Jonathan R. Clague

Clinical experience of entirely subcutaneous implantable cardioverter–defibrillators in children and adults: cause for caution

AIMS This paper describes our clinical experience of using an entirely subcutaneous implantable cardioverter-defibrillator (S-ICD) in children and adults. Maintaining lead integrity and long-term vascular access are critical challenges of ICD therapy, especially in younger patients. The S-ICD has considerable theoretical advantages in selected patients without pacing indications, particularly children and young adults. Although sensing in an S-ICD may be influenced by age, pathology, and posture, there are currently few published data on clinical sensing performance outside the setting of intra-operative testing or in younger patients. METHODS AND RESULTS Patients were selected by a multi-disciplinary team on clinical grounds for S-ICD implantation from a broad population at risk of sudden arrhythmic death. Sixteen patients underwent implantation [median age 20 years (range 10-48 years)]. Twelve had primary electrical disease and four had congenital structural heart disease. There were no operative complications, and ventricular fibrillation (VF) induction testing was successful in all cases. During median follow-up of 9 months (range 3-15 months), three children required re-operation. Eighteen clinical shocks were delivered in six patients. Ten shocks in four patients were inappropriate due to T-wave over-sensing. Within the eight shocks for ventricular arrhythmia, three were delivered for VF, among which two had delays in detection with time to therapy of 24 and 27 s. CONCLUSION The S-ICD is an important new option for some patients. However, these data give cause for caution in light of the limited published data regarding clinical sensing capabilities, particularly among younger patients.

Paced ventricular electrogram fractionation predicts sudden cardiac death in hypertrophic cardiomyopathy.

AIMS Paced electrogram fractionation analysis (PEFA) has been assessed for the prediction of sudden cardiac death (SCD) in a large-scale, prospective study of patients with hypertrophic cardiomyopathy (HCM). METHODS AND RESULTS We determined the positive predictive value (PPV) of PEFA in relation to other risk factors for SCD and outcomes in 179 patients with HCM and no prior history of cardiac arrest. Patients were followed over a mean 4.3 years (range: 1.1-6.3 years). Thirteen patients had SCD-equivalent events: four of these patients died suddenly, three were resuscitated from ventricular fibrillation (VF), and six had implantable cardioverter-defibrillator (ICD) discharges in response to VF. PEFA identified nine of these patients and another 14 non-VF patients yielding a censored PPV of between 0.19 and 0.59 that was greater than the PPV that was the formal stopping point of the trial (0.18). Eighty per cent of patients were followed for 4 years or more. The PPV for the identification of SCD in this group was 0.38 (0.17-0.59). The use of two or more conventional markers to predict SCD identified five patients with SCD-equivalent events in the 4-year follow-up group and 42 other patients without events yielding a PPV of 0.106 (confidence limits 0.02-0.15). CONCLUSION PEFA identifies HCM patients at risk of SCD with greater accuracy than non-invasive techniques and may have an important role in determining indications for ICD prescription.

Outcomes of defibrillator therapy in catecholaminergic polymorphic ventricular tachycardia

BACKGROUND Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmia syndrome characterized by adrenergically induced ventricular arrhythmias in patients with structurally normal hearts. Initiating triggered arrhythmias, such as bidirectional ventricular tachycardia, often degenerate into reentrant arrhythmias, such as ventricular fibrillation (VF). OBJECTIVE To determine whether the effectiveness of implantable cardioverter-defibrillator (ICD) shocks is dependent on rhythm type. METHODS It is a retrospective study of patients with CPVT who had undergone ICD implantation. Thirteen patients received ICDs (median age 15 years; range 9-43 years): 7 of 13 (54%) for cardiac arrest and 6 of 13 (46%) for syncope despite drug therapy. The median follow-up duration was 4.0 years (range 1.7-19.9 years). Nineteen reinterventions occurred, excluding generator replacements. Ten patients received 96 shocks (median 4 shocks; range 1-30 shocks). Eighty-seven shock electrograms were reviewed. Sixty-three (72%) shocks were appropriate, and 24 (28%) were inappropriate (T-wave oversensing 7 [29%], supraventricular arrhythmia 16 [67%], after self-terminating VF 1 [4%]). RESULTS Among appropriate shocks, 20 (32%) were effective in terminating sustained arrhythmia and 43 (68%) were ineffective. Shocks delivered to triggered arrhythmias nearly always failed (1 of 40 [3%] effective), while shocks delivered to VF were usually successful (19 of 23 [83%] effective; P < .001). Four patients received 17 appropriate antitachycardia pacing therapies for ventricular tachycardia: only 2 (12%) were effective. No patient died. CONCLUSIONS The effectiveness of ICD shock therapy in CPVT depends on the mechanism of the rhythm treated. Shocks delivered to initiating triggered arrhythmias nearly always fail, whereas those for subsequent VF are usually effective. ICD programming in these patients is exceptionally challenging.

Femoral haemostasis after transcatheter therapeutic intervention: a prospective randomised study of the angio-seal device vs. the femostop device

BACKGROUND A number of haemostatic devices are available to facilitate early haemostasis following transfemoral interventional procedures. METHODS AND RESULTS We have prospectively compared 150 patients (age: 57+/-12 years, mean+/-S.D.) who were randomly assigned to either external compression using the FemoStop device or direct closure of the arterial puncture using the Angio-Seal device. The Angio-Seal was deployed in the catheter laboratory after the conclusion of the procedure. Patients, randomised to FemoStop, had their sheath removed when the activated clotting time (ACT) was less than 100 s before applying the device. The primary endpoint was the composite of bleeding, haematoma formation, bruise, requirement for blood transfusion, clinical indication for ultrasound examination at 2 h and 24 h following the procedure and crossover to either method at 2 and 24 h after the device deployment. The 95% of the Angio-Seal and 96% of FemoStop patients were discharged on the day following the procedure. An increased number of patients in the Angio-Seal group reached a clinical end-point within the first 2 h (45% vs. 3%, P<0.0001). This difference became insignificant at 24 h (25% vs. 30%, P=0.6). CONCLUSION Although less comfortable, the overall efficacy of the FemoStop appeared to be higher than that of the Angio-Seal device.

Outcomes and costs of left atrial appendage closure from randomized controlled trial and real-world experience relative to oral anticoagulation

AIMS The aim of this study was to analyse randomized controlled study and real-world outcomes of patients with non-valvular atrial fibrillation (NVAF) undergoing left atrial appendage closure (LAAC) with the Watchman device and to compare costs with available antithrombotic therapies. METHODS AND RESULTS Registry data of LAAC from two centres were prospectively collected from 110 patients with NVAF at risk of stroke, suitable and unsuitable for long-term anticoagulation (age 71.3 ± 9.2 years, CHADS2 2.8 ± 1.2, CHA2DS2-VASc 4.5 ± 1.6, and HAS-BLED 3.8 ± 1.1). Outcomes from PROTECT AF and registry study LAAC were compared with warfarin, dabigatran, rivaroxaban, apixaban, aspirin, and no treatment using a network meta-analysis. Costs were estimated over a 10-year horizon. Uncertainty was assessed using sensitivity analyses. The procedural success rate was 92% (103/112). Follow-up was 24.1 ± 4.6 months, during which annual rates of stroke, major bleeding, and all-cause mortality were 0.9% (2/223 patient-years), 0.9% (2/223 patient-years), and 1.8% (4/223 patient-years), respectively. Anticoagulant therapy was successfully stopped in 91.2% (93/102) of implanted patients by 12 months. Registry study LAAC stroke and major bleeding rates were significantly lower than PROTECT AF results: mean absolute difference of stroke, 0.89% (P = 0.02) and major bleeding, 5.48% (P < 0.001). Left atrial appendage closure achieved cost parity between 4.9 years vs. dabigatran 110 mg and 8.4 years vs. warfarin. At 10 years, LAAC was cost-saving against all therapies (range £1162-£7194). CONCLUSION Left atrial appendage closure in NVAF in a real-world setting may result in lower stroke and major bleeding rates than reported in LAAC clinical trials. Left atrial appendage closure in both settings achieves cost parity in a relatively short period of time and may offer substantial savings compared with current therapies. Savings are most pronounced among higher risk patients and those unsuitable for anticoagulation.

Instantaneous effects of resynchronisation therapy on exercise performance in heart failure patients: the mechanistic role and predictive power of total isovolumic time

Background: Cardiac resynchronisation therapy improves peak oxygen uptake (peak VO2) 3–9 months after device implantation. In chronic heart failure, total isovolumic time (t-IVT) is a major determinant of peak VO2 and of cardiac output at peak dobutamine stress. In selected patients, resynchronisation can instantaneously shorten t-IVT. We sought to determine the acute effect of resynchronisation on exercise performance and determine, with pharmacological stress echocardiography, the mechanism underlying this effect. Methods and results: Twenty-two patients with resynchronisation were studied within 3 months after device implantation. On a single study day, sequential cardiopulmonary exercise tests were performed during native activation (left bundle branch block) and resynchronisation (atrio-biventricular pacing) in random order. Total-IVT and cardiac output (at rest and peak dobutamine stress) were then measured in each activation mode. Resynchronisation acutely increased peak VO2 by 1.6 (SD 1.5) ml/kg/min (p<0.001) and shortened peak stress t-IVT by 10 (SD 7) s/min (p<0.001), with the effects in individual patients showing a correlation (r = –0.46, p<0.05). Amongst all measurements during native activation, the best predictor of gain in peak VO2 from resynchronisation was peak stress t-IVT (r = 0.71, p<0.001) with every increment of 5 s/min of peak stress t-IVT during native activation predicting an 8% gain in peak VO2. No conventional measures during native activation at rest or on stress (including QRS duration, Tei index, tissue Doppler intraventricular delay, and resting t-IVT) added significant additional information. Conclusions: In eligible patients, resynchronisation can acutely augment peak VO2, possibly through a mechanism of t-IVT shortening. Under native activation, long t-IVT during peak stress is the single best predictor of acute resynchronisation-mediated increment in peak VO2.

C-type natriuretic peptide production by the human kidney is blunted in chronic heart failure

CNP (C-type natriuretic peptide) is a vasodilatory peptide produced by vascular endothelium and the human heart with a short half-life. CNP has been identified within the human kidney; however, few results are available on whether the human kidney is a systemic source of CNP. The aim of the present study was to establish whether CNP is secreted by the human kidney and if synthesis is blunted in CHF (chronic heart failure). A total of 20 male subjects (age, 57+/-2 years; mean+/-S.E.M.) undergoing CHF assessment (n=13) or investigation of paroxysmal supraventricular arrhythmia (normal left ventricular function in sinus rhythm during procedure) (n=7) were recruited. Renal CNP production was determined from concomitant plasma concentrations in the aorta and renal vein. When considering all subjects, a significant step-up in plasma CNP was found from the aorta to renal vein (3.0+/-0.3 compared with 8.3+/-2.4 pg/ml respectively; P=0.0045). The mean increase in CNP was 5.3+/-2.4 pg/ml (range, -0.9 to +45.3 pg/ml). In patients with CHF, the aortic concentration was 3.3+/-0.4 pg/ml compared with a renal vein concentration of 4.3+/-0.6 pg/ml (P=0.11). In those with normal left ventricular function, the respective values were 2.5+/-0.5 and 15.7+/-6.0 pg/ml (P=0.01). In conclusion, CNP is synthesized and secreted into the circulation by the normal human kidney, where it may have paracrine actions. Net renal secretion of CNP appears to be blunted in patients with CHF.

Non-elective intra-coronary stenting: are the clinical outcomes comparable to elective stenting at 6 months?

The aim of this study was to compare prospectively the clinical outcome of patients treated with intra-coronary stents as a non-elective/bailout procedure for acute or threatened vessel closure, with those undergoing elective stenting at 6 months. Sixty-four patients (60.2+/-11.7 y) who underwent non-elective stenting for abrupt or threatened vessel closure and/or sub-optimal results were prospectively compared with 68 patients (62+/-10.0 y) who were stented electively. All patients had broadly similar pre-procedural clinical profiles. However, patients in the elective group had a higher incidence of previous PTCA (10.2% vs. 0%, P = 0.01) and bypass surgery (30.9% vs. 6.3%, P = 0.0003) compared with the non-elective group. A total of 158 stents (1.19 per patient) were implanted in 132 patients with a procedural success rate of 99.3%. At 6 months follow-up there was no statistical difference in the primary composite end-point of death, myocardial infarction and the need of repeat revascularisation (10.9% vs. 5.8%, P = 0.35) between the two groups. However, patients in the non-elective group showed a higher incidence of unstable angina compared with the elective group (25% vs. 1.4%, P = 0.0004). The findings of this study suggest that stents (single or multiple) can be effectively implanted in non-elective situations with no increase in the incidence of death, non-fatal myocardial infarction, and the need of repeat revascularisation at 6 months compared with elective stenting.

Pacing in congenital heart disease – A four-decade experience in a single tertiary centre

BACKGROUND The increased risk of brady- and tachy-arrhythmias in the congenital heart disease (CHD) population means that cardiac rhythm management devices are often required at an early age and expose patients to device-related complications. The present study drew upon four decades of experience at a tertiary adult congenital heart disease ACHD center and aimed to investigate the indication for cardiac implantable electronic devices (CIEDs) and predictors of late device-related complication requiring re-intervention. METHODS A retrospective review of pacing records of ACHD patients over forty years was carried out. The primary outcome measure was device related complication requiring re-intervention. RESULTS Between 1970 and 2009, 238 structural CHD patients who received CIEDs with follow-up data were identified (structural group). As a comparator group, 98 patients with congenital conduction disease or long QT syndrome with a structurally normal heart (electrical group) were included in the study. During a mean follow-up of 9.6±8.5years, 72 (21%) patients (44 structural group, 28 electrical group) required ≥1 re-intervention due to device related complications. Multivariate analysis showed that age at the time of device implant was an independent predictor of late device-related complications (HR 0.77, 95% CI 0.60-0.98, p=0.04). Sub-analysis of the structural group showed that ACHD complexity (Bethesda guideline) was the only predictor late device-related complication in the structural group (HR 2.96, 95% CI: 1.67-5.26, p<0.01). CONCLUSION Increasing age at device implant was inversely associated with late device-related complications. ACHD patients with complex anatomy are at increased risk of device-related complications at mid and long-term follow-up.