Evolution of cardiac autonomic nervous activity indices in patients presenting with transient left ventricular apical ballooning.

BACKGROUND: Transient left ventricular (LV) apical ballooning (AB) is characterized by a rapidly reversible, acute LV systolic dysfunction, triggered by physical or emotional stress. Despite observations strongly suggesting catecholamine-mediated myocardial stunning due to enhanced sympathetic activity, the early time course of heart rate variability (HRV) has not been described. METHODS: We prospectively enrolled 39 consecutive patients (median age = 68 years, range 35-85 years, 38 women) with LV AB. Indices of HRV were extracted from 24-hour ambulatory electrocardiograms on the day of hospital admission, on days 2 and 3, and 3 months after the hospitalization. RESULTS: Within 48 hours after hospital admission, the indices of HRV were markedly depressed (standard deviation of normal-to-normal [NN] intervals [SDNN] 89.6 +/- 19.9 ms; mean standard deviation of NN intervals for 5-minute segments [SDNNi] 37.8 +/- 6.2 ms; root mean square of consecutive difference of normal-to-normal intervals [rMSSD] 23.0 +/- 9 ms; standard deviation of the averages of NN intervals for all 5-minute segments [SDANN] 70.1 +/- 18.0 ms; geometric triangular index [TI] 23.7 +/- 5.9 ms), recovered in the subacute phase and had normalized at 3 months follow-up (SDNN 124.7 +/- 24 ms; SDNNi 47.1 +/- 5.7 ms; rMSSD 31.1 +/- 10.5 ms; SDANN 118.5 +/- 27 ms; TI 31.2 +/- 8 ms; all P < 0.05). Mean RR-interval increased from 845 +/- 121 ms on day 1, to 929 +/- 84 ms at 3 months (P=0.06). CONCLUSIONS: A marked depression of cardiac parasympathetic activity was observed in the acute phase of LV AB, followed by recovery of autonomic modulation between the subacute and the chronic phases. The rapid return of parasympathetic function may partially explain the favorable outcomes of patients presenting with LV AB.

Effects of gender and aging on differential autonomic responses to orthostatic maneuvers.

BACKGROUND: There are gender differences in heart rate and blood pressure response to postural change. Also, normal aging is often associated with diminished cardiac autonomic modulation during postural change from supine to upright position. Nevertheless, the exact mechanisms of these physiological alterations are not entirely understood. METHODS: A total of 362 volunteers (206 females, age range: 10-88 years) underwent continuous, noninvasive, beat-to-beat blood pressure and ECG recordings in supine and upright position. To calculate spontaneous baroreflex sensitivity (BRS), blood pressure and RR interval fluctuations were reconstructed using the time-domain sequential technique. Furthermore, mean systolic and diastolic blood pressure, mean heart rate, and frequency-domain parameters of heart rate variability (low-frequency power [LF], low-frequency power in normalized units [LFn] high-frequency power [HF], high-frequency power in normalized units [HFn], low-/high-frequency ratio [LF/HF], and total power [TP]) were analyzed in both supine and standing positions. To investigate age-related differences, subjects were divided into four equally sized groups (quartile l: 10-33 years; ll: 34-42 years; III: 43-57 years; and lV: 58-88 years), as well as decades (l: 10-19 years; ll: 20-29 years; lll: 30-39 years; lV: 40-49 years; V: 50-59 years; Vl: 60-69 years; Vll: >or= 70 years). RESULTS: A continuous decline in BRS, LF, HF, and TP was observed with increasing age in both male and female subjects, regardless of posture. Gender comparison showed significantly higher values of LF (supine P < 0.001; upright P < 0.05), LFn (supine P < 0.001; upright P < 0.01), and TP (supine P < 0.05; upright P < 0.05) in men than women in supine and standing positions. HF revealed no gender difference and HFn (supine P < 0.001; upright P < 0.05) was larger in women. Log BRS correlated well with log LF and log HF in both supine and standing positions. CONCLUSIONS: There are significant differences in postural cardiac autonomic modulation between men and women, and the degree of autonomic response to orthostatic maneuvers varies with normal aging. These results may explain gender- and age-related differences in orthostatic tolerance.

Factor Xa inactivation in acute coronary syndrome.

The increasing incidence of patients who develop acute coronary syndrome (ACS) stresses the importance of effective initial treatment to reduce morbidity and mortality. The recommended initial therapeutic regimen for patients with ACS includes both anticoagulants and antiplatelet agents to prevent excessive coronary thrombosis, stroke, and further coronary events. Most commonly, unfractionated heparin (UFH) is used for initial antithrombotic treatment of ACS, despite limited published evidence regarding effectiveness and safety (bleeding complications). Therefore, this treatment regimen is primarily based upon expert opinion rather than evidence-based medicine. Studies addressing the dilemma of effectiveness and increased risk of bleeding when using UFH and low molecular weight heparin (LMWH) in patients with ACS showed superior clinical outcome in patients treated with LMWH. Nevertheless, the concurrent increased risk of bleeding while using anticoagulants is a severe problem and negatively impacts upon clinical outcome. Furthermore, non-hemorrhagic side effects of heparin such as heparin-induced thrombocytopenia (HIT), and skin reactions at the site of subcutaneous injection are reduced but not abolished by replacing UFH with LMWH. The limitations of UFH and LWMH as outlined above provided the impetus for the development of a pentasaccharide, called fondaparinux, which inhibits factor Xa selectively. Fondaparinux has been shown to be as effective as enoxaparin in the prevention of thrombosis in patients undergoing orthopedic surgery and showed similar results compared to enoxaparin or UFH in patients with deep-vein-thrombosis or pulmonary embolism. Recently, a large clinical study addressed the dilemma of the effectiveness and adverse effects of anticoagulation in ACS by comparing fondaparinux and LMWH such as enoxaparin in patients with unstable angina or non ST-segment elevation myocardial infarction (NSTEMI).

Impact of diabetes on QT dynamicity in patients with and without myocardial infarction: The KORA Family Heart Study.

INTRODUCTION: Patients with diabetes mellitus (DM) have an unfavorable prognosis after myocardial infarction (MI), partially due to a higher risk of sudden cardiac death (SCD). QT dynamicity is an independent predictor of SCD in post-MI patients. However, the effects of diabetes on QT dynamicity in patients with MI have not been described. METHODS: We studied 468 survivors of MI (67 with DM) from the population-based MONICA registry (KORA Family Heart Study), Augsburg, Germany, by standardized questionnaire, anthropometry, electrocardiogram (ECG), 30-minute-Holter-ECG-recordings and echocardiography. In addition, 422 siblings without prior MI (22 with DM) were studied by the same protocol. RESULTS: Among post-MI patients, the QT/RR slope was significantly steeper in diabetics than in nondiabetics (0.096 +/- 0.057 vs 0.077 +/- 0.045; P = 0.002). Likewise, among siblings without MI, the QT/RR slope was steeper in diabetics than in nondiabetics (0.104 +/- 0.053 vs 0.080 +/- 0.042; P = 0.008). The association of DM with steeper QT/RR slope remained significant in multivariate models in post-MI patients (beta: -0.14; P = 0.004) as well as in individuals without MI (beta: -0.10; P = 0.047). CONCLUSIONS: In a large population of survivors of MI and unaffected siblings, patients and siblings presenting with DM exhibited an abnormal QT rate-dependence, compared with individuals without DM in both groups. Thus, diabetes itself may be a major determinant of ventricular arrhythmias, independently of a previous MI. These observations might in part explain the higher incidence of sudden cardiac death and ventricular arrhythmias in patients with DM.

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.deltaHR) due to EPR and a secondary, more gradual increase (2.deltaHR) due to BRS. HR then decreases (3.deltaHR), 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.deltaHR, 2.deltaHR, and 3.deltaHR were calculated from the HR recording. From the 1(st) to the 6(th) decade BRS, 2.deltaHR and 3.deltaHR decreased with normal aging ([BRS 11.88 +/- 7.97 ms/mmHg to 1.81 ms/mmHg, P = 0.006], 2.deltaHR [16.75 +/- 3.40 beats to 5.33 +/- 2.52 beats, P = 0.002], 3.deltaHR [52.25 +/- 5.91 beats to 11.33 +/- 4.04 beats, P < 0.001]). However, no such association was noted between 1.deltaHR and age (21.25 +/- 9.35 beats to 12.00 +/- 7.21 beats, ns). BRS while standing was correlated with 1.deltaHR (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.

Modulation of cardiac autonomic nervous activity early after cardioversion of atrial fibrillation by biphasic waveform.

BACKGROUND: Imbalance of cardiac autonomic nervous modulation might prominently contribute to early relapses of atrial fibrillation (AF) after cardioversion (CV). The biphasic (Bi) waveform is more effective than the monophasic (Mo) waveform in CV of AF. Whether these waveforms have different effects on autonomic modulation early after CV is unknown. METHODS: We investigated 171 consecutive patients after successful electrical CV (mean age 65.4 years, 82% male, 80% structural heart disease). Bi waveform was used in 89, Mo waveform in 82. Heart rate variability (HRV) was analyzed from 24-hour Holter recordings, started directly after CV. RESULTS: Mean delivered total energy was significantly lower in the Bi group (Bi 223 +/- 163 W, Mo 355 +/- 211 W, P < 0.001). Mean RR interval decreased within 5 hours after CV and increased again within the remaining hours, without significant differences between Bi and Mo groups. Time courses of time domain parameters of HRV revealed Bi profiles with the lowest levels 6 hours after CV in both groups. However, the hourly values of HRV were significantly higher in the Bi subgroup. CONCLUSION: Our study indicates that waveform and total delivered energy significantly influence autonomic modulation of the sinus node in the early phase after CV of AF. In contrast to Bi CV, Mo CV is characterized by a significant decrease of cardiac vagal modulation, which may have an arrhythmic effect by increasing the degree of early electrical stunning after CV of AF.

Modulation of ventricular repolarization in patients with transient left ventricular apical ballooning: a case control study.

OBJECTIVE: Even though diffuse T wave inversion and prolongation of the QT interval in the surface electrocardiogram (ECG) have been consistently reported in patients with transient stress-induced left ventricular apical ballooning (AB), ventricular repolarization has not yet been systematically investigated in this clinical entity. BACKGROUND: AB, an emerging syndrome that mimics acute ST-segment elevation myocardial infarction (MI), is characterized by reversible left ventricular wall motion abnormalities in the absence of obstructive coronary heart disease and significant QT interval prolongation. METHODS: We prospectively enrolled 22 consecutive patients (21 women, median age 65 years) with transient left ventricular AB. A total of 22 age-, gender-, body-mass-index-, and left-ventricular-function-matched patients with acute anterior ST-segment elevation MI undergoing successful direct percutaneous coronary intervention for a proximal occlusion of the LAD, as well as 22 healthy volunteers served as control groups. Beat-to-beat QT interval and QT interval dynamicity were determined from 24-hour Holter ECGs, recorded on the third day after hospital admission. RESULTS: There were no significant differences in baseline clinical characteristics, except higher peak enzyme release in MI patients. Compared with MI patients, AB patients exhibited significantly prolonged mean QT intervals and rate-corrected QT intervals (QT: 418 +/- 37 vs 384 +/- 33 msec, P < 0.01; QTcBazett: 446 +/- 40 vs 424 +/- 35 msec, P < 0.05; QTcFridericia: 437 +/- 35 vs 412 +/- 31 msec, P < 0.05). Mean RR intervals tended to be higher in AB patients, without reaching statistical significance (877 +/- 96 vs 831 +/- 102 msec, P = NS). The linear regression slope of QT intervals plotted against RR intervals was significantly flatter in AB patients at both day- and nighttime (QT/RR slopeday: 0.18 +/- 0.04 vs 0.22 +/- 0.06, P < 0.01; QT/RR slopenight: 0.12 +/- 0.03 vs 0.17 +/- 0.05, P < 0.01). CONCLUSION: The present study is the first to demonstrate significant differences of QT interval modulation in patients with transient left ventricular AB and acute ST-segment elevation MI. Even though transient AB is associated with a significant QT interval prolongation, rate adaptation of ventricular repolarization (i.e., QT dynamicity) is not significantly altered, suggesting a differential effect of autonomic nervous activity on the ventricular myocardium in transient AB and in acute MI.