Incidence and prevalence of hypertension in 18-40-year-old patients referred for palpitations with normal cardiac monitor findings.

Sixteen percent of patients referred for cardiology evaluation are found to have no cause for palpitations. Studies show that hypertension intricately influences "heart rate" and "contractility,?" the key components of "palpitation." While the prevalence of hypertension is 22.4% in 18-39-year-olds, the relationship between palpitations and hypertension remains unknown in this age group. In our study, we assessed the incidence and prevalence of hypertension over 5 years in 18-40-year-olds referred for palpitations who had no known arrhythmic cause for palpitations between January 1, 206 and December 31, 2017. We found that over a period of 2.2 (0.7-4.1) years, an additional 56% patients were diagnosed with stage 1 (65/130) and stage 2 (28/130) hypertension, increasing the prevalence from 16% at the start of the study period to 72% at the end of the study period (p < .0001). Hypertensive patients were obese (BMI: 29 [24-36] kg/m2 vs. 25 [22-31] kg/m2; p = .03), used nonsteroidal anti-inflammatory drugs (NSAIDs) (62 vs. 35%; p = .04), had a stronger family history of hypertension (55 vs. 4%; p < .0001) and exhibited higher systolic (124[120-130] mmHg vs. 112[108-115] mmHg; p < .0001) and diastolic (80[76-83] mmHg vs. 72[69-75] mmHg; p < .0001) blood pressures. Hypertension is commonly diagnosed in 18-40-year-old predominantly white female patients referred for palpitations without a known arrhythmic cause. The possibility of untreated hypertension causing palpitations in this cohort needs further evaluation.

Longitudinal QTc stability and impact of baseline cardiac rhythm on discharge dose in dofetilide-treated patients.

INTRODUCTION: Dofetilide suppresses atrial fibrillation (AF) in a dose-dependent fashion. The protective effect of AF against QTc prolongation induced torsades de pointe and transient post-cardioversion QTc prolongation may result in dofetilide under-dosing during initiation. Thus, the optimal timing of cardioversion for AF patients undergoing dofetilide initiation to optimize discharge dose remains unknown as does the longitudinal stability of QTc . The purpose of this study was to evaluate the impact of baseline rhythm on dofetilide dosing during initiation and assess the longitudinal stability of QTc-all (Bazzett, Fridericia, Framingham, and Hodges) over time. METHODS: Medical records of patients who underwent preplanned dofetilide loading at a tertiary care center between January 2016 and 2019 were reviewed. RESULTS: A total of 198 patients (66 ± 10 years, 32% female, CHADS2 -Vasc 3 [2-4]) presented for dofetilide loading in either AF (59%) or sinus rhythm (SR) (41%). Neither presenting rhythm, nor spontaneous conversion to SR impacted discharge dose. The cumulative dofetilide dose before cardioversion moderately correlated (r = .36; p = .0001) with discharge dose. Postcardioversion QTc-all prolongation (p < .0001) prompted discharge dose reduction (890 ± 224 mcg vs. 552 ± 199 mcg; p < .0001) in 30% patients. QTc-all in SR prolonged significantly during loading (p < .0001). All patients displayed QTc-all reduction (p < .0001) from discharge to short-term (46 [34-65] days) that continued at long-term (360 [296-414] days) follow-ups. The extent of QTc-all reduction over time moderately correlated with discharge QTc-all (r = .54-0.65; p < .0001). CONCLUSION: Dofetilide initiation before cardioversion is equivalent to initiation during SR. Significant QTc reduction proportional to discharge QTc is seen over time in all dofetilide-treated patients. QTc returns to preloading baseline during follow-up in patients initiated in SR.

Relationship between Surpoint Tag Index, a Radiofrequency Ablation lesion quality indicator, and Atrial wall thickness in Cavotricuspid isthmus Ablations exhibiting bidirectional block.

BACKGROUND: An RFA lesion quality indicator, Surpoint Tag Index® (TI) incorporates key factors: power, time, and contact force, impacting lesion quality. TI accurately estimates lesion depth in animal studies. However, the relationship between TI and in-vivo atrial wall thickness in patients exhibiting bidirectional block remains unknown. OBJECTIVE: To describe the relationship between atrial wall thickness and TI in CTI exhibiting bidirectional block. METHODS: Data from 492 RFA lesions from 25 patients undergoing PVI and CTI ablations in SR with point-by-point RF lesions (<45 W) utilizing a Thermocool Smarttouch® SF ablation catheter and CARTO-3 mapping were retrospectively analyzed. Operators were blinded to TI data and CTI thickness. CTI thickness was obtained using ICE images on Cartosound pre-ablation. Durable lesions were defined as part of a lesion set exhibiting bidirectional block of >30 min. RESULTS: In lesions exhibiting bidirectional block, the thinnest (1-2 mm; 5% lesions) and thickest (8-10 mm; 6% lesions) portions of the CTI correlated with the lowest (429 ± 75) and highest (516 ± 64) TI. The bulk of thickness (2-6 mm; 80%) correlated with a TI of 455 ± 72 (p = 0.001). There was a weak but positive correlation between TI and CTI thickness (r = 0.2; p ≤ 0.01). Examined in sectors, the anterior 1/3rd CTI was the thickest (4.8 ± 1.9 mm) but correlated with a similar TI value (479 ± 75 vs. 471 ± 70; p = 0.34) as the thinner middle 1/3rd (3.8 ± 1.7 mm; p ≤ 0.0001). CONCLUSION: A mean TI value of 455 correlates with bidirectional block across the bulk of CTI with lower and higher values needed for the thinner and thicker portions, respectively. Tissue composition, aside from wall thickness, influences TI values for the creation of the bidirectional block.

Impact of a dedicated atrial fibrillation clinic on diagnosis-to-ablation time.

Background: Outcomes following catheter ablation (CA) for atrial fibrillation (AF) improve as the diagnosis-to-ablation time (DAT) shortens. Use of a protocol-based integrated care model through a dedicated atrial fibrillation clinic (AFC) may serve to standardize treatment pathways and decrease DAT. Objective: To evaluate the DAT and clinical characteristics of patients with AF referred from an AFC vs a conventional electrophysiology clinic (EC). Methods: Retrospective analysis was completed in consecutive patients undergoing index AF ablation at Riverside Methodist Hospital in 2019 with minimum 1 year follow-up. Patients were categorized based off their CA referral source (AFC vs EC) and where the initial visit following index diagnosis of AF occurred (AFC vs EC). Results: A total of 182 patients (mean age 65 years, 64% male) were reviewed. Patients referred from an AFC (21%) had a median DAT of 342 days (interquartile range [IQR], 125-855 days) compared to patients referred from EC (79%) with a median DAT of 813 days (IQR, 241-1444 days; P = .01). Patients with their index visit following AF diagnosis occurring in the AFC (9%) had significantly shorter median DAT (127 days [IQR, 95-188 days]) compared to EC (91%) (789 days [IQR, 253-1503 days]; P = .002). Patients with DAT <1 year had lower AF recurrence than patients with DAT >1 year (P = .04, hazard ratio = 0.58, 95% confidence interval 0.3418-1.000). Conclusion: DAT is a modifiable factor that may affect CA outcomes. Significant reductions in DAT were observed in patients evaluated through a dedicated AF clinic.

Same-day Discharge after Subcutaneous Implantable Cardioverter-defibrillator Implantation is Safe and Cost-effective.

The feasibility and safety of same-day discharge after transvenous implantable cardioverter-defibrillator implantation is well-established. However, subcutaneous ICDs (S-ICDs) are now increasingly being implanted, and the feasibility, safety, and potential cost savings associated with same-day discharge after S-ICD placement has not been widely investigated. In a small cohort of patients (n = 24) who underwent S-ICD implantation at our institution, 54% were successfully discharged on the same day as their implant procedure. Procedure-related complications were not apparent in this sampling and the reduction in health care costs was high, suggesting this protocol has immense benefit in today's health care environment. As such, same-day discharge of S-ICD patients is appropriate to consider and should receive further attention.

Clinical Impact of Saline Volume Infused Through Irrigated-Tip Ablation Catheter in Low Acuity Paroxysmal Atrial Fibrillation Ablation Patients.

BACKGROUND: Radio-Frequency ablation (RFA) to achieve pulmonary vein isolation (PVI) remains mainstay therapy for symptomatic paroxysmal atrial fibrillation (PAF). The clinical consequences of large saline infusions during AF ablation have not been systematically studied. We utilized the differential flow-rates of the two commercially available ablation catheters (AC): 'ThermoCool' (TCAC) and 'Surround Flow' (SFAC) from Biosense-Webster to evaluate the clinical impact of the saline infused in the immediate post-ablation period. METHODS: Consecutive charts of PAF patients between 18 and 81 years who underwent RFA procedure at a tertiary care hospital were reviewed. RESULTS: Forty-seven patients were included in the study (33Males, 65±11years, LVEF 58±7% and left atrial diameter 44±7.5mm, 23TCAC-use). The saline volume infused through the AC was significantly higher with TCAC vs SFAC use (1277±316vs697±299 ml; p<0.001), with no difference in volume infused from other sources, total procedure or RFA times (p>0.05). This led to significant increase in post-ablation weight gain (96±23 vs 97.5±24kg; p=0.002), furosemide usage (39% vs 0%; p=0.0006), urine production (120±79 vs 63±31ml/hr; p=0.003) and post-RFA potassium reduction (4.4±0.42 vs 4±0.32mmol/l; p<0.001) with TCAC use. Significant post-RFA reduction in magnesium, calcium and creatinine, associated hyperchloremic metabolic acidosis and a modest QTc prolongation were also observed with use of both ACs albeit only moderate to weakly correlated with saline volume infused through the AC. No clinical adverse outcomes were encountered. CONCLUSIONS: Higher saline-volume infusing AC use in PAF ablation causes significant post-ablation weight gain despite higher furosemide use, larger urine production and associated post-RFA potassium reduction without increasing morbidity in lower acuity patients. Furthermore, an array of post-ablation electrolyte disturbances causes a modest and clinically insignificant QTc prolongation.

Azithromycin Causes a Novel Proarrhythmic Syndrome.

BACKGROUND: The widely used macrolide antibiotic azithromycin increases risk of cardiovascular and sudden cardiac death, although the underlying mechanisms are unclear. Case reports, including the one we document here, demonstrate that azithromycin can cause rapid, polymorphic ventricular tachycardia in the absence of QT prolongation, indicating a novel proarrhythmic syndrome. We investigated the electrophysiological effects of azithromycin in vivo and in vitro using mice, cardiomyocytes, and human ion channels heterologously expressed in human embryonic kidney (HEK 293) and Chinese hamster ovary (CHO) cells. METHODS AND RESULTS: In conscious telemetered mice, acute intraperitoneal and oral administration of azithromycin caused effects consistent with multi-ion channel block, with significant sinus slowing and increased PR, QRS, QT, and QTc intervals, as seen with azithromycin overdose. Similarly, in HL-1 cardiomyocytes, the drug slowed sinus automaticity, reduced phase 0 upstroke slope, and prolonged action potential duration. Acute exposure to azithromycin reduced peak SCN5A currents in HEK cells (IC50=110±3 µmol/L) and Na+ current in mouse ventricular myocytes. However, with chronic (24 hour) exposure, azithromycin caused a ≈2-fold increase in both peak and late SCN5A currents, with findings confirmed for INa in cardiomyocytes. Mild block occurred for K+ currents representing IKr (CHO cells expressing hERG; IC50=219±21 µmol/L) and IKs (CHO cells expressing KCNQ1+KCNE1; IC50=184±12 µmol/L), whereas azithromycin suppressed L-type Ca++ currents (rabbit ventricular myocytes, IC50=66.5±4 µmol/L) and IK1 (HEK cells expressing Kir2.1, IC50=44±3 µmol/L). CONCLUSIONS: Chronic exposure to azithromycin increases cardiac Na+ current to promote intracellular Na+ loading, providing a potential mechanistic basis for the novel form of proarrhythmia seen with this macrolide antibiotic.

Feasibility, efficacy, and safety of radiofrequency ablation of atrial fibrillation guided by monitoring of the initial impedance decrease as a surrogate of catheter contact.

BACKGROUND: The initial impedance decrease during radiofrequency (RF) ablation is an indirect marker of catheter contact and lesion formation. We aimed to assess feasibility, efficacy, and safety of an ablation approach guided by initial impedance decrease. METHODS: A total of 25 patients with paroxysmal AF had point-by-point, wide antral pulmonary vein (PV) isolation. RF applications were aborted if a decrease of at least 5 Ω did not occur in the first 10 seconds; otherwise, ablation was continued for at least 20 seconds. Power was 30 Watts and reduced to 15-25 Watts on the posterior wall. RESULTS: A total of 28% of RF applications were terminated because of inadequate impedance decrease. The remaining lesions showed a median decrease of 7.6 Ω (IQR 5.0-10.7) at 10 seconds and median duration of RF lesions was 38 seconds. Note that, 100 PVs were isolated with 49 rings. PVI occurred before anatomic completion of the ablation ring of adequate lesions in 39/49 (80%) and concurrent with ring completion in 7/49 (14%). Additional lesions were required in 3/49 (6%) rings. After PVI, additional lesions were required to eliminate dormant conduction in 2/47 (4%) and pace-capture on the ablation line in 24/49 vein pairs (49%). During short-term follow-up, 3 nonfatal esophageal injuries and 2 late pericardial effusions occurred. During a mean follow-up of 431 ± 87 days, 21/25 patients (84%) remained free of recurrent symptomatic atrial arrhythmias. CONCLUSIONS: PVI guided by initial impedance decrease is feasible and results in PVI concurrent with or before completion of the ablation ring in 94% of patients. Single procedure efficacy after one year of follow-up was 84%. Near-term complications suggest that deeper lesions are created, indicating that further reduction of RF-power and duration is warranted.

Relation of the unipolar low-voltage penumbra surrounding the endocardial low-voltage scar to ventricular tachycardia circuit sites and ablation outcomes in ischemic cardiomyopathy.

INTRODUCTION: Magnetic resonance (MR)-imaging has shown that infarct scars causing ventricular tachycardia (VT) can extend deep to and beyond bipolar low-voltage areas (LVAs) and may be a source of ablation failure. We hypothesized that the size of the unipolar LVA "penumbra" beyond the overlying bipolar scar may predict outcome of endocardial VT ablation. METHODS: Twenty consecutive patients with ischemic cardiomyopathy who underwent endocardial VT ablation were retrospectively reviewed. Bipolar (30-500 Hz) LVA defined as <1.5 mV and unipolar (0.5-500 Hz) LVA defined as <8.3 mV were reviewed on an electroanatomic mapping system. VT isthmus sites were identified from entrainment mapping, VT termination by ablation, or pace-mapping with abolition of VT inducibility by ablation. RESULTS: All bipolar LVAs (70.5 ± 20 cm(2) ) had unipolar LVAs that surrounded the bipolar LVA (147 ± 47 cm(2) ). Only 58% of the induced VTs could be mapped and ablated. During a 3-month follow-up 8/20 patients had VT recurrence. The size of the LVA penumbra was not different for those with (88 ± 47 cm(2) ) versus without (69 ± 35 cm(2) ) recurrences. However, all (8/8) of the group that recurred had isthmus/exits in the bipolar LVA border compared to only 3/12 that did not recur (100% vs. 25%; P < 0.05). Furthermore, 5/8 patients who recurred harbored VT isthmuses in the unipolar LVA penumbra than 1/12 who did not recur (63% vs. 8%; P = 0.01). CONCLUSION: In ischemic cardiomyoapthy, unipolar LVA penumbra of varying size surrounds endocardial bipolar LVA, indicating intramural/epicardial scar. Although the size of this area did not predict early recurrence after endocardial ablation, frequent recurrences after VT ablation at scar periphery suggests deeper substrate toward the infarct border.

Incidence of nonphysiologic short VV intervals detected by the sensing integrity counter with integrated bipolar compared with true bipolar leads: clinically inconsequential or cause for concern?

INTRODUCTION: The need to detect impending implantable cardiac defibrillator (ICD) lead failure has grown. Automated sensing diagnostics have been developed for this reason. The sensing integrity counter (SIC) is one such oversensing diagnostic, which forms an integral part of the Medtronic™ lead integrity alert (LIA) feature on implantable defibrillators. It records nonphysiologic short VV intervals (NPSVVIs). It is unclear whether SIC data derived from integrated bipolar (IBP) leads need to be interpreted differently when compared to true bipolar (TBP) leads. We hypothesized that IBP ICD leads by virtue of a larger "antennae" may generate more NPSVVIs on than TBP leads, leading to more false-positive SIC counts. METHODS: Equal durations of remote monitoring records of 44 patients (mean age of 65.9 ± 2.2 years, 52 % female) with IBP ICD leads and Medtronic (MDT) generators (IBP group) were compared with those of 44 randomly selected patients (64.0 ± 2.2 years, 24 % female) who had TBP ICD leads and MDT generators (TBP group). Mean surveillance time, defined as the time over which the cumulative SIC count was acquired, was 614 ± 44 days (TBP group) vs. 620 ± 49 days (IBP group, p = ns). The mean time of follow-up following the first documented short VV interval was 115.2 months in the integrated bipolar group and 66.9 months in the true bipolar group. Leads on advisory were excluded from the study. RESULTS: A total of 26/44 patients in the IBP group displayed NPSVVI compared to 11/44 patients in the TBP group (59 vs. 25 %; p = 0.002, Fisher exact test). When adjusted for gender and lead age, the difference was still significant (p = 0.008). When evaluating the clinical consequence of NPSVVI in this cohort, 3/11 TBP leads with NPSVVI of >0 were eventually extracted due to additional abnormalities vs. 0/26 IBP leads with NPSVVI (p = 0.02, Fisher exact test). None of the IBP group patients with NPSVVI have developed inappropriate therapy from lead noise or a need for abandonment or extraction. CONCLUSION: Integrated bipolar ICD leads are more likely to have elevated SIC counts than true bipolar leads despite revealing no other evidence of lead failure. There does not appear to be a need for heightened surveillance in IBP leads with observed elevated SIC counts that have no other findings to suggest lead malfunction.

Initial impedance decrease as an indicator of good catheter contact: insights from radiofrequency ablation with force sensing catheters.

BACKGROUND: Good catheter-tissue contact force (CF) is critical for transmural and durable lesion formation during radiofrequency (RF) ablation but is difficult to assess in clinical practice. Tissue heating during RF application results in an impedance decrease at the catheter tip. OBJECTIVE: The purpose of this study was to correlate achieved CF and initial impedance decreases during atrial fibrillation (AF) ablation. METHODS: We correlated achieved CF and initial impedance decreases in patients undergoing ablation for AF with two novel open-irrigated CF-sensing RF catheters (Biosense Webster SmartTouch, n = 647 RF applications; and Endosense TactiCath, n = 637 RF applications). We then compared those impedance decreases to 691 RF applications with a standard open-irrigated RF catheter (Biosense Webster ThermoCool). RESULTS: When RF applications with the CF-sensing catheters were analyzed according to an achieved average CF <5 g, 5-10 g, 10-20 g, and >20 g, the initial impedance decreases during ablation were larger with greater CF. Corresponding median values at 20 seconds were 5 Ω (interquartile range [IQR] 2-7), 8 Ω (4-11), 10 Ω (7-16), and 14 Ω (10-19) with the SmartTouch and n/a, 4 Ω (0-10), 8 Ω (5-12), and 13 Ω (8-18) with the TactiCath (P <.001 between categories for both catheters). When RF applications with the SmartTouch (CF-sensing catheter, median achieved CF 12 g) and ThermoCool (standard catheter) were compared, the initial impedance decrease was significantly greater in the CF-sensing group with median decreases of 10 Ω (6-14 Ω) vs 5 Ω (2-10 Ω) at 20 seconds (P <.001 between catheters). CONCLUSION: The initial impedance decrease during RF applications in AF ablations is larger when greater catheter contact is achieved. Monitoring of the initial impedance decrease is a widely available indicator of catheter contact and may help to improve formation of durable ablation lesions.

Triadin regulates cardiac muscle couplon structure and microdomain Ca(2+) signalling: a path towards ventricular arrhythmias.

Since the discovery of triadin >20 years ago as one of the major proteins located in the junctional sarcoplasmic reticulum, the field has come a long way in understanding the pivotal role of triadin in orchestrating sarcoplasmic reticulum Ca(2+)-release and hence excitation-contraction (EC) coupling. Building on the information gathered from earlier lipid bilayer and myocyte overexpression studies, the gene-targeted ablation of Trdn demonstrated triadin's indispensable role for maintaining the structural integrity of the couplon. More recently, the discovery of inherited and acquired diseases displaying altered expression and function of triadin has further emphasized the role of triadin in health and disease. Novel therapeutic approaches could be aimed at correcting the loss of triadin in diseased hearts, and thereby correcting the sub-cellular EC coupling defect. This review summarizes current concepts of the impact of triadin on cardiac EC coupling with a focus towards triadin's role for ventricular arrhythmia.

An electrocardiographic scoring system for distinguishing right ventricular outflow tract arrhythmias in patients with arrhythmogenic right ventricular cardiomyopathy from idiopathic ventricular tachycardia.

BACKGROUND: Ventricular arrhythmias in patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) and idiopathic ventricular tachycardia (VT) can share a left bundle branch block/inferior axis morphology. We previously reported electrocardiogram characteristics during outflow tract ventricular arrhythmias that helped distinguish VT related to ARVD/C from idiopathic VT. OBJECTIVE: To prospectively validate these criteria. METHODS: We created a risk score by using a derivation cohort. Two experienced electrophysiologists blinded to the diagnosis prospectively scored patients with VT/premature ventricular contractions (PVCs) with left bundle branch block/inferior axis pattern in a validation cohort of 37 ARVD/C tracings and 49 idiopathic VT tracings. All patients with ARVD/C had their diagnosis confirmed based on the revised task force criteria. Patients with idiopathic VT were selected based on structurally normal hearts with documented right ventricular outflow tract VT successfully treated with ablation. The scoring system provides 3 points for sinus rhythm anterior T-wave inversions in leads V1-V3 and during ventricular arrhythmia: 2 points for QRS duration in lead I≥120 ms, 2 points for QRS notching, and 1 point for precordial transition at lead V5 or later. RESULTS: A score of 5 or greater was able to correctly distinguish ARVD/C from idiopathic VT 93% of the time, with a sensitivity of 84%, specificity of 100%, positive predictive value of 100%, and negative predictive value of 91%. CONCLUSIONS: We describe a simple scoring algorithm that uses 12-lead electrocardiogram characteristics to effectively distinguish right ventricular outflow tract arrhythmias originating from patients with ARVD/C versus patients with idiopathic VT.

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.