulation was conducted as an open label, balanced, randomized, two‐way crossover, single‐dose study. In this study, a comparison of various pharmacokinetic parameters of venlafaxine hydrochloride 150 mg modified release capsules of Ranbaxy and EFEXOR®‐XR 150 mg capsules of Wyeth, in healthy, adult, male, human subjects under fasting condition was performed to conclude bioequivalence. Venlafaxine and its major active metabolite O‐desmethylvenlafaxine (ODV) are racemates. The “(S)‐(+)” and “(R)‐(−)” enantiomers of venlafaxine and ODV are established as being active. Hence, subject samples were analyzed using nonstereoselective and stereoselective assay methods. Both (S)‐(+) and (R)‐(−) enantiomers of venlafaxine and ODV showed similar absorption and disposition. The 90% confidence intervals for venlafaxine, (R)‐(−)‐venlafaxine as well as (S)‐(+)‐venlafaxine were within acceptance range concluding bioequivalence. The results obtained by stereoselective assay were comparable to the nonstereoselective analysis, as sum of concentrations of (S)‐(+)‐ and (R)‐(−)‐enantiomers of venlafaxine and ODV. The mean (S)‐(+)/(R)‐(−) ratios of the enantiomers of venlafaxine and ODV at various time points were consistent in the study subjects. Therefore, the estimation of venlafaxine and ODV using nonstereoselective assay method is effective in distinguishing formulation differences (if any) in bioequivalence studies in a cost‐effective manner. Chirality, 2011. © 2011 Wiley‐Liss, Inc.     

Noninvasive assessment of left ventricular and myocardial contractility in middle-aged men and women: disparate evolution above the age of 50?

End-systolic elastance (E(es)) is a frequently used index of left ventricular (LV) contractility. However, because of its inherent dependence on LV geometry, E(es) cannot be used to compare myocardial contractile state between ventricles with different geometries, which is the case in any cross-sectional study. Various normalization methods for E(es) have been proposed in the literature, but a standardized method is still lacking. In this study, we introduced a novel alternative normalization technique and compared it with three previously suggested methods. We tested all normalization methods to assess the age- and sex-related differences in myocardial contractility in a large population sample of 2,184 middle-aged (ages, 35-55 yr) untreated subjects free from overt cardiovascular disease. Ventricular contractility E(es) was determined using a previously validated noninvasive single-beat method, based on two-dimensional echocardiographic and brachial blood pressure measurements. Myocardial contractility was estimated as 1) E(es).end-diastolic volume (EDV); 2) E(es).LV mass (LVM); 3) 0.433.E(es).LVM/relative wall thickness (RWT), based on a theoretical LV model; and 4) 0.0941.E(es).LVM(0.455).RWT(-0.159), a novel semiempirical expression derived in this study. Because of the difference in their underlying assumptions, the various myocardial contractility indexes do not provide consistent information with respect to sex differences. Despite these discrepancies, it was found that myocardial contractility in women appears to be better preserved after the age of 50 yr compared with that in men. The physiological mechanisms behind this potentially clinically important phenomenon at population level require further investigation.     

Measurements of left ventricular myocardial longitudinal systolic displacement using spectral and colour tissue Doppler: time for a reassessment?

Background

Echocardiographic measurements of left ventricular (LV) myocardial displacement may produce different results depending on the choice of employed modality and subjective adjustments during data acquisition and analysis.

Methods

In this study, left ventricular longitudinal systolic displacement was quantified in 57 patients (31 women and 26 men, 50 ± 16 years) using colour (colour TD) and spectral tissue Doppler (spectral TD) before and after temporal filtering (30 to 70 milliseconds in 20-millisecond steps) and changed offline gain saturation (0%, 50% and 100%), respectively. The results were compared with those obtained with anatomic M-mode.

Results

Whereas only minor differences occurred between the results of colour TD and anatomic M-mode measurements, spectral TD significantly overestimated the results obtained with both these methods. However, the limits of agreement between the results produced by all three studied methods were not clinically acceptable in any of the cases. The spectral TD displacement values increased along with increasing offline gain saturation whereas the effect of temporal filtering on colour Doppler measurements was insignificant.

Conclusion

Measurements of LV myocardial longitudinal displacement employing spectral TD, colour TD or anatomic M-mode produce different results, thus discouraging interchangeable use of these modalities. Whereas the results of spectral TD measurements can be significantly altered by changing offline gain setting, the effect of temporal filtering on colour TD measurements is insignificant, a fact that increases clinical practicality of the latter method.     

Climate change and perishable food hoards of an avian predator: Is the freezer still working?

Changing climate can modify predator–prey interactions and induce declines or local extinctions of species due to reductions in food availability. Species hoarding perishable food for overwinter survival, like predators, are predicted to be particularly susceptible to increasing temperatures. We analysed the influence of autumn and winter weather, and abundance of main prey (voles), on the food‐hoarding behaviour of a generalist predator, the Eurasian pygmy owl (Glaucidium passerinum), across 16 years in Finland. Fewer freeze–thaw events in early autumn delayed the initiation of food hoarding. Pygmy owls consumed more hoarded food with more frequent freeze–thaw events and deeper snow cover in autumn and in winter, and lower precipitation in winter. In autumn, the rotting of food hoards increased with precipitation. Hoards already present in early autumn were much more likely to rot than the ones initiated in late autumn. Rotten food hoards were used more in years of low food abundance than in years of high food abundance. Having rotten food hoards in autumn resulted in a lower future recapture probability of female owls. These results indicate that pygmy owls might be partly able to adapt to climate change by delaying food hoarding, but changes in the snow cover, precipitation and frequency of freeze–thaw events might impair their foraging and ultimately decrease local overwinter survival. Long‐term trends and future predictions, therefore, suggest that impacts of climate change on wintering food‐hoarding species could be substantial, because their ‘freezers’ may no longer work properly. Altered usability and poorer quality of hoarded food may further modify the foraging needs of food‐hoarding predators and thus their overall predation pressure on prey species. This raises concerns about the impacts of climate change on boreal food webs, in which ecological interactions have evolved under cold winter conditions.