Protection against SARS-CoV-2 after Covid-19 Vaccination and Previous Infection.

BACKGROUND: The duration and effectiveness of immunity from infection with and vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are relevant to pandemic policy interventions, including the timing of vaccine boosters. METHODS: We investigated the duration and effectiveness of immunity in a prospective cohort of asymptomatic health care workers in the United Kingdom who underwent routine polymerase-chain-reaction (PCR) testing. Vaccine effectiveness (≤10 months after the first dose of vaccine) and infection-acquired immunity were assessed by comparing the time to PCR-confirmed infection in vaccinated persons with that in unvaccinated persons, stratified according to previous infection status. We used a Cox regression model with adjustment for previous SARS-CoV-2 infection status, vaccine type and dosing interval, demographic characteristics, and workplace exposure to SARS-CoV-2. RESULTS: Of 35,768 participants, 27% (9488) had a previous SARS-CoV-2 infection. Vaccine coverage was high: 95% of the participants had received two doses (78% had received BNT162b2 vaccine [Pfizer-BioNTech] with a long interval between doses, 9% BNT162b2 vaccine with a short interval between doses, and 8% ChAdOx1 nCoV-19 vaccine [AstraZeneca]). Between December 7, 2020, and September 21, 2021, a total of 2747 primary infections and 210 reinfections were observed. Among previously uninfected participants who received long-interval BNT162b2 vaccine, adjusted vaccine effectiveness decreased from 85% (95% confidence interval [CI], 72 to 92) 14 to 73 days after the second dose to 51% (95% CI, 22 to 69) at a median of 201 days (interquartile range, 197 to 205) after the second dose; this effectiveness did not differ significantly between the long-interval and short-interval BNT162b2 vaccine recipients. At 14 to 73 days after the second dose, adjusted vaccine effectiveness among ChAdOx1 nCoV-19 vaccine recipients was 58% (95% CI, 23 to 77) - considerably lower than that among BNT162b2 vaccine recipients. Infection-acquired immunity waned after 1 year in unvaccinated participants but remained consistently higher than 90% in those who were subsequently vaccinated, even in persons infected more than 18 months previously. CONCLUSIONS: Two doses of BNT162b2 vaccine were associated with high short-term protection against SARS-CoV-2 infection; this protection waned considerably after 6 months. Infection-acquired immunity boosted with vaccination remained high more than 1 year after infection. (Funded by the U.K. Health Security Agency and others; ISRCTN Registry number, ISRCTN11041050.).

Recurrent Takotsubo Syndrome: How Frequent, and How Does It Present?

BACKGROUND: Recurrent Takotsubo syndrome (TS) is not uncommon but experience with TS recurrence is inherently limited by the infrequency of the condition itself and incomplete long-term follow-up. There is limited published data on the clinical features and outcomes of patients with recurrent TS. We aimed to describe the clinical characteristics and outcomes of patients with recurrent TS in a large Auckland cohort. METHOD: The clinical profile, in-hospital, and long-term outcomes were prospectively assessed in consecutive patients with recurrent TS presenting to Auckland's three major hospitals between January 2006 and January 2023. RESULTS: During the study period, 472 TS patients were identified. Of the 467 patients discharged alive after the index event, 45 (9.6%) patients (mean age 62.3±11.0 years), all women, experienced recurrent TS. Median time interval from index event to the first recurrence was 3.14 years (range 27 days to 13.8 years). In 27 (60%) of the 45 patients, the subsequent events involved a stressor (physical triggers, n=8; emotional triggers, n=19). The stressor type differed between the index and recurrent event in 18 (40%) of the 45 patients. Thirteen (28.9%) had a different echocardiographic variant of TS at first recurrence. All patients with recurrent TS were discharged alive. Four patients died late after discharge from the first recurrence, all but one from a non-cardiac cause. CONCLUSIONS: One in 10 patients with TS experience recurrent events. These may occur many years later, and both the stressor type and the echocardiographic variant may be different at the recurrent event.

Cardiogenic Shock Prior to Percutaneous Coronary Intervention in ST-Elevation Myocardial Infarction: Outcomes and Predictors of Mortality (ANZACS-QI 73).

BACKGROUND & AIMS: Cardiogenic shock (CS) is a serious complication of acute myocardial infarction (MI) and is associated with significant mortality. We describe a contemporary, real-world cohort of patients with ST-elevation MI (STEMI) and CS, including 30-day mortality and clinically relevant predictors of mortality. METHODS: All patients presenting with STEMI who were treated with percutaneous coronary intervention (PCI) in New Zealand (2016 to 2020) were identified from the Aotearoa New Zealand All Cardiology Services Quality Improvement (ANZACS-QI) registry and stratified based on their Killip class on arrival to the cardiac catheterisation laboratory. Primary outcome was 30-day all-cause mortality. Multivariable analysis was used to identify predictors of mortality prior to PCI and to develop a mortality scoring system. RESULTS: In total, 6,649 patients were identified, including 192 (2.9%) Killip IV (CS) patients. Thirty-day mortality was 47.5% in patients with CS, 14.6% in those with heart failure without shock, and 3% in those without heart failure. Independent predictors of 30-day mortality for patients with CS were: estimated glomerular filtration rate <60 mL/min/1.73m2 (relative risk [RR] 1.89, 95% confidence interval [CI] 1.39-2.58), cardiac arrest (RR 1.54, 95% CI 1.15-2.06), diabetes (RR 1.31, 95% CI 1.01-1.70), female sex (RR 1.32, 95% CI 1.01-1.72), femoral arterial access (RR 1.42, 95% CI 1.06-1.90) and left main stem culprit (RR 2.16, 95% CI 1.65-2.84). A multivariable Shock score was developed which predicts 30-day mortality with good global discrimination (area under the curve 0.79, 95% CI 0.73-0.85). CONCLUSION: In this national cohort, the 30-day mortality for STEMI patients presenting with CS treated with PCI remains high, at nearly 50%. The ANZACS-QI Shock score is a promising tool for mortality risk stratification prior to PCI but requires further validation.

Validation Study of Cardiovascular International Statistical Classification of Diseases and Related Health Problems, Tenth Edition, Australian Modification (ICD-10-AM) Codes in Administrative Healthcare Databases (ANZACS-QI 77).

BACKGROUND: Administrative healthcare databases can be utilised for research. The accuracy of the International Statistical Classification of Diseases and Related Health Problems, Tenth Edition, Australian Modification (ICD-10-AM) coding of cardiovascular conditions in New Zealand is not known and requires validation. METHOD: International Statistical Classification of Diseases and Related Health Problems, Tenth Edition, Australian Modification coded discharges for acute coronary syndrome (ACS), heart failure (HF) and atrial fibrillation (AF), in both primary and secondary diagnostic positions, were identified from four district health boards between 1 January 2019 and 31 June 2019. A sample was randomly selected for retrospective clinician review for evidence of the coded diagnosis according to contemporary diagnostic criteria. Positive predictive values (PPVs) for ICD-10-AM coding vs clinician review were calculated. This study is also known as All of New Zealand, Acute Coronary Syndrome-Quality Improvement (ANZACS-QI) 77. RESULTS: A total of 600 cases (200 for each diagnosis, 5.0% of total identified cases) were reviewed. The PPV of ACS was 93% (95% confidence interval [CI] 89%-96%), HF was 93% (95% CI 89%-96%) and AF was 96% (95% CI 92%-98%). There were no differences in PPV between district health boards. PPV for ACS were lower in Maori vs non-Maori (72% vs 96%; p=0.004), discharge from non-Cardiology vs Cardiology services (89% vs 96%; p=0.048) and ICD-10-AM coding for unstable angina vs myocardial infarction (81% vs 95%; p=0.011). PPV for HF were higher in the primary vs secondary diagnostic position (100% vs 89%; p=0.001). CONCLUSIONS: The PPVs of ICD-10-AM coding for ACS, HF, and AF were high in this validation study. ICD-10-AM coding can be used to identify these diagnoses in administrative databases for the purposes of healthcare evaluation and research.

Short, Medium and Long-Term Cause-Specific Mortality Following First-Ever Heart Failure Hospitalisation in New Zealand.

BACKGROUND: Heart failure (HF) is associated with high mortality, but there are limited reports on the underlying cause of death. This study reports short-, medium- and long-term cause-specific mortality following first-ever HF hospitalisation in New Zealand. METHOD: First-ever HF hospitalisations were identified from hospital discharge coding between 2010 and 2013. Mortality outcomes were obtained via anonymised linkage to national datasets. Short (0-30 days), medium (31-364 days), and long-term (1-5 years) mortality rates were identified. Cause of death was identified from death certification coding and classified as cardiovascular and non-cardiovascular. Cox regression analysis was performed to adjust for confounding variables. RESULTS: A cohort of 34,264 individuals with first-ever HF hospitalisation were identified. Mean age was 75.8±13 years and 50.5% were male. A total of 21,637 (63.1%) died within 5 years of hospitalisation; 4,122 (12.0%) within the first 30 days, 6,358 (18.6%) between 31-364 days, and 11,157 (32.6%) between 1 and 5 years. Older age, male gender, Maori ethnicity, higher socioeconomic deprivation and increased comorbidity were independent factors associated with higher all-cause mortality. Cardiovascular causes accounted for 51% of total deaths. Cardiovascular mortality was 6.0%, 9.5%, and 16.7% at 30 days, 31-364 days, and 1-5 years, respectively. The most common causes of non-cardiovascular mortality were neoplasms, chronic respiratory diseases and infections, accounting for 14.6%, 11.0%, and 5.5% of total deaths respectively. Comorbidity was associated with higher non-cardiovascular mortality (hazard ratio [HR] 3.35; 95% confidence interval [CI] 3.16-3.55) but not cardiovascular mortality (HR 0.79; 95% CI 0.72-0.86). CONCLUSIONS: In New Zealand, mortality following first-ever HF hospitalisation is high. Non-cardiovascular death is common and there are ethnic inequities.

Functional Activity of Enantiomeric Oximes and Diastereomeric Amines and Cyano Substituents at C9 in 3-Hydroxy-N-phenethyl-5-phenylmorphans.

The synthesis of stereochemically pure oximes, amines, saturated and unsaturated cyanomethyl compounds, and methylaminomethyl compounds at the C9 position in 3-hydroxy-N-phenethyl-5-phenylmorphans provided µ-opioid receptor (MOR) agonists with varied efficacy and potency. One of the most interesting compounds, (2-((1S,5R,9R)-5-(3-hydroxyphenyl)-2-phenethyl-2-azabicyclo[3.3.1]nonan-9-yl)acetonitrile), was found to be a potent partial MOR agonist (EC50 = 2.5 nM, %Emax = 89.6%), as determined in the forskolin-induced cAMP accumulation assay. Others ranged in potency and efficacy at the MOR, from nanomolar potency with a C9 cyanomethyl compound (EC50 = 0.85 nM) to its totally inactive diastereomer, and three compounds exhibited weak MOR antagonist activity (the primary amine 3, the secondary amine 8, and the cyanomethyl compound 41). Many of the compounds were fully efficacious; their efficacy and potency were affected by both the stereochemistry of the molecule and the specific C9 substituent. Most of the MOR agonists were selective in their receptor interactions, and only a few had δ-opioid receptor (DOR) or κ-opioid receptor (KOR) agonist activity. Only one compound, a C9-methylaminomethyl-substituted phenylmorphan, was moderately potent and fully efficacious as a KOR agonist (KOR EC50 = 18 nM (% Emax = 103%)).

Early Warning Surveillance for SARS-CoV-2 Omicron Variants, United Kingdom, November 2021-September 2022.

Since June 2020, the SARS-CoV-2 Immunity and Reinfection Evaluation (SIREN) study has conducted routine PCR testing in UK healthcare workers and sequenced PCR-positive samples. SIREN detected increases in infections and reinfections and delected Omicron subvariant waves emergence contemporaneous with national surveillance. SIREN's sentinel surveillance methods can be used for variant surveillance.

What is the Statin Possession Ratio Cut-Off Which Identifies Those at Increased Risk Following Acute Coronary Syndrome (ANZACS-QI 68)?

AIMS: More optimal dispensing of statins is associated with greater cholesterol lowering; however, it is not known whether this translates to improved outcomes following acute coronary syndrome (ACS). The aim of this study was to assess the association between various levels of statin adherence and outcomes following ACS. METHODS: Patients hospitalised with ACS who underwent coronary angiography between 2014-2018 were identified from the All New Zealand ACS Quality Improvement (ANZACS-QI) registry. Medication possession ratio (MPR) was used to assess statin adherence and calculated over 1 year post-discharge using linked pharmaceutical dispensing datasets. Optimal, adequate and suboptimal adherence was defined as an MPR of ≥1.0, 0.8-0.99 and 0-0.79, respectively. A combined outcome of all-cause mortality and rehospitalisation for atherosclerotic disease was identified from 1 year post-discharge through September 2021. Cox proportional hazard models were used to adjust for confounding variables. RESULTS: Of the 30,452 patients, 68% had optimal adherence, 15% adequate adherence and 16% had suboptimal adherence to statins. Mean follow-up was 3.6 years. Those with suboptimal adherence had a higher adjusted risk of the combined outcome compared with those with optimal adherence (HR 1.18, 95% CI 1.11-1.26). There was no significant difference in adjusted outcome between those with optimal and adequate adherence (HR 0.99, 95% CI 0.92-1.06). CONCLUSIONS: Suboptimal statin adherence following ACS is associated with an increased risk of mortality and rehospitalisation. An MPR cut-off of 0.8 seems reasonable to identify those at higher risk of cardiovascular events that could benefit the most from interventions to improve statin adherence and is appropriate as a target for quality improvement programs.

Invasive Management and Outcomes in Acute Coronary Syndromes and Chronic Kidney Disease (ANZACS-QI 70).

AIMS: Guidelines recommend management with an invasive coronary angiogram in acute coronary syndromes (ACS), but most studies excluded patients with advanced chronic kidney disease (CKD). Our aims were to describe, in a comprehensive ACS cohort, the incidence of CKD, coronary angiography utilisation and outcomes, according to CKD stage. METHODS: National datasets were used to identify hospitalised ACS patients (2013 to 2018) in the Northern region of New Zealand. CKD stage was obtained from a linked laboratory dataset. Outcomes included all-cause and cause-specific mortality, and non-fatal myocardial infarction, heart failure and stroke. RESULTS: Thirty-eight percent (38%) of the 23,432 ACS patients had CKD stage 3 or higher: 2,403 (10%) had stages 4/5 CKD. Overall 61% received coronary angiography. Compared with normal renal function the adjusted rate of coronary angiography was lower in CKD stage 3b (RR 0.75, 95% confidence intervals [CIs] 0.69, 0.82) and stages 4/5 without dialysis (RR 0.41, 95% CIs 0.36, 0.46), but similar for those on dialysis (RR 0.89, 95% CIs 0.77, 1.02). All-cause mortality (mean follow-up 3.2 years) increased with CKD stage from 8% (normal kidney function) to 69% (stages 4/5 CKD without dialysis). Compared with coronary angiography, the adjusted all-cause and CVD mortality risks were higher in those without coronary angiography, except for those on dialysis, where these risks converged. CONCLUSIONS: Invasive management fell below an eGFR of 45 mL/min (≤ stage 3b), and nearly half of all deaths occurred in these patients. Clinical trials are needed to assess the role of invasive management in ACS and advanced CKD.

A Risk Model to Predict Statin Non-Adherence Following an Acute Coronary Syndrome.

BACKGROUND: Patients at risk of statin non-adherence are often not identified during hospital admission with an acute coronary syndrome (ACS). METHODS: In 19,942 patients hospitalised for ACS, statin dispensing was determined from the national pharmaceutical dispensing database. A risk score for non-adherence was developed from a multivariable Poisson regression model of associations between risk factors and the statin Medication Possession Ratio (MPR) <0.8 6-18 months after hospital discharge. RESULTS: Statin MPR was <0.8 in 4,736 (24%) patients. MPR <0.8 was more likely in patients with a history of cardiovascular disease (CVD) (RR 3.79, CI 95% 3.42-4.20) and those without known CVD (RR 2.25, 95% CI 2.04-2.48) who were not taking a statin on ACS admission, compared to patients with low density lipoprotein (LDL) cholesterol <2 mmol/L who were on a statin. For patients taking a statin on admission, higher LDL was associated with MPR <0.8 (≥3 versus <2 mmol/L, RR 1.96, 95%CI 1.72-2.24). Other independent risk factors for MPR <0.8 were age <45 years, female, disadvantaged ethnic groups, and no coronary revascularisation during the ACS admission. The risk score, which included nine variables, had a C-statistic of 0.67. MPR was <0.8 in 12% of 5,348 patients with a score ≤5 (lowest quartile) and 45% of 5,858 patients with a score ≥11 (highest quartile). CONCLUSION: A risk score generated from routinely collected data predicts statin non-adherence in patients hospitalised with ACS. This may be used to target inpatient and outpatient interventions to improve medication adherence.

External Validation of a Clinical Score to Differentiate Takotsubo Syndrome From Non-ST-Elevation Myocardial Infarction in Women.

BACKGROUND AND AIMS: Clinical presentation of Takotsubo Syndrome (TS) mimics acute coronary syndrome (ACS). A score to differentiate TS from ACS would be helpful to facilitate appropriate investigation and management. We have previously developed a clinical score (NSTE-Takotsubo Score) to distinguish women with non-ST-segment elevation myocardial infarction (NSTEMI) from TS with non-ST-segment elevation (NSTE-TS). This study sought to assess the diagnostic validity of this score in an external validation cohort. METHODS: The external cohort consisted of women with NSTE-TS (n=110) and NSTEMI (n=113) from two major tertiary hospitals in New Zealand. The five variables in the arithmetic score (range -6 to +5) and their relative weights are: T-wave inversion (TWI) in ≥6 leads (3 points), recent stress (2 points), diabetes mellitus (DM) (-1 point), prior cardiovascular disease (CVD) (-2 points) and presence of ST depression (-3 points). Two clinicians blinded to the diagnoses calculated the score using clinical and electrocardiogram (ECG) data on day 1 post-admission. RESULTS: The NSTE-Takotsubo Score discriminated well between NSTE-TS and NSTEMI. The sensitivity and specificity of a score ≥1 to distinguish NSTE-TS from NSTEMI were 78% and 85%, respectively. The area under the receiver operator curve was 0.78 (95% CI 0.72 to 0.84). CONCLUSION: In an external validation cohort, the NSTE-Takotsubo Score was easy to apply and useful to identify women likely to have NSTE-TS on day 1 post-admission.

Potent MOR Agonists from 2'-Hydroxy-5,9-dimethyl-N-phenethyl Substituted-6,7-benzomorphans and from C8-Hydroxy, Methylene and Methyl Derivatives of N-Phenethylnormetazocine.

(-)-5,9-Dimethyl-6,7-benzomorphan (normetazocine) derivatives with a para-OH or ortho-F substituent in the aromatic ring of the N-phenethyl moiety were synthesized and found to have subnanomolar potency at MOR, and both were fully efficacious in vitro. These new compounds, (1R,5R,9R)-6,11-dimethyl-3-(2-fluorophenethyl)-1,2,3,4,5,6-hexahydro-2,6-methanobenzo[d]azocin-8-ol and (1R,5R,9R)-6,11-dimethyl-3-(4-hydroxyphenethyl)-1,2,3,4,5,6-hexahydro-2,6-methanobenzo[d]azocin-8-ol, were more potent than the unsubstituted compound N-phenethylnormetazocine and about 30 or 40 times more potent than morphine, respectively. A variety of substituents in the ortho, meta, or para position in the aromatic ring of the N-phenethyl moiety were synthesized, 25 of these compounds, and found to have varying effects on potency and efficacy as determined by the forskolin-induced cAMP accumulation assay. The N-phenethyl moiety was also modified by increasing chain length to form a N-phenylpropyl side chain with and without a para-nitro moiety, and by an N-cinnamyl side chain. Also, an indole ethylamine normetazocine was synthesized to replace the N-phenethylamine side chain in normetazocine. The phenylpropylamine, propenylamine (cinnamyl) and the para-nitropropylamine had little or no MOR potency. The indole-ethylamine on the normetazocine nucleus, however, had moderate potency (MOR EC50 = 12 nM), and was fully efficacious (%Emax = 102%) in the cAMP assay. Retention of the N-phenethyl moiety and the addition of alkyl and alkenyl moieties on C8 in (-)-N-phenethylnormetazocine gave a C8-methylene derivative that had subnanomolar potency at MOR and a C8-methyl analog that had nanomolar potency. Five C8-substituted compounds were synthesized.

Discovery of a Potent Highly Biased MOR Partial Agonist among Diastereomeric C9-Hydroxyalkyl-5-phenylmorphans.

All possible diastereomeric C9-hydroxymethyl-, hydroxyethyl-, and hydroxypropyl-substituted 5-phenylmorphans were synthesized to explore the three-dimensional space around the C9 substituent in our search for potent MOR partial agonists. These compounds were designed to lessen the lipophilicity observed with their C9-alkenyl substituted relatives. Many of the 12 diastereomers that were obtained were found to have nanomolar or subnanomolar potency in the forskolin-induced cAMP accumulation assay. Almost all these potent compounds were fully efficacious, and three of those chosen for in vivo evaluation, 15, 21, and 36, were all extremely G-protein biased; none of the three compounds recruited beta-arrestin2. Only one of the 12 diastereomers, 21 (3-((1S,5R,9R)-9-(2-hydroxyethyl)-2-phenethyl-2-azabicyclo[3.3.1]nonan-5-yl)phenol), was a MOR partial agonist with good, but not full, efficacy (Emax = 85%) and subnanomolar potency (EC50 = 0.91 nM) in the cAMP assay. It did not have any KOR agonist activity. This compound was unlike morphine in that it had a limited ventilatory effect in vivo. The activity of 21 could be related to one or more of three well-known theories that attempt to predict a dissociation of the desired analgesia from the undesirable opioid-like side-effects associated with clinically used opioids. In accordance with the theories, 21 was a potent MOR partial agonist, it was highly G-protein biased and did not attract beta-arrestin2, and it was found to have both MOR and DOR agonist activity. All the other diastereomers that were synthesized were either much less potent than 21 or had either too little or too much efficacy for our purposes. It was also noted that a C9-methoxymethyl compound with 1R,5S,9R stereochemistry (41) was more potent than the comparable C9-hydroxymethyl compound 11 (EC50 = 0.65 nM for 41 vs. 2.05 nM for 11). Both 41 and 11 were fully efficacious.

Cardiovascular risk prediction in type 2 diabetes before and after widespread screening: a derivation and validation study.

BACKGROUND: Until recently, most patients with diabetes worldwide have been diagnosed when symptomatic and have high cardiovascular risk, meaning most should be prescribed cardiovascular preventive medications. However, in New Zealand, a world-first national programme led to approximately 90% of eligible adults being screened for diabetes by 2016, up from 50% in 2012, identifying many asymptomatic patients with recent-onset diabetes. We hypothesised that cardiovascular risk prediction equations derived before widespread screening would now significantly overestimate risk in screen-detected patients. METHODS: New Zealanders aged 30-74 years with type 2 diabetes and without known cardiovascular disease, heart failure, or substantial renal impairment were identified from the 400 000-person PREDICT primary care cohort study between Oct 27, 2004, and Dec 30, 2016, covering the period before and after widespread screening. Sex-specific equations estimating 5-year risk of cardiovascular disease were developed using Cox regression models, with 18 prespecified predictors, including diabetes-related and renal function measures. Equation performance was compared with an equivalent equation derived in the New Zealand Diabetes Cohort Study (NZDCS), which recruited between 2000 and 2006, before widespread screening. FINDINGS: 46 652 participants were included in the PREDICT-1° Diabetes subcohort, of whom 4114 experienced first cardiovascular events during follow-up (median 5·2 years, IQR 3·3-7·4). 14 829 (31·8%) were not taking oral hypoglycaemic medications or insulin at baseline. Median 5-year cardiovascular risk estimated by the new equations was 4·0% (IQR 2·3-6·8) in women and 7·1% (4·5-11·2) in men. The older NZDCS equation overestimated median cardiovascular risk by three times in women (median 14·2% [9·7-20·0]) and two times in men (17·1% [4·5-20·0]). Model and discrimination performance measures for PREDICT-1° Diabetse equations were also significantly better than for the NZDCS equation (eg, for women: R2=32% [95% CI 29-34], Harrell's C=0·73 [0·72-0·74], Royston's D=1·410 [1·330-1·490] vs R2=24% [21-26], C=0·69 [0·67-0·70], and D=1·147 [1·107-1·187]). INTERPRETATION: International treatment guidelines still consider most people with diabetes to be at high cardiovascular risk; however, we show that recent widespread diabetes screening has radically changed the cardiovascular risk profile of people with diabetes in New Zealand. Many of these patients have normal renal function, are not dispensed glucose-lowering medications, and have low cardiovascular risk. These findings have clear international implications as increased diabetes screening is inevitable due to increasing obesity, simpler screening tests, and the introduction of new-generation glucose-lowering medications that prevent cardiovascular events. Cardiovascular risk prediction equations derived from contemporary diabetes populations, with multiple diabetes-related and renal function predictors, will be required to better differentiate between low-risk and high-risk patients in this increasingly heterogeneous population and to inform appropriate non-pharmacological management and cost-effective targeting of expensive new medications. FUNDING: Health Research Council of New Zealand, Heart Foundation of New Zealand, and Healthier Lives National Science Challenge.

Polymeric Nanotubes as Drug Delivery Vectors─Comparison of Covalently and Supramolecularly Assembled Constructs.

Rod-shaped nanoparticles have been identified as promising drug delivery candidates. In this report, the in vitro cell uptake and in vivo pharmacokinetic/bio-distribution behavior of molecular bottle-brush (BB) and cyclic peptide self-assembled nanotubes were studied in the size range of 36-41 nm in length. It was found that BB possessed the longest plasma circulation time (t1\2 > 35 h), with the cyclic peptide system displaying an intermediate half-life (14.6 h), although still substantially elevated over a non-assembling linear control (2.7 h). The covalently bound BB underwent substantial distribution into the liver, whereas the cyclic peptide nanotube was able to mostly circumvent organ accumulation, highlighting the advantage of the inherent degradability of the cyclic peptide systems through their reversible aggregation of hydrogen bonding core units.

Takotsubo syndrome in New Zealand: current knowledge and future challenges.

Takotsubo syndrome (TS), also known as apical ballooning syndrome, is a transient stress-related cardiomyopathy characterised by acute but reversible left ventricular dysfunction. The condition tends to occur in postmenopausal women after a stressful event. At presentation, TS typically mimics acute myocardial infarction (MI) and the incidence of TS has been increasing worldwide. This is likely a consequence of an improved awareness of the existence of this syndrome and easier access to early echocardiography and coronary angiography. However, its aetiology remains poorly understood and it is probably still underdiagnosed. Similar to other countries, TS is being increasingly recognised in New Zealand. In this review, we discuss the demographics, clinical features and outcomes of patients with TS in New Zealand. Doing so informs us not only of the pattern of disease in New Zealand but it also provides insights into the condition itself.

Ten-year trends in cardiac implantable electronic devices in New Zealand: a national data linkage study (ANZACS-QI 51).

BACKGROUND: Implant rates for cardiac implantable electronic devices (CIED), including permanent pacemakers (PPM) and implantable cardioverter defibrillators (ICD), have increased globally in recent decades. AIMS: This is the first national study providing a contemporary analysis of national CIED implant trends by sex-specific age groups over an extended period. METHODS: Patient characteristics and device type were identified for 10 years (2009-2018) using procedure coding in the National Minimum Datasets, which collects all New Zealand (NZ) public hospital admissions. CIED implant rates represent implants/million population. RESULTS: New PPM implant rates increased by 4.6%/year (P < 0.001), increasing in all age groups except patients <40 years. Males received 60.1% of new PPM implants, with higher implant rates across all age groups compared with females. The annual increase in age-standardised implant rates was similar for males and females (3.4% vs 3.0%; P = 0.4). By 2018 the overall PPM implant rate was 538/million. New ICD implant rates increased by 4.2%/year (P < 0.001), increasing in all age groups except patients <40 and ≥ 80 years. Males received 78.1% of new ICD implants, with higher implant rates across all age groups compared to females. The annual increase in age-standardised implant rates was higher in males compared with females (3.5% vs 0.7%; P < 0.001). By 2018 the overall ICD implant rate was 144/million. CONCLUSION: CIED implant rates have increased steadily in NZ over the past decade but remain low compared with international benchmarks. Males had substantially higher CIED implant rates compared with females, with a growing gender disparity in ICD implant rates.

Regional variation in cardiac implantable electronic device implants trends in New Zealand over the past decade (ANZACS-QI 54).

BACKGROUND: Permanent pacemaker (PPM) and implantable cardioverter defibrillator (ICD) implant rates have increased in New Zealand over the past decade. AIMS: To provide a contemporary analysis of regional variation in implant rates. METHODS: New PPM and ICD implants in patients aged ≥15 years were identified for 10 years (2009-2018) using procedure coding in the National Minimum Datasets, which collects all New Zealand public hospital admissions. Age-standardised new implant rates per million adult population were calculated for each of the four regions (Northern, Midland, Central and Southern) and the 20 district health boards (DHB) across those regions. Trend analysis was performed using joinpoint regression. RESULTS: New PPM implant rates increased nationally by 3.4%/year (P < 0.001). The Northern region had the highest new PPM implant rate, increasing by 4.5%/year (P < 0.001). Excluding DHB with <50 000 people, the new PPM implant rate for 2017/2018 was highest in Counties Manukau DHB (854.3/million; 95% confidence interval (CI): 774.9-933.6/million) and lowest in Canterbury DHB (488.6/million; 95% CI: 438.1-539.0/million). New ICD implant rates increased nationally by 3.0%/year (P = 0.002). The Midland region had the highest new ICD implant rate, increasing by 3.8%/year (P = 0.013). Excluding DHB with <50 000 people, the new ICD implant rate for 2017-2018 was highest in the Bay of Plenty DHB (228.5/million; 95% CI: 180.4-276.6/million) and lowest in Canterbury DHB (90.2/million; 95% CI: 69.9-110.4/million). CONCLUSION: There was significant variation in PPM and ICD implant rates across regions and DHB, suggesting potential inequity in patient access across New Zealand.

Clinically Acquired High Sensitivity Cardiac Troponin T is a Poor Predictor of Reduced Left Ventricular Ejection Fraction After ST Elevation Myocardial Infarction: A National Cohort Study-ANZACS-QI 65.

OBJECTIVE: Cardiac troponins (cTn) have been used historically to estimate infarct size in ST elevation myocardial infarction (STEMI). Within a resource constrained health care environment, cTn could therefore be used for prioritisation of patients for cardiac imaging, in particular echocardiography. We aimed to determine how useful routinely collected cTn would be in predicting significant left ventricular (LV) impairment. METHODS: All patients in the All New Zealand Acute Coronary Syndrome Quality Improvement (ANZACS-QI) registry with their first episode of STEMI between January 2013 and November 2018, who had high sensitivity troponin T measured, were included. We excluded patients with no left ventricular ejection fraction (LVEF) assessment, known LV dysfunction, or prior myocardial infarction. RESULTS: In total, 3,698 patients were included in the analysis. A higher mean hsTnT (admission and peak) was seen in patients with more severely impaired LV function but there was significant overlap in the range of hsTnT between the different LVEF categories. Cardiac troponins demonstrated poor discriminative ability to either predict or exclude significant LV impairment (LVEF <40%). At an optimal cutpoint of 3,405 ng/L, peak hsTnT had a sensitivity of 56.5% (95% confidence interval [CI] 42-62%), a specificity of 65.3% (95% CI 62-79%) and an area under the receiver operating curve of 0.62 (95% CI 0.60-0.64). CONCLUSION: This is the largest study comparing clinically measured troponin levels and LV function in patients presenting with STEMI. A definite, but weak, association was seen between peak troponin and the degree of LV dysfunction, with significant overlap in troponin levels between levels of myocardial dysfunction. Routinely acquired troponin is not suitable for clinical use as a method of prioritising patients for cardiac imaging.

Type of Stressor and Medium-Term Outcomes After Takotsubo Syndrome: What Becomes of the Broken Hearted? (ANZACS-QI 59).

BACKGROUND: Takotsubo syndrome (TS) is often triggered by an acute physical or emotional stressor. We hypothesised that medium-term prognosis may be better for TS patients with an associated emotional stressor than for those with an acute physical illness. METHODS: We identified consecutive TS patients presenting in New Zealand (2006-2018). The clinical presentation and outcomes of TS patients according to types of stressor (physical, emotional or no stressor) were assessed. Post-discharge survival after TS was compared with age- and gender-matched patients after myocardial infarction (MI) and people in the community without known cardiovascular disease (CVD). RESULTS: Of 632 TS patients (95.9% women, mean age 65.0±11.1 years), 27.4% had an associated acute physical stressor, 46.4% an emotional stressor and 26.2% no evident stressor. In-hospital mortality was similar for each group (1.7%, 1.2%, 0.3% respectively, p=0.29). In a median 4.4 years post-discharge there were 54 deaths (53 non-cardiac). Compared with patients without known CVD, TS patients with physical stress and those with MI were less likely to survive (HR 4.46, 95%CI 3.10-6.42; HR 4.23, 95%CI 3.81-4.70 respectively) but survival for TS patients associated with emotional stress or no stressor was similar (HR 1.11, 95%CI 0.66-1.85; HR 1.08, 95%CI 0.54-2.18, respectively). Recurrence was similar among the three groups (p=0.14). CONCLUSION: Takotsubo syndrome associated with physical stressor has a post-discharge mortality risk as high as after MI. In contrast, prognosis for TS triggered by an emotional stressor is excellent, and similar to that of those without known CVD.