Lars Lüthje

Biventricular Pacing Improves the Blunted Force–Frequency Relation Present During Univentricular Pacing in Patients With Heart Failure and Conduction Delay

Background— In patients with chronic heart failure (CHF) and conduction delay, biventricular (BiV) and left ventricular (LV) pacing similarly improve systolic function at resting heart rates. We hypothesized that BiV and univentricular pacing differentially affect contractile function at increasing heart rates. Methods and Results— Twenty-two patients (aged 66±2 years, QRS 179±8 ms, LV ejection fraction 23±1%) underwent cardiac catheterization before device implantation to measure LV hemodynamics at baseline (rate 68±2 bpm; sinus rhythm n=18; atrial fibrillation n=4) and during BiV, LV, and right ventricular (RV) stimulation at 80, 100, 120, and 140 bpm. BiV and LV pacing at 80 bpm equally augmented dP/dtmax as compared with baseline and RV pacing (P<0.001). Stimulation rate significantly interacted with the effect of BiV, LV, and RV pacing on LV end-diastolic pressure (LVEDP), systolic pressure (LVSP), and dP/dtmax. Increasing the rate from 80 to 140 bpm enhanced dP/dtmax from 913±28 to 1119±50 mm Hg/s during BiV stimulation (P<0.001) but had no significant effect on contractility during single-site LV (951±47 versus 1002±54 mm Hg/s) or RV (800±46 versus 881±49 mm Hg/s) pacing. At 140 bpm, LVEDP was lower and LVSP higher during BiV pacing than during RV and LV pacing (LVEDP 12±1 versus 17±1 and 16±1 mm Hg, P<0.001; LVSP 112±5 versus 106±5 and 108±6 mm Hg, P<0.01 and P=0.09; BiV versus RV and LV pacing, respectively). Conclusions— Different modes of ventricular stimulation alter the in vivo force–frequency relation of CHF patients. In contrast to single-site LV and RV pacing, contractile function improves with increasing heart rates during BiV stimulation. This effect may contribute to the enhanced exercise capacity during BiV pacing and could provide a functional benefit over LV-only pacing in patients for whom resynchronization therapy is indicated.

Intrathoracic impedance monitoring to detect chronic heart failure deterioration: Relationship to changes in NT-proBNP

An alert algorithm, based on intrathoracic impedance monitoring, has been incorporated into a cardiac resynchronisation device (CRT) to detect pulmonary fluid accumulation, and to audibly alert patients to decompensating chronic heart failure (CHF).

Remote magnetic catheter navigation for cavotricuspid isthmus ablation in patients with common-type atrial flutter

Background—Conventional catheter ablation of cavotricuspid isthmus (CTI)-dependent atrial flutter is a widely applied standard therapy. Remote magnetic catheter navigation (RMN) may provide benefits for different ablation procedures, but its efficacy for CTI ablation has not been evaluated in a randomized, controlled trial. Methods and Results—Ninety patients undergoing de novo ablation of atrial flutter were randomly assigned to conventional manual (n=45) or RMN-guided (n=45) CTI ablation with an 8-mm-tip catheter. Complete bidirectional isthmus block was achieved in 84% (RMN) and 91% (conventional catheter ablation) of the cases (P=0.52). RMN was associated with shorter fluoroscopy time (median, 10.6 minutes; interquartile range [IQR], 7.6 to 19.9, versus 15.0 minutes; IQR, 11.5 to 23.1; P=0.043) but longer total radiofrequency application (17.1 minutes; IQR, 8.6 to 25, versus 7.5 minutes; IQR, 3.6 to 10.9; P<0.0001), ablation time (55 minutes; IQR, 28 to 76, versus 17 minutes; IQR, 7 to 31; P<0.0001), and procedure duration (114±35 versus 77±24 minutes, P<0.0001). Procedure duration in the RMN group did not decrease significantly with case experience. Long-term procedure success, defined as achievement of complete CTI block and freedom from atrial flutter recurrence during 6 months of follow-up, was lower in the RMN group (73% versus 89%, P=0.063). Right atrial angiography after ablation revealed no significant differences between groups in terms of right atrial diameter or CTI length, morphology, and angulation. Furthermore, none of these parameters was predictive for difficult (ablation time >20 minutes) or unsuccessful ablation. Conclusions—RMN-guided CTI ablation is associated with reduced radiation exposure but prolonged ablation and procedure times as compared with conventional catheter navigation. Our findings suggest that ablation lesions produced with an RMN-guided 8-mm catheter are less effective irrespective of CTI anatomy. Trial Registration—clinicaltrials.gov Identifier: NCT00560872

Detection of left atrial thrombus during routine diagnostic work-up prior to pulmonary vein isolation for atrial fibrillation: Role of transesophageal echocardiography and multidetector computed tomography☆

BACKGROUND Transesophageal echocardiography (TEE) and multidetector computed tomography (MDCT) are frequently used imaging modalities prior to pulmonary vein isolation (PVI) in order to exclude left atrial (LA) and left atrial appendage (LAA) thrombus and to visualize the anatomy of LA and pulmonary veins. This study aimed to identify predictors of LA/LAA thrombus and to analyze the diagnostic yield of routine pre-procedural TEE and MDCT. METHODS 329 patients with drug-refractory atrial fibrillation (AF) (age 62 ± 10 years; 65% males; 247 paroxysmal AF) referred for pulmonary PVI were included. Prior to the procedure, all patients underwent 64-slice MDCT and TEE, which was used as the gold standard. Risk parameters for thrombus formation were determined, including the CHADS(2) and CHA(2)DS(2)-VASc scores. RESULTS MDCT identified 10 LA/LAA thrombi (3.0%) (8 false positive, 2 true positive), whereas 7 actual thrombi (2.1%) were detected by TEE (5 false negative by MDCT). Sensitivity and specificity of MDCT was 29% and 98%, respectively, with a negative predictive value of 98% and a positive predictive value of 20%. All patients with thrombus were on effective anticoagulation. In multivariate analysis, diabetes mellitus, CHADS(2) score ≥3, and CHA(2)DS(2)-VASc score ≥4 were significantly associated with LA/LAA thrombus. No thrombus was seen in patients without risk factors. CONCLUSIONS In patients presenting for PVI, MDCT does not reliably exclude LA/LAA thrombus. Our study revealed a small but significant prevalence of thrombus despite effective anticoagulation. Diabetes mellitus, CHADS(2) score ≥3, and CHA(2)DS(2)-VASc score ≥4 were independent risk predictors of LA/LAA thrombus.

Exercise intolerance and systemic manifestations of pulmonary emphysema in a mouse model

BackgroundSystemic effects of chronic obstructive pulmonary disease (COPD) significantly contribute to severity and mortality of the disease. We aimed to develop a COPD/emphysema model exhibiting systemic manifestations of the disease.MethodsFemale NMRI mice were treated 5 times intratracheally with porcine pancreatic elastase (emphysema) or phosphate-buffered saline (control). Emphysema severity was quantified histologically by mean linear intercept, exercise tolerance by treadmill running distance, diaphragm dysfunction using isolated muscle strips, pulmonary hypertension by measuring right ventricular pressure, and neurohumoral activation by determining urinary norepinephrine concentration.ResultsMean linear intercept was higher in emphysema (260.7 ± 26.8 μm) than in control lungs (24.7 ± 1.7 μm). Emphysema mice lost body weight, controls gained weight. Running distance was shorter in emphysema than in controls. Diaphragm muscle length was shorter in controls compared to emphysema. Fatigue tests of muscle strips revealed impaired relaxation in emphysema diaphragms. Maximum right ventricular pressure and norepinephrine were elevated in emphysema compared to controls. Linear correlations were observed between running distance changes and intercept, right ventricular weight, norepinephrine, and diaphragm length.ConclusionThe elastase mouse model exhibited severe emphysema with consecutive exercise limitation, and neurohumoral activation. The model may deepen our understanding of systemic aspects of COPD.

Differential Effects of Theophylline on Sympathetic Excitation, Hemodynamics, and Breathing in Congestive Heart Failure

Background—Patients with heart failure have high levels of central sympathetic outflow and also have a high prevalence of sleep-related breathing disorders, predominantly central sleep apnea. The options for treating central sleep apnea in heart failure are limited and include theophylline. Whether theophylline alters sympathetic activity in heart failure patients is not known. Methods and Results—Using a single-blinded, randomized, placebo-controlled study design, we investigated the sympathetic, hemodynamic, neurohumoral, and ventilatory effects of theophylline in patients with congestive heart failure compared with healthy control subjects closely matched for age, sex, and body mass index. Theophylline increased muscle sympathetic nerve activity and lowered transcutaneous CO2 in the control subjects but only lowered transcutaneous CO2 in the heart failure patients. Theophylline nearly doubled plasma renin concentration in both the healthy subjects (P<0.01) and the heart failure patients (P<0.02). Conclusions—Our study shows that in heart failure patients, there are differential effects of theophylline: in contrast to healthy subjects, theophylline does not increase sympathetic activity in heart failure, whereas increases in plasma renin and ventilation are still evident. These novel findings may have important implications for understanding the potential harmful and beneficial effects of theophylline and related substances in heart failure patients.

Cardiac resynchronization therapy and atrial overdrive pacing for the treatment of central sleep apnoea

The combined therapeutic impact of atrial overdrive pacing (AOP) and cardiac resynchronization therapy (CRT) on central sleep apnoea (CSA) in chronic heart failure (CHF) so far has not been investigated. We aimed to evaluate the effect of CRT alone and CRT + AOP on CSA in CHF patients and to compare the influence of CRT on CHF between CSA positive and CSA negative patients.

Impact of obstructive sleep apnoea on diastolic function

We investigated whether obstructive sleep apnoea (OSA) independently affects diastolic function in a primary care cohort of patients with cardiovascular risk factors. 378 study participants with risk factors for diastolic dysfunction were prospectively included and a polygraphy was performed in all patients. Diastolic dysfunction was assessed by comprehensive echocardiography including tissue Doppler. Sleep apnoea was classified according to apnoea/hypopnoea index (AHI) as none (AHI <5 events·h−1), mild (AHI ≤5 to <15 events·h−1) or moderate-to-severe (AHI ≥15 events·h−1). Patients with central sleep apnoea (n=14) and patients with previously diagnosed sleep apnoea (n=12) were excluded. In the remaining 352 subjects, 21.6% had an AHI ≥15 events·h−1. The prevalence of diastolic dysfunction increased with the severity of sleep apnoea from 44.8% (none) to 56.8% (mild) to 69.7% (moderate-to-severe sleep apnoea) (p=0.002). The degree of diastolic dysfunction also increased with sleep apnoea severity (p=0.004). In univariate regression analysis, age, desaturation index, AHI, cardiac frequency, angiotensin receptor 1 antagonist therapy, body mass index (BMI) and left ventricular mass were associated with diastolic dysfunction. In multivariate regression analysis, only age, BMI, AHI and cardiac frequency were independently associated with diastolic dysfunction. Moderate-to-severe OSA is independently associated with diastolic dysfunction in patients with classical risk factors for diastolic dysfunction.

Left atrial volumetry from routine diagnostic work up prior to pulmonary vein ablation is a good predictor of freedom from atrial fibrillation

AIMS This study aimed to identify whether left atrial (LA) volume assessed by multidetector computed tomography (MDCT) is related to the long-term success of pulmonary vein ablation (PVA). MDCT is used to guide PVA for the treatment of atrial fibrillation (AF). MDCT permits accurate sizing of LA dimensions. METHODS AND RESULTS We analysed data from 368 ablation procedures of 279 consecutive patients referred for PVA due to drug-refractory symptomatic AF (age 62 ± 10; 58% men; 71% paroxysmal AF). Prior to the procedure, all patients underwent ECG-gated 64-MDCT scan for assessment of LA and PV anatomy, LA thrombus evaluation, LA volume estimation, and electroanatomical mapping integration. Within a mean follow-up of 356 ± 128 days, 64% of the patients maintained sinus rhythm after the initial ablation, and 84% when including repeat PVA. LA diameter (P = 0.004), LA volume (P = 0.002), and type of AF (P = 0.001) were independent predictors of AF recurrence in univariate analysis. There was a relatively low correlation between the echocardiographic LA diameter and LA volume from MDCT (P = 0.01, r = 0.5). In multivariate analysis, paroxysmal AF (P < 0.006) and LA volume below the median value of 106 mL (P = 0.042) were significantly associated with the success of PVA, whereas LA diameter was not (P = 0.245). Analysing receiver-operator characteristics, the area under the curve for LA volume was 0.73 (P = 0.001) compared with 0.60 (P = 0.09) for LA diameter from echocardiography. CONCLUSION LA volume assessed by MDCT is a better predictor of AF recurrence after PVA than echocardiograpic LA diameter and can be derived from the pre-procedural imaging data set.

Misleading Long Post-Pacing Interval After Entrainment of Typical Atrial Flutter From the Cavotricuspid Isthmus

OBJECTIVES The purpose of this study was to evaluate the prevalence and mechanism of a misleading long post-pacing interval (PPI) upon entrainment of typical atrial flutter (AFL) from the cavotricuspid isthmus (CTI). BACKGROUND In typical AFL, the PPI from entrainment at the CTI is expected to closely match the tachycardia cycle-length (TCL). METHODS Sixty patients with confirmed CTI-dependent AFL were retrospectively analyzed and grouped into short (≤30 ms) or long (>30 ms) PPI-TCL. Thereafter, we prospectively studied 16 patients to acquire the PPI-TCL at 4 CTI sites with entrainment at pacing cycle-lengths (PCLs) 10 to 40 ms shorter than the TCL. Conduction times during AFL and entrainment were compared in 5 segments of the AFL circuit. RESULTS Eleven patients (18%) in the retrospective analysis had a long PPI-TCL after entrainment from the CTI. Subjects with long PPI-TCL had similar baseline characteristics but greater beat-to-beat TCL variability. In the prospective cohort, PPI-TCL was influenced by the difference between PCL and TCL and site of entrainment. Conduction delays associated with a long PPI-TCL were located predominantly in the segment activated first by the paced orthodromic wave front, and were mainly due to local pacing latency, as confirmed by the use of monophasic action potential catheters. CONCLUSIONS A long PPI upon entrainment of typical AFL from the CTI is common and due to delayed conduction with entrainment. Whether these findings apply to other macro-re-entrant tachycardias warrants further investigation.