Guideline-Directed Medical Therapy Before and After Primary Prevention Implantable Cardioverter Defibrillator Implantation in New Zealand (ANZACS-QI 66).

INTRODUCTION: Guidelines recommend angiotensin converting enzyme inhibitors (ACEi)/angiotensin receptor blockers (ARB)/angiotensin receptor neprilysin inhibitors (ARNI); beta blockers; and mineralocorticoid receptor antagonists (MRA) in patients with symptomatic heart failure and reduced left ventricular ejection fraction before consideration of primary prevention implantable cardioverter defibrillator (ICD). This study aims to investigate dispensing rates of guideline-directed medical therapy (GDMT) before and after primary prevention ICD implantation in New Zealand. METHODS: All patients receiving a primary prevention ICD between 2009 and 2018 were identified using nationally collected data on all public hospital admissions in New Zealand. This was anonymously linked to national pharmaceutical data to obtain medication dispensing. Medications were categorised as low dose (<50% of target dose), 50-99% of target dose or target dose based on international guidelines. RESULTS: Of the 1,698 patients identified, ACEi/ARB/ARNI, beta blockers and MRA were dispensed in 80.2%, 83.6% and 45.4%, respectively, prior to ICD implant. However, ≥50% target doses of each medication class were dispensed in only 51.8%, 51.8% and 34.5%, respectively. Only 15.8% of patients were receiving ≥50% target doses of all three classes of medications. In the 1,666 patients who survived 1 year after ICD implant, the proportions of patients dispensed each class of medications remained largely unchanged. CONCLUSION: Dispensing of GDMT was suboptimal in patients before and after primary prevention ICD implantation in New Zealand, and only a minority received ≥50% target doses of all classes of medication. Interventions are needed to optimise use of these standard evidence-based medications to improve clinical outcomes and avoid unnecessary device implantation.

Search for Low-Mass Axion Dark Matter with ABRACADABRA-10 cm.

Two of the most pressing questions in physics are the microscopic nature of the dark matter that comprises 84% of the mass in the Universe and the absence of a neutron electric dipole moment. These questions would be resolved by the existence of a hypothetical particle known as the quantum chromodynamics (QCD) axion. In this work, we probe the hypothesis that axions constitute dark matter, using the ABRACADABRA-10 cm experiment in a broadband configuration, with world-leading sensitivity. We find no significant evidence for axions, and we present 95% upper limits on the axion-photon coupling down to the world-leading level g_{aγγ}<3.2×10^{-11} GeV^{-1}, representing one of the most sensitive searches for axions in the 0.41-8.27 neV mass range. Our work paves a direct path for future experiments capable of confirming or excluding the hypothesis that dark matter is a QCD axion in the mass range motivated by string theory and grand unified theories.

Impact of cardiac resynchronisation therapy on burden of hospitalisations and survival: a retrospective observational study in the Northern Region of New Zealand.

OBJECTIVE: Cardiac resynchronisation therapy (CRT) devices have been shown to improve heart failure (HF) symptoms, survival and improve quality of life (QoL). We evaluated the overall impact of CRT on recurrent hospitalisations and survival in real-world patients with HF. DESIGN: Retrospective observational study. SETTING: Northern region of New Zealand. PARTICIPANTS: Patients with HF who underwent CRT device implantation in between 2008 and 2014 were followed up for 1 year. INTERVENTIONS: CRT. PRIMARY AND SECONDARY OUTCOMES MEASURED: Survival, all-cause hospitalisations, length of stay, from which days alive and out of hospital (DAOH) were calculated. RESULTS: 177patients were included, of whom eight died (4.5%) within 1 year of follow-up. Pre-CRT implantation, 83% of all patients had been hospitalised for a total 248 hospitalisation events. Following CRT, 47 patients (27%) were readmitted to hospital within 1 year (total of 98 admissions; p<0.01 compared with pre-device implant). Length of hospital stay was significantly shorter than in the year prior to CRT implantation at a median of 4 (IQR 2-6) vs 7 (IQR 3.5-10.5) days (p=0.03). An increase in the median number of DAOH was observed from 362 (IQR 355-364) to 365 (IQR 364-365) (p<0.01) after CRT implant. The improvement in DAOH was seen regardless of gender and type of CRT devices. Greater DAOH was also seen in those with non-ischaemic cardiomyopathy and Caucasians. CONCLUSION: After CRT implant, patients with HF have greater DAOH with reduction of total hospitalisation and fewer hospital days. These results support CRT devices use as a treatment option for appropriate HF patients. DAOH represents an easily measured, patient-centred endpoint that may reflect effectiveness of interventions in future CRT studies.

Outcomes of patients with heart failure after primary prevention ICD unit generator replacement.

OBJECTIVE: Data describing outcomes after implantable cardioverter-defibrillator (ICD) unit generator replacement in patients with heart failure (HF) with primary prevention devices are limited. METHOD: Data on patients with HF who underwent primary prevention ICD/cardiac resynchronisation therapy-defibrillator (CRT-D) implantation from 2007 until mid-2015 who subsequently received unit generator replacement were analysed. Outcomes assessed were mortality, appropriate ICD therapy and shock, and procedural complications. RESULTS: 61 of 385 patients with HF with primary prevention ICD/CRT-D undergoing unit generator replacement were identified. Follow-up period was 1.8±1.5 years after replacement. 43 (70.5%) patients had not received prior appropriate ICD therapy prior to unit replacement. The cumulative risks of appropriate ICD therapy at 1, 3 and 5 years after unit replacement in those without prior ICD therapy were 0%, 6.2% and 50% compared with 6.2%, 59.8% and 86.6%, respectively (p=0.005) in those with prior ICD therapies. No predictive factors associated with appropriate ICD therapy after replacement could be identified. 41 (32.8%) patients no longer met guideline indications at the time of unit replacement but risks of subsequent appropriate ICD interventions were not different compared with those who continued to meet primary prevention ICD indications.The 5-year mortality risk after unit replacement was 18.4% and there were high procedural complication rates (9.8%). CONCLUSION: No predictive marker successfully stratified patients no longer needing ICD support prospectively. Finding such a marker is important in decision-making about device replacement particularly given the concerns about the complication rates. These factors should be considered at the time of ICD unit replacement.

Utilization of cardiac resynchronization therapy in patients with heart failure in the Northern Region of New Zealand.

BACKGROUND: Cardiac resynchronization therapy (CRT) has been shown to improve morbidity and mortality for heart failure (HF) patients. Little is known about the trends in CRT use and outcomes of these patients in New Zealand. METHOD: Mortality, hospitalization events and complications in HF patients in the Northern Region of New Zealand implanted with CRT devices from Jan-2007 to June-2015 were reviewed. RESULTS: Two-hundred patients underwent CRT implantation during the study period. There was a gradual increase in CRT-D implantation (n = 157) but the number remained static for CRT-P (n = 43). Patients who received CRT-P were older (mean age 65.9 ± 14.0 years vs 61.5 ± 10.2 years, P < 0.0007) but had a higher left ventricular ejection fraction (LVEF) (33.7 ± 10.5% vs 24.7 ± 6.1%, P < 0.0001) than those undergoing CRT-D implant procedures. During a median follow-up of 4 (2.8) years, 29 (14.5%) patients (14.7% in CRT-D vs 13.9% in CRT-P, P = 0.91) had died. HF was the cause of death in 73.9% of the patients. There was no difference in all-cause mortality between patients with CRT-D and CRT-P. CONCLUSIONS: Despite the proven benefits of CRT in selected HF patients, there continued to be under-utilization of these devices in HF patients in the Northern Region. Reasons for under-utilization of these devices need further exploration. These data should be useful for benchmarking individual patient management and national practice against wider experience in the country.

Long-term outcomes of heart failure patients who received primary prevention implantable cardioverter-defibrillator: An observational study.

BACKGROUND: Implantable cardioverter-defibrillator (ICD) therapy is indicated for selected heart failure patients for the primary prevention of sudden cardiac death. Little is known about the outcomes in patients selected for primary prevention device therapy in the northern region of New Zealand. METHOD: Heart failure patients with systolic dysfunction who underwent primary prevention ICD/cardiac resynchronization therapy-defibrillator (CRT-D) implantation between January 1, 2007, and June 1, 2015, were included. Complications, mortality, and hospitalization events were reviewed. RESULTS: Three hundred and eighty-five primary prevention devices were implanted (269 ICD, 116 CRT-D). Mean age at implant was 59.1 ± 11.4 years. Mean duration of follow-up was 3.64 ± 2.17 years. The commonest cause of death was heart failure (41.8%). Only 2 patients died from sudden arrhythmic death. The 5-year heart failure mortality rate was 6%, whereas the 5-year sudden arrhythmic death rate was 0.3%. Heart failure hospitalizations were commoner in those who received ICD than CRT-D (67.7% vs 25.8%, P < .001). Maori patients have low implant rates (14%) with relatively high rates of admissions with heart failure and ventricular arrhythmia admissions. CONCLUSIONS: Even in appropriately selected heart failure patients who received primary prevention devices, only a small percentage died as a result of sudden arrhythmic death. CRT-D should be the device of choice where appropriate in heart failure patients. Significant challenges remain to improve access to device therapy and maximize benefit to those who do get implanted.

Gender differences in the use of primary prevention ICDs in New Zealand patients with heart failure.

OBJECTIVE: Women have been under-represented in randomised clinical trials for primary prevention implantable cardioverter defibrillators (ICDs), and there are concerns about the efficacy of devices between genders. Our study aimed to investigate gender differences in the use of primary prevention ICD in patients with heart failure from the northern region of New Zealand. METHODS: Patients with heart failure with systolic dysfunction who received primary prevention ICD/cardiac resynchronisation therapy-defibrillator (CRT-D) in the northern region of New Zealand from 1 January 2007 to 1 June 2015 were included. Complications, mortality and hospitalisation events were reviewed. RESULTS: Of the 385 patients with heart failure implanted with ICD/CRT-D, women comprised 15.1% (n=58), and no change in utilisation of these devices was observed over the study period among women. Women were more likely to have non-ischaemic cardiomyopathy and have higher perioperative complications (8.6% vs 2.5%, P=0.02), with non-significant higher trend towards increased lead displacement (5.2% vs 1.8%, P=0.12). Women appeared to have lower all-cause (10.3% vs 18.7%, P=0.12), cardiovascular (5.2% vs 11.9%, P=0.13) and heart failure (3.5% vs 7.9%, P=0.22) mortalities but was not statistically significant. There were no gender differences in all-cause (70.7% vs 67%, P=0.58) or heart failure (19% vs 25%, P=0.32) readmissions. CONCLUSION: Perioperative complications were significantly more common in women referred for ICD/CRT-D. Although there has been a significant increase in ICD implantation rates, gender differences in the use of these devices still exist in New Zealand, in keeping with the demographics of ischaemic heart disease and systolic dysfunction between genders.

ECG-derived spatial QRS-T angle is associated with ICD implantation, mortality and heart failure admissions in patients with LV systolic dysfunction.

BACKGROUND: Increased spatial QRS-T angle has been shown to predict appropriate implantable cardioverter defibrilIator (ICD) therapy in patients with left ventricular systolic dysfunction (LVSD). We performed a retrospective cohort study in patients with left ventricular ejection fraction (LVEF) 31-40% to assess the relationship between the spatial QRS-T angle and other advanced ECG (A-ECG) as well as echocardiographic metadata, with all-cause mortality or ICD implantation for secondary prevention. METHODS: 534 patients ≤75 years of age with LVEF 31-40% were identified through an echocardiography reporting database. Digital 12-lead ECGs were retrospectively matched to 295 of these patients, for whom echocardiographic and A-ECG metadata were then generated. Data mining was applied to discover novel ECG and echocardiographic markers of risk. Machine learning was used to develop a model to predict possible outcomes. RESULTS: 49 patients (17%) had events, defined as either mortality (n = 16) or ICD implantation for secondary prevention (n = 33). 72 parameters (58 A-ECG, 14 echocardiographic) were univariately different (p<0.05) in those with vs. without events. After adjustment for multiplicity, 24 A-ECG parameters and 3 echocardiographic parameters remained different (p<2x10-3). These included the posterior-to-leftward QRS loop ratio from the derived vectorcardiographic horizontal plane (previously associated with pulmonary artery pressure, p = 2x10-6); spatial mean QRS-T angle (134 vs. 112°, p = 1.6x10-4); various repolarisation vectors; and a previously described 5-parameter A-ECG score for LVSD (p = 4x10-6) that also correlated with echocardiographic global longitudinal strain (R2 = - 0.51, P < 0.0001). A spatial QRS-T angle >110° had an adjusted HR of 3.4 (95% CI 1.6 to 7.4) for secondary ICD implantation or all-cause death and adjusted HR of 4.1 (95% CI 1.2 to 13.9) for future heart failure admission. There was a loss of complexity between A-ECG and echocardiographic variables with an increasing degree of disease. CONCLUSION: Spatial QRS-T angle >110° was strongly associated with arrhythmic events and all-cause death. Deep analysis of global ECG and echocardiographic metadata revealed underlying relationships, which otherwise would not have been appreciated. Delivered at scale such techniques may prove useful in clinical decision making in the future.

Assessment of oesophageal position by direct visualization with luminal contrast compared with segmentation from pre-acquired computed tomography scan-implications for ablation strategy.

AIMS: Atrio-oesophageal fistula is a rare but often fatal complication of catheter ablation for atrial fibrillation (AF). Various strategies are employed to evaluate the oesophageal position in relation to the posterior left atrium (LA). These include segmentation of the oesophagus from a pre-acquired computed tomography (CT) scan and direct, real-time assessment of the oesophageal position using contrast at the time of the procedure. METHODS AND RESULTS: One hundred and fourteen patients with drug-refractory AF underwent CT scanning prior to AF ablation. The LA and oesophagus were segmented from this scan. The oesophagus was deemed midline, ostial if it crossed directly behind any of the pulmonary vein (PV) ostia, or antral if it passed within 5 mm of a PV ostium. Under general anaesthesia at the time of ablation, the same patients were administered contrast via an oro-gastric tube to outline the oesophagus. Catheters were placed at the PV ostia and oesophageal position in relation to the PVs was established radiographically using a postero-anterior view. Oesophageal position assessed by real-time assessment correlated with the CT scan in only 59% of patients. In 34% the oesophagus was more right sided on direct visualization, while in 7% it was more left sided. CONCLUSION: Segmentation of the oesophagus from the CT scan did not correlate the real-time oesophageal position at the time of the procedure in over 40% of patients under general anaesthesia. Reliance on the determination of oesophageal position by previously acquired CT may be misleading at best and provide a false sense of security when ablating in the posterior LA.

Brugada ECG Pattern Unmasked by IV Flecainide in an Individual with Idiopathic Fascicular Ventricular Tachycardia.

A 45-year old man presents with stable monomorphic ventricular tachycardia. He had previously been diagnosed with idiopathic fascicular ventricular tachycardia. Intravenous flecainide results in termination of his tachycardia but unmasks a latent type 1 Brugada ECG pattern not seen on his resting ECG. We discuss his subsequent management and the need to consider an alternative diagnosis in individuals with a Brugada type ECG pattern who present with stable monomorphic ventricular tachycardia.

Vertebral artery dissection secondary to defibrillation threshold testing.

We report a case of vertebral artery dissection presenting 2 days after ICD implantation with defibrillation threshold testing in a 57-year-old man with ischemic cardiomyopathy. The association between vertebral artery dissection and neck trauma and the role of DFT testing in ICD implantation are discussed.

Pulmonary venous isolation versus additional substrate modification as treatment for paroxysmal atrial fibrillation.

BACKGROUND: Pulmonary vein isolation alone is ineffective in maintaining sinus rhythm in up to one third of patients with paroxysmal atrial fibrillation (AF). We compared pulmonary vein antral isolation plus additional limited ablation along the inferoposterior left atrium and epicardially within the adjacent coronary sinus (PVAI + CS) to pulmonary vein antral isolation (PVAI) alone in patients with paroxysmal AF. METHODS: Forty-two consecutive patients with paroxysmal AF were prospectively randomized to PVAI vs. PVAI + CS. All patients were seen 3, 6, 12, and 18 months after ablation and underwent 24-h ambulatory Holter monitoring. RESULTS: Following a single procedure, 17 out of 22 patients (77%) remained arrhythmia free off antiarrhythmic medication after PVAI at 18 months vs. 10 out of 20 (50%) after PVAI + CS (p < 0.01). After PVAI, three patients had recurrent paroxysmal AF, and two had atrial tachycardia, whereas after PVAI + CS, three patients had recurrent paroxysmal AF, and seven had atrial tachycardia. All patients in the PVAI + CS group with atrial tachycardia who underwent a second procedure were found to have peri-mitral macro-reentry as the underlying mechanism. Eighty-one percent of patients remained arrhythmia free off medication after 1.09 procedures in the PVAI group vs. 80% after 1.35 procedures in the PVAI + CS group (p < 0.01). CONCLUSION: The addition of limited ablation along the inferoposterior left atrium and within the adjacent coronary sinus to PVAI alone did not reduce the recurrence rate of paroxysmal atrial fibrillation and was associated with an increased rate of peri-mitral macro-reentrant atrial tachycardia.

Hyperuricemia and adverse outcomes in cardiovascular disease: potential for therapeutic intervention.

High uric acid levels are associated with increased morbidity and mortality rates in cardiovascular disease. In this article we explore the relationship between cardiovascular disease and xanthine oxidase activity. We look at the evidence that uric acid and its production via the xanthine oxidase pathway, may directly contribute to this increased cardiovascular risk. We examine the relationship between uric acid and other established cardiovascular risk factors and look at the evidence that reducing uric acid production may have a beneficial impact on cardiovascular morbidity and mortality. We conclude that although there is currently insufficient evidence to recommend the routine use of xanthine oxidase inhibitors in those with cardiovascular disease and asymptomatic hyperuricemia, there is sufficient evidence to warrant a large scale morbidity and mortality trial.