Total NT-proBNP, a novel biomarker related to recurrent atrial fibrillation.

BACKGROUND: Novel circulating biomarkers may help in understanding the underlying mechanisms of atrial fibrillation (AF), a challenge for AF management and prevention of cardiovascular (CV) events. Whether glycosylation affects the prognostic value of N-terminal pro-B type natriuretic peptide (NT-proBNP) in AF is still unknown. OBJECTIVES: To test how deglycosylated total NT-proBNP, NT-proBNP and a panel of biomarkers are associated with: (1) recurrent AF, (2) first hospitalization for CV reasons. METHODS: A total of 382 patients of the GISSI-AF trial in sinus rhythm with a history of AF, echocardiographic variables, total NT-proBNP, NT-proBNP and nine additional biomarkers [Total N-terminal pro-B type natriuretic peptide (Total NT proBNP), N-terminal pro-B type natriuretic peptide (NTproBNP), Angiopoietin 2 (Ang2), Bone morphogenic protein-10 (BMP10), Dickkopf-related protein-3 (DKK3), Endothelial cell specific molecule-1 (ESM1), Fatty acid-binding protein 3 (FABP3), Fibroblast growth factor 23 (FGF23), Growth differentiation factor-15 (GDF15), Insulin-like growth factor-binding protein-7 (IGFBP7) and Myosin binding protein C3 (MYPBC3)]. were assayed at baseline, 6 and 12 months under blind conditions in a laboratory at Roche Diagnostics, Penzberg, Germany. The associations between circulating biomarkers and AF at the 6- and 12-month visits, and their predictive value, were assessed in multivariable models with logistic regression analysis and Cox proportional hazards regression analysis. Biomarkers associations were modelled for 1SD increase in their level. RESULTS: Over a median follow-up of 365 days, 203/382 patients (53.1%) had at least one recurrence of AF and 16.3% were hospitalized for CV reasons. Total NT-proBNP, NT-proBNP, Ang2 and BMP10 showed the strongest associations with ongoing AF. Natriuretic peptides also predicted recurrent AF (total NT-proBNP: HR:1.19[1.04-1.36], p = 0.026; NT-proBNP: HR:1.19[1.06-1.35], p = 0.016; Ang2: HR:1.07[0.95-1.20], p = 0.283; BMP10: HR:1.09[0.96-1.25], p = 0.249) and CV hospitalization (total NT-proBNP: HR:1.57[1.29-1.90], p < 0.001 1.63], p = 0.097). CONCLUSIONS: The association of total NT-proBNP with the risk of AF first recurrence was similar to that of NT-proBNP, suggesting no influence of glycosylation. Analogous results were obtained for the risk of first hospitalization for CV reasons. Natriuretic peptides, Ang2 and BMP10 were associated with ongoing AF. Findings from the last two biomarkers point to a pathogenic role of cardiac extracellular matrix and cardiomyocyte growth in the myocardium of the right atrium and ventricle.

Cardiac Remodeling, Circulating Biomarkers and Clinical Events in Patients with a History of Atrial Fibrillation. Data from the GISSI-AF Trial.

PURPOSE: Atrial fibrillation (AF) is the most common arrhythmia and has an increasing impact on public health because of its morbidity and mortality. Clinical and diagnostic tests to predict the recurrence of arrhythmia and clinical events before AF becomes permanent are still an open issue. METHODS: 307 out of 1442 patients in sinus rhythm, at high risk of recurrence of AF enrolled in the GISSI-AF study, participated in a substudy with echocardiographic and biohumoral evaluation at baseline and at 12-month follow-up. The relations between biomarker concentrations and echocardiographic parameters with study endpoints in 1 year, were analysed by a stepwise multivariable Cox model (entry criteria p < 0.5 and stay criteria p < 0.2). RESULTS: The echocardiographic variables, cardiac markers and clinical variables considered in the statistical model indicated a higher concentration of NT-proBNP at baseline as the strongest factor related to time of first AF recurrence (HR 1.42; 95 %CI 1.23-1.46), first CV hospitalization (HR 1.58; 95 %CI 1.31-1.92) and increasing duration of recurrent AF (OR 2.16; 95 %CI 1.52-3.08). Valsartan treatment was not related to clinical events. CONCLUSIONS: In patients in sinus rhythm with a history of AF a higher concentration of NT-proBNP at baseline was the strongest independent risk factor for first AF recurrence and its duration, and for the first hospital admission for cardiovascular reasons.

Electroanatomic mapping and late gadolinium enhancement MRI in a genetic model of arrhythmogenic atrial cardiomyopathy.

INTRODUCTION: Although atrial arrhythmias may have genetic causes, very few data are available on evaluation of the arrhythmic substrate in genetic atrial diseases in humans. In this study, we evaluate the nature and evolution of the atrial arrhythmic substrate in a genetic atrial cardiomyopathy. METHODS AND RESULTS: Repeated electroanatomic mapping and tomographic evaluations were used to investigate the evolving arrhythmic substrate in 5 patients with isolated arrhythmogenic atrial cardiomyopathy, caused by Natriuretic Peptide Precursor A (NPPA) gene mutation. Atrial fibrosis was assessed using late gadolinium enhancement magnetic resonance imaging (LGE-MRI). The substrate of atrial tachycardia (AT) and atrial fibrillation (AF) was biatrial dilatation with patchy areas of low voltage and atrial wall scarring (in the right atrium: 68.5% ± 6.0% and 22.2% ± 10.2%, respectively). The evolution of the arrhythmic patterns to sinus node disease with atrial standstill (AS) was associated with giant atria with extensive low voltage and atrial scarring areas (in the right atrium: 99.5% ± 0.7% and 57.5% ± 33.2%, respectively). LGE-MRI-proven biatrial fibrosis (Utah stage IV) was associated with AS. Atrial conduction was slow and heterogeneous, with lines of conduction blocks. The progressive extension and spatial distribution of the scarring/fibrosis were strictly associated with the different types of arrhythmias. CONCLUSION: The evolution of the amount and distribution of atrial scarring/fibrosis constitutes the structural substrate for the different types of atrial arrhythmias in a pure genetic model of arrhythmogenic atrial cardiomyopathy.

Incidence of atrial fibrillation in a population with impaired glucose tolerance: the contribution of glucose metabolism and other risk factors. A post hoc analysis of the Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research trial.

BACKGROUND: The role of dysglycemia as an additional risk factor for atrial fibrillation (AF) is controversial. Therefore, it was of interest to assess risk factors for incident AF in a large, representative population of patients with cardiovascular risk factors and impaired glucose tolerance but not overt diabetes in NAVIGATOR. METHODS: Predictors of incident AF were analyzed in 8,943 patients without AF at baseline by Cox proportional hazards regression. Study treatments (valsartan vs no valsartan and nateglinide vs no nateglinide) and the time-dependent covariate for progression to type 2 diabetes mellitus were added separately to the model. RESULTS: The median age of the 8,943 patients included in the present analysis of the NAVIGATOR trial was 63 years. Half of those patients were men, 6,922 (77.4%) had a history of hypertension, and 255 (2.9%) had heart failure. The median glycated hemoglobin was 6%. During the study, 613 of the 8,943 patients without AF at baseline presented with at least 1 episode of AF (6.9% 5-year incidence). Besides established predictors of incident AF, a 1 mmol/L increment of baseline fasting glucose, but not progression to diabetes, was found to be associated with a 33% increased risk of incident AF. Neither valsartan nor nateglinide affected AF incidence. CONCLUSIONS: In a trial population with impaired glucose tolerance, fasting plasma glucose and well-known risk factors (age, hypertension, and elevated body weight), but not progression to diabetes, predict risk of AF.

The need to modify patient selection to improve the benefits of implantable cardioverter-defibrillator for primary prevention of sudden death in non-ischaemic dilated cardiomyopathy.

Left ventricular ejection fraction (LVEF) ≤35% is a major determinant for implantable cardioverter-defibrillator (ICD) therapy for primary prevention of sudden death (SD) in patients with non-ischaemic dilated cardiomyopathy (DCM). However, as a risk marker for SD, low LVEF has limited sensibility and specificity. Selecting patients according to the current guidelines shows that most DCM patients do not actually benefit from ICD implantation and may suffer collateral effects and that many patients who are at risk of SD are not identified because a large proportion of SD patients exhibit only mildly depressed LVEF. Identifying patients who are at risk of SD on the sole basis of LVEF appears to be an over-simplification which does not maximize the benefit of ICD therapy. Owing to the complexity of the substrates underlying SD, multiple risk factors used in combination could probably predict the risk of SD better than any individual risk marker. Among non-invasive tests, microvolt T-wave alternans and cardiac magnetic resonance with late gadolinium enhancement may contribute to a better SD risk stratification by their high negative predictive value. Genetics may further contribute because approximately one-third of DCM patients have evidence of familial disease, and mutations in some known disease genes, including LMNA, have been associated with a high risk of SD. In this review, we critically analyse the current indications for ICD implantation and we explore existing knowledge about potentially predicting markers for selecting DCM patients who are at high and low risk of SD.

Thromboembolic event rate in paroxysmal and persistent atrial fibrillation: data from the GISSI-AF trial.

BACKGROUND: Few data on the thromboembolic (TE) risk of paroxysmal and persistent atrial fibrillation (AF) are available. This study aimed to assess the incidence of TE events in paroxysmal and persistent AF. METHODS: We performed a subset post hoc analysis of 771 patients with paroxysmal and 463 with persistent AF enrolled in the multicenter, prospective, randomized, double-blind, placebo-controlled GISSI-AF trial - comparing the efficacy of valsartan versus placebo in preventing AF recurrences - where the choice of antithrombotic treatment was left to the judgment of the referring physician. TE and major outcome events were centrally validated. AF recurrences were detected by frequent clinic visits and a transtelephonic monitoring device with weekly and symptomatic transmissions. RESULTS: Eighty-five percent of patients had a history of hypertension, and the 7.7% had heart failure, left ventricular dysfunction, or both. The mean CHADS2 score was 1.41±0.84. TE and major bleeding events were observed at a low incidence among the overall population at 1-year follow-up (0.97% and 0.81%, respectively). The univariate and multivariable analyses revealed no statistically significant differences in the incidence of TE, major bleeding events or mortality in paroxysmal and persistent AF patients. TE events were more common among women than men (p=0.02). The follow-up examination showed under- or overtreatment with warfarin in many patients, according to guideline suggestions. Warfarin was more frequently prescribed to patients with persistent AF (p<0.0001) and patients with AF recurrences (p<0.0001). AF recurrences were noninvasively detected in 632 (51.2%) patients. In patients without AF recurrences, the TE event rate was 0.5% versus 1.74%, 1.28%, and 1.18% for those with only symptomatic, only asymptomatic or both symptomatic and asymptomatic AF recurrences, respectively, but the difference was not statistically significant, even after adjusting for warfarin treatment and the CHADS2 score (HR 2.93; CI 95%; 0.8-10.9; p=0.11). CONCLUSIONS: TE and major bleeding events showed a very low incidence in the GISSI-AF trial population, despite under- or overtreatment with warfarin in many patients. TE events had a similar rate in paroxysmal and persistent AF. TRIAL REGISTRATION NUMBER: NCT00376272.

Valsartan for prevention of recurrent atrial fibrillation.

BACKGROUND: Atrial fibrillation is the most common cardiac arrhythmia, and no current therapy is ideal for control of this condition. Experimental studies suggest that angiotensin II-receptor blockers (ARBs) can influence atrial remodeling, and some clinical studies suggest that they may prevent atrial fibrillation. METHODS: We conducted a large, randomized, prospective, placebo-controlled, multicenter trial to test whether the ARB valsartan could reduce the recurrence of atrial fibrillation. We enrolled patients who were in sinus rhythm but had had either two or more documented episodes of atrial fibrillation in the previous 6 months or successful cardioversion for atrial fibrillation in the previous 2 weeks. To be eligible, patients also had to have underlying cardiovascular disease, diabetes, or left atrial enlargement. Patients were randomly assigned to receive valsartan or placebo. The two primary end points were the time to a first recurrence of atrial fibrillation and the proportion of patients who had more than one recurrence of atrial fibrillation over the course of 1 year. RESULTS: A total of 1442 patients were enrolled in the study. Atrial fibrillation recurred in 371 of the 722 patients (51.4%) in the valsartan group, as compared with 375 of 720 (52.1%) in the placebo group (adjusted hazard ratio, 0.97; 96% confidence interval [CI], 0.83 to 1.14; P=0.73). More than one episode of atrial fibrillation occurred in 194 of 722 patients (26.9%) in the valsartan group and in 201 of 720 (27.9%) in the placebo group (adjusted odds ratio, 0.89; 99% CI, 0.64 to 1.23; P=0.34). The results were similar in all predefined subgroups of patients, including those who were not receiving angiotensin-converting-enzyme inhibitors. CONCLUSIONS: Treatment with valsartan was not associated with a reduction in the incidence of recurrent atrial fibrillation. (ClinicalTrials.gov number, NCT00376272.)

Nodal recovery, dual pathway physiology, and concealed conduction determine complex AV dynamics in human atrial tachyarrhythmias.

The genesis of complex ventricular rhythms during atrial tachyarrhythmias in humans is not fully understood. To clarify the dynamics of atrioventricular (AV) conduction in response to a regular high-rate atrial activation, 29 episodes of spontaneous or pacing-induced atrial flutter (AFL), covering a wide range of atrial rates (cycle lengths from 145 to 270 ms), were analyzed in 10 patients. AV patterns were identified by applying firing sequence and surrogate data analysis to atrial and ventricular activation series, whereas modular simulation with a difference-equation AV node model was used to correlate the patterns with specific nodal properties. AV node response at high atrial rate was characterized by 1) AV patterns of decreasing conduction ratios at the shortening of atrial cycle length (from 236.3 ± 32.4 to 172.6 ± 17.8 ms) according to a Farey sequence ordering (conduction ratio from 0.34 ± 0.12 to 0.23 ± 0.06; P < 0.01); 2) the appearance of high-order alternating Wenckebach rhythms, such as 6:2, 10:2, and 12:2, associated with ventricular interval oscillations of large amplitude (407.7 ± 150.4 ms); and 3) the deterioration of pattern stability at advanced levels of block, with the percentage of stable patterns decreasing from 64.3 ± 35.2% to 28.3 ± 34.5% (P < 0.01). Simulations suggested these patterns to originate from the combined effect of nodal recovery, dual pathway physiology, and concealed conduction. These results indicate that intrinsic nodal properties may account for the wide spectrum of AV block patterns occurring during regular atrial tachyarrhythmias. The characterization of AV nodal function during different AFL forms constitutes an intermediate step toward the understanding of complex ventricular rhythms during atrial fibrillation.

Systematic review and meta-analysis: renin-Angiotensin system inhibitors in the prevention of atrial fibrillation recurrences: an unfulfilled hope.

PURPOSE: To analyze the published data on the role of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II-receptor blockers (ARBs) in secondary prevention of AF. Some post-hoc analyses from trials in different clinical scenarios suggested the efficacy of ACEIs and ARBs in the prevention of new onset atrial fibrillation (AF), while their efficacy in preventing AF recurrences is notably controversial. METHODS: The authors reviewed all published prospective, randomized vs. placebo or no-treatment studies, concerning the effect of ACEIs and ARBs in the prevention of AF recurrences. Four ACEIs studies accounting for a total of 355 patients and six ARBs studies comprising 4.040 patients were analyzed. RESULTS: The pooled ACEIs data showed a statistical significant effect in preventing AF recurrences. However, the studies did not have a robust follow-up algorithm to recognize AF episodes, and were individually very small. On the contrary, pooled ARBs data did not show any effect in preventing AF recurrences (RR 0.90; 95% CI, 0.75-1.08; p = 0.24). The ARBs analyzed population was much larger in three large prospective, randomized, double-blind, placebo-control trials with transtelephoning monitoring of AF recurrences and neutral results. The meta-analysis of ACEIs and ARBs trials together could suggest a publication bias that may result in an overestimation of the treatment effect. CONCLUSIONS: Currently there is no role for ARBs in secondary prevention of AF. With regard to ACEIs, the data are not strong enough for a conclusion, although the efficacy is expected to be the same as that of ARBs.

Clinical characteristics of patients with asymptomatic recurrences of atrial fibrillation in the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico-Atrial Fibrillation (GISSI-AF) trial.

BACKGROUND: Atrial fibrillation (AF) is a common arrhythmia that frequently recurs after restoration of sinus rhythm. In a consistent percentage of cases, AF recurrences are asymptomatic, thus making its clinical management difficult in relation to both therapeutic efficacy and thromboembolic risk. METHODS: The GISSI-AF trial enrolled 1,442 patients in sinus rhythm with previous AF episodes. Patients were randomized to valsartan or placebo and followed for 12 months. To improve the likelihood of detecting arrhythmic recurrences, arrhythmic follow-up was based on both programmed or symptom-related control visits and transtelephonic electrocardiographic transmissions. The present post hoc analysis was performed on 1,638 arrhythmic episodes that occurred in 623 patients. RESULTS: Asymptomatic AF recurrences were present in 49.5% of patients. In multivariable analysis, asymptomatic AF recurrences were significantly associated with a longer duration of qualifying arrhythmias (odds ratio [95% CI] 1.57 (1.26-1.97), P < .0001). A lower ventricular response (P < .001) and a longer duration of the arrhythmic recurrence (P < .001) characterized asymptomatic episodes. Patients with asymptomatic events were more likely to be in AF at the time of electrocardiographic control at the end of the 12-month follow-up (adjusted odds ratio [95% CI] 4.9 (2.8-8.4), P < .001). Moreover, a higher CHADS(2) (Congestive heart failure, history of Hypertension, Age≥75 years, Diabetes mellitus, and past history of Stroke or TIA doubled) score and a more frequent use of amiodarone, calcium-channel blockers, and digitalis characterized patients with asymptomatic, whereas 1C drugs were more often used in subjects with symptomatic recurrences. CONCLUSION: Asymptomatic AF recurrences were frequent in the GISSI-AF study population in patients who were more likely to develop persistent-permanent AF and were characterized by an increased thromboembolic risk.

Acute atrial dilatation slows conduction and increases AF vulnerability in the human atrium.

INTRODUCTION: The mechanisms by which atrial stretch favors the development of a substrate for atrial fibrillation (AF) are not fully understood. In this study, the role of stretch-induced conduction changes in the creation of a proarrhythmic substrate has been investigated by quantifying the spatial distribution of local conduction velocities (CVs) in the human atrium during acute atrial dilatation. METHODS AND RESULTS: Electroanatomic mapping of right atrial activation was performed in 10 patients during coronary sinus pacing under control condition and during acute atrial dilatation. Atrial stretch was obtained by simultaneous atrioventricular (AV) pacing at a cycle length of 450-500 ms. Local CVs were accurately estimated by applying the principle of triangulation and spatially mapped over the whole right atrial endocardial surface. Simultaneous AV pacing significantly increased right atrial volume from 72.0 ± 29.0 to 86.3 ± 31.3 mL (P < 0.001). The 23% increase in atrial volume resulted in an overall decrease in atrial CV from 65.8 ± 5.9 to 55.2 ± 7.2 cm/s (P < 0.001) and an increased incidence of slow conduction sites or local conduction blocks from 10.3 ± 4.2% to 15.9 ± 7.7% (P < 0.01). Acute atrial dilatation concurrently increased AF vulnerability, with 6 of 10 patients developing AF episodes under stretch condition. CONCLUSION: Quantification of stretch-induced conduction changes in the human atrium is feasible by combining simultaneous AV pacing and CV map construction. Acute atrial dilatation results in conduction slowing and significant increase in AF vulnerability, suggesting the role of stretch-induced conduction disturbances in the creation of a substrate for AF.

Clinical predictors of atrial fibrillation recurrence in the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico-Atrial Fibrillation (GISSI-AF) trial.

BACKGROUND: Atrial fibrillation (AF) is a common arrhythmia that frequently recurs after restoration of sinus rhythm (SR). Identifying risk factors for recurrence may help define the best strategy for secondary prevention. METHODS: The GISSI-AF trial enrolled 1,442 patients in SR with at least 2 documented AF episodes in the previous 6 months or after cardioversion in the last 2 weeks. Patients were randomized to valsartan or placebo; all other treatments for AF or underlying heart diseases were allowed. Primary end points were time to first recurrence of AF and proportion of patients with >1 AF episode during 1-year follow-up. We evaluated clinical and electrocardiographic baseline characteristics of all patients to identify independent predictors for AF recurrence using a Cox multivariable model. RESULTS: Risk factors for AF recurrence were a history of 2 or more AF episodes in the previous 6 months, independent of the modality of SR restoration, spontaneous (HR 1.42, 95% CI 1.14-1.77, P = .002), or by cardioversion (HR 1.19, 95% CI 1.01-1.40, P = .038), and a lower heart rate during SR (HR 0.99, 95% CI 0.99-1.00, P = .052). The risk factors were the same for >1 AF recurrence. Patients treated with amiodarone had a lower risk for both end points (P < .0001 and P = .017), whereas those on diuretics had a greater risk (P = .009 and P = .003). CONCLUSIONS: In the GISSI-AF study population, AF history had significant prognostic value independent of the modality of SR restoration. Amiodarone and diuretic treatment affected the rate of AF recurrence.

Myocardial infarction due to late stent thrombosis following epileptic convulsive seizures.

We report the first case in the literature of acute myocardial infarction due to very late (5 years) drug-eluting stent (DES) thrombosis presenting with inferior ST-elevation myocardial infarction immediately after epileptic convulsive seizures in a patient with known coronary artery disease. A bare-metal stent had been implanted in the left anterior descending coronary artery in 2002, and a drug-eluting stent implanted in the right coronary artery in 2003. We discuss the possible pathogenetic mechanisms implied in convulsive epileptic crisis resulting in development of very late DES thrombosis.

Declining clinical benefit of ICD in heart failure patients: Temporal trend of mortality outcomes from randomized controlled trials.

BACKGROUND: The risk of sudden cardiac death in patients with heart failure has declined over time thanks to the sequential introduction of new treatments. However, current guidelines recommendations for implantable cardioverter-defibrillator (ICD) are based on randomized controlled trials (RCTs) carried out in the past three decades and their meta-analyses. To highlight potential changes over time in ICD clinical benefit in primary prevention of sudden cardiac death, we analyzed the temporal trends of RCT risk of mortality outcomes in this time frame. METHODS: By searching MEDLINE and the Cochrane Library electronic databases we identified seven RCTs (6095 patients enrolled between 1990 and 2014) on ICD versus contemporary standard medical therapy for sudden cardiac death prevention, in patients with chronic heart failure of ischemic and non-ischemic origin and reduced ejection fraction. Linear regression analysis was applied to identify the association between RCT mortality outcomes and time. RESULTS: Ordered according to the start of randomization, the trials showed a statistically significant (p=0.03) progressive decline in the baseline annualized event rate of sudden cardiac death in RCT control arms, and a significant (p=0.04) increase in the number of patients unresponsive to ICD treatment (i.e. patients experiencing sudden cardiac death in ICD arms). These two factors synergistically contributed to a significant (p<0.01) and progressive reduction in the clinical benefit of ICD, assessed by the number needed to treat for total mortality at 3 years. CONCLUSIONS: The clinical benefit of ICD, implanted according to the current guidelines, has significantly and progressively declined over time due to the reduction in sudden cardiac death risk and to the increase of ICD unresponsive patients.

Mechanical modulation of atrial flutter cycle length.

Although atrial flutter (AFL) is considered a highly regular rhythm, small fluctuations in cycle length have been described. The mechanisms responsible for these interval oscillations have been investigated by recent studies in humans which have shown that cyclic variations in atrial volume and pressure following ventricular contraction may account for the spontaneous variability of AFL. Other studies have shown that variations in the dimensions of the atria, caused by hemodynamical alterations due to imposed manoeuvres, directly modify the rate of AFL. All this evidence has led to the development of the mechano-electrical feedback (MEF) hypothesis, which assumes that changes in atrial volume directly affect AFL cycle length variability by modifying the conduction properties of the circulating impulse in the atrium. In the present study, we re-examined the variability pattern of typical AFL by spectral analysis aiming to support the MEF hypothesis for AFL cycle length variability. In a study population of 30 patients with typical AFL, we observed that AFL cycle length presented a spontaneous beat-to-beat variability, composed of two oscillations: a main oscillation at the frequency of ventricular contraction (1.70+/-0.48 Hz, spectral power: 15.4+/-17.6 ms2) and a second oscillation at the frequency of respiration (0.32+/-0.07 Hz, spectral power: 2.9+/-2.6 ms2). Both ventricular and respiratory oscillations persisted after pharmacologic autonomic blockade (ventricular spectral power: 17.7+/-14.7 ms2 (before block) vs 20.2+/-18.3 ms2 (after block), p=NS; respiratory spectral power: 6.0+/-3.8 ms2 (before block) vs 5.0+/-3.4 ms2 (after block), p=NS), suggesting a non-neurally mediated underlying mechanism. Contrary to respiratory modulation of heart rate during sinus rhythm, respiratory AFL cycle length oscillations displayed a reverse pattern, with longer cycle lengths during inspiration and shorter during expiration (AA insp=223.2+/-28.6 ms vs AA exp=221.1+/-28.2 ms, p<0.0005), which was consistent with a mechanical modulation of AFL reentry. The use of spectral analysis techniques applied to ventricular interval series and combined with computer simulations of atrioventricular conduction showed that the respiratory oscillation of atrial cycle length determined an oscillation in ventricular intervals with longer intervals during inspiration and shorter during expiration (VV insp=639.9+/-186.0 ms vs VV exp=634.8+/-182.9 ms, p<0.05). Ventricular interval oscillations resulted amplified by a factor 1.8 with respect to corresponding atrial cycle length oscillations. Thus, the mechanical fluctuations in AFL cycle length, although of small amplitude, might become clinically relevant through a magnified effect on ventricular variability.

Cardiorespiratory interactions in patients with atrial flutter.

Respiratory sinus arrhythmia (RSA) is generally known as the autonomically mediated modulation of the sinus node pacemaker frequency in synchrony with respiration. Cardiorespiratory interactions have been largely investigated during sinus rhythm, whereas little is known about interactions during reentrant arrhythmias. In this study, cardiorespiratory interactions at the atrial and ventricular level were investigated during atrial flutter (AFL), a supraventricular arrhythmia based on a reentry, by using cross-spectral analysis and computer modeling. The coherence and phase between respiration and atrial (gamma(AA)(2), phi(AA)) and ventricular (gamma(RR)(2), phi(RR)) interval series were estimated in 20 patients with typical AFL (68.0 +/- 8.8 yr) and some degree of atrioventricular (AV) conduction block. In all patients, atrial intervals displayed oscillations strongly coupled and in phase with respiration (gamma(AA)(2)= 0.97 +/- 0.05, phi(AA) = 0.71 +/- 0.31 rad), corresponding to a paradoxical lengthening of intervals during inspiration. The modulation pattern was frequency independent, with in-phase oscillations and short time delays (0.40 +/- 0.15 s) for respiratory frequencies in the range 0.1-0.4 Hz. Ventricular patterns were affected by AV conduction type. In patients with fixed AV conduction, ventricular intervals displayed oscillations strongly coupled (gamma(RR)(2)= 0.97 +/- 0.03) and in phase with respiration (phi(RR) = 1.08 +/- 0.80 rad). Differently, in patients with variable AV conduction, respiratory oscillations were secondary to Wencheback rhythmicity, resulting in a decreased level of coupling (gamma(RR)(2)= 0.50 +/- 0.21). Simulations with a simplified model of AV conduction showed ventricular patterns to originate from the combination of a respiratory modulated atrial input with the functional properties of the AV node. The paradoxical frequency-independent modulation pattern of atrial interval, the short time delays, and the complexity of ventricular rhythm characterize respiratory arrhythmia during AFL and distinguish it from normal RSA. These peculiar features can be explained by assuming a direct mechanical action of respiration on AFL reentrant circuit.

Atrial fibrillation ablation procedure using electroanatomic reconstruction of the right and left atrium in a patient affected by dextrocardia.

We describe a case report of a patient affected by drug refractory persistent atrial fibrillation and dextrocardia, who underwent an ablation procedure using an electroanatomic mapping system.