Normal Reference Ranges for Transthoracic Echocardiography Following Heart Transplantation.

BACKGROUND: Heart function following heart transplantation (HTx) is influenced by numerous factors. It is typically evaluated using transthoracic echocardiography, but reference values are currently unavailable for this context. The primary aim of the present study was to derive echocardiographic reference values for chamber size and function, including cardiac mechanics, in clinically stable HTx patients. METHODS: The study enrolled 124 healthy HTx patients examined prospectively. Patients underwent comprehensive two-dimensional echocardiographic examinations according to contemporary guidelines. Results were compared with recognized reference values for healthy subjects. RESULTS: Compared with guidelines, larger atrial dimensions were seen in HTx patients. Left ventricular (LV) diastolic volume was smaller, and LV wall thickness was increased. With respect to LV function, both ejection fraction (62 ± 7%, P < .01) and global longitudinal strain (-16.5 ± 3.3%, P < .0001) were lower. All measures of right ventricular (RV) size were greater than reference values (P < .0001), and all measures of RV function were reduced (tricuspid annular plane systolic excursion 15 ± 4 mm [P < .0001], RV systolic tissue Doppler velocity 10 ± 6 cm/sec [P < .0001], fractional area change 40 ± 8% [P < .0001], and RV free wall strain -16.9 ± 4.2% [P < .0001]). Ejection fraction and LV global longitudinal strain were significantly lower in patients with previous rejection. CONCLUSION: The findings of this study indicate that the distribution of routinely used echocardiographic measures differs between stable HTx patients and healthy subjects. In particular, markedly larger RV and atrial volumes and mild reductions in both LV and RV longitudinal strain were evident. The observed differences could be clinically relevant in the assessment of HTx patients, and specific reference values should be applied in this context.

Permanent atrial fibrillation in patients without structural heart disease is not associated with signs of infection by Chlamydia pneumoniae and Helicobacter pylori.

OBJECTIVE: The objective of this study was to explore the role of Chlamydia pneumoniae and Helicobacter pylori infections in patients with idiopathic permanent atrial fibrillation. METHODS AND RESULTS: Sera from 72 patients with permanent atrial fibrillation without structural heart disease (mean age 69.6 years, 23 women) were analysed for IgG antibodies against Chlamydia pneumoniae and Helicobacter pylori and compared in a I:I age- and sex-matched case:control manner with those pooled from a healthy reference population of 72 individuals from the same geographical area. After excluding patients with other possible or definite factors known either to cause atrial fibrillation or to affect the prevalence of seropositivity to these agents, the frequency of seropositivity due to one or both of the infectious agents was compared. Serum C-reactive protein (CRP) level was assessed using immunoturbidimetry technique. Both agents were equally common in men and women. Neither seropositivity to Chlamydia pneumoniae (76% vs. 83%, patients vs. control subjects, ns) nor to Helicobacter pylori (57% contra 55%, patients vs. controls, ns) alone reached significance in the comparisons between patients with atrial fibrillation and control subjects. Serum CRP was higher in patients with AF (5.3 mg/L vs. 2.8 mg/L, P < 0.001). CONCLUSIONS: Though presence of permanent AF is associated with elevated CRP levels, this elevation is not the result of earlier infections with Chlamydia pneumoniae or Helicobacter pylori or their combination.

Age-related changes in P wave morphology in healthy subjects.

BACKGROUND: We have previously documented significant differences in orthogonal P wave morphology between patients with and without paroxysmal atrial fibrillation (PAF). However, there exists little data concerning normal P wave morphology. This study was aimed at exploring orthogonal P wave morphology and its variations in healthy subjects. METHODS: 120 healthy volunteers were included, evenly distributed in decades from 20-80 years of age; 60 men (age 50+/-17) and 60 women (50+/-16). Six-minute long 12-lead ECG registrations were acquired and transformed into orthogonal leads. Using a previously described P wave triggered P wave signal averaging method we were able to compare similarities and differences in P wave morphologies. RESULTS: Orthogonal P wave morphology in healthy individuals was predominately positive in Leads X and Y. In Lead Z, one third had negative morphology and two-thirds a biphasic one with a transition from negative to positive. The latter P wave morphology type was significantly more common after the age of 50 (P < 0.01). P wave duration (PWD) increased with age being slightly longer in subjects older than 50 (121+/-13 ms vs. 128+/-12 ms, P < 0.005). Minimal intraindividual variation of P wave morphology was observed. CONCLUSION: Changes of signal averaged orthogonal P wave morphology (biphasic signal in Lead Z), earlier reported in PAF patients, are common in healthy subjects and appear predominantly after the age of 50. Subtle age-related prolongation of PWD is unlikely to be sufficient as a sole explanation of this finding that is thought to represent interatrial conduction disturbances. To serve as future reference, P wave morphology parameters of the healthy subjects are provided.

Atrial fibrillatory rate and risk of left atrial thrombus in atrial fibrillation.

AIMS: In atrial fibrillation (AF), a relation between electrocardiogram (ECG) fibrillatory wave amplitude and thrombus formation has been sought for long with conflicting results. In contrast, the possible relation between atrial fibrillatory rate obtained from the surface ECG and left atrial thrombus formation in patients with AF is unknown and was consequently evaluated in this study. METHODS AND RESULTS: One-hundred and twenty-five patients (mean age 64 +/- 12 years, 72% male) with persistent non-valvular AF (mean duration 28 +/- 80 days) undergoing transesophageal echocardiography were studied. In all patients, standard 12-lead ECG recordings were acquired before the examination. Atrial fibrillatory rate was determined using spatiotemporal QRST cancellation and time-frequency analysis of lead V1. Atrial fibrillatory rate measured 401 +/- 63 fibrillations per minute (fpm, range 235-566 fpm) and was related with age (R = -0.326, P < 0.001), ventricular rate (R = -0.202, P = 0.024), gender (407 +/- 62 in males vs. 387 +/- 64 fpm in females, P = 0.038) but not AF duration (R = 0.088, P = 0.374), presence of lone AF (408 +/- 66 vs. 394 +/- 58 fpm, P = 0.228), or beta-blocker or calcium channel blocker treatment (398 +/- 63 vs. 405 +/- 62 fpm, P = 0.556). Age was the only independent predictor of fibrillatory rate (B = -1.714, P < 0.001). In patients with left atrial thrombus (n = 10), spontaneous echo contrast (SEC) was more frequently present (70 vs. 29 %, p = 0.007) and left atrial appendage (LAA) outflow velocity was lower (26 +/- 20 vs. 37 +/- 15 cm/s, P = 0.012) than in patients without thrombus (n = 115). In contrast, mean fibrillatory rate, which showed a weak inverse correlation with LAA velocity (R = -0.118, P = 0.048) was not different between both groups (380 +/- 56 vs. 403 +/- 63 fpm, P = 0.226). Similarly, presence of thrombus and SEC combined was not related with fibrillatory rate. CONCLUSION: Atrial fibrillatory rate obtained from surface ECG lead V1 is not a risk marker for left atrial thrombus formation in AF.

Variable interatrial conduction illustrated in a hypertrophic cardiomyopathy population.

BACKGROUND: Patients with hypertrophic cardiomyopathy (HCM) have a high incidence of atrial fibrillation. They also have a longer P-wave duration than healthy controls, indicating conduction alterations. Previous studies have demonstrated orthogonal P-wave morphology alterations in patients with paroxysmal atrial fibrillation. In the present study, the P-wave morphology of patients with HCM was compared with that of matched controls in order to explore the nature of the atrial conduction alterations. METHODS AND RESULTS: A total of 65 patients (45 men, mean age 49 +/- 15) with HCM were included. The control population (n = 65) was age and gender matched (45 men, mean age 49 +/- 15). Five minutes of 12-lead ECG was recorded. The data were subsequently transformed to orthogonal lead data, and unfiltered signal-averaged P-wave analysis was performed. The P-wave duration was longer in the HCM patients compared to the controls (149 +/- 22 vs 130 +/- 16 ms, P < 0.0001). Examination of the P-wave morphology demonstrated changes in conduction patterns compatible with interatrial conduction block of varying severity in both groups, but a higher degree of interatrial block seen in the HCM population. These changes were most prominent in the Leads Y and Z. CONCLUSION: The present study suggests that the longer P-wave duration observed in HCM patients may be explained by a higher prevalence of block in one or more of the interatrial conduction routes.

The diagnostic and prognostic value of brain natriuretic peptides in adults with a systemic morphologically right ventricle or Fontan-type circulation.

BACKGROUND: In acquired heart disease, brain natriuretic peptide (BNP) and N-Terminal pro-brain natriuretic peptide (NT-proBNP) are increasingly used as diagnostic and prognostic markers. In adult congenital heart disease, the abnormal anatomy and physiology complicate assessment of cardiac function. We studied the clinical correlates of measurement of natriuretic peptides (NP) in adults with a right ventricle in the systemic position or with Fontan-type physiology. METHODS: A prospective longitudinal study (follow up time 23+/-13 months, mean+/-S.D.) was conducted in a specialised centre on 61 patients (age 26+/-8 years; NYHA class 1.5+/-0.6) including Senning/Mustard corrected transposition, congenitally corrected transposition and Fontan/total cavopulmonary connection. Plasma NP concentration was compared with NYHA class, exercise capacity and echocardiographically determined systemic systolic ventricular function. RESULTS: Neurohormone concentrations were generally elevated (mean=290% of upper reference limit) and related to NYHA class (P<0.001, NYHA I vs. II-IV). No clinically significant relationship to ventricular function or exercise capacity was found however. An NP measurement could not predict the future course of the disease in terms of functional status or ventricular function. CONCLUSION: In contrast to patients with acquired heart disease, measurement of NP seems to have low clinical value in adults with a right ventricle in the systemic position or with Fontan-type physiology.

Atrial fibrillatory rate and sinus rhythm maintenance in patients undergoing cardioversion of persistent atrial fibrillation.

AIMS: The study set out to explore whether an index of atrial electrical electrophysiology can be used to predict atrial fibrillation (AF) relapse, and if the predictive properties differ as a result of arrhythmia duration. METHODS AND RESULTS: The study comprised 175 consecutive patients with persistent AF (median duration 94 days, range 2 to 1044) referred for cardioversion. Twenty-nine patients had arrhythmia duration under 30 days (median 5 days, range 2-26). Atrial fibrillatory rate (AFR) was estimated using a frequency power spectrum analysis of QRST-cancelled ECG. At 1-month follow-up, 56% of the patients had relapsed to AF. The pre-cardioversion mean AFR of those patients was 399+/-52 fibrillations per minute (fpm) compared with 363+/-63 fpm among patients maintaining SR (P<0.0001). In patients with short AF duration, the difference was even more pronounced (424+/-52 vs. 345+/-65 fpm, P<0.01). In this group, a finding of an AFR above the mean value of the study population predicted AF relapse with high accuracy. CONCLUSION: In patients undergoing cardioversion of persistent AF, AF relapse is predicted by a higher AFR. A stronger association is seen in patients with short arrhythmia duration, reflecting either rapid remodelling or pre-existing changes in those who relapse to AF.

Atrial fibrillation signal organization predicts sinus rhythm maintenance in patients undergoing cardioversion of atrial fibrillation.

AIMS: Electrical remodelling is believed to influence the outcome following cardioversion of patients with persistent atrial fibrillation (AF). However, the results in clinical studies are conflicting. We assessed the hypothesis that non-invasively obtained atrial fibrillatory organization can be used as a predictor of sinus rhythm (SR) maintenance. METHODS AND RESULTS: Fifty-four patients (37 men, age 67+/-11) with persistent AF (median duration 3 months, 1 day to 18 months), without anti-arrhythmic drug treatment, referred for cardioversion were studied. Assessment of the atrial harmonic decay was made by time-frequency analysis of the ECG. At 1-month follow-up, 30 patients had relapsed into AF. The mean harmonic decay at inclusion of those relapsing into AF was 1.5+/-0.3 compared with 1.1+/-0.3 among those maintaining SR (P=0.0004). Using a cut-off value of harmonic decay

Indices of electrical and contractile remodeling during atrial fibrillation in man.

BACKGROUND: Atrial electrical and contractile remodeling have been demonstrated to coincide during atrial fibrillation (AF) in experimental studies. We explored whether electrical and contractile remodeling correlate in man and explored its clinical implications. METHODS: Forty-nine patients with persistent AF were studied. Electrical remodeling was assessed noninvasively using spectral analysis to estimate the average fibrillatory rate (AFR). Atrial contractility was assessed by transesophageal echocardiography (TEE) measurement of left atrial appendage outflow velocity (LAAOV). RESULTS: The AFR was 403+/-43 fibrillations per minute (fpm) and the LAAOV was 0.27+/-0.14 m/s. A significant correlation was found between AFR and LAAOV (r=-0.47, P=0.001). In patients with a LAAOV>or=0.25 m/s, the AFR was 387+/-48 fpm compared to 419+/-31 fpm among patients with LAAOV<0.25 m/s (P<0.01). CONCLUSIONS: This study demonstrates that indices of electrical and contractile remodeling are strongly correlated in persistent AF in man. The interindividual overlap, however, is too large to allow predictions of LAAOV based on fibrillatory frequency alone.

Prediction of sinus rhythm maintenance following DC-cardioversion of persistent atrial fibrillation - the role of atrial cycle length.

BACKGROUND: Atrial electrical remodeling has been shown to influence the outcome the outcome following cardioversion of atrial fibrillation (AF) in experimental studies. The aim of the present study was to find out whether a non-invasively measured atrial fibrillatory cycle length, alone or in combination with other non-invasive parameters, could predict sinus rhythm maintenance after cardioversion of AF. METHODS: Dominant atrial cycle length (DACL), a previously validated non-invasive index of atrial refractoriness, was measured from lead V1 and a unipolar oesophageal lead prior to cardioversion in 37 patients with persistent AF undergoing their first cardioversion. RESULTS: 32 patients were successfully cardioverted to sinus rhythm. The mean DACL in the 22 patients who suffered recurrence of AF within 6 weeks was 152 +/- 15 ms (V1) and 147 +/- 14 ms (oesophagus) compared to 155 +/- 17 ms (V1) and 151 +/- 18 ms (oesophagus) in those maintaining sinus rhythm (NS). Left atrial diameter was 48 +/- 4 mm and 44 +/- 7 mm respectively (NS). The optimal parameter predicting maintenance of sinus rhythm after 6 weeks appeared to be the ratio of the lowest dominant atrial cycle length (oesophageal lead or V1) to left atrial diameter. This ratio was significantly higher in patients remaining in sinus rhythm (3.4 +/- 0.6 vs. 3.1 +/- 0.4 ms/mm respectively, p = 0.04). CONCLUSION: In this study neither an index of atrial refractory period nor left atrial diameter alone were predictors of AF recurrence within the 6 weeks of follow-up. The ratio of the two (combining electrophysiological and anatomical measurements) only slightly improve the identification of patients at high risk of recurrence of persistent AF. Consequently, other ways to asses electrical remodeling and / or other variables besides electrical remodeling are involved in determining the outcome following cardioversion.

Rapid fluctuations in atrial fibrillatory electrophysiology detected during controlled respiration.

Heart rate during sinus rhythm is modulated through the autonomic nervous system, which generates short-term oscillations. The high-frequency components in these oscillations are associated with respiration, causing sinus arrhythmia, mediated by the parasympathetic nervous system. In this study, we evaluated whether slow, controlled respiration causes cyclic fluctuations in the frequency of the fibrillating atria. Eight patients (four women; median age 63 yr, range 53-68 yr) with chronic atrial fibrillation (AF) and third-degree atrioventricular block treated by permanent pacemaker were studied. ECG was recorded during baseline rest, during 0.125-Hz frequency controlled respiration, and finally during controlled respiration after full vagal blockade. We calculated fibrillatory frequency using frequency analysis of the fibrillatory ECG for overlapping 2.5-s segments; spectral analysis of the resulting frequency trend was performed to determine the spectrum of variations of fibrillatory frequency. Normalized spectral power at respiration frequency increased significantly during controlled respiration from 1.4 (0.76-2.0) (median and range) at baseline to 2.7 (1.2-5.8) (P = 0.01). After vagal blockade, the power at respiration frequency decreased to 1.2 (0.23-2.8) (P = 0.01). Controlled respiration causes cyclic fluctuations in the AF frequency in patients with long-duration AF. This phenomenon seems to be related to parasympathetic modulations of the AF refractory period.

Sequential characterization of atrial tachyarrhythmias based on ECG time-frequency analysis.

A new method for characterization of atrial arrhythmias is presented which is based on the time-frequency distribution of an atrial electrocardiographic signal. A set of parameters are derived which describe fundamental frequency, amplitude, shape, and signal-to-noise ratio. The method uses frequency-shifting of an adaptively updated spectral profile, representing the shape of the atrial waveforms, in order to match each new spectrum of the distribution. The method tracks how well the spectral profile fits each spectrum as well as if a valid atrial signal is present. The results are based on the analysis of a learning database with signals from 40 subjects, of which 24 have atrial arrhythmias, and an evaluation database with 211 patients diagnosed with atrial fibrillation. It is shown that the method robustly estimates fibrillation frequency and amplitude and produces spectral profiles with narrower peaks and more discernible harmonics when compared to the conventional power spectrum. The results suggest that a rather strong correlation exist between atrial fibrillation frequency and f wave shape. The developed set of parameters may be used as a basis for automated classification of different atrial rhythms.