Prediction of response to cardiac resynchronization therapy using left ventricular pacing lead position and cardiovascular magnetic resonance derived wall motion patterns: a prospective cohort study

Background

Despite marked benefits in many heart failure patients, a considerable proportion of patients treated with cardiac resynchronization therapy (CRT) fail to respond appropriately. Recently, a “U-shaped” (type II) wall motion pattern identified by cardiovascular magnetic resonance (CMR) has been associated with improved CRT response compared to a homogenous (type I) wall motion pattern. There is also evidence that a left ventricular (LV) lead localized to the latest contracting LV site predicts superior response, compared to an LV lead localized remotely from the latest contracting LV site.

Methods

We prospectively evaluated patients undergoing CRT with pre-procedural CMR to determine the presence of type I and type II wall motion patterns and pre-procedural echocardiography to determine end systolic volume (ESV). We assessed the final LV lead position on post-procedural fluoroscopic images to determine whether the lead was positioned concordant to or remote from the latest contracting LV site. CRT response was defined as a ≥ 15 % reduction in ESV on a 6 month follow-up echocardiogram.

Results

The study included 33 patients meeting conventional indications for CRT with a mean New York Heart Association class of 2.8 ± 0.4 and mean LV ejection fraction of 28 ± 9 %. Overall, 55 % of patients were echocardiographic responders by ESV criteria. Patients with both a type II pattern and an LV lead concordant to the latest contracting site (T2CL) had a response rate of 92 %, compared to a response rate of 33 % for those without T2CL (p = 0.003). T2CL was the only independent predictor of response on multivariate analysis (odds ratio 18, 95 % confidence interval 1.6-206; p = 0.018). T2CL resulted in significant incremental improvement in prediction of echocardiographic response (increase in the area under the receiver operator curve from 0.69 to 0.84; p = 0.038).

Conclusions

The presence of a type II wall motion pattern on CMR and a concordant LV lead predicts superior CRT response. Improving patient selection by evaluating wall motion pattern and targeting LV lead placement may ultimately improve the response rate to CRT.     

Nondecussating retinal-fugal fiber syndrome: Clinical and neuroimaging clues to diagnosis

We report the clinical details and imaging findings for a case of nondecussating retinal-fugal fiber syndrome or isolated achiasma in a 4-year-old female child. Findings included the isolated absence of optic chiasm with unremarkable rest of the optic pathway and midline structures in a child presenting clinically with see-saw nystagmus. Clinically congenital see-saw nystagmus, “mirror reversal” of visual field representation and interocular ipsilateral asymmetry on monocular visual evoked potential point toward achiasma and warrant further evaluation with magnetic resonance imaging (MRI). Isolated achiasma is a rare condition that may remain undiagnosed unless MRI is done.     

Singlet oxygen mediated DNA damage induced phototoxicity by ketoprofen resulting in mitochondrial depolarization and lysosomal destabilization

Ketoprofen (KP) is a widely used nonsteroidal anti-inflammatory drug for the treatment of osteoarthritis and various rheumatic diseases. Currently, KP is applied topically on skin as gel to treat symptoms of pain and inflammation. We have studied the photomodification of KP under natural environmental conditions. KP generates reactive oxygen species (ROS) like ¹O₂ through Type-II photodynamic reaction. ¹O₂ mediated 2′-dGuO photodegradation, single and double strand breakage were significantly induced by photosensitized KP under sunlight/UV-R exposure. Significant intracellular ROS generation was measured through DCF-DA fluorescence. Linoleic acid photoperoxidation and role of ¹O₂ were substantiated by using specific quencher like sodium azide. KP induced cell cycle arrest in G2/M phase and cell death through MTT assay. We found apoptosis as the pattern of cell death which was confirmed through caspase-3 activation, cytochrome-c release from mitochondria, up-regulation of Bax protein and phosphatidylserine translocation. Our RT-PCR result strongly supports our view point of apoptotic cell death through up-regulation of p21 and pro-apoptotic Bax genes expression. Mitochondrial depolarization and lysosomal destabilization were also parallel to apoptotic process. Therefore, much attention should be paid to the topical application of KP and sunlight exposure in the light of skin related photosensitivity and cancers.     

Hairy Cell Leukemia Masquerading as Infective Endocarditis

Hairy cell leukemia is a chronic lymphoproliferative disorder affecting middle-aged adults, with the median age of 50–55 years. We report a case of hairy cell leukemia who presented with fever, splinter haemorrhages and moderate splenomegaly, simulating infective endocarditis. There was bicytopenia at presentation and hairy cells were seen in the peripheral blood.     

Lidocine Infiltration Test: An Useful Test in the Prediction of Results of Styloidectomy for Eagle’s Syndrome

Eagle’s syndrome is caused by elongated styloid process. Its accepted treatment is styloidectomy. However more than one-fourths of patients undergoing styloidectomy do not experience relief. To find the utility of the lidocaine infiltration test to predict the results of styloidectomy in patients clinically diagnosed as having stylalgia. Twenty-six patients undergoing styloidectomy for Eagle’s syndrome were included in the study. They were divided into two groups depending on their response to lidocaine infiltration in the tonsillar fossa. Patients were followed up till 3 months after styloidectomy and their pre operative visual analogue scale for pain was compared with the post operative VAS score. Majority of the patients were females and in the fifth decade of life. There were 18 patients in group I and eight patients in Group II. The groups were similar in terms of age and sex distribution and pre operative VAS score for pain. There was good corelation between post infiltration and post operative VAS scores. The test had 94.44 % sensitivity and 87.5 % specificity. The age and sex distribution and the failure rates in the present study were similar to that reported in other studies. There are many other reasons besides elongation which can cause the typical pain of stylalgia and some of them are not amenable to styloidectomy. The lidocaine infiltration test is an useful test to predict the results of styloidectomy for Eagle’s syndrome.     

Unusual presentation of head and neck neoplasm

We have a 67-year-old Caucasian male presenting with a (T4, N1b, M0) Stage III squamous cell carcinoma of the larynx. He subsequently underwent a total laryngectomy and right radical neck dissection. It was only determined by the pathology report that the cervical nodes in the neck specimen obtained the associated disease, Hodgkin's (mixed cellular lymphoma), rather than the expected well differentiated squamous cell carcinoma found in the larynx. Metastatic work-up was unrevealing. Reviewing the English literature fails to reveal a similar case report of squamous cell carcinoma of the larynx with Hodgkin's disease in the associated neck dissection. It was unfortunate that this patient died of a third pathology, cerebral hemorrhage, in the immediate post-op period.     

Expanding the Arsenal Against Huntington's Disease-Herbal Drugs and Their Nanoformulations

Huntington’s disease (HD) is an autosomal fatal genetic disease in which degeneration of neuronal cells occurs in the central nervous system (CNS). Commonly used therapeutics are cludemonoamine depletors, antipsychotics, antidepressants, and tranquilizers. However, these drugs cannot prevent the psychotic, cognitive, and behavioral dysfunctions associated with HD. In addition to this, their chronic use is limited by their long-term side effects. Herbal drugs offer a plausible alternative to this and have shown substantial therapeutic effects against HD. Moreover, their safety profile is better in terms of side effects. However, due to limited drug solubility and permeability to reach the target site, herbal drugs have not been able to reach the stage of clinical exploration. In recent years, the paradigm of research has been shifted towards the development of herbal drugs based nanoformulations that can enhance their bioavailability and blood-brain barrier permeability. The present review covers the pathophysiology of HD, available biomarkers, phytomedicines explored against HD, ongoing clinical trials on herbal drugs exclusively for treating HD and their nanocarriers, along with their potential neuroprotective effects.