Regina M. Herges

Success of Ablation for Atrial Fibrillation in Isolated Left Ventricular Diastolic Dysfunction: A Comparison to Systolic Dysfunction and Normal Ventricular Function

Background— The efficacy of radiofrequency ablation for atrial fibrillation (AF) in patients with left ventricular (LV) systolic dysfunction and isolated diastolic dysfunction is uncertain. Methods and Results— A prospective cohort of patients with normal and abnormal LV function underwent ablation for antiarrhythmic drug (AAD)-refractory AF. Three groups were compared: 111 patients with systolic dysfunction, defined as LV ejection fraction (LVEF) ≤40%; 157 patients with isolated diastolic dysfunction but preserved LVEF ≥50%; and 100 patients with normal LV function. The primary end point was AAD-free AF elimination at 1 year after ablation. This end point was achieved in 62% of patients with systolic dysfunction, 75% of those with diastolic dysfunction, and 84% of controls ( P =0.007). AF control on or off AADs was achieved in 76% of patients with systolic dysfunction, 85% of those with diastolic dysfunction, and 89% of controls ( P =0.08). In the systolic dysfunction group, 49% experienced an increase in LVEF by ≥5% after ablation, of which 64% achieved normal LVEF. In the diastolic dysfunction group, 30% of patients demonstrated at least 1 grade improvement in diastolic dysfunction. Multivariable analysis demonstrated an increased relative risk of arrhythmia recurrence of 1.8 (95% CI, 1.1 to 3.1; P =0.02) in systolic dysfunction and 1.7 (1.0 to 2.7; P =0.04) in isolated diastolic dysfunction compared with normal function. Conclusions— Although an ablative approach for AF in patients with systolic or diastolic dysfunction is associated with an increased long-term recurrence risk, there is potential for substantial quality-of-life improvement and LV functional benefit.Background— The efficacy of radiofrequency ablation for atrial fibrillation (AF) in patients with left ventricular (LV) systolic dysfunction and isolated diastolic dysfunction is uncertain. Methods and Results— A prospective cohort of patients with normal and abnormal LV function underwent ablation for antiarrhythmic drug (AAD)-refractory AF. Three groups were compared: 111 patients with systolic dysfunction, defined as LV ejection fraction (LVEF) ⩽40%; 157 patients with isolated diastolic dysfunction but preserved LVEF ≥50%; and 100 patients with normal LV function. The primary end point was AAD-free AF elimination at 1 year after ablation. This end point was achieved in 62% of patients with systolic dysfunction, 75% of those with diastolic dysfunction, and 84% of controls (P=0.007). AF control on or off AADs was achieved in 76% of patients with systolic dysfunction, 85% of those with diastolic dysfunction, and 89% of controls (P=0.08). In the systolic dysfunction group, 49% experienced an increase in LVEF by ≥5% after ablation, of which 64% achieved normal LVEF. In the diastolic dysfunction group, 30% of patients demonstrated at least 1 grade improvement in diastolic dysfunction. Multivariable analysis demonstrated an increased relative risk of arrhythmia recurrence of 1.8 (95% CI, 1.1 to 3.1; P=0.02) in systolic dysfunction and 1.7 (1.0 to 2.7; P=0.04) in isolated diastolic dysfunction compared with normal function. Conclusions— Although an ablative approach for AF in patients with systolic or diastolic dysfunction is associated with an increased long-term recurrence risk, there is potential for substantial quality-of-life improvement and LV functional benefit.

Electrophysiological and hemodynamic characteristics associated with obesity in patients with atrial fibrillation.

OBJECTIVES The authors sought to characterize the left atrial (LA) and pulmonary vein (PV) electrophysiological and hemodynamic features in obese patients with atrial fibrillation (AF). BACKGROUND Obesity is associated with increased risk for AF. METHODS A total of 63 consecutive patients with AF who had normal left ventricular (LV) ejection fraction and who underwent catheter ablation were studied. Atrial and PV electrophysiological studies were performed at the time of ablation with hemodynamic assessment by cardiac catheterization, and LA/LV structure and function by echocardiography. Patients were compared on the basis of body mass index (BMI): <25 kg/m(2) (n = 19) and BMI ≥30 kg/m(2) (n = 44). RESULTS At a 600-ms pacing cycle length, obese patients had shorter effective refractory period (ERP) in the left atrium (251 ± 25 ms vs. 233 ± 32 ms, p = 0.04), and in the proximal (207 ± 33 ms vs. 248 ± 34 ms, p < 0.001) and distal (193 ± 33 ms vs. 248 ± 44 ms, p < 0.001) PV than normal BMI patients. Obese patients had higher mean LA pressure (15 ± 5 mm Hg vs. 10 ± 5 mm Hg, p < 0.001) and LA volume index (28 ± 12 ml/m(2) vs. 21 ± 14 ml/m(2), p = 0.006), and lower LA strain (5.5 ± 3.1% vs. 8.8 ± 2.8%; p < 0.001) than normal BMI patients. CONCLUSIONS Increased LA pressure and volume, and shortened ERP in the left atrium and PV are potential factors facilitating and perpetuating AF in obese patients with AF.

Dyssynchrony Indices To Predict Response to Cardiac Resynchronization Therapy A Comprehensive Prospective Single-Center Study

Background—Whether mechanical dyssynchrony indices predict reverse remodeling (RR) or clinical response to cardiac resynchronization therapy (CRT) remains controversial. This prospective study evaluated whether echocardiographic dyssynchrony indices predict RR or clinical response after CRT. Methods and Results—Of 184 patients with heart failure with anticipated CRT who were prospectively enrolled, 131 with wide QRS and left ventricular ejection fraction <35% had 6-month follow-up after CRT implantation. Fourteen dyssynchrony indices (feasibility) by M-mode (94%), tissue velocity (96%), tissue Doppler strain (92%), 2D speckle strain (65% to 86%), 3D echocardiography (79%), and timing intervals (98%) were evaluated. RR (end-systolic volume reduction ≥15%) occurred in 55% and more frequently in patients without (71%) than in patients with (42%) ischemic cardiomyopathy (P=0.002). Overall, only M-mode, tissue Doppler strain, and total isovolumic time had a receiver operating characteristic area under the curve (AUC) greater than the line of no information, but none of these were strongly predictive of RR (AUC, 0.63 to 0.71). In nonischemic cardiomyopathy, no dyssynchrony index predicted RR. In ischemic cardiomyopathy, M-mode (AUC, 0.67), tissue Doppler strain (AUC, 0.79), and isovolumic time (AUC, 0.76) -derived indices predicted RR (P<0.05 for all), although the incremental value was modest. No indices predicted clinical response assessed by Minnesota Living with Heart Failure Questionnaire, 6-minute walk distance, and peak oxygen consumption. Conclusions—These findings are consistent with the Predictors of Response to CRT study and do not support use of these dyssynchrony indices to guide use of CRT.

Primary hyperoxaluria type III gene HOGA1 (Formerly DHDPSL) as a possible risk factor for idiopathic calcium oxalate urolithiasis

BACKGROUND AND OBJECTIVES Primary hyperoxaluria types I and II (PHI and PHII) are rare monogenic causes of hyperoxaluria and calcium oxalate urolithiasis. Recently, we described type III, due to mutations in HOGA1 (formerly DHDPSL), hypothesized to cause a gain of mitochondrial 4-hydroxy-2-oxoglutarate aldolase activity, resulting in excess oxalate. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS To further explore the pathophysiology of HOGA1, we screened additional non-PHI-PHII patients and performed reverse transcription PCR analysis. Postulating that HOGA1 may influence urine oxalate, we also screened 100 idiopathic calcium oxalate stone formers. RESULTS Of 28 unrelated hyperoxaluric patients with marked hyperoxaluria not due to PHI, PHII, or any identifiable secondary cause, we identified 10 (36%) with two HOGA1 mutations (four novel, including a nonsense variant). Reverse transcription PCR of the stop codon and two common mutations showed stable expression. From the new and our previously described PHIII cohort, 25 patients were identified for study. Urine oxalate was lower and urine calcium and uric acid were higher when compared with PHI and PHII. After 7.2 years median follow-up, mean eGFR was 116 ml/min per 1.73 m(2). HOGA1 heterozygosity was found in two patients with mild hyperoxaluria and in three of 100 idiopathic calcium oxalate stone formers. No HOGA1 variants were detected in 166 controls. CONCLUSIONS These findings, in the context of autosomal recessive inheritance for PHIII, support a loss-of-function mechanism for HOGA1, with potential for a dominant-negative effect. Detection of HOGA1 variants in idiopathic calcium oxalate urolithiasis also suggests HOGA1 may be a predisposing factor for this condition.

Dyssynchrony Indices To Predict Response to Cardiac Resynchronization Therapy

Background—Whether mechanical dyssynchrony indices predict reverse remodeling (RR) or clinical response to cardiac resynchronization therapy (CRT) remains controversial. This prospective study evaluated whether echocardiographic dyssynchrony indices predict RR or clinical response after CRT. Methods and Results—Of 184 patients with heart failure with anticipated CRT who were prospectively enrolled, 131 with wide QRS and left ventricular ejection fraction <35% had 6-month follow-up after CRT implantation. Fourteen dyssynchrony indices (feasibility) by M-mode (94%), tissue velocity (96%), tissue Doppler strain (92%), 2D speckle strain (65% to 86%), 3D echocardiography (79%), and timing intervals (98%) were evaluated. RR (end-systolic volume reduction ≥15%) occurred in 55% and more frequently in patients without (71%) than in patients with (42%) ischemic cardiomyopathy (P=0.002). Overall, only M-mode, tissue Doppler strain, and total isovolumic time had a receiver operating characteristic area under the curve (AUC) greater than the line of no information, but none of these were strongly predictive of RR (AUC, 0.63 to 0.71). In nonischemic cardiomyopathy, no dyssynchrony index predicted RR. In ischemic cardiomyopathy, M-mode (AUC, 0.67), tissue Doppler strain (AUC, 0.79), and isovolumic time (AUC, 0.76) -derived indices predicted RR (P<0.05 for all), although the incremental value was modest. No indices predicted clinical response assessed by Minnesota Living with Heart Failure Questionnaire, 6-minute walk distance, and peak oxygen consumption. Conclusions—These findings are consistent with the Predictors of Response to CRT study and do not support use of these dyssynchrony indices to guide use of CRT.

Cardiac Sympathetic Reserve and Response to Cardiac Resynchronization Therapy

Background— The objective of the present study was to investigate the effect of cardiac resynchronization therapy (CRT) on cardiac autonomic function. Methods and Results— This prospective study included 45 consecutive patients with heart failure who received CRT devices with defibrillator and 20 age-matched, healthy control subjects. At baseline and 3 months and 6 months after CRT, we assessed New York Heart Association (NYHA) class, 6-minute walk distance, plasma sympathetic biomarker nerve growth factor, echocardiography, heart rate variability and cardiac presynaptic sympathetic function determined by iodine 123 metaiodobenzylguanidine scintigraphy. After CRT, NYHA class improved by 1 class (P<0.001), and left ventricular ejection fraction increased by 8% (P<0.001). Along with improvement in the standard deviation of all normal-to-normal R-R intervals (85.63±31.66 ms versus 114.79±38.99 ms; P=0.004) and the standard deviation of the averaged normal-to-normal R-R intervals (82.62±23.03 ms versus 100.50±34.87 ms; P=0.004), the delayed heart/mediastinum (H/M) ratio increased (1.82 [0.58] versus 1.97 [0.59]; P=0.03), whereas the mean (SD) H/M washout rate was reduced (48% [19%] versus 37% [22%]; P=0.01). Twenty-two of 45 study patients responded to CRT, with a reduction of left ventricular end-systolic volume index >15%. Compared with nonresponders, responders had a higher delayed H/M ratio (2.11 versus 1.48; P=0.003) and lower H/M washout rate (37% versus 62%; P=0.003) at baseline. Conclusions— CRT improved sympathetic function. Cardiac sympathetic reserve may be a marker for the reversibility of failing myocardial function.

Atorvastatin for prevention of atrial fibrillation recurrence following pulmonary vein isolation: A double-blind, placebo-controlled, randomized trial

BACKGROUND It is known that statins are effective in preventing atrial fibrillation (AF) in patients undergoing cardiac surgery. OBJECTIVE The purpose of this study was to evaluate the efficacy of statins in preventing AF recurrence following left atrial ablation. METHODS One hundred twenty-five patients who had no statin indication undergoing catheter ablation due to drug-refractory paroxysmal (n = 90) or persistent (n = 35) AF were randomized in a prospective, double-blind, placebo-controlled trial to receive 80 mg atorvastatin (n = 62) or placebo (n = 63) for 3 months. The primary endpoint was freedom from symptomatic AF at 3 months. Secondary endpoints included freedom from any atrial arrhythmia recurrence irrespective of symptoms, quality of life (QoL), and reduction in C-reactive protein (CRP). RESULTS At 3 months, 95% of patients in the atorvastatin group were free of symptomatic AF compared with 93.5% in the placebo group (P = .75). Similarly, 85% of patients treated in the atorvastatin group remained free of any recurrent atrial arrhythmia vs 88% of patients in the placebo group (P = .37). Mean CRP levels decreased in the atorvastatin group (mean change -0.75 ± 3, P = .02) and increased in the placebo group (mean change 2.1 ± 19.9, P = .48). Mean QoL score improved significantly in both groups (mean change 13.14 ± 18.2 in the atorvastatin group and 11.10 ± 17.7 in the placebo group, P = .53). CONCLUSION In patients with no standard indication for statin therapy, treatment with atorvastatin 80 mg/day following AF ablation does not decrease the risk of AF recurrence in the first 3 months and should not be routinely administered to prevent periprocedural arrhythmias.

Left Atrial Blood Stasis and Von Willebrand Factor–ADAMTS13 Homeostasis in Atrial Fibrillation

Objective—Left atrial blood stasis is associated with increased risk for left atrial appendage thrombus (LAAT) and stroke in atrial fibrillation (AF). Von Willebrand factor (VWF) is associated with thromboembolism in AF. VWF thrombogenic activity is proportional to multimer size, which is regulated by VWF-cleaving protease (ADAMTS13). Methods and Results—To assess the association between left atrial blood stasis and VWF-ADAMTS13 system, plasma VWF antigen (VWF:Ag), VWF activity (VWF:Act), and ADAMTS13 activity were measured in 414 consecutive patients with nonvalvular AF (age 63±13 years; 25% women) and in 100 patients (age 64±14 years; 39% women) with normal sinus rhythm. Spontaneous echocardiographic contrast (SEC), left atrial appendage emptying velocity, and LAAT were assessed by transesophageal echocardiography. Presence and intensity of SEC varied directly with VWF:Ag and VWF:Act but not with ADAMTS13 activity. AF patients with LAAT had higher VWF:Ag (200±61 versus 155±52, P=0.0006) and VWF:Act (179±57 versus 141±51 P=0.0026) compared with those without LAAT. VWF:Ag and VWF:Act were independent predictors of LAAT after adjustment for CHADS2 score (P=0.0179 and P=0.0497, respectively). Conclusion—The association between VWF and SEC may explain the thrombotic propensity in AF. Elevated VWF:Ag may help identify AF patients at risk for LAAT.

Doppler echocardiography of 240 normal Carpentier-Edwards Duraflex porcine mitral bioprostheses: a comprehensive assessment including time velocity integral ratio and prosthesis performance index.

Normal Doppler-derived echocardiographic data for Carpentier-Edwards Duraflex (Edwards Lifesciences, Irvine, CA) porcine bioprosthesis function in the mitral position are limited to 2 small series that did not include all Doppler-derived variables. The purpose of this study was to provide a comprehensive Doppler echocardiographic assessment of normal Carpentier-Edwards Duraflex mitral bioprosthesis function in a large number of patients assessed in the early postoperative phase. All of the important Doppler-derived hemodynamic variables reported to date were used. All patients had either a mitral valve prosthesis time velocity integral to left ventricular outflow tract time velocity integral ratio < 3.9 or an E velocity < 2.8. The pressure half-time was < 130 msec in all patients. Nearly all patients (97%) had an E velocity < 2.8 msec and a mitral valve prosthesis time velocity integral to left ventricular outflow tract time velocity integral ratio < 3.9 regardless of bioprosthesis size, left ventricular function, heart rate, hemoglobin, or hematocrit. With increasing bioprosthesis size, effective orifice area significantly increased, whereas the prosthesis performance index significantly decreased.

Comprehensive Echocardiographic Assessment of the Hemodynamic Parameters of 285 Tricuspid Valve Bioprostheses Early after Implantation

BACKGROUND Doppler-derived hemodynamic data for normal tricuspid valve bioprostheses are limited. METHODS A comprehensive retrospective Doppler echocardiographic assessment of 285 normal Carpentier-Edwards Duraflex, Medtronic Mosaic, St. Jude Medical Biocor, Carpentier-Edwards Perimount, and Medtronic Hancock II tricuspid valve bioprostheses was performed early after implantation. All the important Doppler-derived hemodynamic variables reported to date for mitral valve prostheses were used. Mean values for hemodynamic variables were obtained by averaging measurements of five and nine consecutive cardiac cycles. RESULTS No clinically significant difference was found in the mean values obtained for the Doppler parameters when measurements were averaged from five or nine consecutive cardiac cycles. The mean value for the mean gradient was 5.2 mm Hg. Regardless of valve type and body surface area, pressure half-time was <200 msec for all 76 patients in whom it could be measured. Mean gradient <9 mm Hg, E velocity <2.1 m/sec, time-velocity integral of the tricuspid valve prosthesis <66 cm, and ratio of the time-velocity integral of the tricuspid valve prosthesis to the time-velocity integral of the left ventricular outflow tract <3.3 were recorded in 254 of the 285 patients (89%). CONCLUSIONS This study establishes parameters for Doppler-derived hemodynamic data for various types of normal tricuspid valve bioprostheses. These threshold values (mean + 2 standard deviations) are specific, but not sensitive, for identifying tricuspid valve bioprosthesis dysfunction. Prostheses with hemodynamic values that are higher than these threshold values are likely dysfunctional, but in select cases, tricuspid valve bioprosthesis dysfunction may be present even when hemodynamic values are lower than these thresholds.