Arshad Jahangir

Long-Term Progression and Outcomes With Aging in Patients With Lone Atrial Fibrillation: A 30-Year Follow-Up Study

Background— The long-term natural history of lone atrial fibrillation is unknown. Our objective was to determine the rate and predictors of progression from paroxysmal to permanent atrial fibrillation over 30 years and the long-term risk of heart failure, thromboembolism, and death compared with a control population. Methods and Results— A previously characterized Olmsted County, Minnesota, population with first episode of documented atrial fibrillation between 1950 and 1980 and no concomitant heart disease or hypertension was followed up long term. Of this unique cohort, 76 patients with paroxysmal (n=34), persistent (n=37), or permanent (n=5) lone atrial fibrillation at initial diagnosis met inclusion criteria (mean age at diagnosis, 44.2±11.7 years; male, 78%). Mean duration of follow-up was 25.2±9.5 years. Of 71 patients with paroxysmal or persistent atrial fibrillation, 22 had progression to permanent atrial fibrillation. Overall survival of the 76 patients with lone atrial fibrillation was 92% and 68% at 15 and 30 years, respectively, similar to 86% and 57% survival for the age- and sex-matched Minnesota population. Observed survival free of heart failure was slightly worse than expected (P=0.051). Risk for stroke or transient ischemic attack was similar to the expected population risk during the initial 25 years of follow-up but increased thereafter (P=0.004), although CIs were wide. All patients who had a cerebrovascular event had developed ≥1 risk factor for thromboembolism. Conclusions— Comorbidities significantly modulate progression and complications of atrial fibrillation. Age or development of hypertension increases thromboembolic risk.

Familial atrial fibrillation is a genetically heterogeneous disorder.

OBJECTIVES The aims of this study were to identify and characterize familial cases of atrial fibrillation (AF) in our clinical practice and to determine whether AF is genetically heterogeneous. BACKGROUND Atrial fibrillation is not generally regarded as a heritable disorder, yet a genetic locus for familial AF was previously mapped to chromosome 10. METHODS Of 2,610 patients seen in our arrhythmia clinic during an 18-month study period, 914 (35%) were diagnosed with AF. Familial cases were identified by history and medical records review. Four multi-generation families with autosomal dominant AF (FAF 1 to 4) were tested for linkage to the chromosome 10 AF locus. RESULTS Fifty probands (5% of all AF patients; 15% of lone AF patients) were identified with lone AF (age 41 +/- 9 years) and a positive family history (1 to 9 additional relatives affected). In FAF 1 to 3, AF was associated with rapid ventricular response. In contrast, AF in FAF-4 was associated with a slow ventricular response and, with progression of the disease, junctional rhythm and cardiomyopathy. Genotyping of FAF 1 to 4 with deoxyribonucleic acid markers spanning the chromosome 10q22-q24 region excluded linkage of AF to this locus. In FAF-4, linkage was also excluded to the chromosome 3p22-p25 and lamin A/C loci associated with familial AF, conduction system disease, and dilated cardiomyopathy. CONCLUSIONS Familial AF is more common than previously recognized, highlighting the importance of genetics in disease pathogenesis. In four families with AF, we have excluded linkage to chromosome 10q22-q24, establishing that at least two disease genes are responsible for this disorder.

Use of Herbal Products and Potential Interactions in Patients With Cardiovascular Diseases

More than 15 million people in the U.S. consume herbal remedies or high-dose vitamins. The number of visits to providers of complementary and alternative medicine exceeds those to primary care physicians, for annual out-of-pocket costs of

Syncope Evaluation in the Emergency Department Study (SEEDS) A Multidisciplinary Approach to Syncope Management

30 billion. Use of herbal products forms the bulk of treatments, particularly by elderly people who also consume multiple prescription medications for comorbid conditions, which increases the risk of adverse herb-drug-disease interactions. Despite the paucity of scientific evidence supporting the safety or efficacy of herbal products, their widespread promotion in the popular media and the unsubstantiated health care claims about their efficacy drive consumer demand. In this review, we highlight commonly used herbs and their interactions with cardiovascular drugs. We also discuss health-related issues of herbal products and suggest ways to improve their safety to better protect the public from untoward effects.

Long-term survival after ablation of the atrioventricular node and implantation of a permanent pacemaker in patients with atrial fibrillation

Background—The primary aim and central hypothesis of the study are that a designated syncope unit in the emergency department improves diagnostic yield and reduces hospital admission for patients with syncope who are at intermediate risk for an adverse cardiovascular outcome. Methods and Results—In this prospective, randomized, single-center study, patients were randomly allocated to 2 treatment arms: syncope unit evaluation and standard care. The 2 groups were compared with &khgr;2 test for independence of categorical variables. Wilcoxon rank sum test was used for continuous variables. Survival was estimated with the Kaplan-Meier method. One hundred three consecutive patients (53 women; mean age 64±17 years) entered the study. Fifty-one patients were randomized to the syncope unit. For the syncope unit and standard care patients, the presumptive diagnosis was established in 34 (67%) and 5 (10%) patients (P<0.001), respectively, hospital admission was required for 22 (43%) and 51 (98%) patients (P<0.001), and total patient-hospital days were reduced from 140 to 64. Actuarial survival was 97% and 90% (P=0.30), and survival free from recurrent syncope was 88% and 89% (P=0.72) at 2 years for the syncope unit and standard care groups, respectively. Conclusions—The novel syncope unit designed for this study significantly improved diagnostic yield in the emergency department and reduced hospital admission and total length of hospital stay without affecting recurrent syncope and all-cause mortality among intermediate-risk patients. Observations from the present study provide benchmark data for improving patient care and effectively utilizing healthcare resources.

KATP channel mutation confers risk for vein of Marshall adrenergic atrial fibrillation

Background In patients with atrial fibrillation that is refractory to drug therapy, radio-frequency ablation of the atrioventricular node and implantation of a permanent pacemaker are an alternative therapeutic approach. The effect of this procedure on long-term survival is unknown. Methods We studied all patients who underwent ablation of the atrioventricular node and implantation of a permanent pacemaker at the Mayo Clinic between 1990 and 1998. Observed survival was compared with the survival rates in two control populations: age- and sex-matched members of the Minnesota population between 1970 and 1990 and consecutive patients with atrial fibrillation who received drug therapy in 1993. Results A total of 350 patients (mean [±SD] age, 68±11 years) were studied. During a mean of 36±26 months of follow-up, 78 patients died. The observed survival rate was significantly lower than the expected survival rate based on the general Minnesota population (P<0.001). Previous myocardial infarction (P< 0.001), a hi...

Global right atrial mapping of human atrial flutter : The presence of posteromedial (sinus venosa region) functional block and double potentials : A study in biplane fluoroscopy and intracardiac echocardiography

Background A 53-year-old female presented with a 10-year history of paroxysmal atrial fibrillation (AF), precipitated by activity and refractory to medical therapy. In the absence of traditional risk factors for disease, a genetic defect in electrical homeostasis underlying stress-induced AF was explored.Investigations Echocardiography, cardiac perfusion stress imaging, invasive electrophysiology with isoproterenol provocation, genomic DNA sequencing of KATP channel genes, exclusion of mutation in 2,000 individuals free of AF, reconstitution of channel defect with molecular phenotyping, and verification of pathogenic link in targeted knockout.Diagnosis KATP channelopathy caused by missense mutation (Thr1547Ile) of the ABCC9 gene conferring predisposition to adrenergic AF originating from the vein of Marshall.Management Disruption of arrhythmogenic gene–environment substrate at the vein of Marshall by radiofrequency ablation.

Molecular cloning and functional expression of a novel brain-specific inward rectifier potassium channel

BACKGROUND Previous studies of atrial flutter have found linear block at the crista terminalis; this was thought to predispose the patient to the arrhythmia. More recent observations, however, have demonstrated crista conduction. We sought to characterize the posterior boundary of atrial flutter. METHODS AND RESULTS Patients with counterclockwise flutter (n=20), clockwise flutter (n=3), or both (n=5) were studied using two 20-pole catheters. Biplane fluoroscopy determined catheter positions. During counterclockwise flutter, craniocaudal activation occurred along the entire lateral and posterior right atrial walls. Septal activation proceeded caudocranially. In all patients, a line of block was seen in the posteromedial (sinus venosa) right atrium; this was manifested by the presence of double potentials where the upward and downward activations collided. Anatomic location was confirmed by intracardiac echocardiography in 9 patients. In patients with clockwise flutter, the line of block and double potentials were seen in the same location during counterclockwise flutter, but the activation sequence around the line of block was reversed. Pacing near the site of double potentials during sinus rhythm excluded a fixed line of block, and premature atrial complexes demonstrated functional block with manifest double potentials. In 2 patients, posterior ectopy organized to subsequently initiate isthmus-dependent atrial flutter. CONCLUSIONS (1) A functional line of block is seen at the posteromedial (sinus venosa region) right atrium during counterclockwise and clockwise atrial flutter. (2) All lateral wall right atrial activation can be uniform during flutter, without linear block or double potentials in the region of the crista terminalis. (3) Activation at the site of posteromedial right atrial functional block can organize to subsequently initiate isthmus-dependent atrial flutter.

Significant effects of atrioventricular node ablation and pacemaker implantation on left ventricular function and long-term survival in patients with atrial fibrillation and left ventricular dysfunction

We have cloned a novel brain‐specific inward rectifier K+ channel from a mouse brain cDNA library and designated it MB‐IRK3. The mouse brain cDNA library was screened using a fragment of the mouse macrophage inward rectifier K+ channel (IRK1) cDNA as a probe. The amino acid sequence of MB‐IRK3 shares 61% and 64% identity to MB‐IRK1 and RB‐IRK2, respectively.Xenopus oocytes injected with cRNA derived from this clone expressed a potassium current which showed inward‐rectifying channel characteristics similar to MB‐IRK1 and RB‐IRK2 currents, but distinct from ROMK1 or GIRK1 current. However, the single channel conductance of MB‐IRK3 was ∼ 10 pS with 140 mM extracellular K+, which was distinct from that of MB‐IRK1 (20 pS). MB‐IRK3 mRNA expressed specifically in the forebrain, which clearly differed from MB‐IRK1 and RB‐IRK2 mRNAs. These results indicate that members of the IRK family with distinct electrophysiological properties express differentially and may play heterogenous functional roles in brain functions.

Potassium channel openers are uncoupling protonophores: Implication in cardioprotection

Control of ventricular rate by atrioventricular node ablation and pacemaker implantation in patients with drug-refractory atrial fibrillation (AF) is associated with improved left ventricular (LV) function. The objective of this study was to determine the effect of atrioventricular node ablation on long-term survival in patients with AF and LV dysfunction. Survival was determined by the Kaplan-Meier method for 56 study patients with LV ejection fraction (EF) < or =40% who underwent atrioventricular node ablation and pacemaker implantation and 56 age- and gender-matched control patients with AF and LVEF >40%, and age- and gender-matched control subjects from Minnesota. Groups were compared using the log-rank test. In study patients (age 69 +/- 10 years; 45 men), LVEF was 26% +/- 8% and 34% +/- 13% (p <0.001) before and after ablation, respectively. During follow-up (40 +/- 23 months), 23 patients died. Observed survival was worse than that of normal subjects (p <0.001) and control patients (p = 0.005). After ablation, LVEF nearly normalized (> or =45%) in 16 study patients (29%), in whom observed survival was comparable to that of normal subjects (p = 0.37). Coronary artery disease, hyperlipidemia, chronic renal failure, previous myocardial infarction, and coronary artery operation were independent predictors for mortality. Near normalization of LVEF occurred in 29% of study patients, suggesting that AF-induced EF reduction is reversible in many patients. Normal survival in patients with reversible LV dysfunction highlights potential survival benefits of rate control. Poor survival in patients with persistent LV dysfunction confirms the importance of optimal medical therapy.