Asymptomatic Bradycardia Research Articles

Clinical characteristics associated with bradycardia and asystole in patients with syncope undergoing long-term electrocardiographic monitoring with implantable loop recorder.

The aim of this retrospective single center cohort study was to assess the occurrence of bradycardia during implantable loop recorder (ILR) monitoring in patients with unexplained syncope and negative conventional testing and to identify clinical predictors of bradycardia and pacemaker implantation. An ILR was implanted in 112 patients (31men, 81women, mean age 64±13years) with syncope which was not explained after conventional diagnostic work-up. Clinical variables were compared between patients with and without pacemaker implantation. A diagnosis was made in 67patients (60%), including non-arrhythmic (vasodepressor) syncope (27patients), sinus bradycardia or asystole (23patients), atrioventricular (AV) block (14patients) and bradycardic atrial fibrillation (3patients). The mean time to diagnosis was 233± 282 days. A pacemaker was implanted in 40patients (36%). Male gender, age above 65years, hypertension, presence of structural heart disease, absence of prodromal symptoms, trauma secondary to syncope, asymptomatic sinus bradycardia and first-degree AV block were clinical predictors of pacemaker implantation in univariate analysis. Of the independent predictive factors three remained significant in multivariate analysis: absence of prodromal symptoms before the loss of consciousness (odds ratio OR3.38, p= 0.01, 95% confidence interval CI1.24-9.20), male gender (OR3.22, p= 0.01, 95% CI1.26-8.20) and age >65 years (OR2.94, p= 0.02, 95% CI1.14-8.33). In patients undergoing ILR implantation bradycardia is afrequent finding despite the negative conventional diagnostic testing. Absence of prodromal symptoms, male gender and age >65years are risk factors for bradycardia and pacemaker implantation.

Association of Asymptomatic Bradycardia with Incident Cardiovascular Disease and Mortality: The Multi-Ethnic Study of Atherosclerosis (MESA): Dharod A, Soliman E, Dawood F, et al. JAMA Intern Med. 2016;176:219-227

Association of Asymptomatic Bradycardia with Incident Cardiovascular Disease and Mortality: The Multi-Ethnic Study of Atherosclerosis (MESA): Dharod A, Soliman E, Dawood F, et al. JAMA Intern Med. 2016;176:219-227

Association of Asymptomatic Bradycardia With Incident Cardiovascular Disease and Mortality

Bradycardia has been associated with lower cardiovascular disease (CVD) risk in selected populations. There is a paucity of information available about heart rate (HR) less than 50 beats per minute (bpm) among middle-aged or older adults. To determine whether asymptomatic bradycardia was associated with a lower cardiovascular risk profile, less subclinical atherosclerosis, and decreased incident CVD and mortality. This retrospective analysis includes 6733 participants of the Multi-Ethnic Study of Atherosclerosis, which recruited men and women free of clinical cardiovascular disease ages 45 to 84 years from 2000 to 2002 and followed them over 10 years for incident CVD events and mortality. The HR was measured by baseline electrocardiogram. The analysis was performed in June 2014. The association between HR categories with CVD events and all-cause mortality were examined using Cox proportional hazards models adjusted for potential confounders and mediators. The 6733 participants had a mean (SD) age of 62 (10.2) years; 47% were male. The mean (SD) HR was 63 (9.5) bpm among the 5831 participants not taking an HR-modifying drug; 5.3% had an HR lower than 50 bpm. Preliminary results revealed significant interaction for HR categories according to use of HR-modifying drugs for mortality (P = .002); thus, all further analyses were stratified. An HR of less than 50 bpm was not associated with incident CVD in either subgroup (participants taking or not taking HR-modifying drugs). Among participants not taking HR-modifying drugs, the fully adjusted mortality risk was not different for an HR less than 50 bpm (hazard ratio, 0.71 [95% CI, 0.41-1.09]; P = .12) and increased among those with an HR greater than 80 bpm (hazard ratio, 1.49 [95% CI, 1.08-2.05]; P = .01) (reference HR, 60-69 bpm). Among the 902 participants taking HR-modifying drugs there was an elevated mortality risk associated with an HR less than 50 bpm (hazard ratio, 2.42 [95% CI, 1.39-4.20]; P = .002) and with an HR greater than 80 bpm (hazard ratio, 3.55 [95% CI, 1.65-7.65]; P = .001) (reference HR, 60-69 bpm). In a contemporary, community-based cohort, bradycardia was generally not associated with incident CVD or mortality except for a potential adverse association between bradycardia among those taking HR-modifying drugs.

Panobinostat-Augmented Cytarabine and Daunorubicin (7+3) Induction for Older Patients with AML or High-Risk MDS Is Well Tolerated and Results in Favorable Clinical Outcomes: The Panda Trial

IntroductionPatients aged >60 years (y) with acute myeloid leukemia (AML) have inferior outcomes compared to those <60y. Even those who tolerate induction chemotherapy achieve lower response rates with standard approaches and experience significant toxicity with more intensive combinations. The histone deacetylase (HDAC) inhibitor panobinostat (pano) potentiates anthracycline and ara-C cytotoxicity, likely through enhancement of DNA double-strand breaks leading to increased apoptosis (Maiso et al. 2009; Xie et al. 2013). We hypothesized that addition of short-course HDAC inhibition with pano prior to and during 7+3 induction therapy would be well-tolerated and lead to favorable outcomes in this patient population.MethodsWe conducted a phase I study in patients >60y with newly diagnosed AML or high-risk MDS combining pano at doses ranging from 20 mg to 60 mg given orally on days 1, 3, 5, and 8 of induction with daunorubicin (dauno) 60 mg/m2 on days 3-5 and ara-C 100mg/m2 continuously on days 3-10 (p+7+3). Patients were allowed retreatment on p+5+2, with pano on days 1, 3, and 5 at the same doses, if the nadir BM biopsy had residual leukemia. Upon attainment of CR/CRi, patients were offered a second p+7+3 or alternative consolidation including allogeneic stem cell transplantation (alloHCT). Dose-limiting toxicity was defined based on unexpected toxicities from 7+3 induction and a standard 3+3 design was utilized for dose escalation. Peripheral blood mononuclear cells were isolated on days 1-5 and HDAC expression and histone acetylation were evaluated by western blot and quantified by densitometry.ResultsOverall, 22 patients were treated on the PanDA protocol. Treatment was well-tolerated in all dose-cohorts and the MTD was not reached. We treated 6 patients each at the 60 mg and 50 mg dose in the dose expansion phase due to recurrent grade 1 bradycardia. The median age was 67y-60-69y (13), 70-79y (5), and >80y (4). Eleven patients had de novo AML, 7 had AML with myelodysplasia related changes, 2 had 2ary AML from MPD, 1 treatment-associated myeloid neoplasm, and 1 had RAEB-2. Two patients had progressed on hypomethylating agents. Thirteen (62%) had intermediate-risk cytogenetics (cyto). Amongst 8 euploid patients, 2 had FLT3-ITDmut, 1 had FLT3-TKDmut and 2 had NPM1mut as the sole abnormality. Seven (33%) patients had complex/monosomic cyto. There were no patients with favorable cyto.There were no protocol-defined DLTs. The most common grade 2-4 TEAEs were febrile neutropenia (77%), electrolyte abnormalities (64%), diarrhea (55%), rash (55%), LFT abnormalities (32%), nausea (27%) and anorexia (27%). Of note, 36% experienced asymptomatic sinus bradycardia peaking on day 6 following pano, dauno, and 5HT3 inhibitor anti-emetics. Additionally, 9% experienced new onset grade 2 atrial fibrillation. There was no evidence of myocardial dysfunction on echocardiogram following induction. SAEs reported on study were sepsis (9%), typhlitis (5%), DIC (5%), pneumonitis (5%), and bowel perforation due to mucorales (5%). There were 2 deaths (9%) during induction, one related to typhlitis and the other to sepsis.Of 20 evaluable patients, 8 (40%) achieved CR/CRi . One patient received study treatment as consolidation, 3 received intermediate/high-dose ara-C, 1 received a hypomethylating agent, 2 underwent alloHCT and 1 had no further therapy. Median overall survival was 10 mos (ITT) and 16 mos for those who achieved a CR/CRi (p=0.005). Median relapse-free survival was 10 mos, range 3-27 mos (Figure 1).Baseline expression of HDAC class 1, 2, 3 and 6 was evaluated and was not found to be associated with response to p+7+3 arguing against a direct role in p+7+3-induced cytotoxicity. However, global histone acetylation change after pano exposure (days 1-3) was significantly associated with eventual chemo-ablation at nadir (Figure 2). Ongoing studies are evaluating markers of DNA damage response and apoptosis in patients treated with PanDA vs. concurrent 7+3 controls.ConclusionsThe addition of pano to 7+3 induction for older patients with AML is well-tolerated and results in clinical outcomes that are favorable in our very high-risk population. The recommended dose of pano is 50 mg daily on days 1, 3, 5, and 8 when combined with 7+3 induction in future studies. Importantly, histone acetylation change following exposure to pano but not baseline HDAC expression predicts sensitivity to combined therapy. [Display omitted] [Display omitted] DisclosuresWieduwilt:Sigma-Tau: Research Funding; Alexion: Honoraria. Off Label Use: Panobinostat is approved for multiple myeloma. This paper reports it's use in patients with acute myeloid leukemia.. Olin:Daiichi-Sankyo: Research Funding. Logan:Pharmacyclics: Consultancy; Jazz Pharmaceuticals: Consultancy; Amgen: Consultancy. Damon:Atara: Consultancy; Sunesis: Research Funding; McGraw-Hill: Patents & Royalties: Book Chapter; Sigma-Tau: Research Funding. Boyer:Onyx: Speakers Bureau. Andreadis:genentech: Employment; novartis oncology: Research Funding; cellerant: Research Funding; karyopharm: Research Funding; McGraw-Hill: Patents & Royalties: Book Chapter; Pfizer: Honoraria; Pharmacyclics: Honoraria.

P-422: Asymptomatic bradycardia due to rivastigmine and delirium in an elderly patient with Lewy Body Dementia

P-422: Asymptomatic bradycardia due to rivastigmine and delirium in an elderly patient with Lewy Body Dementia

Clinical Predictors of Pacemaker Implantation in Patients with Syncope Receiving Implantable Loop Recorder with or without ECG Conduction Abnormalities

Implantable loop recorders (ILR) allow prolonged cardiac rhythm monitoring and improved diagnostic yield in syncope patients. Predictive factors for pacemaker (PM) implantation in the ILR population with unexplained syncope have not been adequately investigated. In this single center, retrospective, observational study we investigated factors that predict PM implantation in this population. We retrospectively analyzed our ILR database of patients aged over 18 years who underwent ILR implantation for unexplained syncope between January 2009 and June 2013. Patient case notes were examined for demographics, history, electrocardiogram (ECG) abnormalities, investigations, and events during follow-up. The primary end-point was the detection of a symptomatic or asymptomatic bradycardia requiring PM implantation. During a period of 4.5 years, 200 patients were implanted with ILR for unexplained syncope, of who n = 33 (16.5%) had clinically significant bradycardia requiring PM implantation. After multivariable analysis, history of injury secondary to syncope was found to be the strongest independent predictor for PM implantation (odds ratio [OR]:9.1; P < 0.001; 95% confidence interval [CI]: (3.26-26.81). Other significant predictors included female sex, PR interval > 200msec, and age >75 years. In patients without conduction abnormalities on the ECG, history of injury secondary to syncope was found to be the strongest independent predictor for PM implantation (OR: 8.16; P = 0.00027; 95% [CI]: (2.67-26.27). A history of injury secondary to syncope and female sex were independent predictive factors for bradycardia necessitating PM implantation in patients receiving an ILR for syncope with or without ECG conduction abnormalities.

A multisystem diagnostic mystery: unilateral weakness, a rash, and lymphadenopathy.

A multisystem diagnostic mystery: unilateral weakness, a rash, and lymphadenopathy.

Oral Propranolol: A Corner Stone in the Therapeutic Strategy of Infantile Haemangiomas

Oral Propranolol: A Corner Stone in the Therapeutic Strategy of Infantile Haemangiomas Infantile hemangiomas are the most common tumors of childhood. Despite their benign and self-limited nature, some hemangiomas can cause complications such as ulceration or life-altering disfigurement. In addition, they may compromise vital organ function, or herald underlying developmental anomalies of the central nervous system or spine [1]. Until recently, high-dose steroid therapy was the mainstay treatment for problematic proliferating infantile hemangioma [2]. Whilst corticosteroids are effective, they are associated with significant adverse effects as cushing syndrome, growth retardation, hirsutism, hypertension, and immunosuppression [3]. Interferon alpha is a potent inhibitor of angiogenesis that can be used in the treatment of infantile hemangiomas [4]. However, its reported severe neurotoxicity, including spastic diplegia, limits its use to cases with life-threatening hemangiomas that have not responded to other forms of treatment [5]. Vincristine was initially used in the treatment of the Kasabach-Merritt phenomenon [6]. Moreover,it is used as an alternative therapy for glucocorticoid-unresponsive, lifethreatening, or severely life-altering hemangiomas[7]. Pulsed dye laser therapyis another treatment option that was found to be beneficial for select infantile hemangiomas including those with small superficial, ulcerated, or involuting lesions [8,9]. In 2008, a French group accidently observed accelerated involution of large facial hemangiomas in two infants following treatment with propranolol for heart failure [10]. These favorable results led to the initiation of some case reports and observational studies to evaluate the efficacy of propranolol in the treatment of proliferating infantile hemangioma [11-14]. To date, the mechanism of action of propranolol on infantile hemangioma is not clear [15]. Moreover, there are some concerns about the potential complications with propranolol usage. The most frequently reported serious side effects were asymptomatic hypotension, asymptomatic bradycardia[16], pulmonary symptoms related to blockade of adrenergic bronchodilation [17], hypoglycemia [17], and hyperkalemia [18]. The most commonly reported non potentially life-threatening side effects were sleep disturbances including nightmares, somnolence, cool or mottled extremities, diarrhea, and gastroesophageal reflux/upset [19]. .

Efficacy and Safety of Ivabradine in Patients with Chronic Systolic Heart Failure and Low Blood Pressure in the SHIFT Trial

Background and objective: Recommended pharmacological agents used in chronic heart failure (HF) usually reduce blood pressure (BP) limiting their application and/or dose in a substantial number of patients. In the SHIFT trial in 61% of participants systolic BP was lower than 130 mmHg. Ivabradine reduces heart rate without impact on BP or myocardial function and improves major HF outcomes, as shown by the SHIFT trial. We investigated 1) the clinical profile and outcomes of the SHIFT population by baseline blood pressure tertiles, and 2) the efficacy and safety of ivabradine in these different BP groups. Methods and results: 6505 patients with chronic HF and LVSD (EF ≤35%) and a HF hospitalization during the previous year, in sinus rhythm, with heart rate ≥70 bpm, randomized to placebo or ivabradine (2.5 to 7.5 mg bid), were divided into tertiles according to baseline systolic BP (SBP): low <115 mmHg (n=2010), intermediate 115-130 mmHg (n=1968), and high SBP≥130 mmHg (n=2427). Multivariate Cox model analyses were performed to assess outcomes in the placebo groups and the treatment effect of ivabradine in the SBP tertiles. Low SBP patients were younger, had CAD less often, higher heart rate, and higher cardiovascular risk profile than the other 2 tertiles. Rate of beta-blocker prescription was similar in all groups, although the doses were lower in patients with low SBP (45% of patients received ≥50% of the target dose vs 63% of patients with SBP≥130 mmHg, P<0.001). ACE inhibitors were less prescribed in low SBP patients (76% vs 81% in patients with SBP≥130 mmHg; P<0.001). In the placebo arm the primary end point and its two components, CV death and HF hospitalization, were more frequent in the low SBP subgroup than in the high SBP subgroup (hazard ratio for primary end point: 1.54, P<0.001; CV death: 1.90, P<0.001; HF hospitalization: 1.60, P<0.001) but all these endpoints were reduced similarly by ivabradine in low SBP (RRR: 16%; 11%; 22%), intermediate SBP (RRR: 14%; 4%; 26%), and high SBP (RRR: 23%; 9%; 29%) tertiles (P interaction=0.68; 0.91; 0.79). The overall occurrence of adverse events was similar in the 3 subgroups. As expected, symptomatic or asymptomatic bradycardia and phosphenes occurred more frequently with ivabradine. Conclusions: SHIFT data confirm that the clinical profile and outcomes in HF patients are influenced by baseline blood pressure. However, the benefits and tolerability of ivabradine are similar irrespective of pre-treatment blood pressure.

Retrospective analysis of beta-blocker instituted for treatment of hemangiomas (RABBIT study).

To evaluate the safety and efficacy of our institutional beta-blocker protocol for treatment of complicated infantile hemangiomas (IH). A retrospective descriptive study of 76 infants/children with IH treated with oral propranolol at the Children's Hospital of Philadelphia between June 2008 and August 2010 was performed, assessing both the safety and efficacy of propranolol. Based on preliminary data showing hemangioma recrudescence off-treatment, we reviewed 9 additional patients with recrudescence between August 2010 and December 2011. Mild adverse events included asymptomatic bradycardia, gastrointestinal symptoms, asymptomatic hypotension, cool hands/feet, asymptomatic hypoglycemia, and sleep disturbance. Sixteen patients had recrudescence of IH off-treatment, with propranolol discontinued at a median age of 14 months (interquartile range 10-15 months). Propranolol appears to be associated with minor, not severe symptomatic adverse events. Propranolol appears to be effective in treating complicated IH. Recrudescence can occur off-treatment, even with discontinuing propranolol as late as 15 months of age.

Prolonged altered mental status and bradycardia following pediatric donepezil ingestion

Context. Donepezil is a centrally-acting, reversible acetylcholinesterase inhibitor that is used in the treatment of Alzheimer disease. Altered mental status, nausea, vomiting, and bradycardia have been reported in therapeutic and supratherapeutic ingestions of donepezil, though pediatric exposures have not been well-described. We report a case of prolonged altered mental status and recurrent bradycardia in a child with a single-pill ingestion of donepezil. Case details. A 14-month-old boy was brought to the Emergency Department 3 hours after ingesting one of his grandfather's donepezil tablets (10mg). Upon arrival, he was somnolent and drooling, with multiple episodes of vomiting and diarrhea. Pupils were normal. Initial vitals: temperature, 36.8°C; blood pressure, 103/56 mmHg; heart rate, 140/min; respiratory rate, 36/min; oxygen saturation, 97%. His drooling, vomiting, and diarrhea resolved, but he remained intermittently agitated. Over the course of the following four days, he had intermittent, episodes of asymptomatic bradycardia to a low of 55/min, primarily when sleeping. A transient episode of junctional rhythm was observed. Serum donepezil level 97 hours post-ingestion was 10 ng/ml. He did not require atropine treatment, and was discharged in stable condition on hospital day 5. Discussion. Donepezil has a prolonged elimination of half-life in adults of approximately 70 hours. Despite its relative specificity for central AChEs, peripheral cholinergic symptoms have been described. We report a case of a symptomatic ingestion of donepezil in a child. Conclusions. Even after a single-tablet ingestion, donepezil may cause prolonged altered mental status and bradycardia in young children.

Asymptomatic Sinus Bradycardia Following Bariatric Surgery

Approximately 121,000 bariatric surgical procedures are performed annually, and salutary effects include a reduction in cardiovascular morbidity and mortality, risk factor modification, and improvement in sympathovagal tone. There are anecdotal accounts of unexplained sinus bradycardia (SB) after significant weight loss but no systematic studies have been conducted. The purpose of this study was to determine the frequency of incident SB, its timing, and association with weight loss, clinical characteristics, and predictors. We evaluated various clinical characteristics including resting heart rate, blood pressure, body mass index (BMI), heart rate reserve (HRR), basal metabolic rate, and exercise regimen in 151 consecutive patients who underwent bariatric surgery. Multiple logistic regression analysis was performed to determine predictors of SB. Twenty-five of 137 patients (18%) experienced postoperative SB. Patients with SB had significantly greater reduction in BMI than those without bradycardia (35 ± 9.6% and 25.7 ± 13%, respectively, p = 0.002). HRR was significantly greater in patients with SB (116 ± 14 beats/min) compared with those without bradycardia (105 ± 14 beats/min, p = 0.007). Multiple logistic regression analysis revealed that the odds of developing SB were 1.96 and 1.91 and associated with the percent decrease in BMI (95% confidence interval 1.3 to 3.0, p = 0.002) or increase in HRR (95% confidence interval 1.28 to 2.85, p = 0.002), respectively. In conclusion, SB occurred 14 ± 11 months postoperatively and its predictors were the percent reduction in BMI or increase in HRR.

Nuestra experiencia con fingolimod

IntroductionMultiple Sclerosis (M.S.) is a progressive, autoimmune degenerative disease that is characterized by central nervous system neuro-inflammation. Fingolimod is a medicinal product that has been marketed in the European Union since March 2011, as the first oral treatment for very active and rapidly evolving Relapsing Remitting Multiple Sclerosis. A first dose 6 hour protocol is recommended, due to the effect of bradycardia or heart blockages. This includes monitoring the patient for 6hours after the first dose of Fingolimod, with an electrocardiogram being performed at baseline and at 6hours, as well as monitoring the heart rate and blood pressure. ObjectiveTo assess the immediate cardiac safety of Fingolimod. MethodA record was made of the electrocardiograms, the vital constants graph, and records from the MS patient register from August 2011 to October 2013, as well as those recorded prior to Fingolimod treatment (normal or abnormal electrocardiogram, or medicated or non-medicated bradycardia, prolongation of the 6h of Protocol, and interruption of treatment). ResultsA total 42 patients have started treatment with Fingolimod in our unit. Of this total, 15 patients had been treated with Natalizumab previously (reason for the change: 8 by JC Virus, 3 by hypersensitivity reaction, and inadequate response 4). Asymptomatic bradycardia was observed in 40/42 patients, with none needing treatment. A longer monitoring time was required in 5/42. Treatment was suspended with Fingolimod during follow-up in 3 patients, resumed in 2, and 1 of them re-established with Interferon beta. ConclusionThe immediate cardiac safety of Fingolimod is very good.

Efficacy and safety of ivabradine in patients with chronic systolic heart failure and low blood pressure in the shift trial

Background and objective: Recommended pharmacological agents used in chronic heart failure (HF) usually reduce blood pressure (BP) limiting their application and/or dose in a substantial number of patients. In the SHIFT trial in 61% of participants systolic BP was lower than 130 mmHg. Ivabradine reduces heart rate without impact on BP or myocardial function and improves major HF outcomes, as shown by the SHIFT trial. We investigated 1) the clinical profile and outcomes of the SHIFT population by baseline blood pressure tertiles, and 2) the efficacy and safety of ivabradine in these different BP groups. Methods and results: 6505 patients with chronic HF and LVSD (EF ≤35%) and a HF hospitalization during the previous year, in sinus rhythm, with heart rate ≥70 bpm, randomized to placebo or ivabradine (2.5 to 7.5 mg bid), were divided into tertiles according to baseline systolic BP (SBP): low <115 mmHg (n=2010), intermediate 115-130 mmHg (n=1968), and high SBP≥130 mmHg (n=2427). Multivariate Cox model analyses were performed to assess outcomes in the placebo groups and the treatment effect of ivabradine in the SBP tertiles. Low SBP patients were younger, had CAD less often, higher heart rate, and higher cardiovascular risk profile than the other 2 tertiles. Rate of beta-blocker prescription was similar in all groups, although the doses were lower in patients with low SBP (45% of patients received ≥50% of the target dose vs 63% of patients with SBP≥130 mmHg, P<0.001). ACE inhibitors were less prescribed in low SBP patients (76% vs 81% in patients with SBP≥130 mmHg; P<0.001). In the placebo arm the primary end point and its two components, CV death and HF hospitalization, were more frequent in the low SBP subgroup than in the high SBP subgroup (hazard ratio for primary end point: 1.54, P<0.001; CV death: 1.90, P<0.001; HF hospitalization: 1.60, P<0.001) but all these endpoints were reduced similarly by ivabradine in low SBP (RRR: 16%; 11%; 22%), intermediate SBP (RRR: 14%; 4%; 26%), and high SBP (RRR: 23%; 9%; 29%) tertiles (P interaction=0.68; 0.91; 0.79). The overall occurrence of adverse events was similar in the 3 subgroups. As expected, symptomatic or asymptomatic bradycardia and phosphenes occurred more frequently with ivabradine. Conclusions: SHIFT data confirm that the clinical profile and outcomes in HF patients are influenced by baseline blood pressure. However, the benefits and tolerability of ivabradine are similar irrespective of pre-treatment blood pressure.

Predictive factors for pacemaker implantation in patients receiving an implantable loop recorder for syncope remained unexplained after an extensive cardiac and neurological workup

Several previous implantable loop recorder (ILR) studies have shown bradyarrhythmic events requiring a pacemaker implantation in a significant proportion of patients with unexplained syncope (US). The aim of this observational, two-centre, study was to identify the predictive factors for pacemaker implantation in a population of patients receiving an ILR for US with suspected arrhythmic aetiology. Fifty-six patients (mean age 68 years, 61% male) with a history of US and negative cardiac and neurological workup, who underwent ILR implantation, were enrolled. After the implantation, a follow-up visit was undertaken after symptomatic events or every 3 months in asymptomatic subjects. The end-point of the study was the detection of a bradyarrhythmia (with or without a syncopal recurrence) requiring pacemaker implantation. After a median ILR observation of 22 months, a clinically significant bradyarrhythmia was detected in 11 patients (20%), of which 9 cases related to syncopal relapses. In the multivariable analysis, three independent predictive factors for pacemaker implantation were identified: an age >75 years (odd ratio [OR]: 29.9; p=0.035); a history of trauma secondary to syncope (OR: 26.8; p=0.039); and the detection of periods of asymptomatic bradycardia, not sufficient to explain the mechanism of syncope, during conventional ECG monitoring (through 24 h Holter or in hospital telemetry), performed before ILR implantation (OR: 24.7; p=0.045). An advanced age, a history of trauma secondary to syncope, and the detection of periods of asymptomatic bradycardia during conventional ECG monitoring were independent predictive factors for bradyarrhythmias requiring pacemaker implantation in patients receiving an ILR for US.

Peripheral Artery Disease as a Manifestation of Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy (CADASIL) and Practical Implications

48-year-old white man was seen in November in the emergency room of a county hospital in Houston with cold blue toes on both feet after exposure to temperatures that were above freezing, and with no snow on the ground. Besides the blue toes, the foot pulses were diminished. The skin over the feet was intact. An arteriogram revealed the absence of flow in multiple digital arteries (Figure 1). Subsequently over the following 2 months, the worst affected toes developed dry gangrene (Figure 2).One month earlier, in October, the patient had been admitted to the same hospital with migranous headaches and memory loss. He had severe dementia on cognitive testing, ataxia, and resting tremors. He had mildly impaired renal function that reversed with hydration. We noted transient, easy to control hypertension and asymptomatic bradycardia. A 12-lead ECG showed sinus bradycardia with no evidence of conduction pathway abnormalities or ongoing acute ischemia (Figure 3). A pharmacological stress test suggested nonreversible single vessel disease in the right coronary artery territory. MRI of the brain showed chronic ischemic changes involving the watershed areas of the frontal and the parietal lobes (Figure 4). On direct questioning, the patient recalled a half-brother who volunteered that they shared the same father, also with severe dementia.With this history of a familial dementia, and ruling out other commoner causes of dementia, a skin biopsy was performed. Electron microscopy showed granular osmiophilic material, confirming the diagnosis of cerebral autosomal dominant arte-riopathy with subcortical infarcts and leukoencephalopathy (CADASIL; Figure 5).At 3 months follow-up after the first encounter, the patient was still severely demented and with dry gangrene of the right 1st through 3rd toes. Unfortunately, he left unannounced from a personal care home before completion of the process of making him a ward of state.

Circulation Editors’ Picks

<i>Circulation</i> Editors’ Picks

ST-Elevation Myocardial Infarction Following Heart Transplantation as an Unusual Presentation of Coronary Allograft Vasculopathy: A Case Report

BackgroundThe presentation, mechanisms, and incidence of ST elevation myocardial infarction (STEMI) in heart transplant recipients have been characterized only to a limited degree in the current literature. Herein, we present a unique case of STEMI years after heart transplantation with a focus on the salient features of its diagnosis and interventions. We also provide a review of the epidemiology of this phenomenon. Case ReportA 33-year-old woman who was status post cardiac transplantation for dilated cardiomyopathy presented to the clinic with mild nonspecific fatigue and concern after having noticed relative bradycardia compared with her posttransplantation baseline heart rate. Electrocardiogram (ECG) showed junctional rhythm and inferior ST elevations, likely reflecting nodal ischemia. Troponins were grossly positive and echocardiogram showed marked right ventricular dysfunction. ResultsSuccessful percutaneous coronary intervention (PCI) with aspiration thrombectomy and drug-eluting stent placement was emergently performed. The heart's rhythm soon returned to sinus tachycardia. Right ventricular wall-motion abnormalities resolved. The patient suffered no clinical sequelae of her STEMI. ConclusionThis case illustrated that “classic” symptoms of STEMI may not occur at all in the setting of heart transplantation. To our knowledge, this is the first case of posttransplantation STEMI presenting as asymptomatic bradycardia, and highlights the importance of maintaining high clinical suspicion for ischemia in transplant recipients with subtle changes. In reviewing the epidemiology of this case, we locate and bundle different types of studies that have directly or indirectly looked at STEMI in heart transplantation. For a variety of putative pathophysiological reasons, STEMI is indeed a rare manifestation of the common transplant phenomenon of coronary artery vasculopathy (CAV).

Recurrent Bradycardia Episodes Induced by Cisplatin Infusion

Chemotherapy may induce entire spectrum of cardiac pathology. Cisplatin has been used in oncology practice for a long time, but no sufficient clinical evidence exists about arrhythmogenic potential of this drug. We report a rarely diagnosed case of asymptomatic bradycardia probably induced by cisplatin infusion. In December 2010, a 28 years of woman was diagnosed with Sertoli-Leydig cell tumor. Three courses of BEP (bleomycine, etoposide, and cisplatin) chemotherapy was planned because of the poor prognostic factors. During the third course of chemotherapy, she had bradycardia during cisplatin infusion on routine vital sign assesments. Her physical examination including blood pressure was within normal limits. Electrocardiogram (ECG) revealed sinus bradycardia (40 beats/min). The patient had no clinical symptoms consistent with vagal stimulation. Blood pressure remained normal during and after the bradycardia episode. Concomitant serum concentrations of urea, creatinine, and electrolites (sodium, potassium, calcium, chloride, and magnesium) were within normal ranges. Her chemotherapy was terminated and 24-hour holter ECG was performed to reveal the bradycardia episodes. She had asyptomatic bradycardia during the records of holter ECG. After a few days of follow up her bradycardia episodes resolved. It was worthwile for this case presentation because the patient presented with asymptomatic bradycardia after cisplatin infusion. Cisplatin-induced sinus bradycardia is an unusual adverse effect with underlying mechanisms that remain to be clarified.

Pyridostigmine-induced high grade SA-block in a patient with myasthenia gravis

Patient: Female, 70Final Diagnosis: SA block induced by pyridostigmineSymptoms: AsymptomaticMedication: PyridostigmineClinical Procedure: Pacemaker insertionSpecialty: ElectrophysiologyObjective:Unusual clinical courseBackground:Myasthenia gravis requires a long-term treatment with a parasympathomimetic agent, which may result in bradycardia and asystole. Pharmacologic treatment with a reversible inhibitor of inosine monophosphate dehydrogenase (IMPDH) and Methylprednisolone is seen to improve the muscular symptoms but may reinforce potential bradyarrhythmias. This potential side effect can be treated with the levo isomer of atropine, Hyoscyamine, or Glycopyrollate in an intact conduction system.Case Report:A 70-year old Caucasian female patient with a family history of myasthenia gravis presented with mild weakness of the bilateral facial muscles, moderate dysarthria, dysphagia, diplopia predominantly on the right side and difficulty tracking ocular movements bilaterally. The treatment with pharmacological agents was initiated. Subsequently she developed asymptomatic bradycardia and SA-block. An improvement on Hyoscyamine failed to appear. A dual chamber pacemaker was placed.Conclusions:In symptomatic or asymptomatic bradycardia with significant high grade SA-block in patients with myasthenia gravis the insertion of a permanent pacemaker can be the definitive solution.