Ventricular arrhythmias in Kearns-Sayre syndrome: A cohort study using the National Inpatient Sample database 2016-2019.

BACKGROUND: Degeneration of the cardiac conduction system resulting in complete heart block (CHB), ventricular arrhythmias (VA), and sudden cardiac death (SCD) is recognized in patients with Kearns-Sayre syndrome (KSS) and is potentially preventable with permanent pacemaker (PPM) implantation. However, other mechanisms for SCD have been proposed, and the efficacy of implanting a defibrillator instead of PPM remains to be investigated. METHODS: We utilized the National Inpatient Sample (NIS) database 2016-2019 to investigate the risk of VA or dysrhythmic cardiac arrest (dCA) in KSS patients. We compared the outcomes of KSS to myotonic dystrophy (MD), a more common genetic disorder with similar clinical cardiac features and course. RESULTS: We identified 640 admissions for KSS. VA or dCA were lower in admissions for KSS than MD patients (2.3% vs. 4.5%, p = .009). Device implantation differed between study groups. Approximately, 70% of cases with KSS and conduction abnormalities had pacemaker (± defibrillator) on hospital discharge, compared to 35% in MD. Conduction abnormalities were associated with higher rates of VA or dCA in both study groups. None of the admissions for KSS patients who developed VA or dCA had a pacemaker, and all of them had conduction abnormalities. One-third of admissions for MD patients who developed VA or dCA had a device already implanted prior to the event. CONCLUSION: Despite its effectiveness in preventing VA, PPM remains underutilized in patients with KSS or MD who have conduction abnormalities. PPM alone do not fully prevent VA in MD patients; therefore, addition of defibrillator capacity might be necessary.

Verification of a novel atrial fibrillation cryoablation dosing algorithm guided by time-to-pulmonary vein isolation: Results from the Cryo-DOSING Study (Cryoballoon-ablation DOSING Based on the Assessment of Time-to-Effect and Pulmonary Vein Isolation Guidance).

BACKGROUND: There are no recommendations on the optimal dosing for cryoablation of atrial fibrillation (Cryo-AF). OBJECTIVE: The purpose of this study was to develop and prospectively test a Cryo-AF dosing protocol guided exclusively by time-to-pulmonary vein (PV) isolation (TT-PVI) in patients undergoing a first-time Cryo-AF. METHODS: In this multicenter study, we examined the acute/long-term safety/efficacy of Cryo-AF using the proposed dosing algorithm (Cryo-AFDosing; n = 355) against a conventional, nonstandardized approach (Cryo-AFConventional; n = 400) in a nonrandomized fashion. RESULTS: Acute PV isolation was achieved in 98.9% of patients in Cryo-AFDosing (TT-PVI = 48 ± 16 seconds) vs 97.2% in Cryo-AFConventional (P = .18). Cryo-AFDosing was associated with shorter (149 ± 34 seconds vs 226 ± 46 seconds; P <.001) and fewer (1.7 ± 0.8 vs 2.9 ± 0.8; P <.001) cryoapplications, reduced overall ablation (16 ± 5 minutes vs 40 ± 14 minutes; P <.001), fluoroscopy time (13 ± 6 minutes vs 29 ± 13 minutes; P <.001), left atrial dwell time (51 ± 14 minutes vs 118 ± 25 minutes; P <.001), and total procedure time (84 ± 23 minutes vs 145 ± 49 minutes; P <.001) but similar nadir balloon temperature (-47°C ± 8°C vs -48°C ± 6°C; P = .41) and total thaw time (43 ± 27 seconds vs 45 ± 19 seconds; P = .09) as compared to Cryo-AFConventional. Adverse events (2.0% vs 2.7%; P = .48), including persistent phrenic nerve palsy (0.6% vs 1.2%; P = .33) and 12-month freedom from all atrial arrhythmias (82.5% vs 78.3%; P = .14), were similar between Cryo-AFDosing and Cryo-AFConventional. However, Cryo-AFDosing was specifically associated with fewer atypical atrial flutters/tachycardias during long-term follow-up (8.5% vs 13.5%; P = .02) as well as fewer late PV reconnections at redo procedures (5.0% vs 18.5%; P <.001). CONCLUSION: A novel Cryo-AF dosing algorithm guided by TT-PVI can help individualize the ablation strategy and yield improved procedural endpoints and efficiency as compared to a conventional, nonstandardized approach.

Catheter ablation using the third-generation cryoballoon provides an enhanced ability to assess time to pulmonary vein isolation facilitating the ablation strategy: Short- and long-term results of a multicenter study.

BACKGROUND: Limited data exist on cryoablation of atrial fibrillation (Cryo-AF) using the newly available third-generation (Arctic Front Advance-Short Tip [AFA-ST]) cryoballoon. OBJECTIVE: In this multicenter study, we evaluated the safety and efficacy of Cryo-AF using the AFA-ST vs the second-generation (Arctic Front Advance [AFA]) cryoballoon. METHODS: We examined the procedural safety and efficacy and the short- and long-term clinical outcomes associated with a first-time Cryo-AF performed in 355 consecutive patients (254/355 [72%] with paroxysmal AF), using either the AFA-ST (n = 102) or the AFA (n = 253) cryoballoon catheters. RESULTS: Acute isolation was achieved in 99.6% of all pulmonary veins (PVs) (AFA-ST: 100% vs AFA: 99.4%; P = .920). Time to pulmonary vein isolation was recorded in 89.2% of PVs using AFA-ST vs 60.2% using AFA (P < .001). PVs targeted using AFA-ST required fewer applications (1.6 ± 0.8 vs 1.7 ± 0.8; P = .023), whereas there were no differences in the balloon nadir temperature (AFA-ST: -47.0°C ± 7.3°C vs AFA: -47.5°C ± 7.8°C; P = .120) or thaw time (AFA-ST: 41 ± 24 seconds vs AFA: 44 ± 28 seconds; P = .056). However, AFA-ST was associated with shorter left atrial dwell time (43 ± 5 minutes vs 53 ± 16 minutes; P < .001) and procedure time (71 ± 11 minutes vs 89 ± 25 minutes; P < .001). Furthermore, Cryo-AF using AFA-ST was completed more frequently by "single-shot" PV ablation (27.4% vs 20.2%; P = .031). Persistent phrenic nerve palsy (AFA-ST: 0% vs AFA: 0.8%; P = .507) and procedure-related adverse events (AFA-ST: 1.0% vs AFA: 1.6%; P = .554) were similar, as was the freedom from recurrent atrial arrhythmias at 10 months of follow-up (AFA-ST: 81.8% vs AFA: 79.9%; P = .658). CONCLUSION: Cryo-AF using the AFA-ST cryoballoon offers an enhanced ability to assess time to pulmonary vein isolation, allowing for fewer cryoapplications and shorter left atrial dwell time and procedure time. Consequently, this allowed for procedural completion more frequently using a "single-shot" PV ablation with equivalent safety and efficacy.

Novel Noxipoint Therapy versus Conventional Physical Therapy for Chronic Neck and Shoulder Pain: Multicentre Randomised Controlled Trials.

As chronic pain affects 115 million people and costs $600B annually in the US alone, effective noninvasive nonpharmacological remedies are desirable. The purpose of this study was to determine the efficacy and the generalisability of Noxipoint therapy (NT), a novel electrotherapy characterised by site-specific stimulation, intensity-and-submodality-specific settings and a immobilization period, for chronic neck and shoulder pain. Ninety-seven heavily pretreated severe chronic neck/shoulder pain patients were recruited; 34 and 44 patients were randomly allocated to different treatment arms in two patient-and-assessor-blinded, randomised controlled studies. The participants received NT or conventional physical therapy including transcutaneous electrical nerve stimulation (PT-TENS) for three to six 90-minute sessions. In Study One, NT improved chronic pain (-89.6%, Brief Pain Inventory, p < 0.0001, 95% confidence interval), function (+77.4%, range of motion) and quality of life (+88.1%) at follow-up (from 4 weeks to 5 months), whereas PT-TENS resulted in no significant changes in these parameters. Study Two demonstrated similar advantages of NT over PT-TENS and the generalisability of NT. NT-like treatments in a randomised rat study showed a similar reduction in chronic hypersensitivity (-81%, p < 0.01) compared with sham treatments. NT substantially reduces chronic neck and shoulder pain, restores function, and improves quality of life in a sustained manner.

True bipolar defibrillator leads have increased sensing latency and threshold compared with the integrated bipolar configuration.

BACKGROUND: Dual-coil implantable defibrillator (ICD) leads with true bipolar pacing and sensing (quadripolar leads) have been introduced to provide improved sensing characteristics without sacrificing defibrillation efficacy. Electrode configuration has been shown to have little effect on the amplitude or slew rate of the intracardiac electrogram, but does have an effect on the duration of the sensed electrogram. Closer spacing of the electrodes and smaller surface area of the anode may, therefore, result in a different latency of sensing relative to the onset of the QRS complex. METHODS: We tested the difference in ventricular sensing latency between integrated bipolar and true bipolar electrode configurations in 40 patients undergoing ICD implantation for standard indications (Medtronic Sprint Quattro lead in 26 and St. Jude Riata in 16). In addition, we compared R wave amplitude, pacing threshold, impedance, and slew rate. RESULTS: Sensing latency was significantly longer in the true bipolar configuration (Medtronic Sprint Quattro 45.2 +/- 14.7 msec in the true bipolar configuration, vs 37.4 +/- 18.2 msec in the integrated bipolar configuration, and St. Jude Riata, 43.5 +/- 9.8 msec true bipolar, vs 33.8 +/- 10.1 msec integrated bipolar, P < 0.01). There was no difference in R wave amplitude or slew rate. Pacing threshold and impedance were also greater in the true bipolar configuration than in the integrated bipolar configuration. CONCLUSION: The true bipolar configuration has a longer sensing latency than the integrated bipolar configuration. In some patients, this may require a longer programmed AV delay to avoid ventricular pseudofusion.

Coronary sinus and fossa ovalis ablation: effect on interatrial conduction and atrial fibrillation.

BACKGROUND: Interatrial conduction occurs via discrete pathways along the coronary sinus musculature, fossa ovalis region, and Bachman's bundle. We assessed the feasibility of altering interatrial conduction by selectively ablating two of these conduction pathways using a novel mesh electrode ablation catheter. METHODS: Circular radiofrequency energy catheter ablation lesions were created in the proximal coronary sinus in four dogs and in both the fossa ovalis and the proximal coronary sinus regions in seven pigs. Interatrial conduction was assessed by analyzing intracardiac electrogram and noncontact isopotential mapping data. Inducibility of atrial fibrillation was assessed before and after ablation (in six pigs). RESULTS: Ablation lesions in the proximal coronary sinus eliminated interatrial conduction along the coronary sinus musculature in four dogs and five of seven pigs. Ablation lesions in the fossa ovalis region eliminated interatrial conduction via midseptal pathways in six of seven pigs. Atrial fibrillation, inducible in five of seven pigs at baseline, was rendered noninducible in all five. There was no adverse effect on AV nodal conduction. CONCLUSIONS: (1) Using a novel mesh electrode ablation catheter, we were able to ablate interatrial conduction pathways along the proximal coronary sinus and fossa ovalis regions. (2) This altered interatrial conduction and altered atrial fibrillation inducibility and maintenance. (3) Catheter ablation of interatrial conduction pathways may be useful in the therapy of atrial fibrillation.

Pattern of proliferative index (Ki-67) after anti-androgen manipulation reflects the ability of irradiation to control prostate cancer.

Anti-androgen (AA) therapy will cause hormone-sensitive prostate cancer cells to undergo apoptosis and/or enter the resting phase of the cell cycle. Although the decrease of tumor burden would be an advantage for tumor control when irradiation is subsequently added, the cells in resting phase would seemingly be less vulnerable to the usual type of radiation-induced cell killing via DNA strand breakage. In this study of patients with prostate cancer, we examined the proliferative index via Ki-67 staining of biopsy material before, during, and after withdrawal of leuprolide. We studied 15 previously untreated patients with locally advanced prostate cancer. Prostate biopsies were taken at three times: 1) initial diagnosis; 2) after 3 consecutive months of intramuscular 7.5 mg depot; and c) 6 weeks after the last dose. External beam radiation (EBRT) then delivered 66 Gy in 33 sessions to local fields. We used the ASTRO definition of prostate-specific antigen (PSA) failure. We measured serum luteinizing hormone and total testosterone coinciding with each biopsy date. Immunohistochemical staining was performed using Ki-67 antibody clone MIB-1. The follow-up ranged from 36 to 73 months (median 52 months). We discerned two perturbation patterns of Ki-67 with hormonal manipulation. Pattern 1 demonstrated a drop of Ki-67 labeling after leuprolide was in effect and then after leuprolide withdrawal, the Ki-67 rebounded to less than 120% of baseline. Pattern 2 also showed an initial drop with leuprolide but rebounded to more than 120%. Among eight patients demonstrating pattern 1, only one patient had a PSA failure. In contrast among patients with pattern 2, six of seven failed biochemically (Fisher's exact, p = 0.018). All patients had a LH less than 1.0 during leuprolide effect that rose with its withdrawal. There was no correlation of PSA failure with whether total testosterone did or did not rise to more than 100 ng/dl by the time of the withdrawal phase biopsy. Neither the percent of PSA decline during leuprolide nor the minor PSA rebound 6 to 8 weeks after leuprolide withdrawal correlated with the Ki-67 pattern. The pattern of perturbation of immunohistochemical staining for Ki-67 predicts biochemical failure after moderate-dose EBRT in patients with prostate cancer. Several recent analyses of combined EBRT and AA suggest that some patients may benefit from more prolonged use of AA. Because AA can have substantial side effects and is expensive, a method to select patients likely to benefit from long-term AA would be useful. After neoadjuvant AA manipulation, the Ki-67 perturbation pattern, but not the early PSA changes, may help select patients for long-term AA. The Ki-67 pattern might also be used to select patients needing escalated radiation dosage. Further validation of these concepts beyond this pilot study is suggested.

Primary prevention of sudden cardiac death: trials in patients with coronary artery disease.

Over the past decade, four randomized, controlled trials have evaluated therapies for prevention of sudden cardiac death in patients with coronary disease. Three of the four trials have shown significant reductions in mortality with implanted defibrillators. Two studies failed to demonstrate any benefit from pharmacologic antiarrhythmic therapy. The results of these studies in similar patient populations have erased any doubt regarding the ability of implanted defibrillators to reduce the risk of sudden death in patients with coronary disease. Our major challenge at this time is understanding how best to utilize this therapy in order to bring the benefit to the maximum number of patients while minimizing expense.

Excessive oral zinc supplementation.

The use of megadoses of vitamin and mineral supplements has become common. The authors describe a 17-year-old boy who presented with fatigue after taking large daily doses of zinc supplements for 6 to 7 months in an attempt to treat his acne. A zinc-induced hypocupremia developed, causing anemia, leukopenia, and neutropenia. Anemia and neutropenia resolved 6 months after he stopped taking the zinc. Excessive zinc intake can have toxic effects, and questions about patients' use of vitamin and mineral supplements should be asked when medication histories are taken.