Obstructive sleep apnea and the risk of sudden cardiac death: a longitudinal study of 10,701 adults.

OBJECTIVES: This study sought to identify the risk of sudden cardiac death (SCD) associated with obstructive sleep apnea (OSA). BACKGROUND: Risk stratification for SCD, a major cause of mortality, is difficult. OSA is linked to cardiovascular disease and arrhythmias and has been shown to increase the risk of nocturnal SCD. It is unknown if OSA independently increases the risk of SCD. METHODS: We included 10,701 consecutive adults undergoing their first diagnostic polysomnogram between July 1987 and July 2003. During follow-up up to 15 years, we assessed incident resuscitated or fatal SCD in relation to the presence of OSA, physiological data including the apnea-hypopnea index (AHI), and nocturnal oxygen saturation (O2sat) parameters, and relevant comorbidities. RESULTS: During an average follow-up of 5.3 years, 142 patients had resuscitated or fatal SCD (annual rate 0.27%). In multivariate analysis, independent risk factors for SCD were age, hypertension, coronary artery disease, cardiomyopathy or heart failure, ventricular ectopy or nonsustained ventricular tachycardia, and lowest nocturnal O2sat (per 10% decrease, hazard ratio [HR]: 1.14; p = 0.029). SCD was best predicted by age >60 years (HR: 5.53), apnea-hypopnea index >20 (HR: 1.60), mean nocturnal O2sat <93% (HR: 2.93), and lowest nocturnal O2sat <78% (HR: 2.60; all p < 0.0001). CONCLUSIONS: In a population of 10,701 adults referred for polysomnography, OSA predicted incident SCD, and the magnitude of risk was predicted by multiple parameters characterizing OSA severity. Nocturnal hypoxemia, an important pathophysiological feature of OSA, strongly predicted SCD independently of well-established risk factors. These findings implicate OSA, a prevalent condition, as a novel risk factor for SCD.

Comprehensive hemodynamic assessment of 368 normal St. Jude Medical mechanical mitral valve prostheses based on early postimplantation echocardiographic studies.

BACKGROUND: Two-dimensional and Doppler-derived echocardiographic data on normal St. Jude Medical mechanical mitral valve prosthesis function have been reported but remain limited. METHODS: Comprehensive retrospective two-dimensional and Doppler echocardiographic assessment of 368 normal St. Jude Medical mechanical mitral valve prostheses was performed early after implantation. The early postimplantation hemodynamic profiles of 98 patients were compared with profiles obtained by follow-up transthoracic echocardiography performed <13 months after implantation. RESULTS: Using mean ± 2 SDs to define the normal distribution of values for Doppler-derived hemodynamic variables, the calculated normal ranges of values were as follows: mean gradient, 2 to 7 mm Hg; peak early mitral diastolic velocity (E velocity), 1.1 to 2.4 m/sec; time-velocity integral of the mitral valve prosthesis (TVIMVP) 20 to 50 cm; ratio of the TVIMVP to the time-velocity integral of the left ventricular outflow tract (TVILVOT), 0.9 to 2.5; pressure half-time, 35 to 99 msec; and effective orifice area, 1.12 to 3.24 cm(2). Patients with severe prosthesis-patient mismatch (ie, indexed effective orifice area ≤ 0.9 cm(2)/m(2)) had significantly higher mean gradients, E velocity, TVIMVP, and TVIMVP/TVILVOT. There was a trend for longer pressure half-times for patients with severe prosthesis-patient mismatch than for patients without severe prosthesis-patient mismatch, but none of these patients had pressure half-times > 130 msec. Among the 98 patients with follow-up transthoracic echocardiography <1 year after implantation, no significant differences were observed between early postimplantation findings and follow-up hemodynamic profiles. CONCLUSIONS: This study establishes parameters (mean ± 2 SDs) defining the distribution of values for Doppler-derived hemodynamic data with normal St. Jude Medical mechanical mitral valve prostheses. Prostheses with hemodynamic values outside these parameters are likely dysfunctional; however, prosthesis dysfunction may be present even when hemodynamic values are within these ranges.

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.

Comprehensive hemodynamic assessment of 305 normal CarboMedics mitral valve prostheses based on early postimplantation echocardiographic studies.

BACKGROUND: Two-dimensional (2D) and Doppler-derived echocardiographic data on normal CarboMedics (CM) mechanical mitral valve prosthesis function have been reported but are limited. METHODS: Comprehensive retrospective 2D and Doppler echocardiographic assessment of 305 normal CM mechanical mitral valve prostheses (272 Standard and 33 Optiform) was performed early after implantation. The early postimplantation hemodynamic profiles of 80 patients were compared with profiles obtained by follow-up transthoracic echocardiography performed <1 year after implantation. RESULTS: CM Standard and Optiform prostheses had similar hemodynamic profiles. With mean ± 2 SDs used to define the normal distribution of values for hemodynamic variables, the calculated normal range of values was as follows: mean gradient, 2 to 7 mm Hg; peak early mitral diastolic velocity, 1.3 to 2.4 m/sec; time-velocity integral (TVI) of the mitral valve prosthesis (TVI(MVP)), 20 to 50 cm; ratio of TVI(MVP) to the TVI of the left ventricular outflow tract, 0.9 to 2.5; pressure half-time, 35 to 99 msec; and effective orifice area, 1.17 to 3.25 cm(2). Patients with severe prosthesis-patient mismatch (indexed effective orifice area ≤ 0.9 cm(2)/m(2)) had significantly higher mean gradients, peak early mitral diastolic velocities, TVI(MVP), ratios of TVI(MVP) to the TVI of the left ventricular outflow tract, and pressure half-time values than values without severe prosthesis-patient mismatch, but none had pressure half-time values > 120 msec. Among the 80 patients with follow-up transthoracic echocardiography within 1 year after implantation, no significant differences were noted between early postimplantation findings and follow-up hemodynamic profiles. CONCLUSIONS: This study establishes parameters (mean ± 2 SD) defining the distribution of findings for Doppler-derived hemodynamic data with normal CM mechanical mitral valve prostheses. Prostheses with hemodynamic values outside these parameters are likely dysfunctional; however, prosthesis dysfunction may be present even when hemodynamic values are within these ranges.

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.

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.

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.

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.

Comprehensive echocardiographic assessment of mechanical tricuspid valve prostheses based on early post-implantation echocardiographic studies.

BACKGROUND: Doppler-derived hemodynamic data for normal tricuspid mechanical valve prostheses are limited. METHODS: A comprehensive retrospective Doppler echocardiographic assessment of 78 normal St. Jude Medical Standard (St. Jude Medical, Inc., St. Paul, MN), CarboMedics Standard (CarboMedics, Inc., Sorin Group, Burnaby, British Columbia, Canada), and Starr-Edwards (Edwards Lifesciences, LLC, Irvine, CA) mechanical tricuspid valve prostheses was performed early after implantation. We used all the important Doppler-derived hemodynamic variables reported to date, including peak early diastolic velocity (E velocity), mean gradient, pressure half-time, time velocity integral of the tricuspid valve prosthesis (TVI(TVP)), and ratio of the time velocity integral of the tricuspid valve prosthesis to the time velocity integral of the left ventricular outflow tract (TVI(TVP)/TVI(LVOT)). RESULTS: The mean values obtained for the Doppler parameters did not differ significantly when the measurements from five or nine consecutive cardiac cycles were averaged. Pressure half-time was <130 msec in all 43 patients with St. Jude Medical Standard and CardioMedics Standard prostheses in whom it could be measured. Mean gradient <6 mm Hg, E velocity <1.9 m/s, TVI(TVP) <46 cm, and TVI(TVP)/TVI(LVOT) <2.1 were recorded in 59 (87%) of the 68 patients with either of these prostheses. Hemodynamic variables were considerably less favorable in patients with Starr-Edwards prostheses. CONCLUSION: These calculated threshold values (mean + 2 SD) are useful for identifying normal tricuspid mechanical valve function. Prostheses with values for hemodynamic variables that are outside the mean + 2 SD parameters that we have calculated are most likely to be dysfunctional. However, in rare cases, mechanical tricuspid valve prostheses may be dysfunctional even when their hemodynamic parameters are within these specified ranges because of small body surface area or other factors.

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.

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.

Comprehensive echocardiographic assessment of normal mitral Medtronic Hancock II, Medtronic Mosaic, and Carpentier-Edwards Perimount bioprostheses early after implantation.

BACKGROUND: Normal Doppler-derived hemodynamic data for mitral valve bioprostheses are limited. METHODS: To establish parameters for identifying normal function for each of the 3 types of bioprostheses examined, we conducted a comprehensive, retrospective, two-dimensional, and Doppler echocardiographic assessment of 179 patients who underwent implantation of the Medtronic Hancock II or the Medtronic Mosaic (Medtronic, Inc, Minneapolis, MN) porcine mitral valve bioprosthesis or the Carpentier-Edwards Perimount (Edwards Lifesciences LLC, Irvine, CA) bovine pericardial mitral valve bioprosthesis. RESULTS: All bioprostheses were normal by clinical examination, intraoperative transesophageal echocardiography, and postoperative transthoracic echocardiography. Regardless of valve type and body surface area, the pressure half-time was < 124 ms in all patients. Mean gradient < 9.5 mm Hg, mitral E velocity < 2.6 m/s, mitral valve prosthesis time-velocity integral < 69 cm, and ratio of the mitral valve prosthesis time-velocity integral to the left ventricular outflow tract time-velocity integral < 3.4 were recorded in nearly all patients. CONCLUSION: These cutoff values (mean + 2 standard deviation) are specific, but not sensitive, for identifying mitral valve prosthesis dysfunction. Prostheses with hemodynamic values that are higher than these cutoff values are likely dysfunctional, but in select cases, mitral valve prosthesis dysfunction may be present even when hemodynamic values are lower than these thresholds.

Role of smoking in the recurrence of atrial arrhythmias after cardioversion.

We aimed to determine whether smoking status affects the recurrence of atrial fibrillation or atrial flutter in patients after cardioversion. The clinical data of patients undergoing cardioversion for atrial flutter from January 1, 2000 to December 31, 2005 were prospectively collected. Arrhythmia recurrences were detected by retrospective review of comprehensive medical records and were determined using electrocardiography. The smoking history was prospectively collected through a standardized clinical form and subsequently categorized as lifetime nonsmoker, exsmoker, or current smoker. Univariate and multivariate associations with end points for clinical and lifestyle variables were assessed with Cox proportional hazards models. Women who were current smokers at cardioversion had a greater risk of atrial arrhythmia recurrence than did nonsmokers (hazard ratio 1.71, 95% confidence interval 1.10 to 2.67, p = 0.02). The increased risk of arrhythmia recurrence in female smokers was not seen in male smokers. Compared to lifetime nonsmokers, the mortality hazard ratio among men was 1.18 (95% confidence interval 0.88 to 1.58; p = 0.28) in exsmokers and 1.93 (95% confidence interval 1.20 to 3.11; p = 0.007) in current smokers. The risk of death after cardioversion was not increased in women. In conclusion, smoking is an independent predictor of atrial arrhythmia recurrence after cardioversion in women; however, an increased mortality risk, but not arrhythmia recurrence risk, was seen in men.

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.

Doppler echocardiography of 79 normal CarboMedics mitral prostheses: a comprehensive assessment including time-velocity integral ratio and prosthesis performance index.

Few reports have been published on the normal Doppler-derived echocardiographic data for CarboMedics (CarboMedics Inc., Austin, TX) prosthesis function in the mitral position. The purpose of this study was to provide a comprehensive Doppler echocardiographic assessment of normal CarboMedics mitral prosthesis function in a large number of patients. All of the important Doppler-derived hemodynamic variables reported to date were used. The pressure half-time was less than 130 msec in all patients, and nearly all patients (95%) had either a peak early mitral diastolic velocity of 2 m/s or less or a mitral valve prosthesis-to-left ventricular outflow tract time-velocity integral ratio of less than 2.2, regardless of prosthesis size or left ventricular function. No significant differences were found among different prosthesis sizes for effective orifice area, effective orifice area indexed to body surface area, or prosthesis performance index.

Prognostic value of ankle-brachial index and dobutamine stress echocardiography for cardiovascular morbidity and all-cause mortality in patients with peripheral arterial disease.

BACKGROUND: Peripheral arterial disease (PAD) is associated with an excessive risk for cardiovascular events and mortality. To determine measures prognostic of adverse events, ankle-brachial index (ABI) was compared with dobutamine stress echocardiography (DSE) in patients referred to our vascular center for the evaluation of PAD. METHODS: The medical records of consecutive patients referred for the concurrent evaluation of PAD and coronary artery disease (CAD) between 1992 and 1995 were reviewed for subsequent cardiovascular events and death. RESULTS: Among 395 patients (mean age, 69.7 +/- 9.6 years; 40% women), 341 had abnormal ABI and 268 had abnormal DSE (95 fixed and 173 stress-induced wall motion abnormalities). During a mean follow-up of 4.7 years, 27.3% of patients experienced a cardiovascular event, and 39.4% died. By multivariate analysis, ABI provided the strongest prediction of all-cause mortality (hazard ratio [HR], 2.34; 95% confidence interval [CI], 1.36 to 4.05; P = .002). Conversely, DSE with inducible or fixed wall motion abnormalities showed no association with cardiovascular events or increased mortality in multivariate analysis. The only DSE variable independently predictive of mortality was decreased left ventricular ejection fraction (<50%) at peak stress (HR, 1.70; 95% CI, 1.22 to 2.36; P = .002). Statin and aspirin therapy, but not beta-blockers, were protective. There was no relation between ABI and wall motion index score at rest or after stress. CONCLUSIONS: In high-risk patients referred to our vascular center for the evaluation of PAD, the assessment of ABI provided a strong independent prediction of all-cause mortality. Therefore, proper interpretation of this simple, affordable, and reproducible measure extends beyond the assessment of PAD severity. Although a poor left ventricular response to dobutamine was also predictive, other echo variables were not.

Obstructive sleep apnea, obesity, and the risk of incident atrial fibrillation.

OBJECTIVES: This study sought to identify whether obesity and obstructive sleep apnea (OSA) independently predict incident atrial fibrillation/flutter (AF). BACKGROUND: Obesity is a risk factor for AF, and OSA is highly prevalent in obesity. Obstructive sleep apnea is associated with AF, but it is unknown whether OSA predicts new-onset AF independently of obesity. METHODS: We conducted a retrospective cohort study of 3,542 Olmsted County adults without past or current AF who were referred for an initial diagnostic polysomnogram from 1987 to 2003. New-onset AF was assessed and confirmed by electrocardiography during a mean follow-up of 4.7 years. RESULTS: Incident AF occurred in 133 subjects (cumulative probability 14%, 95% confidence interval [CI] 9% to 19%). Univariate predictors of AF were age, male gender, hypertension, coronary artery disease, heart failure, smoking, body mass index, OSA (hazard ratio 2.18, 95% CI 1.34 to 3.54) and multiple measures of OSA severity. In subjects <65 years old, independent predictors of incident AF were age, male gender, coronary artery disease, body mass index (per 1 kg/m2, hazard ratio 1.07, 95% CI 1.05 to 1.10), and the decrease in nocturnal oxygen saturation (per 0.5 U log change, hazard ratio 3.29, 95% CI 1.35 to 8.04). Heart failure, but neither obesity nor OSA, predicted incident AF in subjects > or =65 years of age. CONCLUSIONS: Obesity and the magnitude of nocturnal oxygen desaturation, which is an important pathophysiological consequence of OSA, are independent risk factors for incident AF in individuals <65 years of age.

The effect of patient sex on recurrence of atrial fibrillation following successful direct current cardioversion.

BACKGROUND: The effect of patient sex on recurrence of atrial fibrillation after a successful direct current cardioversion is unknown. METHODS: This prospective study included 773 patients (486 [63%] men and 287 [37%] women) undergoing successful direct current cardioversion of atrial fibrillation between May 2000 and July 2003. Patient characteristics at presentation were recorded. The primary end point was the time between cardioversion and the first documented recurrence of arrhythmia. RESULTS: At presentation, women were older and had a higher prevalence of hypertension and valvular disease compared with men. In addition, women had worse mechanical left atrial appendage function. Arrhythmia recurrence was more prevalent in women (50.0% at 1 year compared with 43.4% in men, and 75.8% at 2 years compared with 67.0% in men; P = .03). On the basis of multivariate analysis, patient sex was a significant predictor of arrhythmia recurrence. There was no significant difference in overall mortality between men and women. CONCLUSIONS: Women were more likely than men to have recurrence of atrial fibrillation after successful direct current cardioversion. Patient sex should be taken into account with other clinical factors when making the decision about cardioversion for atrial fibrillation.

Trends in prevalence and outcome of heart failure with preserved ejection fraction.

BACKGROUND: The prevalence of heart failure with preserved ejection fraction may be changing as a result of changes in population demographics and in the prevalence and treatment of risk factors for heart failure. Changes in the prevalence of heart failure with preserved ejection fraction may contribute to changes in the natural history of heart failure. We performed a study to define secular trends in the prevalence of heart failure with preserved ejection fraction among patients at a single institution over a 15-year period. METHODS: We studied all consecutive patients hospitalized with decompensated heart failure at Mayo Clinic Hospitals in Olmsted County, Minnesota, from 1987 through 2001. We classified patients as having either preserved or reduced ejection fraction. The patients were also classified as community patients (Olmsted County residents) or referral patients. Secular trends in the type of heart failure, associated cardiovascular disease, and survival were defined. RESULTS: A total of 6076 patients with heart failure were discharged over the 15-year period; data on ejection fraction were available for 4596 of these patients (76 percent). Of these, 53 percent had a reduced ejection fraction and 47 percent had a preserved ejection fraction. The proportion of patients with the diagnosis of heart failure with preserved ejection fraction increased over time and was significantly higher among community patients than among referral patients (55 percent vs. 45 percent). The prevalence rates of hypertension, atrial fibrillation, and diabetes among patients with heart failure increased significantly over time. Survival was slightly better among patients with preserved ejection fraction (adjusted hazard ratio for death, 0.96; P=0.01). Survival improved over time for those with reduced ejection fraction but not for those with preserved ejection fraction. CONCLUSIONS: The prevalence of heart failure with preserved ejection fraction increased over a 15-year period, while the rate of death from this disorder remained unchanged. These trends underscore the importance of this growing public health problem.

Secular trends in renal dysfunction and outcomes in hospitalized heart failure patients.

BACKGROUND: Renal dysfunction and worsening renal function (WRF) during heart failure (HF) therapy predict outcomes. We determined whether the severity of renal dysfunction, the incidence of WRF or outcomes have changed over time (secular trends) in patients hospitalized for HF therapy. METHODS AND RESULTS: A total of 6440 consecutive unique patients admitted for HF to Mayo Clinic Hospitals Rochester, MN, January 1, 1987, to December 31, 2002, were identified and data extracted from electronic databases. Over the study period, age and admission creatinine increased, whereas estimated glomerular filtration rate and hemoglobin decreased (P < .0001 for all). The prevalence of hypertension and diabetes among HF patients also increased over time (P < .0001). The incidence of WRF was stable. Renal dysfunction and development of WRF were associated with mortality. When adjusted for the changes in baseline characteristics of HF patients, mortality declined over the study period. CONCLUSION: Hospitalized HF patients are increasingly elderly, have a greater prevalence of diseases that lead to renal dysfunction, and have more severe renal dysfunction and anemia on admission. However, adjusting for these secular trends in patient characteristics, mortality after HF admission is improving. These data enhance our understanding of the changing natural history of HF.