台灣二尖瓣膜脫垂病人與正常族群心率變異性之性別與姿勢差異

Abstract

心率變異性(Heart rate variability, HRV)分析是一種測量連續心跳中，心搏與心搏之間變化程度的方法。過去二十年間對於自主神經系統(autonomic nervous system, ANS)和心血管疾病致死率的關係性有顯著增長的認識，包括心因性的猝死。HRV的研究對於預測心肌梗塞、心臟瓣膜疾病、或是先天性心臟病的病人之長期存活率是有用的，HRV的降低是危險因子，能預測致死與心律不整的併發。短時HRV能作為急性心肌梗塞預後的最初檢視。在標準的心電圖(electrocardiogram, ECG)中，兩個R波波峰之間稱為R-R間隔(R-R interval)，由連續的R-R間隔所構成的連續間距則定稱為N-N間隔(N-N interval)，心率變異性就是測量N-N間隔的變異性。正常的心跳會因為受到自主神經系統的調控而產生波動，因此當變異消失或明顯降低時，會產生沒有波動而完全規律的心率，這種心率被認為是心臟自主神經調節系統異常的表現。HRV的目的在於測量心率快慢差異的規律，提供非侵入性的方式來測量自主神經系統的平衡性。本研究的目地是評估在台灣二尖瓣膜脫垂的病人及正常族群中，性別與姿勢的差異是否影響HRV數值。 參與實驗的二尖瓣膜脫垂病人總數118人，其中含7位男性及111位女性，在2008年十一月至2013年一月期間，於台北醫學大學附屬醫院經超音波診斷確診為二尖瓣膜脫垂之病人；另有148名交通大學學生及新竹地區居民，其中含54位男性及94位女性，經過12導程心電圖檢查及確定無其他疾病者參加實驗，所有參加者皆為自願參與且簽下實驗同意書。本實驗所使用的機器為台灣達楷生醫科技所研發的DailyCare BioMedical’s ReadMyHeart®，使用單導程ECG (設定於第二導程)來做訊號的收集及分析，之後以人工編輯方式來檢查所收集到之訊號是否出現R波上的錯誤。實驗過程中，受測者需變化躺姿、坐姿、站姿三種姿勢以測量HRV，而每一種HRV測量前受測者皆須休息五分鐘。所有的實驗皆於白天時間(早上九點至下午四點)進行，以避免日夜差異對自主神經系統造成影響。於時域分析上採用SDNN、RMSSD及NN50三項數值，頻域分析採用TP、LF、HF 及 LF/HF比值。 由實驗可得知，二尖瓣膜脫垂病人與正常人相比，於時域分析中只有SDNN在三種姿勢中都具有統計上的差異，且此結果與頻域分析中的TP差異情況相符。頻域分析中，除了躺姿測量不具有差異外，其餘姿勢的數值全部都顯示了病人與正常人在自主神經調控上的差異。在時域分析中，無論是二尖瓣膜脫垂病人還是正常人，男女之間在躺姿測量的RMSSD和NN50具有顯著差異。頻域分析中，除了與SDNN相符的TP以外，其餘在各姿勢測量中都具有男女差異，顯示男性與女性在自主神經調控上的不同。而各姿勢之間的差異，在正常族群中的時域分析都顯示姿勢上具有差異，除了坐姿和躺姿相比時僅RMSSD具有統計上差異。頻域分析也都具有意義，除了坐姿和躺姿相比時TP不具有顯著差異。而在頻域統計方面，全部都顯示具有姿勢上的差異，除了在坐姿和站姿的比較中，時域分析的SDNN和頻域分析的TP都不具有姿勢改變造成的顯著差異。 從結果來看，我們可以得知SDNN數值相當於TP，此結果與往昔發表的著作相符合。正常台灣人在性別上的HRV差異此前也由我們實驗室做過發表，此實驗更加一步推論在二尖瓣膜脫垂的病人測量HRV也應做性別的區分。未來我們應更多收集二尖瓣膜脫垂的男性病人以求完整這份研究。儘管時域分析或許不適合用來評估二尖瓣膜脫垂病人的狀況，但頻域分析佐以姿勢變化的測量或許在評估二尖瓣膜脫垂的風險上將會是有效的工具。

Heart rate variability (HRV) is the temporal variation between sequences of consecutive heartbeats. On a standard electrocardiogram (ECG), the duration between two adjacent R wave peaks is termed the R-R interval. The resulting period between adjacent QRS complexes resulting from sinus node depolarization is termed the N-N (normal-normal) interval, and HRV is the measurement of the variability of the N-N intervals. The last two decades have witnessed the recognition of a significant relationship between the autonomic nervous system and cardiovascular mortality, including sudden cardiac death. HRV investigation has its use in the prediction of long-term survival in patients who had suffered from congestive myocardial infarction, or had valvular or congenital heart disease. Depressed HRV is a predictor of mortality and arrhythmic complications independent of other recognized risk factors. HRV assessed from short-term recordings may be used for initial screening of all survivors of an acute myocardial infarction. The purpose is to evaluate the gender and postural effects in HRV parameters between symptomatic MVPS patients and an apparently healthy population. A total of 118 patients, 7 males and 111 females, who had been echocardiographically diagnosed as having MVPS at Taipei Medical University Hospital cardiology clinic from November 2008 to January 2013, and 148 healthy people (54 males and 94 females) with normal 12-lead ECG without previous history of medical disease from National Chiao-Tung University and residents in Hsinchu were recruited for the study. All subjects had sign an informed consent and agree to take part in the research. A locally developed Taiwanese machine (DailyCare BioMedical’sReadMyHeart®) was used to record the HRV. One lead ECG (modified lead Ⅱ) was used for signals collection and analysis. The QRS complexes were detected and labelled automatically. The results of the automatic analysis were reviewed subsequently, and any errors in R-wave detection and QRS labelled were then edited manually. The subjects were asked to rest 5 minutes before each HRV recording (Lying, sitting and standing.) All the recordings were taken during the daytime (between 9:00 AM to 4:00 PM) to avoid the diurnal influence of the autonomic difference. For time-domain HRV measures, the mean N-N intervals and the standard deviation of N-N intervals during 5 minutes (SDNN) were then calculated. For frequency-domain HRV parameters analysis, spectral power was quantified by fast Fourier transformation and autoregressive method for the following frequency bands: 0.15-0.4 Hz (high frequency), 0.04-0.15 Hz (low frequency). Time domain parameters used were SDNN, RMSSD and NN50. Frequency domain parameters selected were TP, LF, HF and LF/HF. These parameters were defined in accordance with the 1996 ACC/AHA/ESC consensus. To make sure our data is normal distribution, Kolmogorov–Smirnov test was used at first. And then Paired Student t test was used to characterize differences in HRV variables. All HRV variables were expressed as mean ± SD. All statistical analyses were performed using Microsoft Excel 2007. A P value <0.05 was determined as statistically significant. In Time domain only SDNN between MVPS and Normal was statistically significantly different in all positions, and so as Frequency domain’s Total Power. In Frequency domain all Parameters were shown to have significant differences except in lying position. Between male and female in time domain, there were statistically differences of RMSSD and NN50 at lying both in MVPS and Normal. In frequency domain, all parameters were statistically significantly different in all postures both in MVPS and normal except total power. For postural changes, in normal group that time domain parameters only RMSSD was statistically differences between lying and sitting, but in other postural compared, all parameters were significantly different. And it is the same as in frequency domain parameters, only TP in lying compared with sitting posture had no difference. In MVPS group, the result of time domain parameters and frequency domain were the same as in normal group, except in sitting compared with standing posture. SDNN of time domain, and TP of frequency domain had no significant difference. From the results, we concluded that the SDNN is compatible with Total Power as demonstrated in the previous reports. Gender specific HRV variation had been reported in our previous study in normal Taiwanese. It is further strengthened the digenetic criteria for HRV should be gender specific in MVPS as well. Moreover, more male MVPS cases should be recruited for further clarification of this issue. Although time domain parameters might not be of use for the evaluation MVPS, frequency domain with postural changes might be a useful tool in MVPS diagnosis risk stratification.