A common ß1-adrenergic receptor polymorphism predicts favorable response to rate-control therapy in atrial fibrillation.

OBJECTIVES: In this study, we evaluated the impact of 2 common ß1-adrenergic receptor (ß1-AR) polymorphisms (G389R and S49G) in response to ventricular rate control therapy in patients with atrial fibrillation (AF). BACKGROUND: Randomized studies have shown that ventricular rate control is an acceptable treatment strategy in patients with AF. However, identification of patients who will adequately respond to rate-control therapy remains a challenge. METHODS: We studied 543 subjects (63% men; age 61.8 ± 14 years) prospectively enrolled in the Vanderbilt AF registry and managed with rate-control strategy. A "responder" displayed adequate ventricular rate control based on the AFFIRM (Atrial Fibrillation Follow-Up Investigation of Rhythm Management) criteria: average heart rate (HR) at rest ≤80 beats/min; and maximum HR during a 6-min walk test ≤110 beats/min or average HR during 24-h Holter ≤100 beats/min. RESULTS: A total of 295 (54.3%) patients met the AFFIRM criteria. Baseline clinical characteristics were similar in responders and nonresponders except for mean resting HR (76 ± 20 beats/min vs. 70 ± 15 beats/min; p < 0.01) and smoking (6% vs. 1%; p < 0.01). Multiple clinical variables (age, gender, hypertension) failed to predict response to rate-control therapy. By contrast, carriers of Gly variant at 389 were more likely to respond favorably to rate-control therapy; 60% versus 51% in the Arg389Arg genotype, p = 0.04. This association persisted after correction for multiple clinical factors (odds ratio: 1.42, 95% confidence interval: 1.00 to 2.03, p < 0.05). Among responders, subjects carrying the Gly389 variant required the lowest doses of rate-control medications; atenolol: 92 mg versus 68 mg; carvedilol: 44 mg versus 20 mg; metoprolol: 80 mg versus 72 mg; diltiazem: 212 mg versus 180 mg, and verapamil: 276 mg versus 200 mg, respectively (p < 0.01 for all comparisons). CONCLUSIONS: We have identified a common ß1-AR polymorphism, G389R, that is associated with adequate response to rate-control therapy in AF patients. Gly389 is a loss-of-function variant; consequently, for the same adrenergic stimulation, it produces reduced levels of adenyl cyclase, and hence, attenuates the ß-adrenergic cascade. Mechanistically, the effect of rate-control drugs will be synergistic with that of the Gly389 variant, which could possibly explain our findings. These findings represent a step forward in the development of a long-term strategy of selecting treatment options in AF based on genotype.

Arrhythmogenic Munchausen syndrome culminating in caffeine-induced ventricular tachycardia.

We report a patient with numerous abnormal electrocardiograms (ECGs) in both inpatient and outpatient settings. Our patient both simulated and stimulated her arrhythmias with an ECG rhythm generator and intentional caffeine intoxication. To our knowledge, this is the first report of caffeine overdose for arrhythmogenesis.

Clinical characteristics and outcomes of patients with hypertrophic cardiomyopathy with latent obstruction.

BACKGROUND: The purpose of this article is to describe the demographic and clinical features of patients with hypertrophic cardiomyopathy (HCM) and latent obstruction, with an emphasis on identifying factors associated with disease progression and survival. The presence of a resting left ventricular outflow obstruction in patients with HCM has been well described and is associated with increased symptoms and adverse long-term outcomes. However, less is known about patients with latent obstruction. METHODS: Four hundred fifteen patients with echocardiographic or catheterization findings of latent obstruction, defined as a left ventricular outflow pressure gradient <30 mm Hg at rest, which increases to > or =30 mm Hg with provocation, were identified and included in the study group. RESULTS: The mean age was 55.0 +/- 17.9, and 226 (54.6%) patients were male. There were 330 (79.5%) patients with New York Heart Association (NYHA) functional class I and II at baseline. Fifty-nine (17.9%) of these patients had symptom progression requiring septal reduction therapy. Eighty-five patients had severe symptoms (NYHA functional class III and IV) at baseline, and 23 (27.1%) underwent septal reduction. Overall survival at 1, 5, and 10 years was 98%, 91%, and 81%, respectively. Survival among patients after undergoing invasive relief of outflow obstruction was equivalent to the general US population. CONCLUSIONS: Latent obstruction in HCM is an important pathophysiologic entity and may cause heart failure symptoms. One-third of patients in this referral series required invasive therapy for relief of symptoms. The evaluation of HCM patients with resting outflow tract gradients <30 mm Hg must include provocative maneuvers to identify this substantial subset of patients, preferably by physiologic exercise.

Ambulatory monitoring of aborted sudden cardiac death related to hypertrophic cardiomyopathy.

BACKGROUND: A 47-year-old woman with obstructive hypertrophic cardiomyopathy presented with chest pain that had persisted despite treatment with verapamil and alpha-receptor antagonists. The patient had no other significant cardiac symptoms, no history of hypertension, and no familial predisposition to hypertrophic cardiomyopathy or sudden cardiac death. A loud (grade III/VI), dynamic, systolic ejection murmur was noted that could be heard diffusely over the precordium. INVESTIGATIONS: Radionuclide perfusion imaging, coronary angiography, intracoronary Doppler flow measurements, and ambulatory electrocardiographic monitoring. DIAGNOSIS: Obstructive hypertrophic cardiomyopathy, myocardial ischemia and sudden cardiac arrest. MANAGEMENT: Surgical myectomy and cardioverter-defibrillator implantation.