Gender-Related Association of Serum Uric Acid Levels with Premature Ventricular Contraction.

In this study, we aim to investigate the association of serum uric acid (SUA) with the prevalence of premature ventricular contraction (PVC). The relationship between SUA and the prevalence of PVC in 98,965 subjects (79,034 male subjects, mean age: 51.9 ± 12.6 years old) in the Kailuan cohort study (n = 101,510, age range: 18-98 years) from June 2006 to October 2007 was investigated. These subjects were divided into five groups on the basis of their SUA levels. A multivariate logistic regression model was constructed to evaluate the association between SUA and the prevalence of PVC. The prevalence of PVC was 1.1% in all subjects, 1.1% in male subjects, and 1.0% in female subjects. Compared with the first quintile of SUA, the odds ratio (OR) and 95% confidence interval (95% CI) of other quintiles were 1.33 (1.05-1.69), 1.14 (0.90-1.46), 1.37 (1.08-1.74), and 1.63 (1.30-2.06) in male subjects; 1.12 (0.68-1.87), 1.27 (0.77-2.09), 1.45 (0.90-2.36), and 1.33 (0.81-2.18) in female subjects; and 1.30 (1.04-1.61), 1.20 (0.96-1.50), 1.33 (1.07-1.66), and 1.57 (1.26-1.95) for all subjects. The correlation between SUA and the prevalence of PVC was significant in all subjects and in male subjects, but not in female subjects. We demonstrated that SUA was apparently associated with the prevalence of PVC. The significant relationship between SUA and PVC identified in male subjects suggests the potential involvement of a gender-specific mechanism. Prospective studies are needed to further corroborate our results.

Chronic median nerve modulation reduces ventricular arrhythmia and improves ventricular function in a postmyocardial infarction rabbit model.

AIM: Median nerve stimulation (MNS) is a novel neuromodulation approach for treatment of ventricular arrhythmia, but little is known about its chronic effects. The aim of this study was to investigate the effects of chronic MNS on ventricular arrhythmia and ventricular dysfunction postmyocardial infarction (MI). METHOD: Two weeks after MI, 12 rabbits were randomly divided into control and MNS groups, and chronic MNS was performed in MNS group for 2 weeks. Ventricular function and arrhythmias; sympathetic innervation and activity; and interleukin-1 ß (IL-1 ß) and norepinephrine (NE) levels were analyzed. RESULTS: Both the total number of premature ventricular complex and episodes of ventricular tachycardia were lower in MNS group than in control group (20 560 ± 10 314 beats vs 70 079 ± 37 184 beats, P = .021, and 115 ± 63 episodes vs 307 ± 164 episodes, P = .034, respectively). Compared with control group, MNS decreased the cardiac sympathetic nerve density and level of circulating NE in MNS group (1798.42 ± 644.07 µm2 /mm2 vs 1003.79 ± 453.00 µm2 /mm2, P = .041, and 20.86 ± 4.54 pg/mL vs 11.07 ± 1.43 pg/mL, P = .002, respectively). MNS also improved the left ventricular ejection fraction (59.07 ± 1.91% vs 49.77 ± 3.47%, P = .003) and inhibited the level of IL-1 ß in serum (69.19 ± 4.71 pg/mL vs 85.93 ± 12.80 pg/mL, P = .013). CONCLUSION: Chronic MNS appears to protect against ventricular arrhythmia and improves ventricular function post-MI, which may be mediated by suppressing cardiac sympathetic activity and anti-inflammatory effects.

The inhibitory effect of rosmarinic acid on overexpression of NCX1 and stretch- induced arrhythmias after acute myocardial infarction in rats.

The incidence of arrhythmias is the main cause of high mortality after myocardial infarction (AMI). The aim of the present study was to determine whether the rosmarinic acid (RA) could reduce the stretch-induced arrhythmias (SIAs) related to overexpression of NCX1 after AMI. Adult male Sprague-Dawley rats were randomly allocated into six groups: Sham, MI (100 mg/kg of isoproterenol (Iso), subcutaneously, on two consecutive days), RA (30 mg/kg, orally, 14 days), and RA (10, 15 and 30 mg/kg, 14 days) + I. MI induction was performed on the 13th and 14th days of the study period. Forty-eight hours after the first injection of Iso, the parameters of hypertrophy, plasma levels of malondialdehyde (MDA) and lipid profile were evaluated. Using Langendorff apparatus, the isolated hearts were transiently stretched for 5 s with three different end-diastolic volumes (ΔV1to3 = 0.05, 0.1 and 0.2 mL). Cardiac function parameters were measured for 30 s, and ventricular arrhythmias were recorded for 3 min after each stretch. Finally, the levels of cardiac troponin-I and NCX1 mRNA expression were examined. The rats of MI group showed a significant increase in hypertrophy index, MDA, triglyceride and cholesterol (P < 0.001). Additionally, a marked impairment in cardiac parameters, an increase in the rates of SIAs and NCX1 expression, and a decrease in troponin-I (P < 0.001) were observed. RA at three doses especially 15 mg/kg strongly improved almost all the mentioned factors (P < 0.001). Our results confirm that RA pretreatment could prevent hypertrophia, arrhythmia and cardiac dysfunction following AMI which is associated with inhibition of lipid peroxidation and overexpression of NCX1.

Analysis of the correlation between the neutrophil-lymphocyte ratio in peripheral blood and perioperative myocardial damage in pediatric patients with frequent ventricular premature beat.

OBJECTIVE: The objective of the present study was to investigate the relationship between the neutrophil-lymphocyte ratio (NLR) in peripheral blood and myocardial damage in pediatric patients with frequent ventricular premature beat (FVPB), and provide a reference for myocardial preservation in these patients. PATIENTS AND METHODS: A total of 212 pediatric patients who were treated in the Department of Cardiology, Xuzhou Children's Hospital between December 2014 and March 2016 for FVPB, were selected. The results of routine blood exam, and levels of cardiac troponin I (cTnI) and creatine kinase-MB (CK-MB) in patients after the onset of FVPB were analyzed, and NLR was calculated. According to NLR levels, patients were divided into four groups using quartiles. RESULTS: With increases of NLR, the proportion of patients with a history of hypertension and ejection fraction < 50% increased gradually, and white blood cells (WBCs), the peaks of CK-MB and cTnI, and serum creatinine levels were significantly increased (p<0.05, p<0.01). There were no significant differences (p>0.05) in age, sex, body mass index, serum creatinine before treatment, fasting blood glucose, TG, TC, LDL-C, and HDL-C among the four groups. Multiple stepwise regression analysis showed that for patients with FVPB, NLR in peripheral blood was positively correlated with the peak of cTnI (r=0.538, p<0.05). NLR was positively correlated with levels of WBCs (r=0.661, p<0.05) and there was no correlation between NLR and history of hypertension, ejection fraction, and the laboratory results of creatinine peak and CK-MB. The differences were not statistically significant (p>0.05). However, the peak of cTnI was positively correlated with the levels of WBCs (r=0.189, p=0.003). CONCLUSIONS: NLR and WBCs in patients with FVPB are positively related to the peak of cTnI. NLR may serve as an excellent marker that reflects myocardial damage in pediatric patients with FVPB.

Higher High-Sensitivity C Reactive Protein is Associated with Future Premature Ventricular Contraction: a Community Based Prospective Cohort Study.

We aimed to determine whether hs-CRP is a predictor of future premature ventricular contraction (PVC) events in a community based population. A total of 101,510 participants were recruited at baseline (2006-2007). The follow-up visits were conducted every two years. Participants who were free from PVC at baseline and achieved the fourth visit, or diagnosed of PVC during the subsequent visits were included for analyses. Diagnosis of PVC was based on standard supine resting, 10-s 12-lead ECG. Cox regression was applied to evaluate the association between quartiles of hs-CRP and the incidence of PVCs. 60710 participants (male: 79.9%, mean age 49.4 years) were included for analyses. During a mean follow-up of 74.9 ± 7.4 months, 908 (1.5%) participants were diagnosed with PVC. Participants of the highest quartile of hs-CRP had significantly increased risk of PVC events as compared with the lowest quartile (HR 1.36; 95% CI 1.12-1.66); and stratified analyses showed similar result in males (HR 1.45; 95% CI 1.16-1.80), but not in females (HR 1.12; 95% CI 0.71-1.79). Moreover, elevated serum hs-CRP was associated with future PVC in participants without history of myocardial infarction or stroke (HR 1.34; 95% CI 1.09-1.65). Elevated hs-CRP was an independent predictor of PVC in Chinese population, especially in men.

Premature Ventricular Complex is More Prevalent During Acute Exacerbated than Stable States of Chronic Obstructive Pulmonary Disease, and Is Related to Cardiac Troponin T.

During acute exacerbation of chronic obstructive pulmonary disease (AECOPD), myocardial stress may be aggravated. Sparse data exist concerning the prevalence and correlates of cardiac arrhythmias in the stable and exacerbated states of COPD. We hypothesized that AECOPD is associated with increased prevalence of cardiac arrhythmias independent of COPD-severity and co-morbidity, and explored possible mechanisms. A 24-hour Holter recording was obtained in 74 patients with stable COPD and 45 patients with AECOPD (mean age 54 years, 56% women). Any incidence of supraventricular tachycardia (SVT), frequent premature ventricular complex (PVC, >30/hour) and complex ventricular ectopy (bigeminy, trigeminy or non-sustained ventricular tachycardia) was recorded and compared between the two groups. Adjustments were made for by stable disease-related co-variates (demography, co-morbidity, COPD-severity) and by acute disease-related co-variates (heart rate, cardiac troponin T (cTnT), PO2, PCO2 and C-reactive protein (CRP)) in explorative analyses. The prevalence of SVT, frequent PVCs or complex ventricular ectopy was 40%, 27% and 33% in AECOPD, and 31%, 31% and 12% in stable COPD, respectively. Frequent PVC, but not SVT or complex ventricular ectopy, was significantly increased in AECOPD compared to stable COPD, odds ratio 3.03 (1.03-10.5, p = 0.039) when adjusted for stable disease-related co-variates. Higher heart rate, cTnT and CRP attenuated the association between AECOPD and frequent PVC to non-significant, while heart rate remained associated with frequent PVC. In conclusion, frequent PVC is more prevalent in exacerbated than in the stable states of COPD. Attenuation effects of cTnT, tachycardia and CRP suggest that cardiac stress or inflammation may be involved in mechanisms causing frequent PVC i AECOPD.

Risk factors for premature ventricular contractions in young and healthy adults.

BACKGROUND: Premature ventricular contractions (PVCs) are associated with an increased risk of morbidity and mortality. Therefore, it was aimed to assess risk factors for the frequency of PVCs in young and healthy adults. METHODS: Our population-based study included 2048 healthy adults from the general population aged 25-41 years. PVC frequency was determined by 24-hour Holter ECG. We performed multivariable regression analysis using stepwise backward selection to identify factors independently associated with PVC frequency. RESULTS: Median age was 37 years, 953 (46.5%) were male. At least one PVC during the 24-hour monitoring period was observed in 69% of participants. Median number of detected PVCs was 2, the 95th percentile was 193. In multivariable regression analyses, we found 17 significant risk factors for PVC frequency. Low educational status (risk ratio (RR) 3.33; 95% CI 1.98 to 5.60), body height>median (1.58, 95% CI 1.11 to 2.24) and increasing levels of waist:hip ratio (2.15, 95% CI 1.77 to 2.61), N-terminal pro brain natriuretic peptide (1.52, 95% CI 1.30 to 1.76) and Sokolow-Lyon Index (1.38, 95% CI 1.15 to 1.66) (all p≤0.01) were associated with a higher PVC frequency. Physical activity (RR fourth vs first quartile 0.51, 95% CI 0.34 to 0.76) and increasing levels of haemoglobin (0.58, 95% CI 0.47 to 0.70) and glucagon-like peptide-1 (0.72, 95% CI 0.64 to 0.82) (all p<0.001) were related to a lower PVC frequency. CONCLUSIONS: PVC occurrence is common even in healthy low-risk individuals, and its frequency is associated with several covariates mainly related to cardiovascular risk factors, markers of cardiac structure and function and socioeconomic status.

Biomarkers of cardiovascular injury and stress are associated with increased frequency of ventricular ectopy: a population-based study.

BACKGROUND: Asymptomatic ventricular arrhythmias are common and associated with increased risk of cardiovascular mortality. Cardiac troponins, natriuretic peptides and C-reactive protein (CRP) are also predictive of adverse cardiovascular events in the general population, but limited information is available on the relationship between these biomarkers and ventricular ectopy in a community-based population. The objectives were to evaluate the associations between ventricular ectopic activity and N-terminal pro-B-type natriuretic peptide (NT-proBNP), high sensitivity-troponin I (hs-TnI) and hs-CRP in a community-based setting. METHODS: We performed a 24 h Holter-recording and blood sampling in 498 subjects. Premature ventricular complexes (PVC) were classified as frequent at >5/h and the presence of any bigeminy, trigeminy or non-sustained ventricular tachycardia were classified as complex ventricular ectopy. The associations between biomarkers and ventricular arrhythmias were investigated by univariate and multivariate logistic regression analyses. RESULTS: Frequent PVC's and complex ventricular ectopy were detected in 46 (9%) and 47 (9%) participants respectively, and were associated with significantly (p < 0.001) higher concentrations of NT-proBNP and hs-TnI. The association between NT-proBNP and both frequent PVC's (p = 0.020) and complex ventricular ectopy (p = 0.001) remained significant after adjusting for conventional risk markers in multivariate analyses. CONCLUSION: Increased level of NT-proBNP was independently associated with ventricular ectopy, whereas no independent association was observed between hs-TnI and hs-CRP levels and ventricular ectopy in this community-based sample.

Fatigue as Presenting Symptom and a High Burden of Premature Ventricular Contractions Are Independently Associated With Increased Ventricular Wall Stress in Patients With Normal Left Ventricular Function.

BACKGROUND: High idiopathic premature ventricular contractions (PVC) burden has been associated with PVC-induced cardiomyopathy. Patients may be symptomatic before left ventricular (LV) dysfunction develops. N-terminal pro-B-type natriuretic peptide (NT-proBNP) and circumferential end-systolic wall stress (cESS) on echocardiography are markers for increased ventricular wall stress. This study aimed to evaluate the relation between presenting symptoms, PVC burden, and increased ventricular wall stress in patients with frequent PVCs and preserved LV function. METHODS AND RESULTS: Eighty-three patients (41 men; 49±15 years) with idiopathic PVCs and normal LV function referred for PVC ablation were included. Type of symptoms (palpitations, fatigue, and [near-]syncope), PVC burden on 24-hour Holter, NT-proBNP levels, and cESS on echocardiography were assessed before and 3 months after ablation. Sustained successful ablation was defined as ≥80% PVC burden reduction during follow-up. Patients were symptomatic for 24 months (Q1-Q3, 16-60); 73% reported palpitations, 47% fatigue, and 30% (near-)syncope. Baseline PVC burden was 23±13%, median NT-proBNP 92 pg/mL (Q1-Q3 50-156), and cESS 143±35 kdyne/cm(2). Fatigue was associated with higher baseline NT-proBNP and cESS (P<0.001, P=0.011, respectively). After sustained successful ablation, achieved in 81%, NT-proBNP and cESS decreased significantly (P<0.001 and P=0.036, respectively). Fatigue was independently associated with a significantly larger reduction in NT-proBNP. In patients with nonsuccessful ablation, NT-proBNP and cESS remained unchanged. CONCLUSIONS: In patients with frequent PVCs and preserved LV function, fatigue was associated with higher baseline NT-proBNP and cESS, and with a significantly larger reduction in NT-proBNP after sustained successful ablation. These findings support a link between fatigue and PVC-induced increased ventricular wall stress, despite preserved LV function.

Decreased prevalence of cardiac arrhythmias during and after vigorous and prolonged exercise in healthy male marathon runners.

BACKGROUND: Vigorous exercise such as marathon running results in an increased risk of sudden cardiac death. Malignant arrhythmias seem to be the primary cause. However, continuous electrocardiographic monitoring for detection of arrhythmias during a marathon race has not been performed yet. METHODS: Twenty male marathon runners (age 45 ± 8 years) free of cardiovascular disease underwent 24-hour Holter monitoring 5 weeks before a marathon race (baseline). Subsequently, wireless Holter monitoring started immediately before the race, recorded up to 70 hours postrace. Electrocardiograms were analyzed for the presence of arrhythmias. Additionally, cardiac troponin, interleukin-6 (IL-6), and electrolytes were assessed prerace and postrace. RESULTS: At baseline Holter recordings, runners showed a median of 9 (interquartile range 3-25) atrial premature complexes (APCs) and 4 (2-16) ventricular premature complexes (VPCs) per 100,000 beats. Compared to baseline, the number of APCs decreased significantly during and 1 hour after the marathon race (0 [0-3] and 0 [0-0], all P < .001) as well as the number of VPCs during the race (0 [0-0], P = .008). No malignant arrhythmias occurred. Mean postrace levels for troponin and IL-6 were significantly augmented after the race (prerace to postrace: troponin 4 times, IL-6 17 times, all P < .001); however, no significant influence of these biomarkers or electrolytes on the prevalence of arrhythmias was observed (all P > .05). CONCLUSIONS: In this cohort of male runners free of cardiovascular disease, the prevalence of arrhythmias during and after a marathon race was decreased. Arrhythmogenic risk was independent of changes in biomarkers assessing cardiac injury, inflammation, and changes in electrolytes.

The Association Between the Neutrophil-to-Lymphocyte Ratio and the Presence of Ventricular Premature Contractions in Young Adults.

Inflammation has recently emerged in the pathogenesis of several cardiovascular disorders, including arrhythmias. The neutrophil-lymphocyte ratio (NLR) is a simple marker for the assessment of inflammatory status. Therefore, we aimed to investigate the relationship between the NLR and the ventricular premature contraction (VPC) existence. Patients aged between 18 and 40 years who were referred to the cardiology clinic were enrolled in the study. All patients' complete blood counts and 24-hour Holter recordings were analyzed. The NLR was higher within the VPC group compared to the control group (P < .001). According to the NLR tertiles, VPCs were more common in the higher NLR tertile (P < .001). A cutoff point of 1.80 for the NLR had 71% sensitivity and 60% specificity in predicting VPC in apparently healthy individuals. After multivariate analysis, only the NLR remained significant predictor of presence of VPC. In conclusion, the NLR is independently and significantly associated with VPC existence.

[Variability of glycemia and ventricular rhythm disturbances in patients with chronic heart failure and type 2 diabetes mellitus].

Aim of this observational study was assessment of effect of variability of glycemia on ventricular ectopic activity in patients with chronic heart failure (CHF) and type 2 diabetes mellitus (n=80). According to study protocol 24-hour Holter ECG monitoring was carried out at baseline, and after 3 and 6 months. Measurements of blood glucose level were made at 8 points during ECG monitoring - before and in 2 hours after main meals, before bedtime and at 3 o'clock in the morning. In 20 patients continuous combined monitoring of ECG and of blood glucose level was carried out. During monitoring of ECG high grade ventricular arrhythmias were found in 42 patients (53%). Pronounced variations of blood glucose level (mean amplitude of glycemic excursion >5 mmol/L) were associated with 2.3 fold increase risk of ventricular arrhythmias (p=0.04). A conclusion was made that pronounced 24-hour variations of glucose level in blood was associated with elevation of ventricular ectopic activity. High 24-hour variability of glycemia appeared to be proarrhythmogenic factor in patients with CHF and concomitant diabetes.

Neurohormonal, structural, and functional recovery pattern after premature ventricular complex ablation is independent of structural heart disease status in patients with depressed left ventricular ejection fraction: a prospective multicenter study.

OBJECTIVES: This study aimed to assess the benefit after ablation of premature ventricular complexes (PVC) in patients with frequent PVC and left ventricular (LV) dysfunction, regardless of previous structural heart disease (SHD) diagnosis, PVC morphology, or estimated site of origin. BACKGROUND: Ablation of PVC in patients with LV dysfunction is usually restricted to patients with suspected PVC-induced cardiomyopathy. METHODS: Consecutive patients with frequent PVC and LV dysfunction accepted for ablation at 4 centers were prospectively included. Of the 80 patients included, 27 (34%) had a diagnosis of SHD. RESULTS: Successful sustained ablation (SSA) was achieved in 53 (66%) patients, and LVEF improved in these patients from 33.7 ± 8% to 43.8 ± 9.4% and 45.8 ± 10.9% at 6 and 12 months, respectively (p < 0.05), without differences related to previous diagnosis of SHD (p = 0.69). BNP decreased from 109 [64 to 242] pg/ml to 60 [25 to 170] pg/ml, 50 [14 to 130] pg/ml, and 60 [19 to 81] pg/ml at 1, 6, and 12 months (p < 0.05). Patients in NYHA class I increased from 12 (23%) to 42 (79%) at 12 months (p < 0.05). A 13% baseline PVC burden had 100% sensitivity and 85% specificity to predict an absolute increase ≥ 5% in LVEF after SSA. Although 20 patients with >13% PVC and SSA had class I indication for cardioverter defibrillator implantation, these indications were absent at 6 months post-ablation. CONCLUSIONS: Independently of the presence of SHD, the SSA of frequent PVC in patients with depressed LVEF induced a progressive clinical and functional improvement. Improvement in heart failure parameters was related to baseline PVC burden and persistence of ablation success.

Ventricular arrhythmia in dialysis patients: a link with higher hemoglobin levels?

We investigated the frequencies and associated risk factors of cardiac arrhythmias and heart rate variability (HRV) in hemodialysis (HD) patients. One hundred fifty prevalent HD patients underwent 48-hour Holter monitoring. Holter monitoring was analyzed in 4 phases: early post-HD phase (12 hours), late post-HD phase (20 hours), pre-HD phase (12 hours), and HD phase (4 hours). Echocardiography was applied to measure the left ventricular mass index in a subgroup of patients (n: 52). Patients with ventricular premature contraction (VPC) were significantly older, had a longer HD duration, and higher hemoglobin (Hb) levels. Left ventricular mass index was significantly correlated with the frequency of VPC, during the HD and pre HD phases (r: 0.435, 0.312, respectively). In logistic regression analysis, patients with Hb level >11.9 g/dL (high tertile) had a 4.5-fold increased risk of VPC compared with those with Hb levels <10.8 g/dL (P: 0.04). In HRV analysis, age (P<0.001), and diabetes (P: 0.03) were found to be independent predictors of low standard deviation of all mean normal-to-normal RR intervals. Increased left ventricular mass index is associated with a high frequency of VPC in the pre-HD and HD periods. The occurrence of VPC is predicted by older age, longer dialysis duration, and higher Hb levels, while older age and diabetes are the determinants of HRV. The relation between higher Hb levels and the frequency of VPC might provide a clue for the explanation of the detrimental effect of higher Hb levels on HD patients.

Effect of oestrogen replacement therapy on idiopathic outflow tract ventricular arrhythmias in postmenopausal women.

BACKGROUND: Sex hormones and gender differences are associated with the occurrence of ventricular arrhythmias. AIM: To investigate the relationship between sex hormones and idiopathic outflow tract ventricular arrhythmias (IOTVA), and the effect of oestrogen replacement therapy on IOTVA, in postmenopausal female patients. METHODS: Plasma sex hormone concentrations and ventricular arrhythmia counts were estimated in postmenopausal patients with IOTVA and control postmenopausal women. The effect of oestrogen replacement therapy on IOTVA was observed in postmenopausal patients with IOTVA. RESULTS: The concentration of oestradiol in postmenopausal patients with IOTVA was significantly lower than that in control postmenopausal women (8.4 ± 3.4 vs 36.9 ± 12.8pg/mL, respectively; P<0.001). The ventricular arrhythmia count in postmenopausal patients with IOTVA was significantly higher than that in controls (10,171 ± 6091 vs 209 ± 468 counts/24 hours, respectively; P<0.001). After 3 months of oestrogen replacement therapy, the ventricular arrhythmia count was significantly lower than that before therapy (3958 ± 1972 vs 10171 ± 6091 counts/24 hours, respectively; P<0.001). CONCLUSION: This study showed that the concentration of oestradiol was lower in postmenopausal patients with IOTVA than in control postmenopausal women, and that oestrogen replacement therapy can inhibit effectively the genesis of IOTVA.

Differential effects of statins (pravastatin or simvastatin) on ventricular ectopic complexes: Galpha(i2), a possible molecular marker for ventricular irritability.

Retrospective studies suggest that statins might exert an antiarrhythmic effect on the heart. The mechanism of this effect is unclear. Parasympathetic stimulation of the heart has been shown to protect against ventricular arrhythmias. The goal of this study was to determine the effect of statins on ventricular arrhythmias and its correlation with changes in parasympathetic responsiveness and Galpha(i2) expression. Patients were randomized to pravastatin and simvastatin in a double-blind crossover design. Ventricular arrhythmias were determined by analysis of 24-hour Holter recordings. Spectral RR interval analysis of Holter studies determined peak high-frequency power fraction, which reflects parasympathetic modulation of heart rate. Expression of Galpha(i2), a molecular component of the parasympathetic response pathway, was determined by Western blots of patients' lymphocytes. Pravastatin treatment decreased the incidence of ventricular premature complexes by 22.5 + or - 3.4% (n = 20, p <0.05), couplets, and runs of 3 to 6 beats of nonsustained ventricular tachycardia from 9.8 + or - 2.67 to 3.9 + or - 1.25 events/patient/24 hours (n = 12, p <0.05). Pravastatin increased peak high-frequency fraction by 29.8 + or - 4.3% (n = 33, p <0.001), while Galpha(i2) expression increased by 51.3 + or - 22.5% (n = 21, p <0.05). Effects of simvastatin on ventricular premature complexes and nonsustained ventricular tachycardia were not significant. Relative changes in couplets and nonsustained ventricular tachycardia in pravastatin-treated patients correlated negatively with changes in Galpha(i2) and high-frequency fraction (rho = -0.588 and rho = -0.763, respectively, n = 12, p <0.05). In conclusion, these data suggest that pravastatin might decrease cardiac irritability via an increase in parasympathetic responsiveness and that changes in Galpha(i2) expression might serve as a molecular marker for this effect, which might play a role in the molecular mechanism of the antiarrhythmic effect of statins.

High-frequency ventricular ectopy can increase sympathetic neural activity in humans.

BACKGROUND: Sudden cardiac death is usually caused by ventricular arrhythmias and in many cases, is preceded by frequent ventricular ectopy. It is known that ectopic beats cause transient increases in sympathetic nerve activity (SNA). OBJECTIVE: Because high SNA is known to be arrhythmogenic, we hypothesized that high rates of ectopy increase SNA, thereby creating a milieu that favors development of ventricular tachycardia and/or fibrillation. METHODS: This study measured muscle SNA, coronary sinus catecholamine, and arterial pressure during graded rates of ventricular ectopy (from 4:1 to 1:1, sinus to ectopic beat ratio) in a total of 21 patients referred for electrophysiologic testing. RESULTS: Both muscle SNA and coronary sinus norepinephrine increased significantly with increased ectopy frequency (P < .05). Moreover, the change in muscle SNA correlated significantly with the change in coronary sinus norepinephrine levels (r = .72, P < .001). CONCLUSION: These data demonstrate that sympathoexcitation evoked by high rates of ventricular ectopy can contribute to a state of elevated SNA both in peripheral tissues and within the heart. This altered autonomic state may contribute to an increased susceptibility to life-threatening tachyarrhythmias in patients with high rates of ectopy.

Predictors of ventricular arrhythmias in patients with mitral valve prolapse.

Arrhythmias have been reported to occur frequently in symptomatic patients with mitral valve prolapse (MVP). The mechanisms causing ventricular arrhythmias in patients with MVP have not been fully investigated. The purpose of this study was to determine the clinical, echocardiographic and heart rate variability parameters, and plasma concentrations of electrolytes and inflammatory markers in predicting ventricular arrhythmias in patients with MVP. A total of 58 consecutive patients with MVP were included in this study. We performed electrocardiography, echocardiography, holter analysis, routine biochemical tests including plasma concentrations of electrolytes and inflammatory markers, and evaluated the clinical characteristics. Ventricular arrhythmia defined as occurrence of any of the followings: ventricular premature contractions (VPCs), VPC couplets, and ventricular tachycardia documented by holter analysis, continuous monitoring or by electrocardiography. Twenty patients (34%) had ventricular arrhythmias, and 38 (66%) patients had no ventricular arrhythmias. Seventeen patients had VPC, 2 patients had VPC couplets and 1 patient had ventricular tachycardia. Univariable predictors of ventricular arrhythmias included isovolumetric relaxation time and the occurrence of moderate to severe mitral regurgitation. Multivariable logistic regression analysis showed that occurrence of moderate to severe mitral regurgitation was the only independent predictor of ventricular arrhythmias (relative risk: 8.42, 95% confidence interval: 1.49-47.64, p = 0.01). Present study showed that the only independent predictor of ventricular arrhythmias in patients with MVP is the occurrence of moderate to severe mitral regurgitation.