Pulmonary artery sensor system pressure monitoring to improve heart failure outcomes (PASSPORT-HF): rationale and design of the PASSPORT-HF multicenter randomized clinical trial.

BACKGROUND: Remote monitoring of patients with New York Heart Association (NYHA) functional class III heart failure (HF) using daily transmission of pulmonary artery (PA) pressure values has shown a reduction in HF-related hospitalizations and improved quality of life in patients. OBJECTIVES: PASSPORT-HF is a prospective, randomized, open, multicenter trial evaluating the effects of a hemodynamic-guided, HF nurse-led care approach using the CardioMEMS™ HF-System on clinical end points. METHODS AND RESULTS: The PASSPORT-HF trial has been commissioned by the German Federal Joint Committee (G-BA) to ascertain the efficacy of PA pressure-guided remote care in the German health-care system. PASSPORT-HF includes adult HF patients in NYHA functional class III, who experienced an HF-related hospitalization within the last 12 months. Patients with reduced ejection fraction must be on stable guideline-directed pharmacotherapy. Patients will be randomized centrally 1:1 to implantation of a CardioMEMS™ sensor or control. All patients will receive post-discharge support facilitated by trained HF nurses providing structured telephone-based care. The trial will enroll 554 patients at about 50 study sites. The primary end point is a composite of the number of unplanned HF-related rehospitalizations or all-cause death after 12 months of follow-up, and all events will be adjudicated centrally. Secondary end points include device/system-related complications, components of the primary end point, days alive and out of hospital, disease-specific and generic health-related quality of life including their sub-scales, and laboratory parameters of organ damage and disease progression. CONCLUSIONS: PASSPORT-HF will define the efficacy of implementing hemodynamic monitoring as a novel disease management tool in routine outpatient care. TRIAL REGISTRATION: ClinicalTrials.gov; NCT04398654, 13-MAY-2020.

A roadmap to improve the quality of atrial fibrillation management: proceedings from the fifth Atrial Fibrillation Network/European Heart Rhythm Association consensus conference.

At least 30 million people worldwide carry a diagnosis of atrial fibrillation (AF), and many more suffer from undiagnosed, subclinical, or 'silent' AF. Atrial fibrillation-related cardiovascular mortality and morbidity, including cardiovascular deaths, heart failure, stroke, and hospitalizations, remain unacceptably high, even when evidence-based therapies such as anticoagulation and rate control are used. Furthermore, it is still necessary to define how best to prevent AF, largely due to a lack of clinical measures that would allow identification of treatable causes of AF in any given patient. Hence, there are important unmet clinical and research needs in the evaluation and management of AF patients. The ensuing needs and opportunities for improving the quality of AF care were discussed during the fifth Atrial Fibrillation Network/European Heart Rhythm Association consensus conference in Nice, France, on 22 and 23 January 2015. Here, we report the outcome of this conference, with a focus on (i) learning from our 'neighbours' to improve AF care, (ii) patient-centred approaches to AF management, (iii) structured care of AF patients, (iv) improving the quality of AF treatment, and (v) personalization of AF management. This report ends with a list of priorities for research in AF patients.

EuroEco (European Health Economic Trial on Home Monitoring in ICD Patients): a provider perspective in five European countries on costs and net financial impact of follow-up with or without remote monitoring.

AIM: Remote follow-up (FU) of implantable cardiac defibrillators (ICDs) allows for fewer in-office visits in combination with earlier detection of relevant findings. Its implementation requires investment and reorganization of care. Providers (physicians or hospitals) are unsure about the financial impact. The primary end-point of this randomized prospective multicentre health economic trial was the total FU-related cost for providers, comparing Home Monitoring facilitated FU (HM ON) to regular in-office FU (HM OFF) during the first 2 years after ICD implantation. Also the net financial impact on providers (taking national reimbursement into account) and costs from a healthcare payer perspective were evaluated. METHODS AND RESULTS: A total of 312 patients with VVI- or DDD-ICD implants from 17 centres in six EU countries were randomised to HM ON or OFF, of which 303 were eligible for data analysis. For all contacts (in-office, calendar- or alert-triggered web-based review, discussions, calls) time-expenditure was tracked. Country-specific cost parameters were used to convert resource use into monetary values. Remote FU equipment itself was not included in the cost calculations. Given only two patients from Finland (one in each group) a monetary valuation analysis was not performed for Finland. Average age was 62.4 ± 13.1 years, 81% were male, 39% received a DDD system, and 51% had a prophylactic ICD. Resource use with HM ON was clearly different: less FU visits (3.79 ± 1.67 vs. 5.53 ± 2.32; P < 0.001) despite a small increase of unscheduled visits (0.95 ± 1.50 vs. 0.62 ± 1.25; P < 0.005), more non-office-based contacts (1.95 ± 3.29 vs. 1.01 ± 2.64; P < 0.001), more Internet sessions (11.02 ± 15.28 vs. 0.06 ± 0.31; P < 0.001) and more in-clinic discussions (1.84 ± 4.20 vs. 1.28 ± 2.92; P < 0.03), but with numerically fewer hospitalizations (0.67 ± 1.18 vs. 0.85 ± 1.43, P = 0.23) and shorter length-of-stay (6.31 ± 15.5 vs. 8.26 ± 18.6; P = 0.27), although not significant. For the whole study population, the total FU cost for providers was not different for HM ON vs. OFF [mean (95% CI): €204 (169-238) vs. €213 (182-243); range for difference (€-36 to 54), NS]. From a payer perspective, FU-related costs were similar while the total cost per patient (including other physician visits, examinations, and hospitalizations) was numerically (but not significantly) lower. There was no difference in the net financial impact on providers [profit of €408 (327-489) vs. €400 (345-455); range for difference (€-104 to 88), NS], but there was heterogeneity among countries, with less profit for providers in the absence of specific remote FU reimbursement (Belgium, Spain, and the Netherlands) and maintained or increased profit in cases where such reimbursement exists (Germany and UK). Quality of life (SF-36) was not different. CONCLUSION: For all the patients as a whole, FU-related costs for providers are not different for remote FU vs. purely in-office FU, despite reorganized care. However, disparity in the impact on provider budget among different countries illustrates the need for proper reimbursement to ensure effective remote FU implementation.

Remodeling of cardiac passive electrical properties and susceptibility to ventricular and atrial arrhythmias.

Coordinated electrical activation of the heart is essential for the maintenance of a regular cardiac rhythm and effective contractions. Action potentials spread from one cell to the next via gap junction channels. Because of the elongated shape of cardiomyocytes, longitudinal resistivity is lower than transverse resistivity causing electrical anisotropy. Moreover, non-uniformity is created by clustering of gap junction channels at cell poles and by non-excitable structures such as collagenous strands, vessels or fibroblasts. Structural changes in cardiac disease often affect passive electrical properties by increasing non-uniformity and altering anisotropy. This disturbs normal electrical impulse propagation and is, consequently, a substrate for arrhythmia. However, to investigate how these structural changes lead to arrhythmias remains a challenge. One important mechanism, which may both cause and prevent arrhythmia, is the mismatch between current sources and sinks. Propagation of the electrical impulse requires a sufficient source of depolarizing current. In the case of a mismatch, the activated tissue (source) is not able to deliver enough depolarizing current to trigger an action potential in the non-activated tissue (sink). This eventually leads to conduction block. It has been suggested that in this situation a balanced geometrical distribution of gap junctions and reduced gap junction conductance may allow successful propagation. In contrast, source-sink mismatch can prevent spontaneous arrhythmogenic activity in a small number of cells from spreading over the ventricle, especially if gap junction conductance is enhanced. Beside gap junctions, cell geometry and non-cellular structures strongly modulate arrhythmogenic mechanisms. The present review elucidates these and other implications of passive electrical properties for cardiac rhythm and arrhythmogenesis.

Differences in clinical and echocardiographic parameters between paroxysmal and persistent atrial flutter in the AURUM 8 study: targets for prevention of persistent arrhythmia?

PURPOSE: Cavotricuspid isthmus-dependent atrial flutter (AFL) can occur in a paroxysmal or persistent pattern. The aim of this study was to identify clinical, echocardiographic, and electrophysiological risk factors independently associated with persistence of AFL. METHODS: Patients of the recently published AURUM 8 study with paroxysmal versus persistent AFL were compared with respect to clinical and echocardiographic baseline characteristics as well as procedural parameters. The AURUM 8 study is a randomized, multicenter clinical trial comparing the efficacy and safety of gold versus platinum-iridium 8-mm-tip ablation. AFL was paroxysmal in 218 patients and persistent in 210 patients. RESULTS: Univariate analysis revealed that patients with persistent AFL had higher New York Heart Association class (P = 0.002), shorter time since 1st AFL episode (median 0.18 vs 0.34, P = 0.037), a higher prevalence of previous coronary artery bypass grafting surgery (17% vs 9%, P = 0.02), left ventricular hypertrophy (17% vs 8%, P = 0.005), dyspnea during AFL (P < 0.001), mitral regurgitation (P = 0.002), tricuspid regurgitation (P = 0.049), and pulmonary hypertension (P = 0.01). Palpitations during AFL were less frequent in patients with persistent AFL (P = 0.001). Multivariate analysis revealed that age, weight, AFL diagnosis after initiation of class IC or III antiarrhythmic drugs for atrial fibrillation, history of left ventricular hypertrophy, dyspnea during AFL and mitral regurgitation on echocardiography were significant independent variables associated with persistent AFL. A history of atrial fibrillation and palpitations during AFL were independently associated with paroxysmal AFL. CONCLUSIONS: We were able to identify clinical and echocardiographic risk factors associated with persistence of typical AFL. Treatment of these risk factors can potentially not only prevent the transition from paroxysmal to persistent AFL, but maybe also the development or initiation of AFL in general.

Gold vs. platinum-iridium tip catheter for cavotricuspid isthmus ablation: the AURUM 8 study.

AIMS: Gold electrodes have the theoretical advantage of creating bigger lesions than platinum-iridium (Pt-Ir) electrodes. We performed a prospective randomized study to compare the clinical efficacy of standard 8 mm Pt-Ir tip catheter (control) and 8 mm gold-tip catheters in the ablation of the cavotricuspid isthmus (CTI)-dependent atrial flutter. METHODS AND RESULTS: A total of 463 patients undergoing CTI ablation in 19 clinical centres were randomized to receive the treatment by gold-tip or control catheter. The primary endpoint was cumulative radiofrequency (RF) application duration until achieving bidirectional CTI block. It did not differ significantly for the two catheters. The gold-tip catheter was, however, associated with a higher ablation success rate (94.3 vs. 89.0%, P = 0.042) and a substantially lower incidence of char and coagulum formation (4.8 vs. 37.9%, P < 0.001), which required exchange of 1 gold-tip (0.4%) and 10 control catheters (4.6%, P = 0.005). The gold-tip catheter delivered more mean power (52 ± 12 W) than the control catheter (48 ± 13 W, P < 0.001). Both mean and maximum temperatures measured by the thermocouple integrated in the catheter tip were statistically significantly lower in the gold (mean: 53.2 ± 4.7°C, max: 68.7 ± 6.6°C) than in the control catheter (54.3 ± 5.2 and 70.2 ± 7.0°C, respectively, P < 0.05). Fluoroscopy time, procedure duration, procedural-related complications, and arrhythmia recurrence during 6 months of follow-up did not differ between the two catheters. CONCLUSION: Owing to a higher primary ablation success rate and reduced incidence of char/coagulum formation, gold may be preferred over Pt-Ir as electrode material for 8 mm tip catheters for CTI ablation. ClinicalTrials.gov: NCT00326001 (http://clinicaltrials.gov/ct2/show/NCT00326001).

Two completely separated arrhythmias in one single heart chamber.

A 61-year-old male patient underwent an electrophysiological study and ablation for symptomatic atypical atrial flutter which was most likely related to previous intraoperative cryoablation for treatment of paroxysmal atrial fibrillation during open heart surgery. During the procedure, a tachycardia was induced in the electrically isolated left inferior pulmonary vein (PV). With the routine induction protocol, perimitral flutter was induced, whereas, independently, the PV tachycardia was still maintained. After ablation of the mitral isthmus, no tachycardias were inducible anymore.

Adverse effects of Wolff-Parkinson-White syndrome with right septal or posteroseptal accessory pathways on cardiac function.

AIMS: Wolff-Parkinson-White syndrome with right septal or posteroseptal accessory pathways causes eccentric septal mechanical activation and may provoke left ventricular (LV) dyssynchrony and dysfunction. The aim of the study was to evaluate the effect of radiofrequency catheter ablation (RFA) of the accessory pathways on LV function. METHODS AND RESULTS: Retrospectively, transthoracic echocardiography and electrocardiogram recordings were analysed in 34 patients (age: 14.2 +/- 2.5 years) with right septal or posteroseptal accessory pathways prior and after (median: 1 day) successful RFA. Results prior to RFA, LV ejection fraction was decreased (<55%) in 19/34 patients (56%). After RFA, QRS duration was normalized (129 +/- 23 vs. 90 +/- 11, P < 0.0001), LV function improved (ejection fraction: 50 +/- 10 vs. 56 +/- 4%, P = 0.0005) and septal-to-posterior wall motion delay as a global measure for LV dyssynchrony decreased (110 +/- 94 vs. 66 +/- 53, P = 0.012). Longitudinal two-dimensional strain evaluated in five patients demonstrated a decrease of left intraventricular mechanical delay from 292 +/- 125 to 118 +/- 37 ms after RFA. CONCLUSION: Wolff-Parkinson-White syndrome with right septal or posteroseptal accessory pathways may cause LV dyssynchrony and jeopardize global LV function. Radiofrequency catheter ablation resulted in normalized QRS duration, mechanical resynchronization, and improved LV function. Even in the absence of arrhythmias, RFA of right septal or posteroseptal pathways may be considered in patients with significantly decreased LV function.

The quick-implantable-defibrillator trial.

AIMS: Earlier ICD therapy included an electrophysiological study (EPS), an extensive defibrillation threshold test (DFT), and a pre-discharge test. Now that ICD-therapy is widely accepted, an EPS is no longer performed in most patients, extensive DFT-tests have been reduced to a minimum of two effective shocks and discharge tests have been discarded in most centres. However, it has never been demonstrated prospectively that this simplification is safe. METHODS AND RESULTS: The Quick-Implantable-Defibrillator (Quick-ICD) Trial was a prospective multi-centre trial, which randomized patients, who had survived a cardiac arrest (SCD) or an unstable ventricular tachycardia (VT), to two different clinical strategies: (a) The extensive strategy included an EPS, an extensive DFT-test, and a pre-discharge test; (b) In the simplified approach (quick strategy) the ICD was implanted without an EPS and a pre-discharge test. Two effective shocks during implantation at 21 J were sufficient. The primary endpoint of this trial was a cluster of adverse events related to the diagnostic approach and to ICD-therapy. One hundred and ninety patients were included, 97 randomized to the extensive-, 93 to the quick strategy. Mean follow-up was 12 +/- 7 months. Twenty-seven patients reached the endpoint in the quick group and 32 in the extensive group. During follow-up, the event-free survival was equal in the two study arms (test for equivalence, P = 0.0044). The initial hospital stay was significantly shorter in the quick population (8.4 +/- 4.7 vs. 11.2 +/- 7.4 days, P = 0.004) CONCLUSION: It is safe and cost-effective to implant an ICD without an EPS, an extensive DFT-, and a pre-discharge test in carefully selected patients after survived SCD or unstable VTs.

Outcome parameters for trials in atrial fibrillation: executive summary.

Atrial fibrillation (AF), the most common atrial arrhythmia, has a complex aetiology and causes relevant morbidity and mortality due to different mechanisms, including but not limited to stroke, heart failure, and tachy- or bradyarrhythmia. Current therapeutic options (rate control, rhythm control, antithrombotic therapy, 'upstream therapy') only prevent a part of this burden of disease. Several new treatment modalities are therefore under evaluation in controlled trials. Given the multifold clinical consequences of AF, trials in AF patients should assess the effect of therapy in each of the main outcome domains. This paper describes an expert consensus of required outcome parameters in seven relevant outcome domains, namely death, stroke, symptoms and quality of life, rhythm, left ventricular function, cost, and emerging outcome parameters. In addition to these 'requirements' for outcome assessment in AF trials, further, more detailed outcome parameters are described. In addition to a careful selection of a relevant primary outcome parameter, coverage of outcomes in all major domains of AF-related morbidity and mortality is desirable for any clinical trial in AF.

Outcome parameters for trials in atrial fibrillation: recommendations from a consensus conference organized by the German Atrial Fibrillation Competence NETwork and the European Heart Rhythm Association.

Atrial fibrillation (AF), the most common atrial arrhythmia, has a complex aetiology and causes relevant morbidity and mortality due to different mechanisms, including but not limited to stroke, heart failure, and tachy- or bradyarrhythmia. Current therapeutic options (rate control, rhythm control, antithrombotic therapy, 'upstream therapy') only prevent a part of this burden of disease. New treatment modalities are therefore currently under evaluation in clinical trials. Given the multifold clinical consequences of AF, controlled trials in AF patients should assess the effect of therapy in each of the main outcome domains. This paper describes an expert consensus of required outcome parameters in seven relevant outcome domains, namely death, stroke, symptoms and quality of life, rhythm, left ventricular function, cost, and emerging outcome parameters. In addition to these 'requirements' for outcome assessment in AF trials, further outcome parameters are described in each outcome domain. In addition to a careful selection of a relevant primary outcome parameter, coverage of outcomes in all major domains of AF-related morbidity and mortality is desirable for any clinical trial in AF.

Restitution of sinus rhythm plus stentless mitral valve replacement at three years.

BACKGROUND AND AIM OF THE STUDY: The study aim was to examine results after stentless mitral valve (SMV) replacement (Quattro) and restitution of physiological cardiac rhythm by intraoperative left atrial ablation therapy. METHODS: Twenty patients (13 females; mean age 69.7 +/- 5.9 years) with severe degenerative mitral valve disease (six with valve stenosis, six with valve incompetence, eight with combined lesion) were prospectively evaluated since 1998. The mean NYHA functional class was 3.2 +/- 0.4, and cardiac index 1.8 +/- 0.5 l/min/m2. Ablation therapy was performed by inducing left atrial linear lesion lines to avoid reentrant circuits. RESULTS: Surgery was performed using conventional sternotomy (n = 10) or lateral minithoractomy (n = 10). Sinus rhythm was successfully restituted in 17 patients either postoperatively or in the long term (success rate 85%). However, three patients required DDD-pacemaker implantation, and another three had to be discharged with persistent atrial fibrillation. Intermittent medical therapy (sotalol or amiodarone) was required in nine patients postoperatively, in four patients at six months, and in two patients at one-year follow up. One patient was reoperated on for paravalvular leak after one year, but subsequently died due to sepsis. In the other patients, echocardiographic control proved good SMV function with atrial contraction. CONCLUSION: Restitution of physiological cardiac function is possible by combined stentless MV implantation and left atrial ablation therapy. A persistent benefit, without need for additional re-intervention, was shown at mid-term follow up.

Esophageal perforation during left atrial radiofrequency ablation: Is the risk too high?

OBJECTIVE: Intraoperative radiofrequency ablation of atrial fibrillation (IRAAF) is a recently developed procedure being performed in an increasing number of patients. We have performed left atrial IRAAF in 387 patients since August 1998. The purpose of this article is to describe a serious complication of this procedure, namely IRAAF-induced esophageal perforation, in detail to identify possible risk factors. METHODS: Left atrial IRAAF was performed with a commercially available unipolar probe as an isolated procedure (n = 129) or in combination with mitral valve surgery (n = 163) or other surgical procedures (n = 95). Operations were performed either through a conventional sternotomy or right minithoracotomy. RESULTS: Four (1%) patients had esophageal perforation after radiofrequency ablation. All 4 patients presented after an initially unremarkable postoperative course, with sudden neurologic symptoms from esophagoatrial air embolization occurring in 3 of the patients. Three patients were successfully treated with extensive esophageal resection, and one died from massive air embolism. All perforations occurred in patients undergoing minimally invasive IRAAF. Comparison with other patients undergoing isolated minimally invasive IRAAF (n = 129) failed to reveal any reliable predictors of esophageal injury, including patient body size, operating times, or radiofrequency biophysical parameters. CONCLUSIONS: Left atrial IRAAF is associated with a small but definite risk of esophageal perforation. Unfortunately, we were unable to identify any risk factors for this life-threatening complication. A high degree of vigilance must be maintained for esophageal injury after IRAAF, particularly in patients with new neurologic deficits. Until safer methods of ablation are developed, we currently recommend against the use of IRAAF in patients undergoing cardiac surgery.

Curative treatment of atrial fibrillation with intraoperative radiofrequency ablation: short-term and midterm results.

OBJECTIVE: This report describes the early and midterm results after intraoperative radiofrequency ablation of atrial fibrillation for patients with isolated chronic atrial fibrillation or atrial fibrillation in combination with additional valvular and nonvalvular cardiac diseases. METHODS: From August 1998 to March 2001, a total of 234 patients with chronic atrial fibrillation underwent isolated intraoperative radiofrequency ablation alone (n = 74, 31.6%) or in combination with other cardiac procedures, such as mitral valve reconstruction (n = 57, 24.4%), mitral valve replacement (n = 38, 16.2%), aortic valve replacement (n = 11, 5.1%), coronary artery bypass grafting (n = 8, 5.0%), or a combination of the last with other cardiac procedures (n = 46, 19.7%). In all cases anatomic reentrant circuits confined within the left atrium were eliminated by placing contiguous lesion lines involving the mitral anulus and the orifices of the pulmonary veins through the use of radiofrequency energy application (exposure time, 20 seconds). A median sternotomy was used in 101 cases (43.2%), and video assistance through a right lateral minithoracotomy was used in 133 cases (56.8%). RESULTS: A total of 188 patients (83.9%) were discharged in sinus rhythm, 17 patients (7.6%) had atrial fibrillation, and 19 patients (8.5%) had atypical flutter. Pacemakers were implanted in 23 patients (9.8%). There were 10 in-hospital deaths (4.2%), and 30-day mortality was 5 patients (2.1%). In 3 cases (1.3%) an atrioesophageal fistula developed, necessitating surgical repair. Six months' follow-up was complete for 122 (61.0%) of 200 patients, with 99 patients still in stable sinus rhythm (81.1%, 95% confidence interval 73.1%-89.9%). Twelve months' follow-up was complete for 80 (90.9%) of 88 patients, with 58 patients still in sinus rhythm (72.5%, 95% confidence interval 61.3%-83.2%). CONCLUSIONS: Intraoperative radiofrequency ablation is a curative procedure for chronic atrial fibrillation. It is technically less challenging than the maze procedure and can be applied through a minimally invasive approach. Protection of the esophagus seems mandatory to avoid the deleterious complication of a left atrioesophageal fistula, such as was observed in 3 cases.