Left ventricular assist devices for treatment of refractory advanced heart failure: the Western Australian experience.

BACKGROUND: Left ventricular (LV) assist devices (LVADs) can prolong survival and improve quality of life in end-stage heart failure. AIMS: Review outcomes of the Western Australian LVAD programme. METHODS: Retrospective database and medical record review. RESULTS: One hundred forty-seven LVADs have been implanted in 23 years, of which 95 were newer-generation devices (HeartWare HVAD [HW], HeartMate II and HeartMate 3). Presented data refer to these devices only. Most patients (94%) were classed as bridge-to-transplant or -candidacy/decision, with the remainder classed as 'destination therapy' (DT). Mean LV ejection fraction was 20%, and 36% had severe right ventricular dysfunction. Sixty-two percent of patients had a nonischaemic cardiomyopathy. Following LVAD implant, the median length of stay in intensive care was 2 days, and in the hospital overall was 23 days. Ninety-six percent of patients survived to hospital discharge, and, following discharge, 98% of days with LVAD were spent as an outpatient. The median number of hospital readmissions was 1.5 per patient per year. LVAD-associated infection requiring admission or intravenous antibiotics at any time after implant occurred in 36%, significant gastrointestinal bleeding in 19% and stroke in 11%. The percentage of patients alive with LVAD still in situ at 1, 2 and 5 years was 94%, 88% and 62% respectively, which exceeds current international registry outcomes. All DT patients survived at least 4 years, spending 97% of days with LVAD as an outpatient. The two longest-surviving HW DT patients worldwide (11.3 and 10.5 years) are among this cohort. CONCLUSIONS: Excellent outcomes can be achieved with LVADs in appropriately selected patients.

New ECG algorithms with improved accuracy for prediction of culprit vessel in inferior ST-segment elevation myocardial infarction.

BACKGROUND: In addition to diagnosing acute myocardial infarction (MI), the electrocardiogram (ECG) may also predict the culprit coronary artery. We aimed to assess the diagnostic accuracy of ECG algorithms predicting the occluded vessel in inferior ST-segment elevation myocardial infarction (STEMI). METHODS: This retrospective cohort study included 300 consecutive patients with inferior STEMI undergoing acute coronary angiography. A new method based on the summation of ST-segment deviations in multiple leads from the first 12-lead-ECG was used to develop algorithms to discriminate between right coronary artery (RCA) and circumflex artery (CX) occlusion. Additionally, older algorithms were reassessed. RESULTS: The RCA was occluded in 235 patients (78%) and the CX in 65 (22%). ST-segment deviations differed significantly between RCA and CX occlusions in leads I, III, aVR, aVL, aVF and V1. ST-segment deviations in lead I showed the highest discriminatory ability of a single lead (area under the receiver operating curve [AUC]=0.77). The summation of multiple leads further increased the discriminatory ability ("III-II+aVF+aVR+V1:" AUC=0.86; "III-II-I+aVF+V1:" AUC=0.85). The best binary algorithm "III-II-I+aVF+V1>0.1 mV" classified 86% of cases correctly and was better than the best old algorithm (83.3%). The simpler algorithm "III+aVR+V1≥0.1 mV" still predicted 85.0% correctly. All algorithms had higher sensitivities for RCA than for CX detection and performed better in right-dominant anatomy. CONCLUSIONS: A new approach summating multiple ST-segment deviations generated ECG algorithms with higher diagnostic accuracy to predict the occluded vessel in inferior STEMI compared to previous studies. These algorithms may facilitate earlier risk stratification for patients at risk of postinfarct complications.

Post-Myocardial Infarction Ventricular Septal Defect Successfully Treated with Impella as Bridge to Cardiac Transplantation.

A 63-year-old female presented late with anterior ST-elevation myocardial infarction and cardiogenic shock. This was complicated by acute ventricular septal defect with large left-to-right shunt. An Impella CP was inserted on day seven with rapid haemodynamic improvement. This facilitated bridge to cardiac transplant on day twelve post-MI.

Galectin-3 is an independent predictor of postoperative atrial fibrillation and survival after elective cardiac surgery.

BACKGROUND: Postoperative atrial fibrillation (POAF) is a frequent complication after heart surgery and is associated with thromboembolic events, prolonged hospital stay, and adverse outcomes. Inflammation and fibrosis are involved in the pathogenesis of atrial fibrillation. OBJECTIVE: The purpose of this study was to assess whether galectin-3, which reflects preexisting atrial fibrosis, has the potential to predict POAF and mortality after cardiac surgery. METHODS: Four hundred seventy-five consecutive patients (mean age 67.4 ± 11.8 years; 336 (70.7%) male) undergoing elective heart surgery at the Medical University of Vienna were included in this prospective single-center cohort study. Galectin-3 plasma levels were assessed on the day before surgery. RESULTS: The 200 patients (42.1%) who developed POAF had significantly higher galectin-3 levels (9.60 ± 6.83 ng/mL vs 7.10 ± 3.54 ng/mL; P < .001). Galectin-3 significantly predicted POAF in multivariable logistic regression analysis (adjusted odds ratio per 1-SD increase 1.44; 95% confidence interval 1.15-1.81; P = .002). During a median follow-up of 4.3 years (interquartile range 3.4-5.4 years), 72 patients (15.2%) died. Galectin-3 predicted all-cause mortality in multivariable Cox regression analysis (adjusted hazard ratio per 1-SD increase 1.56; 95% confidence interval 1.16-2.09; P = .003). Patients with the highest-risk galectin-3 levels according to classification and regression tree analysis (>11.70 ng/mL) had a 3.3-fold higher risk of developing POAF and a 4.4-fold higher risk of dying than did patients with the lowest-risk levels (≤5.82 ng/mL). CONCLUSION: The profibrotic biomarker galectin-3 is an independent predictor of POAF and mortality after cardiac surgery. This finding highlights the role of the underlying arrhythmogenic substrate in the genesis of POAF. Galectin-3 may help to identify patients at risk of POAF and adverse outcome after cardiac surgery.

Blood urea nitrogen has additive value beyond estimated glomerular filtration rate for prediction of long-term mortality in patients with acute myocardial infarction.

OBJECTIVES: Blood urea nitrogen (BUN) has been shown to independently predict short- and intermediate-term outcomes in patients with acute myocardial infarction (AMI). We aimed to assess the additive predictive value of BUN beyond estimated glomerular filtration rate (eGFR) in AMI patients with an 8.6-year follow-up. METHODS: This retrospective, observational single-centre study included 1332 consecutive AMI patients (median age 64 years, 58.4% male). BUN, creatinine and eGFR were determined at hospital admission. RESULTS: During a median follow-up of 8.6 years (interquartile range [IQR] 4.0-11.6), 408 patients (30.6%) experienced the study endpoint of cardiovascular mortality. BUN (median 17.0 mg/dL [IQR 13.5-22.7]) was a significant predictor of cardiovascular mortality in univariate Cox regression (hazard ratio (HR) per 1 standard deviation increase 2.10, 95% confidence interval [CI] 1.94-2.28, p < .001). This association remained significant after multivariable adjustment for demographics, clinical variables and eGFR (adjusted HR 1.52 [CI 1.16-2.00, p = .003]). The association between BUN and outcome was more pronounced in patients with eGFR >60 mL/min/1.73m2 (HR 2.81 [CI 2.20-3.58, p < .001]). The discriminatory abilities (Harrell's C-statistic) for BUN, eGFR and creatinine were 0.75, 0.76 and 0.67, respectively. The addition of BUN to eGFR significantly improved the C-statistic (0.78, p for comparison = 0.017), net reclassification (23.7%, p < .001) and integrated discrimination (2.9%, p < .001). CONCLUSIONS: Circulating BUN on admission is an independent predictor of long-term cardiovascular mortality in AMI patients and adds predictive power beyond eGFR. BUN reflects not only kidney function, but also acute haemodynamic and neurohumoral alterations during AMI, and may help to identify high-risk patients.

Does Furosemide Increase Oxidative Stress in Acute Kidney Injury?

Furosemide, a loop diuretic, is used to increase urine output in patients with acute kidney injury (AKI). It remains uncertain whether the benefits of furosemide in AKI outweigh its potential harms. We investigated if furosemide influenced oxidative stress in 30 critically ill patients with AKI by measuring changes in F2-isoprostanes (F2-IsoPs), markers of in vivo oxidative stress, in plasma and urine following intravenous furosemide. Urine F2-IsoPs were higher in sepsis (p = 0.001) and increased in proportion to urine furosemide (p = 0.001). The furosemide-induced increase in urine F2-IsoPs differed depending on AKI severity (p < 0.001) and was greatest in those with the most severe AKI. Furosemide had no effect on plasma F2-IsoPs. We demonstrate for the first time that furosemide increases renal oxidative stress in AKI and find that patients with the most severe AKI-to whom the largest doses are likely to be administered-showed the greatest increase in oxidative stress. These findings lead to the hypothesis that the common practice of administering high-dose furosemide to convert oliguric to nonoliguric AKI may induce harmful oxidative stress in the kidneys, and an adequately powered, randomized controlled trial is required to determine if clinical benefits of this dosing strategy justify its potential harms. Antioxid. Redox Signal. 26, 221-226.

Determinants of Urinary Output Response to IV Furosemide in Acute Kidney Injury: A Pharmacokinetic/Pharmacodynamic Study.

OBJECTIVES: This study assessed the determinants of urinary output response to furosemide in acute kidney injury; specifically, whether the response is related to altered pharmacokinetics or pharmacodynamics. DESIGN: Prospective cohort. SETTING: Tertiary ICU. PATIENTS: Thirty critically ill patients with acute kidney injury without preexisting renal impairment or recent diuretic exposure. INTERVENTION: A single dose of IV furosemide. MEASUREMENTS AND MAIN RESULTS: Baseline markers of intravascular volume status were obtained prior to administering furosemide. Six-hour creatinine clearance, hourly plasma/urinary furosemide concentrations, and hourly urinary output were used to assess furosemide pharmacokinetics/pharmacodynamics parameters. Of 30 patients enrolled, 11 had stage-1 (37%), nine had stage-2 (30%), and 10 had stage-3 (33%) Acute Kidney Injury Network acute kidney injury. Seventy-three percent were septic, 47% required norepinephrine, and 53% were mechanically ventilated. Urinary output doubled in 20 patients (67%) following IV furosemide. Measured creatinine clearance was strongly associated with the amount of urinary furosemide excreted and was the only reliable predictor of the urinary output after furosemide (area under the receiver-operating-characteristic curve, 0.75; 95% CI, 0.57-0.93). In addition to an altered pharmacokinetics (p < 0.01), a reduced pharmacodynamics response to furosemide also became important when creatinine clearance was reduced to less than 40 mL/min/1.73 m (p = 0.01). Acute kidney injury staging and markers of intravascular volume, including central venous pressure, brain-natriuretic-peptide concentration, and fractional urinary sodium excretion were not predictive of urinary output response to furosemide. CONCLUSIONS: The severity of acute kidney injury, as reflected by the measured creatinine clearance, alters both pharmacokinetics and pharmacodynamics of furosemide in acute kidney injury, and was the only reliable predictor of the urinary output response to furosemide in acute kidney injury.

The Role of Botulinum Toxin Type A in the Clinical Management of Refractory Anterior Knee Pain.

Anterior knee pain is a highly prevalent condition affecting largely young to middle aged adults. Symptoms can recur in more than two thirds of cases, often resulting in activity limitation and reduced participation in employment and recreational pursuits. Persistent anterior knee pain is difficult to treat and many individuals eventually consider a surgical intervention. Evidence for long term benefit of most conservative treatments or surgical approaches is currently lacking. Injection of Botulinum toxin type A to the distal region of vastus lateralis muscle causes a short term functional "denervation" which moderates the influence of vastus lateralis muscle on the knee extensor mechanism and increases the relative contribution of the vastus medialis muscle. Initial data suggest that, compared with other interventions for anterior knee pain, Botulinum toxin type A injection, in combination with an active exercise programme, can lead to sustained relief of symptoms, reduced health care utilisation and increased activity participation. The procedure is less invasive than surgical intervention, relatively easy to perform, and is time- and cost-effective. Further studies, including larger randomized placebo-controlled trials, are required to confirm the effectiveness of Botulinum toxin type A injection for anterior knee pain and to elaborate the possible mechanisms underpinning pain and symptom relief.

Evidence for an excitatory GABAA response in human motor cortex in idiopathic generalised epilepsy.

PURPOSE: Impaired GABAergic inhibition has been implicated in the pathophysiology of epilepsy. The possibility of a paradoxical excitatory effect of GABA in epilepsy has been suggested, but has not been investigated in vivo. We investigated pre- and post-synaptic GABAergic mechanisms in patients with idiopathic generalised epilepsy (IGE). METHOD: In 10 patients and 12 control subjects we explored short- and long-interval intracortical inhibition (SICI, LICI; post-synaptic GABAA and GABAB-mediated respectively) and long-interval intracortical facilitation (LICF; pre-synaptic disinhibition) using transcranial magnetic stimulation. RESULTS: While post-synaptic GABAB-mediated inhibition was unchanged in IGE (p=0.09), LICF was reduced compared to controls (controls: 141±17% of baseline; untreated patients: 107±12%, p=0.2; treated patients: 79±10%, p=0.003). GABAA-mediated inhibition was reduced in untreated patients (response amplitude 56±4% of baseline vs. 26±6% in controls, p=0.004) and normalised with treatment (37±12%, p=0.5 vs. controls). When measured during LICI, GABAA-mediated inhibition became excitatory in untreated IGE (response amplitude 120±10% of baseline, p=0.017), but not in treated patients. CONCLUSION: Pre- and post-synaptic GABA-mediated inhibitory mechanisms are altered in IGE. The findings lend in vivo support to evidence from experimental models and in vitro studies of human epileptic brain tissue that GABA may have a paradoxical excitatory role in ictogenesis.

Prognostic significance of blood-brain barrier disruption in patients with severe nonpenetrating traumatic brain injury requiring decompressive craniectomy.

OBJECT: The authors assessed the risk factors and outcomes associated with blood-brain barrier (BBB) disruption in patients with severe, nonpenetrating, traumatic brain injury (TBI) requiring decompressive craniectomy. METHODS: At 2 major neurotrauma centers in Western Australia, a retrospective cohort study was conducted among 97 adult neurotrauma patients who required an external ventricular drain (EVD) and decompressive craniectomy during 2004-2012. Glasgow Outcome Scale scores were used to assess neurological outcomes. Logistic regression was used to identify factors associated with BBB disruption, defined by a ratio of total CSF protein concentrations to total plasma protein concentration > 0.007 in the earliest CSF specimen collected after TBI. RESULTS: Of the 252 patients who required decompressive craniectomy, 97 (39%) required an EVD to control intracranial pressure, and biochemical evidence of BBB disruption was observed in 43 (44%). Presence of disruption was associated with more severe TBI (median predicted risk for unfavorable outcome 75% vs 63%, respectively; p = 0.001) and with worse outcomes at 6, 12, and 18 months than was absence of BBB disruption (72% vs 37% unfavorable outcomes, respectively; p = 0.015). The only risk factor significantly associated with increased risk for BBB disruption was presence of nonevacuated intracerebral hematoma (> 1 cm diameter) (OR 3.03, 95% CI 1.23-7.50; p = 0.016). Although BBB disruption was associated with more severe TBI and worse long-term outcomes, when combined with the prognostic information contained in the Corticosteroid Randomization after Significant Head Injury (CRASH) prognostic model, it did not seem to add significant prognostic value (area under the receiver operating characteristic curve 0.855 vs 0.864, respectively; p = 0.453). CONCLUSIONS: Biochemical evidence of BBB disruption after severe nonpenetrating TBI was common, especially among patients with large intracerebral hematomas. Disruption of the BBB was associated with more severe TBI and worse long-term outcomes, but when combined with the prognostic information contained in the CRASH prognostic model, this information did not add significant prognostic value.

Vertebral artery dissection as a cause of cervical radiculopathy.

The acute onset of neck pain and arm weakness is most commonly due to cervical radiculopathy or inflammatory brachial plexopathy. Rarely, extracranial vertebral artery dissection may cause radiculopathy in the absence of brainstem ischemia. We describe a case of vertebral artery dissection presenting as cervical radiculopathy in a previously healthy 43-year-old woman who presented with proximal left arm weakness and neck pain aggravated by movement. Cervical magnetic resonance imaging (MRI) and angiography revealed dissection of the left vertebral artery with an intramural hematoma compressing the left C5 and C6 nerve roots. Antiplatelet treatment was commenced, and full power returned after 2 months. Recognition of vertebral artery dissection on cervical MRI as a possible cause of cervical radiculopathy is important to avoid interventions within the intervertebral foramen such as surgery or nerve root sleeve injection. Treatment with antithrombotic agents is important to prevent secondary ischemic events.

Inverse correlation between resting motor threshold and corticomotor excitability after static magnetic stimulation of human motor cortex.

BACKGROUND: High-strength static magnetic field stimulation (SMS) results in a period of reduced corticomotor excitability that may be mediated through a decrease in membrane excitability. OBJECTIVE: As resting motor threshold (RMT) is thought to reflect membrane excitability, we hypothesized that SMS may increase RMT and that there would be an inverse relationship between RMT and motor-evoked potential (MEP) amplitude. METHODS: Ten healthy subjects (aged 20-29; 4 females) participated in a double-blinded crossover design comparing MEP amplitude and RMT before and after a 15-min period of SMS or sham stimulation over primary motor cortex (M1). RESULTS: MEP amplitude was initially significantly reduced post-SMS (∼20%), and returned to baseline by 6 min post-intervention. MEP amplitude and RMT were inversely correlated (r(2) = 0.924; P = 0.001). Sham stimulation had no effect on MEP amplitude (P = 0.969) or RMT (P = 0.549). CONCLUSION: After SMS, corticomotor excitability is transiently reduced in association with a correlated modulation of RMT. SMS after effects may be mediated in part by a reduction in membrane excitability, suggesting a possible role for non-synaptic (intrinsic) plasticity mechanisms.

Conditioning the cortical silent period with paired transcranial magnetic stimulation.

BACKGROUND: A single supra-threshold pulse of transcranial magnetic stimulation (TMS) over human motor cortex elicits multiple descending volleys (I-waves) that generate a motor evoked potential (MEP) followed by a period of electromyographic silence in the tonically contracted target muscle (silent period; SP). A sub-threshold conditioning stimulus (CS) delivered at inter-pulse intervals (IPIs) of 1-5 ms after a supra-threshold test stimulus (TS) conditions I-waves elicited by TS and can increase MEP amplitude (short-interval intracortical facilitation; SICF), however its effect on the SP remains unknown. OBJECTIVE: We investigated whether it is possible to modulate the SP resulting from a TS by delivering a sub-threshold CS 1-5 ms later. METHODS: Paired-pulse TMS was delivered while subjects performed slight contraction of the first dorsal interosseous muscle. SICF and SP duration were measured at each IPI and compared to amplitude-matched MEPs evoked by single-pulse TMS. RESULTS: Paired stimulation at IPI 2-5 ms prolonged the SP by 21 ± 3% (P < 0.001) but had no effect on MEP amplitude. At shorter IPIs the CS increased MEP amplitude (by 170 ± 31%), but the SP was not prolonged when compared to an amplitude-matched single-pulse stimulus. CONCLUSION: The SP can be modified by a CS applied during the early phase of its genesis. We suggest that this is in keeping with an early GABAA contribution to the SP, and it is possible that this new conditioning paradigm may offer another means for probing the excitability of cortical inhibitory networks in human motor cortex.

Postprocedural inflammatory inferior alveolar neuropathy: an important differential diagnosis.

Lingual or inferior alveolar nerve (IAN) injury after dental procedures may result from direct trauma or local anesthetic agent and presents with immediate onset of typically nonprogressive symptoms, including pain and sensory changes. We report a case of delayed-onset pain and progressive sensory symptoms after IAN block for amalgam restoration. A 54-year-old man presented with progressive right-sided facial pain 48 hours after IAN block for amalgam restoration, followed 1 week later by hypoesthesia and allodynia in IAN distribution. The presentation is more consistent with inflammatory neuropathy, as is well recognized in brachial plexopathy. Imaging was used to exclude local and central causes, following which the clinical diagnosis was made. Inflammatory neuropathies may be distinguished from iatrogenic causes on the basis of delayed symptom onset, early severe pain, and progressive sensory symptoms. Awareness of this condition is important, because early steroid therapy followed by medications for neuropathic pain may provide benefit.

Peer-assisted learning in teaching clinical examination to junior medical students.

BACKGROUND: In medical education, peer-assisted learning (PAL) refers to teaching occurring between fellow students. Few descriptions of its use to teach clinical examination have been published. Student Grand Rounds (SGR) is a student-led initiative whereby senior students volunteer to teach clinical examination to pre-clinical peers. Student tutors attend a modified Teaching on the Run (TOTR) course originally designed to train clinicians to teach students and junior doctors. AIM: We investigated the value of SGR in teaching pre-clinical students, and evaluated the effectiveness of TOTR. METHODS: Over 9 months, tutors and participants in each SGR tutorial completed an online survey. At the conclusion of annual TOTR workshops (2004-2010), participants evaluated their impressions of the course. RESULTS: A total of 64 SGR tutorials were attended by a total of 321 students. All agreed that tutorials were beneficial and enjoyable, with a threefold increase in the number of students self-identifying as able to perform the skills required. TOTR participants classified the course as both relevant and beneficial, and all course outcomes were achieved. SGR tutors reported improved knowledge and confidence in teaching following SGR and TOTR. CONCLUSION: PAL is effective in supplementing teaching of clinical examination. Senior students learn valuable skills and gain experience in teaching.

Enduring efficacy of Botulinum toxin type A injection for refractory anterior knee pain.

PURPOSE: To examine long-term outcomes of Botulinum toxin type A (BoNT-A) injection to vastus lateralis (VL) for refractory anterior knee pain (AKP). METHODS: Two cohorts (private clinic referrals and previous research participants) injected with BoNT-A for AKP by one neurologist were surveyed retrospectively. Primary outcomes were self-reported benefit, duration of symptom relief, and knee surgery post-injection. Secondary outcomes were changes in utilization of medication/physiotherapy treatment, AKP symptoms and activity limitation. RESULTS: Overall, average symptom duration was 76 months (SD 98). Responses were available from 46 of 53 private patients. Thirty-eight reported benefit from injection, which was ongoing in 29. Average benefit was 25 months (SD 21). Nine individuals reported symptom recurrence after an average of 14 months (SD 21). Ten had knee surgery post-injection; six of whom had not benefitted from BoNT-A injection. Nineteen of 23 previous research participants were contactable. Initially, all responded favorably to injection. Symptomatic benefit, with an average duration of 44 months (SD 20), persisted in 15. Two subjects proceeded to surgical intervention. CONCLUSIONS: A single BoNT-A treatment to VL led initially to improved function and relief of knee-related symptoms in 57 of 65 individuals. Improvements were sustained at follow-up, with an average benefit of 34 months (SD 25) post-injection, in 44 of 57 cases.