Tandem lesions associate with angiographic progression of coronary artery stenoses.

Background: Although the clinical factors associated with progression of coronary artery disease have been well studied, the angiographic predictors are less defined. Objectives: Our objective was to study the clinical and angiographic factors that associate with progression of coronary artery stenoses. Methods: We conducted a retrospective analysis of consecutive patients undergoing multiple, clinically indicated invasive coronary angiograms with an interval greater than 6 months, between January 2013 and December 2016. Lesion segments were analysed using Quantitative Coronary Angiography (QCA) if a stenosis ≥ 20 % was identified on either angiogram. Stenosis progression was defined as an increase ≥ 10 % in stenosis severity, with progressor groups analysed on both patient and lesion levels. Mixed-effects regression analyses were performed to evaluate factors associated with progression of individual stenoses. Results: 199 patients were included with 881 lesions analysed. 108 (54.3 %) patients and 186 (21.1 %) stenoses were classified as progressors. The median age was 65 years (IQR 56-73) and the median interval between angiograms was 2.1 years (IQR 1.2-3.0). On a patient level, age, number of lesions and presence of multivessel disease at baseline were each associated with progressor status. On a lesion level, presence of a stenosis downstream (OR 3.07, 95 % CI 2.04-4.63, p < 0.001) and circumflex artery stenosis location (OR 1.81, 95 % CI 1.21-2.7, p = 0.004) were associated with progressor status. Other lesion characteristics did not significantly impact progressor status or change in stenosis severity. Conclusion: Coronary lesions which have a downstream stenosis may be at increased risk of stenosis progression. Further research into the mechanistic basis of this finding is required, along with its implications for plaque vulnerability and clinical outcomes.

Anti-Anginal Efficacy of Zibotentan in the Coronary Slow-Flow Phenomenon.

BACKGROUND: Patients with coronary microvascular disorders often experience recurrent angina for which there are limited evidence-based therapies. These patients have been found to exhibit increased plasma levels of endothelin; thus, selective endothelin-A (Et-A) receptor blockers such as zibotentan may be an effective anti-anginal therapy in these patients. The study evaluated the impact of a 10 mg daily dose of zibotentan on spontaneous angina episodes in patients with the coronary slow-flow phenomenon who had refractory angina (i.e., experiencing angina at least three times/week despite current anti-anginal therapy). METHODS: Using a randomized, double-blind, placebo-controlled, crossover trial design with 4-week treatment periods, 18 patients (63.2 ± 9.9 years, 33% females) were recruited. The primary endpoint was angina frequency as measured by an angina diary, with secondary endpoints including nitrate consumption, angina duration/severity and the Seattle Angina Questionnaire (SAQ) domains. RESULTS: During the 4 weeks of therapy, angina frequency significantly improved with zibotentan therapy (placebo 41.4 (58.5) vs. zibotentan 29.2 (31.6), p < 0.05), and sublingual nitrate consumption significantly reduced (placebo 11.8 (15.2) vs. zibotentan 8.8 (12.9), p < 0.05. CONCLUSIONS: Zibotentan improved the frequency of spontaneous angina episodes and reduced sublingual nitrate consumption in patients unresponsive to standard anti-anginal therapy.

Angina and Non-Obstructive Coronary Artery (ANOCA) Patients with Coronary Vasomotor Disorders.

Angina and Non-Obstructive Coronary Artery (ANOCA) patients often lack a clear explanation for their symptoms, and are frequently discharged with the label of "unspecified chest pain", despite the availability of functional coronary angiography (provocative spasm and microvascular function testing) to identify potential underlying coronary vasomotor disorders. This study compared the outcomes of ANOCA patients with a coronary vasomotor disorder diagnosis post elective coronary angiography to patients discharged with unspecified chest pain. Using the CADOSA (Coronary Angiogram Database of South Australia) registry, consecutive symptomatic patients (n = 7555) from 2012 to 2018 underwent elective angiography; 30% had ANOCA (stenosis <50%). Of this cohort, 9% had documented coronary vasomotor disorders diagnosed, and 91% had unspecified chest pain. Patients with coronary vasomotor disorders were younger and had a similar female prevalence compared with those with unspecified chest pain. New prescriptions of calcium channel blockers and long-acting nitrates were more common for the coronary vasomotor cohort at discharge. In the 3 years following angiography, both groups had similar all-cause mortality rates. However, those with coronary vasomotor disorders had higher rates of emergency department visits for chest pain (39% vs. 15%, p < 0.001) and readmissions for chest pain (30% vs. 10%, p < 0.001) compared with those with unspecified chest pain. This real-world study emphasizes the importance of identifying high-risk ANOCA patients for personalized management to effectively address their symptoms.

Do Chest Pain Characteristics in Patients with Acute Myocardial Infarction Differ between Those with and without Obstructive Coronary Artery Disease?

The universal definition of acute myocardial infarction (MI) requires both evidence of myocardial injury and myocardial ischaemia. In MINOCA (MI with non-obstructive coronary arteries), patients must fulfil this MI criteria, but is their chest pain similar to those who have MI with obstructive CAD (MICAD)? This study compares prospectively collected chest pain features between patients with MINOCA and MICAD. Utilising the Coronary Angiogram Database of South Australia (CADOSA), consecutive MI patients were categorized as MINOCA or MICAD based on angiographic findings. Chest pain data were collected via direct patient interviews by trained staff members. Of 6811 consecutive patients fulfilling a clinical MI diagnosis, 411 (6.0%) were MINOCA, and 5948 MICAD. The MINOCA patients were younger, more often female and had less cardiovascular risk factors than those with MICAD. There were no significant differences in chest pain characteristics between the MINOCA and MICAD cohorts in relation to pain location, quality, associated symptoms, or duration. In conclusion, MINOCA patients have chest pain characteristics that are indistinguishable from MICAD patients, suggesting that their pain is ischaemic in nature. Thus, in the presence of positive myocardial injury markers, ischaemic chest pain fulfils the universal criteria for MI, despite the absence of obstructive coronary artery disease.

Trends in myocardial infarction and coronary revascularisation procedures in Australia, 1993-2017.

OBJECTIVE: Prior data have shown rising acute myocardial infarction (MI) trends in Australia; whether these increases have continued in recent years is not known. This study thus sought to characterise contemporary nationwide trends in MI hospitalisations and coronary procedures in Australia and their associated economic burden. METHODS: The primary outcome measure was the incidence and time trends of total MI, ST-elevation myocardial infarction (STEMI) and non-ST-elevation myocardial infarction (NSTEMI) hospitalisations from 1993 to 2017. The incidence and time trends of coronary procedures were additionally collected, alongside MI hospitalisation costs. RESULTS: Adjusted for population changes, annual MI incidence increased from 216.2 cases per 100 000 to a peak of 270.4 in 2007 with subsequent decline to 218.7 in 2017. Similarly, NSTEMI incidence increased from 68.0 cases per 100 000 in 1993 to a peak of 192.6 in 2007 with subsequent decline to 162.6 in 2017. STEMI incidence decreased from 148.3 cases per 100 000 in 1993 to 56.2 in 2017. Across the study period, there were annual increases in MI hospitalisations of 0.7% and NSTEMI hospitalisations of 5.6%, and an annual decrease in STEMI hospitalisations of 4.8%. Angiography and percutaneous coronary intervention increased by 3.4% and 3.3% annually, respectively, while coronary artery bypass graft surgery declined by 2.2% annually. MI hospitalisation costs increased by 100% over the study period, despite a decreased average length of stay by 45%. CONCLUSIONS: The rising incidence of MI hospitalisations appear to have stabilised in Australia. Despite this, associated healthcare expenditure remains significant, suggesting a need for continual implementation of public health policies and preventative strategies.

'Bushfire Season' in Australia: Determinants of Increases in Risk of Acute Coronary Syndromes and Takotsubo Syndrome.

BACKGROUND: Climate change has resulted in an increase in ambient temperatures during the summer months as well as an increase in risk of associated air pollution and of potentially disastrous bushfires throughout much of the world. The increasingly frequent combination of elevated summer temperatures and bushfires may be associated with acute increases in risks of cardiovascular events, but this relationship remains unstudied. We evaluated the individual and cumulative impacts of daily fluctuations in temperature, fine particulate matter of less than 2.5 µm (PM2.5) pollution and presence of bushfires on incidence of acute coronary syndromes and Takotsubo syndrome. METHODS: From November 1, 2019, to February 28, 2020, all admissions with acute coronary syndromes or Takotsubo syndrome to South Australian tertiary public hospitals were evaluated. Univariate and combined associations were sought among each of 1) maximal daily temperature, 2) PM2.5 concentrations, and 3) presence of active bushfires within 200 km of the hospitals concerned. RESULTS: A total of 504 patients with acute coronary syndromes and 35 with Takotsubo syndrome were studied. In isolation, increasing temperature was associated (rs = 0.26, P = .005) with increased incidence of acute coronary syndromes, while there were similar, but nonsignificant correlations for PM2.5 and presence of bushfires. Combinations of all these risk factors were also associated with a doubling of risk of acute coronary syndromes. No significant associations were found for Takotsubo syndrome. CONCLUSION: The combination of high temperatures, presence of bushfires and associated elevation of atmospheric PM2.5 concentrations represents a substantially increased risk for precipitation of acute coronary syndromes; this risk should be factored into health care planning including public education and acute hospital preparedness.

Prevalence and real-world management of NSTEMI with multivessel disease.

Background: Non-ST elevation myocardial infarction (NSTEMI) has higher post-discharge mortality than ST-elevation myocardial infarction (STEMI). Prognosis worsens in those with multivessel coronary disease (MVD). However, information about the prevalence and extent of MVD in NSTEMI is limited, in turn limiting insights into optimal treatment strategies. This study aimed to define the prevalence and extent of MVD, preferred treatment strategies and the predictors of MVD in a real-world NSTEMI population. Methods: The Coronary Angiogram Database of South Australia (CADOSA) was used to identify consecutive patients presenting to major teaching hospitals with NSTEMI between 2012 and 2016. Obtaining clinical and angiographic details, patients were stratified by the number of significantly diseased vessels (0,1,2,3-VD), defined by a stenosis of ≥70%, or ≥50% in the left main coronary artery. Data was analysed retrospectively. Results: The prevalence of MVD (2- or 3-VD) was 42% amongst 3,722 NSTEMI presentations. Multivariate logistic regression modelling showed age, male gender, diabetes, dyslipidaemia and prior myocardial infarction predicted MVD over 1-VD or 0-VD. Percutaneous coronary intervention (PCI) was performed in 42% of patients with MVD. This comprised 61% of 2-VD patients and only 22% of 3-VD patients, with 24% and 66% of each group referred for coronary bypass grafting, respectively. Among MVD patients treated with PCI, 76% had their culprit lesion treated alone in the index admission. Conclusions: In this NSTEMI cohort, over 40% had MVD. Notably, a minority of patients with MVD undergoing PCI received multivessel revascularisation. This real-world practice emphasises that further evaluation is required to determine whether complete revascularisation is beneficial in NSTEMI, as reported for STEMI.

Atrial fibrillation incidence, prevalence, predictors, and adverse outcomes in acute coronary syndromes: A pooled analysis of data from 8 million patients.

OBJECTIVE: To summarize data on the prevalence/incidence, risk factors and prognosis of atrial fibrillation (AF) in patients with acute coronary syndromes (ACS). METHODS: MEDLINE, Embase, and Web of Science were searched to identify all published studies providing relevant data through August 23, 2020. Random-effects meta-analysis method was used to pool estimates. RESULTS: We included 109 studies reporting data from a pooled population of 8 239 364 patients. The prevalence rates were 5.8% for pre-existing AF, 7.3% for newly diagnosed AF, and 11.3% for prevalent (total) AF, in patients with ACS. Predictors of newly diagnosed AF included age (per year increase) (adjusted odds ratio [aOR]: 1.05), C-reactive protein (aOR: 1.49), left atrial (LA) diameter (aOR: 1.08), LA dilatation (aOR: 2.32), left ventricular ejection fraction <40% (aOR: 1.82), hypertension (aOR: 1.87), and Killip ˃ 1 (aOR: 1.85), p < .01 in all analyzes. Newly diagnosed AF was associated with an increased risk of acute heart failure (adjusted hazard ratio [aHR]: 3.20), acute kidney injury (aHR: 3.09), re-infarction (aHR: 1.96), stroke (aHR: 2.15), major bleeding (aHR: 2.93), and mortality (aHR: 1.80) in the short term; and with an increased risk of heart failure (aHR: 2.21), stroke (aHR: 1.75), mortality (aHR: 1.67), CV mortality (aHR: 2.09), sudden cardiac death (aHR: 1.53), and a composite of major adverse cardiovascular events (aHR: 1.54) in the long term (beyond 1 month), p < .05 in all analyzes. CONCLUSION: One in nine patients with ACS has AF, with a high proportion of newly diagnosed AF. AF, in particular newly diagnosed AF, is associated with poor short-term and long-term outcomes in patients with ACS.

Predictors of Obstructive Sleep Apnoea (OSA) Population in the Coronary Angiogram Database of South Australia (CADOSA).

Obstructive sleep apnoea (OSA) is increasingly recognized to be a risk factor for cardiovascular disease. This study assessed the prevalence and clinical predictors of OSA in patients undergoing coronary angiography. Consecutive patients undergoing coronary angiography in South Australian public hospitals from 2015 to 2018 were included. Clinical details for consecutive patients undergoing coronary angiography in South Australian public hospitals were captured by the Coronary Angiogram Database of South Australia (CADOSA) registry staff, with OSA identified by patient report. Among the 9,885 patients undergoing coronary angiography for the investigation of chest pain, 11% (n = 1,089) were documented as having OSA. Independent clinical predictors of OSA included male gender (OR 2.22, 1.86-2.65, P < 0.001), diabetes mellitus (OR 1.84, 1.58-2.14, P < 0.001), depression (OR 1.81, 1.55-2.12, P < 0.001), prior heart failure (OR 1.63, 1.22-2.18, P = 0.001), hypertension (OR 1.61, 1.32-1.95, P ≤ 0.001), asthma (OR 1.61, 1.34-1.93, P < 0.001), not a current smoker (OR 1.60, 1.30-1.96, P < 0.001), dyslipidaemia (OR 1.46, 1.22-1.76, P < 0.001), non-acute coronary syndrome presentation (OR 1.45, 1.25-1.69, P < 0.001), chronic lung disease (OR 1.40, 1.12-1.73, P = 0.003), cerebrovascular disease (OR 1.36, 1.07-1.73, P = 0.012), non-obstructive coronary artery disease (NOCAD) (OR 1.30, 1.10-1.55, P = 0.003) and atrial fibrillation/flutter (OR 1.30, 1.06-1.60, P = 0.012). Finally, stable angina (32.1% vs 22.7%) and NOCAD (29.1% vs 26.3%, P = 0.051) were trended more common in patients with OSA versus no OSA. In addition to established risk factors for OSA, this study found NOCAD to be independent predictor of OSA; especially in those presenting with a stable angina presentation. This suggests that coronary vasomotor disorders may be associated with OSA, although further detailed studies are required.

Randomized Evaluation of Beta Blocker and ACE-Inhibitor/Angiotensin Receptor Blocker Treatment for Post Infarct Angina in Patients With Myocardial Infarction With Non-obstructive Coronary Arteries: A MINOCA-BAT Sub Study Rationale and Design.

Introduction: Myocardial infarction with non-obstructive coronary arteries (MINOCA) occurs in ~10% of all patients with acute myocardial infarction (AMI), with an over-representation amongst women. Remarkably, it is estimated that as many as 1 in 4 patients with MINOCA experience ongoing angina at 12 months despite having no flow-restricting stenoses in their epicardial arteries. This manuscript presents the rationale behind Randomized Evaluation of Beta Blocker and Angiotensin-converting enzyme inhibitors/Angiotensin Receptor Blocker Treatment (ACEI/ARB) for Post Infarct Angina in MINOCA patients-The MINOCA BAT post infarct angina sub study. Methods: This trial is a registry-based, randomized, parallel, open-label, multicenter trial with 2 × 2 factorial design. The primary aim is to determine whether oral beta blockade compared with no oral beta blockade, and ACEI/ARB compared with no ACEI/ARB, reduce post infarct angina in patients discharged after MINOCA without clinical signs of heart failure and with left ventricular ejection fraction ≥40%. A total of 664 patients will be randomized into four groups; (i) ACEI/ARB with beta blocker, (ii) beta blocker only, (iii) ACEI/ARB only, or (iv) neither ACEI/ARB nor beta blocker and followed for 12 months. Results: The trial is currently recruiting in Australia and Sweden. Fifty six patients have been recruited thus far. Both sexes were equally distributed (52% women and 48% men) and the mean age was 56.3 ± 9.9 years. Conclusions: It remains unclear whether conventional secondary preventive therapies are beneficial to MINOCA patients in regard to post infarct angina. Existing registry-based literature suggest cardioprotective agents are less likely to be used in MINOCA patients. Thus, results from this trial will provide insights for future treatment strategies and guidelines specific to MINOCA patients.

Omega-3 fatty acids ameliorate vascular inflammation: A rationale for their atheroprotective effects.

BACKGROUND AND AIMS: Clinical trials have demonstrated reductions in major adverse cardiovascular events with purified high-dose eicosapentaenoic acid (EPA), independent of effects on lipids. We aimed to investigate whether omega-3 fatty acids reduce vascular inflammation, a critical mediator of atherosclerosis, and hypothesised that EPA is superior to docosahexaenoic acid (DHA). METHODS: In a double-blind randomised controlled trial and cell-culture study, 40 healthy volunteers were supplemented with 4 g daily of either EPA, DHA, fish oil (2:1 EPA:DHA), or placebo for 30 days. Serum was incubated with TNF-stimulated human umbilical vein endothelial cells (HUVECs), and markers of acute vascular inflammation (AVI) were measured. The effects of EPA, DHA (600 mg/kg/day), olive oil, or no treatment were also measured in preclinical models of [1] AVI using a periarterial collar (C57Bl/6J; n = 40 mice) and [2] atherosclerosis where ApoE-/- mice (n = 40) were fed a 16-week atherogenic diet. RESULTS: EPA supplementation reduced expression of C-C motif chemokine ligand 2 (CCL2) by 25% compared to placebo (p = 0.03). In the AVI model, EPA reduced vascular expression of VCAM1 by 43% (p = 0.02) and CCL2 by 41% (p = 0.03). Significant inverse correlations were observed between EPA levels and vascular expression of VCAM1 (r = -0.56, p = 0.001) and CCL2 (r = -0.56, p = 0.001). In ApoE-/- mice, EPA reduced aortic expression of Il1b by 44% (p = 0.04) and Tnf by 49% (p = 0.04), with similar inverse correlations between EPA levels and both Il1b (r = -0.63, p = 0.009) and Tnf (r = -0.50, p = 0.04). CONCLUSIONS: Supplementation with EPA, more so than DHA, ameliorates acute and chronic vascular inflammation, providing a rationale for the cardiovascular benefit observed with high dose omega-3 fatty acid administration.

The LACE Index: A Predictor of Mortality and Readmission in Patients With Acute Myocardial Infarction.

INTRODUCTION: Improving patient outcomes after acute myocardial infarction (AMI) may be facilitated by identifying patients at a high risk of adverse events before hospital discharge. We aimed to determine the accuracy of the LACE (Length of stay, Acuity, Comorbidities, Emergency presentations within prior 6 months) index score (a prediction tool) for predicting 30-day all-cause mortality and readmission rates (independently and combined) in South Australian AMI patients who had an angiogram. METHODS: All consecutive AMI patients enrolled in the Coronary Angiogram Database of South Australia Registry at two major tertiary hospitals and discharged alive between July 2016 to June 2017. A LACE score was calculated for each patient, and receiver operating characteristic curve analysis was performed. RESULTS: Analysis of registry patients found a 30-day unplanned readmission rate of 11.8% and mortality rate of 0.7%. Moreover, the LACE index was a moderate predictor (C-statistic = 0.62) of readmissions in this cohort, and a score ≥10 indicated moderate discriminatory capacity to predict 30-day readmissions. CONCLUSION: The LACE index shows moderate discriminatory capacity to predict 30-day readmissions and mortality. A cut-off score of nine to optimize sensitivity may assist clinicians in identifying patients at a high risk of adverse outcomes.

Multimodality Tachycardia-Induced Stress Testing Predicts a Low-Risk Group for Early Cardiovascular Mortality After Renal Transplantation.

BACKGROUND: Cardiovascular events remain a major cause of death in kidney transplant recipients. The optimal noninvasive workup to prevent peritransplant cardiac mortality remains contentious. METHODS: We conducted a retrospective analysis to assess the renal transplantation cardiovascular assessment protocol within a single-center population over a 5-year period. Asymptomatic patients aged less than 45 years with no history of cigarette smoking, without diabetes mellitus, and dialysis-dependent for less than 24 months did not undergo cardiac testing before listing. All other asymptomatic patients underwent a noninvasive, tachycardia-induced stress test, where a target heart rate of 85% predicted for age and gender was required. The primary endpoints were rates of acute myocardial infarction (AMI) and cardiovascular death at 30 days after renal transplantation. RESULTS: Between 2015 and 2019, 380 recipients underwent cardiac evaluation: 79 (20.8%) were deemed low cardiovascular risk and placed on the renal transplant waitlist without further assessment; 270 (71.1%) underwent a tachycardia-induced stress test; and 31 (8.1%) were deemed high risk and proceeded directly to invasive coronary angiography (ICA). In the 5-year follow-up, 3 patients (0.8%) experienced an AMI 30 days after renal transplantation, all of which occurred in the high-risk "direct to ICA" cohort. No events were documented in the low-risk cohort or in patients who had a negative tachycardia-induced stress test. There were no cardiovascular deaths within 30 days after transplantation. CONCLUSION: A negative tachycardia-induced cardiac stress test, achieving 85% of predicted heart rate, was associated with a 0% AMI rate and no cardiovascular deaths at 30 days after renal transplantation.

Long-Term Impact of Arteriovenous Fistula Ligation on Cardiac Structure and Function in Kidney Transplant Recipients: A 5-Year Follow-Up Observational Cohort Study.

Background: The long-term effects of arteriovenous fistula (AVF) ligation on cardiovascular structure following kidney transplantation remain uncertain. A prospective randomized, controlled trial (RCT) examined the effect of AVF ligation at 6 months on cardiovascular magnetic resonance imaging (CMR)-derived parameters in 27 kidney transplant recipients compared with 27 controls. A mean decrease in left ventricular mass (LVM) of 22.1 g (95% CI, 15.0 to 29.1) was observed compared with an increase of 1.2 g (95% CI, -4.8 to 7.2) in the control group (P<0.001). We conducted a long-term follow-up observational cohort study in the treated cohort to determine the evolution of CMR-derived parameters compared with those documented at 6 months post-AVF ligation. Methods: We performed CMR at long-term follow-up in the AVF ligation observational cohort from our original RCT published in 2019. Results were compared with CMR at 6 months postintervention. The coprimary end point was the change in CMR-derived LVM and LVM index at long-term follow-up from imaging at 6 months postindex procedure. Results: At a median of 5.1 years (interquartile range, 4.7-5.5 years), 17 patients in the AVF ligation group were studied with repeat CMR with a median duration to follow-up imaging of 5.1 years (IQR, 4.7-5.5 years). Statistically significant further reductions in LVM (-17.6±23.0 g, P=0.006) and LVM index (-10.0±13.0 g/m2, P=0.006) were documented. Conclusions: The benefit of AVF ligation on LVM and LVM index regression appears to persist long term. This has the potential to lead to a significant reduction in cardiovascular mortality.

Impact of Young Age and Gender on Outcomes of Transradial Versus Transfemoral Access Coronary Angiography.

The differential impact of young age and female gender on transradial access (TRA) outcomes remains to be confirmed. The primary objective was to assess the impact of young age and female gender on in-hospital net adverse cardiovascular events (NACE). Among 12 346 patients from the Coronary Angiogram Database of South Australia (CADOSA) Registry, the impact of gender; men (transfemoral access [TFA] 1995, TRA 6168) and women (TFA 1249, TRA 2934), and a median split of age, ≤63 years (TFA 1617, TRA 4727) and >63 years (TFA 1627, TRA 4375) were analyzed on in-hospital outcomes by creating 5 separate propensity-matched cohorts (entire cohort, men, women, ≤63 and > 63 years). Net adverse cardiovascular event reduction with TRA was limited to the >63 years old cohort (odds ratio [OR] = 0.56, 95% CI: 0.34-0.93, P = .02) and women (OR = 0.37, 95% CI: 0.18-0.76, P = .007). In both the age groups and genders, TRA was associated with a lower risk of bleeding and all-cause mortality. On multivariate logistic regression, TRA was associated with a significant reduction in NACE, major bleeding, and mortality in the overall cohort. In conclusion, a reduction in bleeding and mortality was noted with TRA in all the subgroups in this observational study.

Management of multivessel coronary artery disease in patients with non-ST-elevation myocardial infarction: a complex path to precision medicine.

Recent analyses suggest the incidence of acute coronary syndrome is declining in high- and middle-income countries. Despite this, overall rates of non-ST-elevation myocardial infarction (NSTEMI) continue to rise. Furthermore, NSTEMI is a greater contributor to mortality after hospital discharge than ST-elevation myocardial infarction (STEMI). Patients with NSTEMI are often older, comorbid and have a high likelihood of multivessel coronary artery disease (MVD), which is associated with worse clinical outcomes. Currently, optimal treatment strategies for MVD in NSTEMI are less well established than for STEMI or stable coronary artery disease. Specifically, in relation to percutaneous coronary intervention (PCI) there is a paucity of randomized, prospective data comparing multivessel and culprit lesion-only PCI. Given the heterogeneous pathological basis for NSTEMI with MVD, an approach of complete revascularization may not be appropriate or necessary in all patients. Recognizing this, this review summarizes the limited evidence base for the interventional management of non-culprit disease in NSTEMI by comparing culprit-only and multivessel PCI strategies. We then explore how a personalized, precise approach to investigation, therapy and follow up may be achieved based on patient-, disease- and lesion-specific factors.

The N-AcetylCysteine and RAMipril in Takotsubo Syndrome Trial (NACRAM): Rationale and design of a randomised controlled trial of sequential N-Acetylcysteine and ramipril for the management of Takotsubo Syndrome.

BACKGROUND: Takotsubo Syndrome(TTS), contrary to historical reports, is now increasingly recognised to be associated with substantial mortality and morbidity, both in the short- and long-term. Although TTS is often precipitated by a catecholamine "pulse", in-hospital hypotension is a common occurrence, increasing the risk of mortality. Furthermore, despite the transient catecholamine stimulus, there is increasing evidence that there are significant long term sequelae, including persistently impaired left ventricular(LV) systolic dysfunction, myocardial oedema with fibrosis, as well as persistent impairment of quality of life. A definitive therapeutic option to limit the extent of initial myocardial injury, and to accelerate recovery in TTS is therefore justified. However to date, there has been a lack of prospective studies in this area. DESIGN AND RATIONALE: NACRAM is a multi-centre, randomised, placebo-controlled trial, sequentially testing early use of intravenous N-acetylcysteine(NAC), followed by/or oral ramipril for 12 weeks. The rationale for utilising these agents is related to their effects on limiting nitrosative stress and expression of the inflammasome activator thioredoxin interacting protein(TXNIP); both processes fundamental to the pathogenesis of TTS. END POINTS: NACRAM is assessing resolution of myocardial oedema on cardiac magnetic resonance imaging(CMR), improvements in LV systolic function as measured by global longitudinal strain(GLS) on echocardiography, quality of life, and inflammatory markers. DISCUSSION: To the best of our knowledge, NACRAM will be the first prospective study to help definitively evaluate a therapeutic option in acute attacks of TTS.