Variable Effects of Physical Training of Heart Rate Variability, Heart Rate Recovery, and Heart Rate Turbulence in Chronic Heart Failure

Background: Heart rate variability (HRV), heart rate turbulence (HRT), and heart rate recovery (HRR), indices that reflect autonomic nervous system (ANS) activity, are outcome predictors in patients with chronic heart failure (CHF). It is not clear, however, whether they reflect the same components of ANS activity. No study has examined the effects of physical training (PT) training on HRV, HRT, and HRR in CHF.
Study Objective: To examine the responses of HRV, HRT, and HRR to a PT program in patients presenting with CHF.
Methods: In 41 patients (mean age = 58.7 ± 10.2 years) in New York Heart Association CHF functional classes II or III, and with a left ventricular ejection fraction <40%, HRV, HRT, and HRR were measured before and after 8 weeks of PT.
Results: The training was clinically effective in all patients. Before versus after PT, standard deviation of all normal RR intervals increased from 107 ± 30 to 114 ± 32 ms (P = 0.047), high frequency increased from 210 ± 227 to 414 ± 586 ms²/Hz (P = 0.02), and the low/high frequency ratio decreased from 1.8 ± 1.55 to 1.1 ± 1.2 (P = 0.002). HRT and HRR did not change significantly after PT.
Conclusions: In patients with CHF, the positive effects of PT were limited to HRV indices, which reflect parasympathetic activity, without significantly changing HRR and HRT. These observations indicate that different mechanisms modulate HRV, HRR, and HRT, which provide complementary information regarding ANS activity. The 8-week PT program failed to completely normalize ANS function.     

Survival and Appropriate Device Interventions in Recipients of Cardioverter Defibrillators Implanted for the Primary Versus Secondary Prevention of Sudden Cardiac Death

Background: Implantable cardioverter-defibrillators (ICD) implanted after an episode of ventricular tachyarrhythmia (VTA) or in patients at high risk of VTA lower the long-term mortality. Comparisons of the clinical outcomes of the two indications are scarce.
Methods: The study enrolled 360 consecutive ICD recipients. The device was implanted for secondary prevention in 150 patients, whose mean age was 60 ± 14 years, and mean left ventricular ejection fraction (LVEF) was 40 ± 16%, and for primary prevention in 210 patients, whose mean age was 61 ± 11 years, and mean LVEF was 31 ± 13%. All-cause mortality and time to first appropriate ICD therapy were measured.
Results: The two study groups were similar with respect to age and prevalence of coronary artery disease. Mean LVEF was higher in the secondary prevention group (P = 0.001). Cox regression analysis revealed a significantly shorter time to first appropriate ICD therapy in the secondary prevention group (HR = 0.51, 95% CI = 0.30 – 0.87, P = 0.01). Over a mean follow-up of 37 ± 19 months, the all-cause mortality in the overall population was 12.7%, and was similar in both subgroups (HR = 0.99, 95% CI = 0.55–1.77, P = 0.97).
Conclusions: The long-term mortality in this unselected population of ICD recipients was low. Patients treated for secondary prevention received earlier appropriate ICD therapy than patients treated for primary prevention. Long-term mortality was similar in both groups. The higher VT incidence of VTA was effectively treated by the ICD and was not associated with a higher mortality.     

Rate responsive pacemakers: a rapid assessment protocol

Background: Rate responsive (RR) pacemakers are commonly implanted with nominal conservative factory-set responsiveness, which is usually accepted because established exercise protocols are time-consuming. We aimed for efficient assessment of RR pacemaker settings.
Methods: We tested exercise heart rates in controls and paced patients using a brief exercise test that approximates real-life levels of exertion. The test used a nonmotorized treadmill: 30 seconds walking at patient-determined speed followed by 15 seconds brisk exertion. Subjects totaled 110: 26 with RR pacemakers; 22 with non-RR pacers; 27 "sick" nonpaced control patients; and 35 healthy controls. Heart rate (HR) was measured prior to exercise, after 30 seconds of casual walk, after 15 seconds of brisk walk, and 1 minute into recovery. Testing required <5 minutes from set-up to recovery.
Results: The 26 RR pacer patients had a mean HR at rest = 74 ± 10 beats per minute (bpm), walk = 87 ± 14, and brisk = 94 ± 18 (increase 27%). Non-RR pacer patients (n = 22): rest = 73 ± 12 bpm, walk = 88 ± 14, and brisk = 94 ± 17 (increase 24.3%, P = 0.60 vs RR patients). "Sick" controls (n = 27): rest = 78 ± 14 bpm, walk = 102 ± 17, and brisk = 117 ± 18 (increase 51.9%, P< 0.001 vs RR pts). For the healthy controls, HRs were at rest 83+/11 bpm, walk = 104 ± 12, and brisk = 117 ± 13 (P< 0.001 compared to both paced groups; P = NS vs sick controls).
Conclusions: Nominal RR settings may be suboptimal for many patients. The nonmotorized treadmill test allows quick and inexpensive assessment of RR programming, with the potential for efficient RR optimization.     

Effects of Aging on Reflex Autonomic Nervous Response Induced by Orthostatic Maneuvers

Background: Baroreflex sensitivity (BRS), exercise pressor reflex (EPR), and aging influence the autonomic nervous response associated with orthostatic maneuvers. Standing significantly increases heart rate (HR), with an initial increase (1.ΔHR) due to EPR and a secondary, more gradual increase (2.ΔHR) due to BRS. HR then decreases (3.ΔHR), which is also attributable to BRS. Thus far, however, few data are available regarding the interdependence of these variables.
Methods and Results: Ninety-five healthy volunteers (mean age 37 ± 11 years, range 10–70 years; 50 women) underwent continuous noninvasive measurements of beat-to-beat blood pressure, HR, and spontaneous BRS in the supine (10 minutes) and upright (10 minutes) positions. After tilt, 1.ΔHR, 2.ΔHR, and 3.ΔHR were calculated from the HR recording. From the 1^st to the 6^th decade BRS, 2.ΔHR and 3.ΔHR decreased with normal aging ([BRS 11.88 ± 7.97 ms/mmHg to 1.81 ms/mmHg, P = 0.006], 2.ΔHR [16.75 ± 3.40 beats to 5.33 ± 2.52 beats, P = 0.002], 3.ΔHR [52.25 ± 5.91 beats to 11.33 ± 4.04 beats, P < 0.001]). However, no such association was noted between 1.ΔHR and age (21.25 ± 9.35 beats to 12.00 ± 7.21 beats, ns). BRS while standing was correlated with 1.ΔHR (r = 0.432, P < 0.001).
Conclusions: EPR, in contrast to BRS, was not significantly influenced by normal aging. Furthermore, not only was BRS influenced by EPR, as is generally acknowledged, but EPR and BRS were interrelated. These observations offer new insights into the complex interactions of orthostasis-induced physiological autonomic reflexes associated with normal aging.     

Direct comparison of a contractility and activity pacemaker sensor during treadmill exercise testing

There are limited data about the chronotropic capacity of the peak endocardial acceleration (PEA) sensor. This study directly compared the chronotropic function from the PEA and the activity (ACT) sensor. The study included 18 patients (age 73 ± 7 years) with ≥ 75% pacemaker-driven heart rate (HR) and a PEA sensor and 11 healthy controls (age 67 ± 7 years) underwent a chronotropic assessment exercise protocol (CAEP) exercise test with the pacemaker patients in VVIR mode after programming the sensors in the default setting with adjustment of the upper sensor rate as an age related maximum value (220-age). The ACT sensor was externally strapped on the thorax. Achieved exercise duration for the patients and controls was, respectively, 9.2 ± 3 vs 18.4 ± 4 minutes (P < 0.001). The maximal achieved HR with the PEA sensor was 124 ± 25 beats/min, versus the ACT with 140 ± 23, versus the controls with 153 ± 26 beats/min (P < 0.001 between the groups). For the PEA, ACT, and controls, the time to peak HR was, respectively, 11 ± 3, 7 ± 3.6, and 18 ± 4 (P < 0.001 between groups) and HR after 10 minutes recovery was, respectively, 80 ± 20, 65 ± 15, and 82 ± 4 beats/min (P < 0.001 between groups). The PEA sensor functions hypochonotroop during exercise programmed as a single sensor system. It is, therefore, preferable to combine the PEA sensor with an activity-based sensor in a dual sensor system. Although both groups had normal left ventricular functions, the exercise capacity of pacemaker patients is significantly lower than in the controls.     

PR Interval Adaptation in the Denervated Transplanted Heart

In the present study, the dynamic PR response upon standardized treadmill exercise was investigated in 21 transplant recipients (recipient age 48 ± 17 years, donor age 31 ± 12 years, > 1 year after transplantation). MR and PR interval were measured at rest and at the end of each 25-Wincrease in workload till peak exercise. In 17 cases norepinephrine (NE) was assessed at rest, and at the end of each workload the MR increased from 99.3 ± 14 to 143.4 ± 25 beats/min at individual peak exercise, and NE increased from 1.307 ± 1,163 to 3.688 ± 2.036 pg/mL. while the PR interval shortened from 149.2 ± 13 to 119.3 ± 20 ms. On average. PR decreased by 3.4 ms for a 10-beat increase in HR, and the HR-PR interval relationship was described by a linear regression (y = 176.8–0.3469x, P = 0.0001). One patient who was unable to increase his NE levels upon exercise showed virtually no decrease in the PR interval and no HR increase. Both recipient age and donor age were moderately and significantly related to the minimum PR interval achieved at peak exercise (r = 0.6. P = 0.008 and r = 0.51. P = 0.049, respectively). These data show the following: (1) adaptation of the PR interval upon exercise does occur in the denervated transplanted heart; (2) the HR-PR relation is similar to that reported in the innervated heart; (3) the overall decline in PR interval is blunted, since denervated patients start at shorter resting PR intervals and achieve relatively longer PR intervals at peak exercise when compared to their innervated counterparts; (4) these exercise induced changes of the PR interval may be explained by circulating NE; and (5) NE levels achieved at peak exercise and the sensitivity of the AV node to NE seem to be age related. (PACE 1997; 20[Pt. I]:1247-1251)     

Determinants of exercise capacity in patients with type 2 diabetes

OBJECTIVE: Type 2 diabetes is associated with reduced exercise capacity, but the cause of this association is unclear. We sought the associations of impaired exercise capacity in type 2 diabetes. RESEARCH DESIGN AND METHODS: Subclinical left ventricular (LV) dysfunction was sought from myocardial strain rate and the basal segmental diastolic velocity (Em) of each wall in 170 patients with type 2 diabetes (aged 56 +/- 10 years, 91 men), good quality echocardiographic images, and negative exercise echocardiograms. The same measurements were made in 56 control subjects (aged 53 +/- 10 years, 29 men). Exercise capacity was calculated in metabolic equivalents, and heart rate recovery (HRR) was measured as the heart rate difference between peak and 1 min after exercise. In subjects with type 2 diabetes, exercise capacity was correlated with clinical, therapeutic, biochemical, and echocardiographic variables, and significant independent associations were sought using a multiple linear regression model. RESULTS: Exercise capacity, strain rate, Em, and HRR were significantly reduced in type 2 diabetes. Exercise capacity was associated with age (r = -0.37, P < 0.001), male sex (r = 0.26, P = 0.001), BMI (r = -0.19, P = 0.012), HbA(1c) (A1C; r = -0.22, P = 0.009), Em (r = 0.43, P < 0.001), HRR (r = 0.42, P < 0.001), diabetes duration (r = -0.18, P = 0.021), and hypertension history (r = -0.28, P < 0.001). Age (P < 0.001), male sex (P = 0.007), BMI (P = 0.001), Em (P = 0.032), HRR (P = 0.013), and A1C (P = 0.0007) were independent predictors of exercise capacity. CONCLUSIONS: Reduced exercise capacity in patients with type 2 diabetes is associated with diabetes control, subclinical LV dysfunction, and impaired HRR.     

A Prospective Multicenter Study Demonstrating Clinical Benefit with a New Accelerometer-Based DDDR Pacemaker

From November 1994 to October 1995, 63 patients (average age 66 years; 41 men) from 15 centers implanted with the Biotronik Dromos DR and Ergos TC 03 pulse generators were prospectively screened with an exercise test in the DDD mode for the presence of chronotropic incompetence (CI). Both pulse generators incorporate an identical accelerometer-based motion sensor. CI was defined as a maximum heart rate < 60% of age predicted maximum heart rate or 100 beats/min. Twenty-five patients (40%) met the criteria for CI. Two weeks later, CI patients were required to complete paired metabolic exercise testing in the DDD and DDDR modes on consecutive days with a 24-hour rest period. The order of testing was randomized and performed double blinded to minimize potential biases. Three patients who did not reach the anaerobic threshold (AT) and one patient who was unable to perform the metabolic testing were excluded from the analysis. Compared to the DDD mode, there were statistically significant improvements in the DDDR mode for all five endpoints: heart rate (84 ± 3.6 vs 113 ± 3.5 beats/min; P < 0.0001); total exercise time (8.23 ± 0.71 vs 9.15 ± 0.65 min; P = 0.0005); maximum VO₂ (17.76 ± 1.36 vs 20.43 ± 1.75 mL/kg per min; P = 0.0001); V0₂ at AT (13.1 ± 0.87 vs 14.59 ± 0.79 mL/kg per min; P < 0.01); and exercise time to AT (5.65 ± 0.61 vs 6.33 ± 0.53 min; P = 0.02). In conclusion, the results of paired metabolic exercise tests with the Dromos DR and Ergos TC 03 pulse generators demonstrate a clear clinical benefit using the accelerometer-based sensor in the CI patient     

The Effects of Rate-Adaptive Atrial Pacing Versus Ventricular Backup Pacing on Exercise Capacity in Patients with Left Ventricular Dysfunction

Background: Atrial rate-adaptive pacing may improve cardiopulmonary reserve in patients with left ventricular dysfunction.
Methods: A randomized, blinded, single-crossover design enrolled dual-chamber implantable defibrillator recipients without pacing indications and an ejection fraction ≤40% to undergo cardiopulmonary exercise treadmill stress testing in both atrial rate-adaptive pacing (AAIR) and ventricular demand pacing (VVI) pacing modes. The primary endpoint was change in peak oxygen consumption (VO₂). Secondary endpoints were changes in anaerobic threshold, perceived exertion, exercise duration, and peak blood pressure.
Results: Ten patients, nine males, eight with New York Heart Association class I, mean ejection fraction 24 ± 7%, were analyzed. Baseline VO₂ was 3.6 ± 0.5 mL/kg/min. Heart rate at peak exercise was significantly higher during AAIR versus VVI pacing (142 ± 18 vs 130 ± 23 bpm; P = 0.05). However, there was no difference in peak VO₂ (AAIR 23.7 ± 6.1 vs VVI 23.8 ± 6.3 mL/kg/min; P = 0.8), anaerobic threshold (AAIR 1.3 ± 0.3 vs VVI 1.2 ± 0.2 L/min; P = 0.11), rate of perceived exertion (AAIR 7.3 ± 1.5 vs VVI 7.8 ± 1.2; P = 0.46), exercise duration (AAIR 15 minutes, 46 seconds ± 2 minutes, 54 seconds vs VVI 16 minutes, 3 seconds ± 2 minutes, 48 seconds; P = 0.38), or peak systolic blood pressure (AAIR 155 ± 22 vs VVI 153 ± 21; P = 0.61) between the two pacing modes.
Conclusion: In this study, AAIR pacing did not improve peak VO_2, anaerobic threshold, rate of perceived exertion, or exercise duration compared to VVI backup pacing in patients with left ventricular dysfunction and no pacing indications.     

Risk factors for cardiovascular disease in patients with subclinical hypothyroidism

INTRODUCTION: The relationship between subclinical hypothyroidism (SCH) and cardiovascular disease is not fully understood. We investigated risk factors for cardiovascular disease (lipid profile, lipoproteins, insulin resistance, C-reactive protein [CRP] homocysteine [Hcy] and fibrinogen levels) and their relationships with thyroid hormones in SCH patients and controls. METHODS: Thirty-eight SCH patients and 44 controls were enrolled in this study. No patients had any substantial confounding medical conditions (including diabetes mellitus or coronary heart disease) or were taking thyroid-related medication. RESULTS: Serum total cholesterol (P<0.05), low-density lipoprotein cholesterol (P<0.05) and triglycerides (P<0.001) were higher in patients with SCH than in controls. Serum lipoprotein(a) (Lp[a]) levels were higher in SCH subjects but this difference did not reach statistical significance (P=0.07). No significant differences were noted in CRP, Hcy, fibrinogen, high-density lipoprotein cholesterol, apolipoprotein A-1, apolipoprotein B (Apo B) or insulin resistance between patients with SCH and controls (in all cases, P>0.05). Free triiodothyronine (FT3) negatively correlated with Apo B (r=.0.46, P=0.005) and Lp(a) (r=.0.31, P=0.03) in patients with SCH and negatively correlated with Lp(a) (r=.0.30, P=0.04) in controls. All of these parameters were comparable between patients with thyroid-stimulating hormone (TSH) >10 microIU/ml and TSH <10 microIU/ml (in SCH patients, P>0.05). CONCLUSION: Our results suggest that SCH is associated with some lipid and lipoprotein abnormalities. Our results also suggest that this association does not depend on the subject's TSH level.     

Reversal of Atrial Remodeling after Cardioversion of Persistent Atrial Fibrillation Measured with Magnetocardiography

Background : Atrial fibrillation (AF) causes electrical, functional, and structural changes in the atria. We examined electrophysiologic remodeling caused by AF and its reversal noninvasively by applying a new atrial signal analysis based on magnetocardiography (MCG).
Methods : In 26 patients with persistent AF, MCG, signal-averaged electrocardiography (SAECG), and echocardiography were performed immediately after electrical cardioversion (CV), and repeated after 1 month in 15 patients who remained in sinus rhythm (SR). Twenty-four matched subjects without history of AF served as controls. P-wave duration (Pd) and dispersion (standard deviation of Pd values in individual channels) and root mean square amplitudes of the P wave over the last 40 ms portions (RMS40) were determined.
Results : In MCG Pd was longer (122.8 ± 18.2 ms vs 101.5 ± 14.6 ms, P < 0.01) and RMS40 was higher (60.4 ± 28.2 vs 46.9 ± 19.1 fT) in AF patients immediately after CV as compared to the controls. In SAECG Pd dispersion was increased in AF patients. Mitral A-wave velocity and left atrial (LA) contraction were decreased and LA diameter was increased (all P < 0.01). After 1 month, Pd in MCG still remained longer and LA diameter greater (both P < 0.05), while RMS40 in MCG, Pd dispersion in SAECG, mitral A-wave velocity, and LA contraction were recovered.
Conclusions : Magnetocardiographically detected atrial electrophysiologic alterations in persistent AF diminish rapidly although incompletely during maintained SR after CV. This might be related to the known early high and late lower, but still existent tendency to AF relapses.     

Abnormal Nocturnal Heart Rate Variability and QT Dynamics in Patients with Brugada Syndrome

Background: In Brugada syndrome (BSY), most of the ventricular arrhythmic events are nocturnal, suggesting an influence of the autonomic nervous system.
Methods: In 46 patients (mean age = 41 ± 14 years, 43 men) with electrocardiograms (ECG) consistent with BSY and structurally normal hearts, we measured heart rate variability (HRV) and QT dynamics (QT/RR slopes) on 24-hour ambulatory ECG. Type 1 BSY-ECG was spontaneous in 23 (50%) and induced in 23 patients.
Results: History of syncope was present in 23 patients (50%). Programmed ventricular stimulation induced ventricular tachyarrhythmias (VTA) in 13 patients (28%). A single patient developed ventricular tachycardia during a mean follow-up of 34 months. Compared to a control group matched for age and sex, HRV was decreased over 24 hours and during nighttime in patients with BSY (SDNN 122 ± 44 vs 93 ± 36 ms, P = 0.0008 and SDANN 88 ± 39 vs 54 ± 24 ms, P < 0.0001). QTend /RR slopes were decreased over 24 hours in patients with BSY (0.159 ± 0.05 vs 0.127 ± 0.05, P = 0.003) and particularly at night (0.123 ± 0.04 vs 0.089 ± 0.04, P = 0.0001). QTend /RR slopes were significantly decreased during nighttime in patients with spontaneous versus provoked BSY-ECG patterns. By contrast, HRV and QT/RR slopes were similar in symptomatic and asymptomatic patients, whether VTA were induced or not.
Conclusions: Patients with a BSY-ECG pattern had lower HRV and QT/RR slopes than control subjects during nighttime. High-risk patients with spontaneous BSY-ECG patterns had the lowest nocturnal QTend/RR slopes. These unique repolarization dynamics might be related to the frequent nocturnal occurrence of VTA in BSY.     

Asymmetric dimethylarginine concentration and early recurrence of atrial fibrillation after electrical cardioversion

Background: The purpose of this study was to determine whether high asymmetric dimethylarginine (ADMA) levels could predict early recurrence of atrial fibrillation (AF) after successful electrical cardioversion (CV).
Methods : Seventy patients with persistent AF, but without known heart disease, who underwent elective electrical CV were enrolled. Blood samples for ADMA determination were drawn from all patients just before the CV.
Results : The study population comprised 64 patients (men 73%, age 62.56 ± 7.72 years, duration of AF 6.00 ± 1.90 months) in whom sinus rhythm was restored. After 1-month follow-up, 30 (47%) patients had recurrence of AF. The median ADMA concentration was significantly higher in patients with AF recurrence (1.93 μmol/L vs 1.43 μmol/L; P = 0.001). AF recurrence was associated with higher pre-CV ADMA levels (odds ratio [OR]= 4.20; 95% confidence interval [CI], 1.44–12.22; P = 0.001). On multivariate analysis, ADMA was the only independent predictor of arrhythmia recurrence (OR = 4.19; 95%CI, 1.12–15.77; P = 0.034).
Conclusion : Our data suggest that high levels of ADMA are associated with an increased risk of AF recurrence within 1 month after electrical CV, supporting the hypothesis that ADMA might participate in the process of atrial remodeling.     

Association of triglyceride-to-HDL cholesterol ratio with heart rate recovery

OBJECTIVE: Insulin resistance is associated with autonomic dysfunction. An attenuated decrease in heart rate after exercise (or heart rate recovery [HRR]) predicts all-cause mortality and is believed to reflect decreased parasympathetic activity. Utilizing triglyceride/HDL cholesterol concentration as a marker of insulin resistance, we sought to assess the association between insulin resistance and HRR. RESEARCH DESIGN AND METHODS: Our study population included 4,963 healthy adults who participated in the Lipid Research Clinics Prevalence Study and underwent exercise testing. HRR was considered abnormal if it did not drop > or = 42 bpm 2 min after completion of exercise. Fasting blood specimens were drawn. RESULTS: Individuals in the highest quartile of triglyceride/HDL cholesterol had a significantly higher prevalence of abnormal HRR (40 vs. 30%, multivariable-adjusted prevalence ratio 1.18, 95% CI 1.01-1.39; P = 0.04). As a continuous variable, an increase in 1 SD of triglyceride-to-HDL cholesterol ratio was associated with a greater likelihood of an abnormal HRR, even after adjusting for >20 covariates (adjusted OR 1.16, 95% CI 1.07-1.25; P < 0.001). During 12 years of follow-up, there were 284 deaths. In age- and sex-adjusted analysis, participants with an abnormal HRR and high triglyceride-to-HDL cholesterol ratio had significantly higher mortality than those with a normal HRR and high triglyceride-to-HDL cholesterol ratio (hazard ratio = 1.49, 95% CI 1.08-2.04; P = 0.015). CONCLUSIONS: HRR is associated with triglyceride-to-HDL cholesterol ratio and identifies patients with insulin resistance who are at increased risk of death.     

Long-Term Outcomes of CRT-PM Versus CRT-D Recipients

Objective: To compare the rates of all-cause mortality in recipients of cardiac resynchronization therapy devices without (CRT-PM) versus with defibrillator (CRT-D).
Methods: Between February 1999 and July 2004, 233 patients (mean age = 69 ± 8 years, 180 men) underwent implantation of CRT-PM or CRT-D devices. New York Heart Association (NYHA) heart failure functional class II was present in 11%, class III in 69%, and class IV in 20% of patients; mean left ventricle ejection fraction (LVEF) was 26.5 ± 6.5 %, 48% presented with idiopathic dilated cardiomyopathy and 49% with ischemic heart disease. Cox multiple variable regression analysis was performed in search of predictors of death.
Results: The clinical characteristics of the 117 CRT-PM and 116 CRT-D recipients were similar, except for LVEF (28.2 ± 6.2% vs 25.0 ± 6.5%, respectively; P < 0.001), and ischemic versus nonischemic etiology of heart failure (41% vs 56%, respectively P = 0.02). Over a mean follow-up of 58 ± 15 months, no significance difference in overall mortality rate was observed between the two study groups. Male sex, NYHA functional class IV, and atrial fibrillation at implant were significant predictors of death.
Conclusions: There was no difference in long-term survival rate among patients with CRT-D versus CRT-PM, although CRT-D more effectively lowered the sudden death rate. Male sex, NYHA functional class IV, and atrial fibrillation predicted the worst prognosis.     

Atrial Fibrillation Significantly Increases Total Mortality and Stroke Risk Beyond that Conveyed by the CHADS2 Risk Factors

Background: Atrial fibrillation (AF) is associated with an increased risk of mortality and stroke. However, it is unclear if AF is independently associated with these poor outcomes or it is merely a risk marker of other processes that convey the risk.
Methods: Consecutive patients who underwent angiography for suspicion of coronary artery disease, but without a history of AF, were studied. Traditional CHADS2 (congestive heart failure, hypertension, age >75 years, diabetes, stroke/transient ischemic attack) risk factors for each patient were recorded.
Results: A total of 343 AF patients (age = 69 ± 10 years, 215 [63%] male) and 2,945 non-AF patients (age = 63 ± 12 years, 2,012 [67%] male) were studied. Among AF patients, 51 (15%) had a myocardial infarction (MI), 35 (10%) had a stroke, and 180 (52%) died. CHADS2 score incrementally increased risk of stroke (adjusted hazard ratio [HR] for 1:1.92, 2:2.30, 3:1.14, 4:3.83, 5:10.96; P-trend = 0.14), death (HR for 1:1.83, 2:2.34, 3:3.69, 4:2.27, 5:4.53; P-trend < 0.001), and major adverse cardiac event (MACE) (HR for 1:1.29, 2:1.54, 3:2.07, 4:2.41, 5:2.68; P-trend = 0.002). Among non-AF patients, CHADS2 score incrementally increased risk of stroke (HR for 1:1.18, 2:3.17, 3:5.08, 4:10.78, 5:7.50; P-trend < 0.001), MI (HR for 1:1.05, 2:1.46, 3:1.57, 4:0.53, 5:4.76; P-trend = 0.002), death (HR for 1:1.79, 2:3.22, 3:6.23, 4:9.09, 5:14.00; P-trend < 0.001), and MACE (HR for 1:1.47, 2:2.36, 3:4.16, 4:5.91, 5:7.56; P-trend < 0.001). Among all patients, both CHADS2 score (all P ≤ 0.001) and AF were independent risk factors for stroke (AF: P = 0.002), MI (AF: P = 0.035), death (AF: P < 0.001), and MACE (AF: P < 0.001).
Conclusion: The CHADS2 score is a powerful predictor of stroke and death. AF increases the risk of these outcomes in an independent manner. These data support the concept that AF is a risk factor of future cardiovascular disease.     

Age and Gender Influences on Rate and Duration of Paroxysmal Atrial Fibrillation

The influence of age and gender on the character of paroxysmal atrial fibrillation (PAF) has not been described. Methods: The heart rate (HR) during PAF in patients receiving placebo or antiarrhythmic therapy was analyzed. Data from 177 24-hour Holter recordings were analyzed to mark the onset and termination of PAF and converted into RR interval files. PAF episodes lasting at least 2 minutes and containing ± 20% noise were included. HR during the first 30-second segment versus during the remainder of the episode, and the duration of PAF episodes were compared among groups of different ages and sex (Wilcoxon test). Results: 236 episodes from 55 recordings in 32 patients (all patients: 61.4 ± 12.8 years; men (19): 58.5 ± 12.6 years; women (13) 65.5 ± 12.4 years, P = ns for difference in age) fulfilled the inclusion criteria. Women had a higher mean heart rate at AF onset (123 ± 35 beats/min vs 115 ± 20 beats/min, P = 0.02) and during the remainder of the episode (120 ± 25 beats/min vs 112 ± 22 beats/min at the start, P = 0.01, and 116 ± 26 beats/min vs 108 ± 18 beats/min subsequently, P = 0.01). Episodes tended to be longer in women (mean 89.8 min vs 50.5 min, P = NS) and in the aged (mean 83.8 min vs 46.9 min, P = NS). Conclusion: PAF episodes are associated with faster heart rates and last longer in women, which may reflect differing autonomic responses to AF. A slower ventricular rate during PAF in older patients probably reflects an increasing prevalence of impaired atrioventricular conduction.     

Relation of heart rate recovery after exercise testing to coronary artery calcification

Background: We examined whether slow heart rate recovery (HRR) after exercise testing as an estimate of impaired autonomic function is related to coronary artery calcification (CAC), an emerging marker of coronary atherosclerosis.

Methods: We evaluated 2088 men who participated in a health-screening program that included measures of CAC and peak or symptom-limited cardiopulmonary exercise testing. HRR was calculated as the difference between peak heart rate (HR) during exercise testing and the HR at 2?min of recovery after peak exercise. We measured CAC using multidetector computed tomography to calculate the Agatston coronary artery calcium score. Advanced CAC was defined as a mean CAC >75th percentile for each age group.

Results: HRR was negatively correlated with CAC (r?=??.14, p?52 bpm). Each 1 bpm decrease in HRR was associated with 1% increase in advanced CAC after adjusting for potential confounders.

Conclusions: An attenuated HRR after exercise testing is associated with advanced CAC, independent of coronary risk factors and other related hemodynamic response.

• KEY MESSAGES

• Slow heart rate recovery (HRR) after maximal exercise testing, indicating decreased autonomic function, is associated with an increased risk of cardiovascular event and mortality.

• Slow HRR has been linked with the occurrence of malignant ventricular arrhythmias, but it remains unclear whether slow HRR is associated with an increased risk of coronary artery calcification (CAC), an emerging marker of coronary atherosclerosis.

• An attenuated HRR after exercise testing was associated with advanced CAC, independent of coronary risk factors and other potential hemodynamic confounder, supporting the hypothesis that slow HRR is related to the burden of atherosclerotic coronary artery disease.

     

Ventricular repolarization and heart rate responses during cardiovascular autonomic function testing in LQT1 subtype of long QT syndrome

Background: In the most prevalent LQT1 form of inherited long QT syndrome symptoms often occur during abrupt physical or emotional stress. Sympathetic stimulation aggravates repolarization abnormalities in experimental LQT1 models. We hypothesized that autonomic function tests might reveal the abnormal repolarization in asymptomatic LQT1 patients.
Methods: We measured heart rates (HRs) and QT intervals in nine asymptomatic carriers of a C-terminal KCNQ1 mutation and 8 unaffected healthy subjects using an approach of global QT values derived from 28 simultaneous electrocardiographic leads on beat-to-beat base during Valsalva maneuver, mental stress, sustained handgrip, and light supine exercise.
Results: LQT1 patients exhibited impaired shortening of both QTpeak and QTend intervals during autonomic interventions but exaggerated lengthening of the intervals—a QT overshoot—during the recovery phases. The number of tests with a QT overshoot was 2.4 ± 1.7 in LQT1 patients and 0.8 ± 0.7 in unaffected subjects (P = 0.02). Valsalva strain prolonged T wave peak to T wave end interval (TPE) in LQT1 but not in unaffected patients. LQT1 patients showed diminished HR acceleration in response to adrenergic challenge whereas HR responses to vagal stimuli were similar in both groups.
Conclusions: Standard cardiovascular autonomic provocations induce a QT interval overshoot during recovery in asymptomatic KCNQ1 mutation carriers. Valsalva maneuver causes an exaggerated fluctuation of QT and TPE intervals partly explaining the occurrence of cardiac events during abrupt bursts of autonomic activity in LQT1 patients.