Implanted cardiac arrhythmia devices can detect atrial tachyarrhythmias (atrial high-rate episodes AHREs) that are considered to correlate with atrial fibrillation and risk of stroke. In the IMPACT ...trial, oral anticoagulation was initiated when AHREs were detected by implanted cardioverter-defibrillators and withdrawn when they abated, according to a protocol accounting both for AHRE duration as detected by remote device monitoring and stroke risk assessment. In this analysis, we ascertained determinants of time in therapeutic range (TTR) among protocol-determined vitamin K antagonist–treated patients during the trial. We enrolled 2,718 patients with at least 1 additional stroke risk factor (CHADS2 score ≥1) at 104 arrhythmia centers. The sex, age <60, medical history, treatments interacting with VKA, tobacco use (2 points) and race (2 points for non-Caucasian) (SAMe-TT2 R2 ) score is a simple clinical-derived score designed to aid decision-making on whether a patient is likely to achieve good anticoagulation control on vitamin K antagonist (e.g., warfarin), which was calculated and related to TTR achieved using the Rosendaal method. We analyzed 229 patients (mean age 66.7 years; mean CHADS2 score 2.85 SD 1.1) with mean TTR of 0.536 (SD 0.23) overall. Univariate analysis identified 5 variables associated with differences in mean TTR. Mean TTR was lower in those who were women (p = 0.031), of black race (p = 0.005) and in New York Heart Association class IV (p = 0.014), whereas hemoglobin >13.5 g/dl (p = 0.010) and New York Heart Association class I (p = 0.037) were associated with higher mean TTR. There was a significant difference in mean TTR value between US and non-US sites (Canada and Germany) (mean TTR for US: 0.513 vs non-US: 0.686; p <0.0001). Mean TTR was significantly lower (Δ = 0.1382, 95% CI 0.0382 to 0.2382) for patients with SAMe-TT2 R2 scores of 4 (p = 0.007) and higher (Δ = 0.0612, 95% CI 0.0005 to 0.1219) for patients with SAMe-TT2 R2 scores of 1 (p = 0.048). Linear regression confirmed a significant association between lower SAMe-TT2 R2 score and improved anticoagulation control (p = 0.0021) with a 1-unit decrease in SAMe-TT2 R2 score associated with an increase in TTR of 0.0404 (95% CI 0.0149 to 0.0659). In conclusion, clinical, geographical, and demographic factors were associated with the quality of anticoagulation control as reflected by TTR. Although overall TTR in this population was poor, lower SAMe-TT2 R2 scores were associated with better TTR.
The role of atrial-based pacing algorithms in preventing atrial fibrillation (AF) remains controversial. The inconsistent results noted in previous trials may be due in part to differences in ...endpoints, pacing algorithms, and study design. SAFARI, a worldwide, prospective, randomized clinical trial, was designed to address these issues and to evaluate the safety and efficacy of a suite of prevention pacing therapies (PPTs) among patients with paroxysmal AF.
Patients who met standard pacemaker indications and documented symptomatic AF were implanted with a pacemaker (Vitatron Selection 9000). At 4 months, only patients with documented AF despite dual-chamber pacing were randomized to PPTs ON or PPTs OFF and followed for 6 months. Incidence of permanent AF and change in AF burden were compared between the two groups. Among the 555 patients enrolled, 240 had AF burden at 4 months and were randomized. The risk of developing permanent AF was similar in both groups (0 in the PPTs ON group vs. 3 in the OFF group). However, there was a significant reduction in AF burden between baseline and 10-month follow-up in the ON group compared with the OFF group (median decrease of 0.08 hours/day vs no change, P = .03).
Among patients with paroxysmal AF and standard bradycardia indications, PPTs are safe and associated with less AF burden compared with conventional pacing.
Beyond MADIT Deeprasertkul, Peerawut; Sharma, Amit B.; Ip, John
Journal of arrhythmia,
December 2013, Volume:
29, Issue:
6
Journal Article
Peer reviewed
Open access
Abstract Sudden cardiac death remains the global burden. The most common associated arrhythmia is ventricular fibrillation. From current guidelines, defibrillation is the most critical step to rescue ...the cardiac arrest victims. Internal defibrillators were invented for prompt treating the ventricular arrhythmia. The MADIT trial the benchmark randomized controlled trial that demonstrated the efficacy of defibrillators for sudden death protection and not only that MADIT-RIT which addresses the issue of inappropriate therapy with ICD and MADIT-CRT which highlights the importance of biventricular pacing in patients with cardiomyopathy with mild heart failure symptoms. Hereby, we review the articles the MADIT trials.
Atrial fibrillation and atrial flutter are common cardiac arrhythmias associated with an increased risk of stroke in patients with additional risk factors. Anticoagulation ameliorates stroke risk, ...but because these arrhythmias may occur intermittently without symptoms, initiation of prophylactic therapy is often delayed until electrocardiographic documentation is obtained. The IMPACT study is a multicenter, randomized trial of remote surveillance technology in patients with implanted dual-chamber cardiac resynchronization therapy defibrillator (CRT-D) devices designed to test the hypothesis that initiation and withdrawal of oral anticoagulant therapy guided by continuous ambulatory monitoring of the atrial electrogram improve clinical outcomes by reducing the combined rate of stroke, systemic embolism, and major bleeding compared with conventional clinical management. For those in the intervention group, early detection of atrial high-rate episodes (AHRE) generates an automatic alert to initiate anticoagulation based on patient-specific stroke risk stratification. Subsequently, freedom from AHRE for predefined periods prompts withdrawal of anticoagulation to avoid bleeding. Patients in the control arm are managed conventionally, the anticoagulation decision prompted by incidental detection of atrial fibrillation or atrial flutter during routine clinical follow-up. The results will help define the clinical utility of wireless remote cardiac rhythm surveillance and help establish the critical threshold of AHRE burden warranting anticoagulant therapy in patients at risk of stroke. In this report, we describe the study design and baseline demographic and clinical features of the initial cohort (227 patients).
Background Recent observations suggest statin treatment may be associated with lower mortality in heart failure (HF). The SCD-HeFT was a study of 2521 functional class II and III HF patients with ...left ventricular ejection fractions ≤35% and ischemic and nonischemic cardiomyopathy followed up for a median of 45.5 months. The study length, size, and degree of background HF, including the use of implantable defibrillator therapy, provide a unique opportunity to evaluate the impact of statin use in HF with mechanistic insights from subgroup analyses. Methods and Results Statin use was reported in 965 (38%) of 2521 patients at baseline and 1187 (47%) at last follow-up. The relationships between statin use, randomization arm, disease category, and functional class and all cause mortality were assessed. Statin use was studied as a time-dependent covariate in a multivariable Cox proportional hazards model, adjusted for imbalances between statin and no-statin groups. Mortality risk was significantly lower in those taking a statin (HR 95% CI, 0.70 0.58-0.83). Mortality risk was lower with statin use in all prespecified subgroups: ischemic cardiomyopathy (0.69 0.56-0.86), nonischemic cardiomyopathy (0.67 0.47-0.96), implantable cardioverter defibrillator (ICD) (0.66 0.46-0.95, non-ICD (0.71 0.57-0.87), New York Heart Association II (0.62 0.48-0.79), and New York Heart Association III (0.79 0.61-1.03). Conclusions Statin use is associated with reduced all-cause mortality in HF patients. Statins appear to benefit patients with nonischemic and ischemic cardiomyopathy similarly. Statin benefits are similar in ICD and non-ICD patients.
Invasive pneumococcal disease remains an important health priority owing to increasing disease incidence caused by pneumococci expressing non-vaccine serotypes. We previously defined 621 Global ...Pneumococcal Sequence Clusters (GPSCs) by analysing 20 027 pneumococcal isolates collected worldwide and from previously published genomic data. In this study, we aimed to investigate the pneumococcal lineages behind the predominant serotypes, the mechanism of serotype replacement in disease, as well as the major pneumococcal lineages contributing to invasive pneumococcal disease in the post-vaccine era and their antibiotic resistant traits.
We whole-genome sequenced 3233 invasive pneumococcal disease isolates from laboratory-based surveillance programmes in Hong Kong (n=78), Israel (n=701), Malawi (n=226), South Africa (n=1351), The Gambia (n=203), and the USA (n=674). The genomes represented pneumococci from before and after pneumococcal conjugate vaccine (PCV) introductions and were from children younger than 3 years. We identified predominant serotypes by prevalence and their major contributing lineages in each country, and assessed any serotype replacement by comparing the incidence rate between the pre-PCV and PCV periods for Israel, South Africa, and the USA. We defined the status of a lineage as vaccine-type GPSC (≥50% 13-valent PCV PCV13 serotypes) or non-vaccine-type GPSC (>50% non-PCV13 serotypes) on the basis of its initial serotype composition detected in the earliest vaccine period to measure their individual contribution toward serotype replacement in each country. Major pneumococcal lineages in the PCV period were identified by pooled incidence rate using a random effects model.
The five most prevalent serotypes in the PCV13 period varied between countries, with only serotypes 5, 12F, 15B/C, 19A, 33F, and 35B/D common to two or more countries. The five most prevalent serotypes in the PCV13 period varied between countries, with only serotypes 5, 12F, 15B/C, 19A, 33F, and 35B/D common to two or more countries. These serotypes were associated with more than one lineage, except for serotype 5 (GPSC8). Serotype replacement was mainly mediated by expansion of non-vaccine serotypes within vaccine-type GPSCs and, to a lesser extent, by increases in non-vaccine-type GPSCs. A globally spreading lineage, GPSC3, expressing invasive serotypes 8 in South Africa and 33F in the USA and Israel, was the most common lineage causing non-vaccine serotype invasive pneumococcal disease in the PCV13 period. We observed that same prevalent non-vaccine serotypes could be associated with distinctive lineages in different countries, which exhibited dissimilar antibiotic resistance profiles. In non-vaccine serotype isolates, we detected significant increases in the prevalence of resistance to penicillin (52 21% of 249 vs 169 29% of 575, p=0·0016) and erythromycin (three 1% of 249 vs 65 11% of 575, p=0·0031) in the PCV13 period compared with the pre-PCV period.
Globally spreading lineages expressing invasive serotypes have an important role in serotype replacement, and emerging non-vaccine serotypes associated with different pneumococcal lineages in different countries might be explained by local antibiotic-selective pressures. Continued genomic surveillance of the dynamics of the pneumococcal population with increased geographical representation in the post-vaccine period will generate further knowledge for optimising future vaccine design.
Bill & Melinda Gates Foundation, Wellcome Sanger Institute, and the US Centers for Disease Control.
The Atrial Dynamic Overdrive Pacing Trial (ADOPT) was a single blind, randomized, controlled study to evaluate the efficacy and safety of the atrial fibrillation (AF) Suppression Algorithm (St. Jude ...Medical Cardiac Rhythm Management Division, Sylmar, California) in patients with sick sinus syndrome and AF.
This algorithm increases the pacing rate when the native rhythm emerges and periodically reduces the rate to search for intrinsic atrial activity.
Symptomatic AF burden (percentage of days during which symptomatic AF occurred) was the primary end point. Patients underwent pacemaker implantation, were randomized to DDDR with the algorithm on (treatment) or off (control), and were followed for six months.
Baseline characteristics and antiarrhythmic drugs used were similar in both groups. The percentage of atrial pacing was higher in the treatment group (92.9% vs. 67.9%, p < 0.0001). The AF Suppression Algorithm reduced symptomatic AF burden by 25% (2.50% control vs. 1.87% treatment). Atrial fibrillation burden decreased progressively in both groups but was lower in the treatment group at each follow-up visit (one, three, and six months) (p = 0.005). Quality of life scores improved in both groups. The mean number of AF episodes (4.3 +/- 11.5 control vs. 3.2 +/- 8.6 treatment); total hospitalizations (17 control vs. 15 treatment); and incidence of complications, adverse events, and deaths were not statistically different between groups.
The ADOPT demonstrated that overdrive atrial pacing with the AF Suppression Algorithm decreased symptomatic AF burden significantly in patients with sick sinus syndrome and AF. The decrease in relative AF burden was substantial (25%), although the absolute difference was small (2.50% control vs. 1.87% treatment).
Pneumococcal disease outbreaks of vaccine preventable serotype 4 sequence type (ST)801 in shipyards have been reported in several countries. We aimed to use genomics to establish any international ...links between them.
Sequence data from ST801-related outbreak isolates from Norway (n = 17), Finland (n = 11) and Northern Ireland (n = 2) were combined with invasive pneumococcal disease surveillance from the respective countries, and ST801-related genomes from an international collection (n = 41 of > 40,000), totalling 106 genomes. Raw data were mapped and recombination excluded before phylogenetic dating.
Outbreak isolates were relatively diverse, with up to 100 SNPs (single nucleotide polymorphisms) and a common ancestor estimated around the year 2000. However, 19 Norwegian and Finnish isolates were nearly indistinguishable (0–2 SNPs) with the common ancestor dated around 2017.
The total diversity of ST801 within the outbreaks could not be explained by recent transmission alone, suggesting that harsh environmental and associated living conditions reported in the shipyards may facilitate invasion of colonising pneumococci. However, near identical strains in the Norwegian and Finnish outbreaks does suggest that transmission between international shipyards also contributed to those outbreaks. This indicates the need for improved preventative measures in this working population including pneumococcal vaccination.
This randomized crossover double-blind trial compared the efficacy of buccal infiltration with 4% articaine and 2% lidocaine (both with 1:100,000 epinephrine) in securing mandibular first molar pulp ...anesthesia. Injections were given at least 1 week apart in 31 healthy adult volunteers. Electronic pulp testing was undertaken at baseline and at 2 minute intervals until 30 minutes postinjection. A successful outcome was recorded in the absence of pulp sensation on two consecutive maximal pulp tester stimulations (80 μA). 64.5% of articaine and 38.7% of lidocaine infiltrations were successful (p = 0.008). Articaine infiltration produced significantly more episodes of no response to maximum stimulation in first molars than lidocaine (236 and 129, respectively, p < 0.001). Mandibular buccal infiltration is more effective with 4% articaine with epinephrine compared to 2% lidocaine with epinephrine. Both injections were associated with mild discomfort.
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