No Correlation Between Atrial Natriuretic Peptide Concentrations and Echocardiographic Measurements of Left Atrial Size or Left Ventricular Size and Function in Patients with Persistent Atrial Fibrillation

Atrial fibrillation (AF) may be associated with activation of atrial natriuretic peptide (ANP). The exact trigger for the release of ANP is still being debated. Atrial volume, pressure, and wall stretch are considered to be the main determinants of ANP activation. The aim of the study was to evaluate plasma ANP concentrations in patients with persistent AF and to analyze the echocardiographic determinants of ANP concentration in this group. The study population included 67 patients, 59 ± 7 years of age, with a median AF duration of 5.5 months (range 0.1–12). The relationship between plasma ANP concentrations and echocardiographic left atrial (LA) diameter and volume, and left ventricular (LV) diameter and ejection fraction (EF) was analyzed by logistic regression analysis. The median baseline plasma ANP concentration was 63 pg/mL (range 21–126) in the study group versus 34 pg/mL (range 16–73) in a control group. The mean left antero-posterior atrial dimension, LA volume, LV enddiastolic diameter, and LVEF were 48 mm, 104 mL, 52 mm, and 54%, respectively. A significant linear positive correlation was found between plasma ANP concentration and maximal LA volume (r = 0.62, P < 0.01). A negative correlation was found between LVEF and plasma ANP concentration (r =−0.42, P = 0.01). However, by multivariate regression analysis, no echocardiographic parameter was an independent predictor of plasma ANP concentration. Plasma ANP concentrations were independent of echocardiographic measurements of LA size or LV size and function in patients with persistent AF.     

Circadian and Sex-Dependent QT Dynamics

The dynamic QT relationship between the QT and RR intervals in normal individuals, including sex differences, has not been well examined. The aim of this Holter monitor-based study was to assess circadian and sex-related variations in QT dynamics in healthy subjects. The study population consisted of 50 healthy volunteers (mean age = 32 ± 6 years, 25 men), in whom 24-hour digital Holter monitoring and QT interactive, beat-by-beat analyses were performed. The mean lengths of QT and RR intervals were measured from the 24-hour recordings. In order to assess QT dynamics, QT/RR linear regression was performed, and the slope was calculated over 24 hour and for day and night periods, and both genders separately. In the whole population, the mean QT interval was 356.5 ± 19.2 ms and RR interval was 785.9 ± 80.7 ms. The mean value of the slope over 24 hour was 0.17 ± 0.03, though significantly steeper during the day (0.13 ± 0.03) than at night (0.09 ± 0.03, P < 0.001). The analysis of QT/RR dynamics over 24 hour revealed a significantly steeper slope in women (0.18 ± 0.03) than in men (0.16 ± 0.03, P = 0.006), as well as during daytime (0.14 ± 0.03 vs 0.12 ± 0.03, P = 0.04). Circadian variations and sex differences were observed in QT dynamics. The latter may explain the greater susceptibility of women to torsades de pointes during treatment with drugs that prolong repolarization.     

The Influence of Left Ventricle Diastolic Function on Natriuretic Peptides Levels in Patients with Atrial Fibrillation

Background: The diagnosis of the impaired left ventricle (LV) diastolic function during atrial fibrillation (AF) using traditional methods is very difficult. Natriuretic peptides seem to be useful for assessment of diastolic function in patients with AF. Aim: To evaluate the influence of LV diastolic dysfunction on natriuretic peptides concentrations and to assess the diagnostic value of atrial natriuretic peptide (ANP) and B‐type natriuretic peptide (BNP) in patients with AF and impaired LV diastolic function. Methods: The study included 42 patients (23 males, 19 females), aged 58.6 ± 8.2 years with nonvalvular persistent AF with preserved LV systolic function who were converted into sinus rhythm by DC cardioversion (CV) and maintained sinus rhythm for at least 30 days. Echocardiography (ECG), ANP, and BNP level measurements were taken at baseline 24 hours before CV and 24 hours and 30 days after CV. On the 30th day following CV in patients with sinus rhythm, Doppler ECG was performed to assess LV diastolic function. Results: Thirty days after CV, normal LV diastolic function in 15 patients and impaired diastolic function in 27 patients was diagnosed: 20 with impaired LV relaxation and seven with impaired LV compliance. During AF and 24 hours, and 30 days after sinus rhythm restoration, significantly higher ANP and BNP levels were observed in patients with LV diastolic dysfunction as compared to the subgroup with normal LV diastolic function. The average values of ANP during AF in patients with normal and impaired diastolic function were 167.3 ± 70.1 pg/mL and 298.7 ± 83.6 pg/mL, respectively (P < 0.001), and the average values of BNP in the above mentioned subgroups were 49.5 ± 14.7 pg/mL and 145.6 ± 49.6 pg/mL respectively (P < 0.001). While comparing the diagnostic value of both natriuretic peptides it was noted that BNP was a more specific and sensitive marker of impaired LV diastolic function. ANP value >220.7 pg/mL measured during AF identified patients with impaired LV diastolic function with 85% sensitivity and 90% specificity. BNP value >74.7 pg/mL proved 95% sensitive and 100% specific in the diagnosing of such a group. Conclusions: The increase of ANP/BNP concentration in patients with AF results not only from the presence of AF, but also reflects the impaired LV diastolic function. Natriuretic peptides, especially BNP, may be useful in diagnosing LV diastolic dysfunction in patients with AF.     

Effects of Cardiac Resynchronization Therapy on Heart Rate Turbulence

Background: Cardiac resynchronization therapy (CRT) improves the clinical status of patients with heart failure (HF), though its effects on heart rate turbulence (HRT) are unknown.
Methods: We measured HRT indices in 58 recipients of CRT systems (mean age = 56 ± 9 years, 41 men) in New York Heart Association HF functional class III–IV, and with a left ventricular (LV) ejection fraction ≤35%. At 6 months of follow-up, 42 patients were responders and 13 nonresponders to CRT, and three patients died suddenly. The HRT indices turbulence onset (TO%) and turbulence slope (TS ms/RR interval) were calculated from digital 24-hour electrocardiogram before and after 6 months of CRT. TO ≥ 0% and TS ≤ 2.5 ms/RR interval were considered abnormal.
Results: Mean TO in the entire population was 0.4 ± 1.5 before CRT, and decreased to −0.8 ± 7.0 during the 6 months of CRT (ns). TS increased significantly from 2.0 ± 1.7 at baseline, to 3.9 ± 3.1 (P < 0.05), and a significantly lower proportion of patients had abnormal HRT indices at 6 months. In contrast to the significant increase observed in responders, not significant change in TS was observed among the nonresponders.
Conclusions: During 6 months of CRT, improvements in HRT indices and a decrease in the proportion of patients with abnormal HRT were observed. CRT may have beneficial effects on baroreflex sensitivity.     

A Decrease in Serum Aldosterone Level is Associated with Maintenance of Sinus Rhythm after Successful Cardioversion of Atrial Fibrillation

Background: The activation of the renin–angiotensin–aldosterone system has been implicated in the progression of atrial structural remodeling during atrial fibrillation (AF). However, consequences of the changes of aldosterone in AF have not been evaluated. Objectives: This study's aim was to evaluate changes of serum aldosterone concentration after successful cardioversion of persistent AF and to determine the prognostic value of these changes. Methods: The prospective, single center study included 45 consecutive patients with nonvalvular persistent AF and preserved left ventricular systolic function, referred for cardioversion. None of the patients were taking aldosterone antagonists. Blood samples for aldosterone measurement were collected twice: 24 hours before and 24 hours after cardioversion. Results: Forty‐three patients were successfully converted to sinus rhythm. On the 30th day following cardioversion, 24 patients maintained sinus rhythm (group A), 19 patients relapsed to AF (group B). Serum aldosterone concentration before cardioversion did not differ significantly between both groups (175.6 ± 112.82 pg/mL vs 125.8 ± 51.2 pg/mL; P = 0.25). However, in group A serum aldosterone level decreased significantly within 24 hours after cardioversion, from 175.6 ± 112.8 pg/mL to 101.4 ± 44.2 pg/mL (P = 0.0034). In group B, the aldosterone level before and after cardioversion did not differ significantly (125.8 ± 51.2 pg/mL vs 118.2 ± 59.6 pg/mL; P = 0.68). Logistic regression analysis revealed that a decrease in plasma aldosterone concentration after direct current cardioversion more than 13.2 pg/mL predicted sinus rhythm maintenance in a 30‐day follow‐up, with 87% sensitivity and 64% specificity. Conclusions: There is a positive correlation between the fall in aldosterone concentration 24 hours after cardioversion and maintenance of sinus rhythm during 30 days of observation. (PACE 2010; 561–565)     

COMMENTS

Within the human testis, three entities of germ cell tumours are distinguished: the teratomas and yolk sac tumors of newborn and infants, the seminomas and nonseminomas of adolescents and young adults, referred to as testicular germ cell tumours (TGCT), and the spermatocytic seminomas. Characteristic chromosomal anomalies have been reported for each group, supporting their distinct pathogenesis. TGCT are the most common cancer in young adult men. The initiating pathogenetic event of these tumours occurs during embryonal development, affecting a primordial germ cell or gonocyte. Despite this intra-uterine initiation, the tumour will only be clinically manifest after puberty, with carcinoma in situ (IS) as the precursor. All invasive TGCT, both seminomas and nonseminomas, as well as CIS cells are aneuploid. The only consistent (structural) chromosomal abnormalities in invasive TGCT are gains of the short arm of chromosome 12, mostly due to isochromosome (i(12p)) formation. This suggests that an increase in copy number of a gene(s) on 12p is associated with the development of a clinically manifest TGCT. Despite the numerous (positional) candidate gene approaches that have been undertaken thus far, identification of a causative gene(s) has been hampered by the fact that most 12p gains involve rather large genomic intervals, containing unmanageable numbers of candidate genes. Several years ago, we initiated a search for 12p candidate genes using TGCT with a restricted 12p-amplification, cytogenetically identified as 12p11.2-p12.1. This approach is mainly based on identification of candidate genes mapped within the shortest region of overlap of amplification (SROA). In this review, data will be presented, which support the model that gain of 12p-sequences is associated with suppression of apoptosis and Sertoli cell-independence of CIS cells. So far, DAD-R is one of the most likely candidate genes involved in this process, possibly via N-glycosylation. Preliminary results on high through-put DNA- and cDNA array analyses of 12p-sequences will be presented.     

Triple-Site Versus Standard Cardiac Resynchronization Therapy Study (TRUST CRT): Clinical Rationale, Design, and Implementation

Background: Cardiac resynchronization therapy (CRT) reduces morbidity and mortality in patients with heart failure (HF), lowered LV ejection fraction, and wide QRS. However, many patients (≤40%) do not respond to this form of pacing. TRUST CRT is a prospective, single-center, randomized, single-blind, parallel, and controlled study that has been designed to treat patients with moderate to severe HF (NYHA III-IV), QRS ≥120 ms, sinus rhythm, LV dysfunction (EF ≤ 35%), and signs of mechanical dyssynchrony.
Objective: The primary objective will evaluate the 6-month's combined endpoint of alive status, freedom from hospitalization for HF or heart transplantation, relative ≥10% increase in LV ejection fraction, ≥10% in peak oxygen consumption, and ≥10% in 6-minute walking distance.
Methods: Patients with HF receiving optimal pharmacotherapy, with LV dysfunction, mechanical dyssynchrony, wide QRS and sinus rhythm will be randomized in a 1: 1 fashion to standard or triple-site CRT-D. Patients will be followed for 1 week, 1, 3, and 6 months during a blind phase, then every 6 months until study completion. One hundred patients will be enrolled by the study center.
Conclusions: TRUST CRT is a randomized, clinical trial in CRT candidates to evaluate the effectiveness of triple-site pacing versus standard resynchronization in patients with HF.     

Exercise‐Induced Natriuretic Peptide Secretion Predicts Cardioversion Outcome in Patients with Persistent Atrial Fibrillation: Discordant ANP and B‐Type Natriuretic Peptide Response to Exercise Testing

Background: Measurement of natriuretic peptide's (NP) release in response to hemodynamic stress may be complementary to its baseline assessment in individuals. Atrial natriuretic peptide (ANP) and B‐type natriuretic peptide (BNP) increase in patients with atrial fibrillation (AF) and decrease after successful cardioversion, suggesting that AF may stimulate secretion of NPs. However, there are conflicting data on the predictive value of NPs on the cardioversion outcome. Objectives: The purpose of this study was to investigate whether baseline and exercise‐induced NP plasma levels can be useful in predicting successful cardioversion of persistent AF and maintenance of sinus rhythm during 6‐month follow‐up. Methods: A prospective study enrolled 77 consecutive subjects with persistent AF with normal left ventricular function, referred for elective cardioversion. Patients underwent a modified Bruce protocol treadmill exercise test 24 hours before cardioversion. Blood samples for ANP and BNP analyses were obtained at rest and 5 minutes after exercise peak. Results: The group of successful cardioversion and stable sinus rhythm presented higher exercise ANP (110.6 ± 41.2 pg/mL vs 43.8 ± 36.1; pg/mL, P < 0.0001) and lower BNP increase (5.2 ± 5.2 pg/mL vs 40.5 ± 34.2 pg/mL, P < 0.0001) than the group of unsuccessful cardioversion or AF recurrence. Using an optimized cutoff level of ≤12% of relative exercise‐induced increase in BNP concentration, and of >50 pg/mL of ANP increase, successful cardioversion can be predicted with high accuracy. Conclusions: An increase in ANP and stability of BNP plasma concentration during exercise testing are independently associated with successful cardioversion and maintenance of sinus rhythm during 6‐month follow‐up. (PACE 2010; 33:1203–1209)