Dan Wichterle

Heart Rate Turbulence: Standards of Measurement, Physiological Interpretation, and Clinical Use: International Society for Holter and Noninvasive Electrophysiology Consensus

This consensus statement has been compiled on behalf of the International Society for Holter and Noninvasive Electrophysiology. It reviews the topic of heart rate turbulence (HRT) and concentrates on technologies for measurement, physiologic background and interpretation, and clinical use of HRT. It also lists suggestions for future research. The phenomenon of HRT refers to sinus rhythm cycle-length perturbations after isolated premature ventricular complexes. The physiologic pattern of HRT consists of brief heart rate acceleration (quantified by the so-called turbulence onset) followed by more gradual heart rate deceleration (quantified by the so-called turbulence slope) before the rate returns to a pre-ectopic level. Available physiologic investigations confirm that the initial heart rate acceleration is triggered by transient vagal inhibition in response to the missed baroreflex afferent input caused by hemodynamically inefficient ventricular contraction. A sympathetically mediated overshoot of arterial pressure is responsible for the subsequent heart rate deceleration through vagal recruitment. Hence, the HRT pattern is blunted in patients with reduced baroreflex. The HRT pattern is influenced by a number of factors, provocations, treatments, and pathologies reviewed in this consensus. As HRT measurement provides an indirect assessment of baroreflex, it is useful in those clinical situations that benefit from baroreflex evaluation. The HRT evaluation has thus been found appropriate in risk stratification after acute myocardial infarction, risk prediction, and monitoring of disease progression in heart failure, as well as in several other pathologies.

Electrical reconnection after pulmonary vein isolation is contingent on contact force during initial treatment: results from the EFFICAS I study

Background—Pulmonary vein isolation is the most prevalent approach for catheter ablation of paroxysmal atrial fibrillation. Long-term success of the procedure is diminished by arrhythmia recurrences occurring predominantly because of reconnections in previously isolated pulmonary veins. The aim of the EFFICAS I multicenter study was to demonstrate the correlation between contact force (CF) parameters during initial procedure and the incidence of isolation gaps (gap) at 3-month follow-up. Method and Results—A radiofrequency ablation catheter with integrated CF sensor (TactiCath, Endosense, Geneva, Switzerland) was used to perform pulmonary vein isolation in 46 patients with paroxysmal atrial fibrillation. During the ablation procedure, the operator was blinded to CF information. At follow-up, an interventional diagnostic procedure was performed to assess gap location as correlated to index procedure ablation parameters. At follow-up, 65% (26/40) of patients showed ≥1 gaps. Ablations with minimum Force–Time Integral (FTI) <400 gs showed increased likelihood for reconnection (P<0.001). Reconnection correlated strongly with minimum CF (P<0.0001) and minimum FTI (P=0.0007) at the site of gap. Gap occurrence showed a strong trend with lower average CF and average FTI. CF and FTI are generally higher on the right side, although the left anterior segment presents a unique challenge to achieve stable position with good CF. Conclusions—Minimum CF and minimum FTI values are strong predictors of gap formation. Optimal CF parameter recommendations are a target CF of 20 g and a minimum FTI of 400 gs for each new lesion.

Both fenofibrate and atorvastatin improve vascular reactivity in combined hyperlipidaemia (fenofibrate versus atorvastatin trial — FAT)

OBJECTIVE It has been repeatedly proven that statins improve endothelial function in isolated hypercholesterolaemia but there is far less evidence in the case of combined hyperlipidaemia. Studies assessing the effects of fibrates on endothelium have been neglected. Therefore, we conducted a trial in which the effects of fenofibrate and atorvastatin monotherapy on both endothelium-dependent vascular reactivity and biochemical parameters were compared in patients with combined hyperlipidaemia. METHODS 29 otherwise healthy males (aged 47.4+/-7.8 years) with combined hyperlipidaemia (total cholesterol 7.55+/-1.20 mmol/l, triglycerides 5.41+/-4.54 mmol/l) were included into the randomised, single-blind, cross-over study to receive either 200 mg of micronised fenofibrate or 10 mg of atorvastatin daily--each of the drugs for a period of 10 weeks. Analysed biochemical parameters were as follows: serum total-, LDL- and HDL-cholesterol, apolipoproteins A-I and B, triglycerides, fibrinogen, uric acid, C-reactive protein (CRP), insulin, and homocysteine. Endothelial function was investigated by duplex Doppler ultrasonography at the brachial artery. Two indices of endothelial-dependent postischaemic changes were used - the recently introduced index of peak blood flow (PBF) representing the level of reactive hyperaemia and traditional flow-mediated dilatation (FMD). RESULTS We observed a small improvement in FMD after both fenofibrate and atorvastatin (from 2.26% to 2.98% and 2.87%, respectively; NS). PBF increased from 448 ml/min to 536 ml/min after fenofibrate (P=0.04) and to 570 ml/min after atorvastatin (P=0.03). The effects of both fenofibrate and atorvastatin on endothelial function did not differ significantly (P-values of 0.82 and 0.47 for FMD and PBF, respectively). Significant correlations (P<0.01) between the changes of vascular reactivity and biochemical indices were found between FMD and CRP (r=-0.60) and between both FMD and PBF, and insulinaemia (r=-0.48 and -0.56, respectively) only during treatment with fenofibrate. CONCLUSIONS Both fenofibrate and atorvastatin significantly improved endothelium-dependent vascular reactivity without mutual difference. The PBF was superior to FMD for the detection of this improvement. The beneficial effect of both drugs did not correlate with the change of lipid profile during therapy. The improvement of vascular reactivity during treatment with fenofibrate (opposed to atorvastatin) was related to the reduction of indirect marker of chronic vessel wall inflammation and of insulin resistance. The PBF was more reproducible than FMD because of considerably lower intra-subject variability.

Electrical Reconnection After Pulmonary Vein Isolation Is Contingent on Contact Force During Initial TreatmentClinical Perspective

Background—Pulmonary vein isolation is the most prevalent approach for catheter ablation of paroxysmal atrial fibrillation. Long-term success of the procedure is diminished by arrhythmia recurrences occurring predominantly because of reconnections in previously isolated pulmonary veins. The aim of the EFFICAS I multicenter study was to demonstrate the correlation between contact force (CF) parameters during initial procedure and the incidence of isolation gaps (gap) at 3-month follow-up. Method and Results—A radiofrequency ablation catheter with integrated CF sensor (TactiCath, Endosense, Geneva, Switzerland) was used to perform pulmonary vein isolation in 46 patients with paroxysmal atrial fibrillation. During the ablation procedure, the operator was blinded to CF information. At follow-up, an interventional diagnostic procedure was performed to assess gap location as correlated to index procedure ablation parameters. At follow-up, 65% (26/40) of patients showed ≥1 gaps. Ablations with minimum Force–Time Integral (FTI) <400 gs showed increased likelihood for reconnection (P<0.001). Reconnection correlated strongly with minimum CF (P<0.0001) and minimum FTI (P=0.0007) at the site of gap. Gap occurrence showed a strong trend with lower average CF and average FTI. CF and FTI are generally higher on the right side, although the left anterior segment presents a unique challenge to achieve stable position with good CF. Conclusions—Minimum CF and minimum FTI values are strong predictors of gap formation. Optimal CF parameter recommendations are a target CF of 20 g and a minimum FTI of 400 gs for each new lesion.

EFFICAS II: optimization of catheter contact force improves outcome of pulmonary vein isolation for paroxysmal atrial fibrillation

Aims A challenge of pulmonary vein isolation (PVI) in catheter ablation for paroxysmal atrial fibrillation (PAF) is electrical reconnection of the PV. EFFICAS I showed correlation between contact force (CF) parameters and PV durable isolation but no prospective evaluation was made. EFFICAS II was a multicentre study to prospectively assess the impact of CF guidance for an effective reduction of PVI gaps. Methods and results Pulmonary vein isolation using a radiofrequency (RF) ablation catheter with an integrated force sensor (TactiCath™) was performed in patients with PAF. Operators were provided EFFICAS I-based CF guidelines [target 20 g, range 10–30 g, minimum 400 g s force-time integral (FTI)]. Conduction gaps were assessed by remapping of PVs after 3 months, and gap rate was compared with EFFICAS I outcome. At follow up, 24 patients had 85% of PVs remaining isolated, compared with 72% in EFFICAS I (P = 0.037) in which CF guidelines were not used. The remaining 15% of gaps correlated to the number of catheter moves at creating the PVI line, quantified as Continuity Index. For PV lines with contiguous lesions and low catheter moves, durable isolation was 81% in EFFICAS I and 98% in EFFICAS II (P = 0.005). At index procedure, the number of lesions was reduced by 15% in EFFICAS II vs. EFFICAS I. Conclusion The use of CF with the above guidelines and contiguous deployment of RF lesions in EFFICAS II study resulted in more durable PVI in catheter ablation of PAF.

Precise assessment of noncompliance with the antihypertensive therapy in patients with resistant hypertension using toxicological serum analysis

Background: The aim of our study was to assess the prevalence of pseudo-resistance caused by noncompliance with treatment among patients with severe resistant hypertension and to analyze the contributing factors. Method: Three hundred and thirty-nine patients (195 men) with resistant essential hypertension were studied. The first group consisted of 176 patients admitted for hospitalization for exclusion of a secondary cause to our hypertension centre (103 men); the second one consisted of 163 out-patients (92 men) investigated for the first time in an out-patient hypertension clinic. Unplanned blood sampling for assessment of serum antihypertensive drug concentrations by means of liquid chromatography–mass spectrometry was performed in all patients. Results: Our main finding is a surprisingly low compliance with drug treatment in out-patients with resistant hypertension (23% partially noncompliant and 24% totally noncompliant – in total, 47% prevalence of noncompliance). Eighty-one percent of hospitalized patients were positive, in 10% the results were partially positive and in 9% of the patients, the drugs were all negative. The compliance among hospitalized patients was probably better due to lower numbers of prescribed drugs and expected thorough investigation. More frequently, noncompliance was found in nonworking (potential purpose-built behaviour), younger and less well educated patients. The most frequent noncompliance was to doxazosine, spironolactone and hydrochlorothiazide. We have observed a surprisingly low compliance with treatment among out-patients with severe hypertension. Conclusion: We conclude that the evaluation of antihypertensive drugs concentrations is a useful and precise method for assessment of noncompliance in patients with resistant hypertension. This evaluation is useful before starting the diagnostic work-up of secondary forms of hypertension and before assignment patients into protocols with new therapy modalities such as renal denervation.

The durability of pulmonary vein isolation using the visually guided laser balloon catheter: Multicenter results of pulmonary vein remapping studies

BACKGROUND The visually guided laser ablation (VGLA) catheter is a compliant, variable-diameter balloon that delivers laser energy around the pulmonary vein (PV) ostium under real-time endoscopic visualization. While acute PV isolation has been shown to be feasible, limited data exist regarding the durability of isolation. OBJECTIVE We sought to determine the durability of PV isolation following ablation using the balloon-based VGLA catheter. METHODS The VGLA catheter was evaluated in patients with paroxysmal atrial fibrillation (3 sites, 10 operators). Following transseptal puncture, the VGLA catheter was advanced through a 12-F deflectable sheath and inflated at the target PV ostium. Under endoscopic guidance, the 30° aiming arc was maneuvered around the PV and laser energy was delivered to ablate tissue in a contiguous/overlapping manner. At ∼3 months, all patients returned for a PV remapping procedure. RESULTS In 56 patients, 202 of 206 PVs (98%) were acutely isolated. At 105 ± 44 (mean ± SD) days, 52 patients returned for PV remapping at which time 162 of 189 PVs (86%) remained isolated and 32 of 52 patients (62%) had all PVs still isolated. On comparing the operators performing <10 vs ≥ 10 procedures, the durable PV isolation rate and the percentage of patients with all PVs isolated were found to be 73% vs 89% (P = .011) and 57% vs 66% (P = .746), respectively. After 2 procedures and 12.0 ± 1.9 months of follow-up, the drug-free rate of freedom from atrial fibrillation was 71.2%. CONCLUSIONS In this multicenter, multioperator experience, VGLA resulted in a very high rate of durable PV isolation with a clinical efficacy similar to that of radiofrequency ablation.

Prevalent Low-Frequency Oscillation of Heart Rate Novel Predictor of Mortality After Myocardial Infarction

Background—This study evaluates a novel method for postinfarction risk stratification based on frequency-domain characteristics of heart rate variability (HRV) in 24-hour Holter recordings. Methods and Results—A new risk predictor, prevalent low-frequency oscillation (PLF), was determined in the placebo population of the European Myocardial Infarction Amiodarone Trial (EMIAT). Frequencies of peaks detected in 5-minute low-frequency HRV spectra were averaged to obtain the PLF index. PLF ≥0.1 Hz was the strongest univariate predictor of all-cause mortality associated with relative risk of 6.4 (95% CI, 3.9 to 10.6; P<10−12). In a multivariate Cox’s regression model including clinical risk factors, mean RR interval, HRV index, low- and high-frequency HRV spectral power, and heart rate turbulence, PLF was the most powerful mortality predictor, with a relative risk of 4.6 (95% CI, 2.2 to 9.3; P=0.00003). Predictive power of PLF was blindly validated in the population of the Autonomic Tone and Reflexes After Myocardial Infarction (ATRAMI) trial. PLF ≥0.1 Hz was associated with univariate relative risk of 6.1 (95% CI, 2.9 to 12.9; P<10−5) for cardiac mortality or resuscitated cardiac arrest. In multivariate Cox’s regression model including age, left ventricular ejection fraction, baroreflex sensitivity, mean RR interval, standard deviation of normal RR intervals, low- and high-frequency HRV spectral power, and heart rate turbulence, only left ventricular ejection fraction and PLF were significant predictors, with relative risks of 4.2 (95% CI, 1.5 to 11.7; P=0.007) and 3.6 (95% CI, 1.3 to 10.5; P=0.02), respectively. Conclusions—An innovative analysis of frequency-domain HRV, which characterizes the distribution of spectral power within the low-frequency band, is a potent and independent risk stratifier in postinfarction patients.

Increased intima-media thickness of the common carotid artery in primary aldosteronism in comparison with essential hypertension.

Background Aldosterone contributes to the accumulation of collagen fibers and extracellular matrix in arterial wall. The aim of this study was to compare intima–media thickness (IMT) of the common carotid artery and carotid bifurcation in patients with primary aldosteronism, essential hypertension and healthy controls. Methods Carotid ultrasound studies were carried out in 33 patients aged 42–72 years with primary aldosteronism, 52 patients with essential hypertension and in 33 normotensive controls. Results The patients with primary aldosteronism had significantly higher IMT of the common carotid artery than patients with essential hypertension and controls (0.987 ± 0.152 mm; 0.892 ± 0.154 mm versus 0.812 ± 0.124 mm; P < 0.001; P < 0.05). There was also significantly higher IMT of the common carotid in patients with essential hypertension compared to control group (0.892 ± 0.154 mm versus 0.812 ± 0.124 mm; P < 0.01). The differences between both hypertensive groups remained statistically significant after adjustment for age and 24-h systolic blood pressure (P = 0.001). The differences of the IMT in the carotid bifurcation were statistically significant only between patients with primary aldosteronism and controls (1.157 ± 0.243 mm versus 0.994 ± 0.199 mm; P <0.05). Conclusion Patients with primary aldosteronism have increased common carotid IMT compared to the patients with essential hypertension. This finding could be caused by the deleterious effects of aldosterone excess on the fibrosis and thickening of the arterial wall, mainly in the straight segments of vessels.

Locations of High Contact Force During Left Atrial Mapping in Atrial Fibrillation Patients Electrogram Amplitude and Impedance Are Poor Predictors of Electrode-Tissue Contact Force for Ablation of Atrial Fibrillation

Background—During radiofrequency ablation, high electrode-tissue contact force (CF) is associated with increased risk of steam pop and perforation. The purpose of this study, in patients undergoing ablation of paroxysmal atrial fibrillation, was to: (1) identify factors producing high CF during left atrial (LA) and pulmonary vein mapping; (2) determine the ability of atrial potential amplitude and impedance to predict CF; and (3) explore the feasibility of controlling radiofrequency power based on CF. Methods and Results—A high-density map of LA/pulmonary veins (median 328 sites) was obtained in 18 patients undergoing atrial fibrillation ablation using a 7.5-Fr irrigated mapping/ablation catheter to measure CF. Average CF was displayed on the 3D map. For 5682 mapped sites, CF ranged 1–144 g (median 8.2 g). High CF (≥35 g) was observed at only 118/5682 (2%) sites, clustering in 6 LA regions. The most common high CF site (48/113 sites in 17/18 patients) was located at the anterior/rightward LA roof, directly beneath the ascending aorta (confirmed by merging the CT image and map). Poor relationship between CF and either unipolar amplitude, bipolar amplitude, or impedance was observed. During ablation, radiofrequency power was modulated based on CF. All pulmonary veins were isolated without steam pop, impedance rise, or pericardial effusion. Conclusions—High CF often occurs at anterior/rightward roof, where the ascending aorta provides resistance to the LA. Atrial potential amplitude and impedance are poor predictors of CF. Controlling radiofrequency power based on CF seems to prevent steam pop and impedance rise without loss of lesion effectiveness.