Prevalence and Predictors of Emergency Medical Service Use in Patients Undergoing Primary Percutaneous Coronary Intervention for ST-Elevation Myocardial Infarction.

AIM: We aim to describe prevalence of Emergency Medical Service (EMS) use, investigate factors predictive of EMS use, and determine if EMS use predicts treatment delay and mortality in our ST-elevation myocardial infarction (STEMI) cohort. METHOD: We prospectively collected data on 5,602 patients presenting with STEMI for primary percutaneous coronary intervention (PCI) transported to PCI-capable hospitals in Victoria, Australia, from 2013-2018 who were entered into the Victorian Cardiac Outcomes Registry (VCOR). We linked this dataset to the Ambulance Victoria and National Death Index (NDI) datasets. We excluded late presentation, thrombolysed, and in-hospital STEMI, as well as patients presenting with cardiogenic shock and out-of-hospital cardiac arrest. RESULTS: In total, 74% of patients undergoing primary PCI for STEMI used EMS. Older age, female gender, higher socioeconomic status, and a history of prior ischaemic heart disease were independent predictors of using EMS. EMS use was associated with shorter adjusted door-to-balloon (53 vs 72 minutes, p<0.001) and symptom-to-balloon (183 vs 212 minutes, p<0.001) times. Mode of transport was not predictive of 30-day or 12-month mortality. CONCLUSIONS: EMS use in Victoria is relatively high compared with internationally reported data. EMS use reduces treatment delay. Predictors of EMS use in our cohort are consistent with those prevalent in prior literature. Understanding the patients who are less likely to use EMS might inform more targeted education campaigns in the future.

Pharmacologic therapy among patients with type 2 diabetes mellitus admitted to the cardiology service.

AIM: To review the management of diabetes control in patients with type 2 diabetes admitted to the cardiology service at Auckland City Hospital for over 48 hours; to assess how many would potentially benefit from introduction of empagliflozin under current Pharmac guidelines. METHODS: A retrospective audit of all admissions into cardiology between 1 November 2020 and 31 January 2021 prior to the availability of empagliflozin. Data collected included diagnosis and presence of type 2 diabetes, HbA1c and diabetes medications. RESULTS: A total of 449 patients were admitted, of whom 98 had type 2 diabetes. The median age was 64 years old (IQR 56-76) and 66% of patients were male. Pacific peoples were over-represented in this study population. Fifty percent had an HbA1c>60mnmol/mol and diabetes medication was changed in 50% of these. Overall, 50% of patients would be eligible for empagliflozin under current criteria. CONCLUSIONS: High proportions of patients have poor glycaemic control and are not up-titrated, suggesting a missed opportunity for medication optimisation. Pacific peoples are over-represented in this group, suggesting that they are at high risk of diabetes and cardiovascular admissions. Empagliflozin provides a targeted way to address renal and cardiovascular outcomes.

Cardiac complications of COVID-19 infection.

Since the start of the COVID-19 pandemic, studies emerged reporting the occurrence of cardiovascular complications in patients affected by SARS-CoV-2. Initial data were likely skewed by higher risk populations and those with severe disease. Recent, larger studies have corroborated this association and provide estimates for risk of cardiovascular complications. Patients affected by COVID-19 are at increased risk of myocardial infarction, myocarditis, venous thromboembolism, arrhythmias, and exacerbation of heart failure. Furthermore, a subset of patients who recover from the acute illness have persistent symptoms, a condition termed "long COVID", and management of these symptoms is challenging. Clinicians treating patients affected by COVID-19 should remain vigilant for cardiac complications during the acute illness, particularly in high-risk populations.

Revascularisation and outcomes after acute coronary syndromes in patients with prior coronary artery bypass grafting-ANZACS-QI 67.

AIMS: Coronary angiography in patients with previous coronary artery bypass grafts (CABG) is technically more difficult with increased procedure time, radiation exposure and in-hospital complications. In a contemporary national registry of acute coronary syndrome (ACS) patients undergoing an invasive strategy, we compared the management and outcomes of patients with and without prior CABG. METHODS: The All New Zealand ACS Quality Improvement (ANZACS-QI) registry was used to identify patients admitted to New Zealand public hospitals with an ACS who underwent invasive coronary angiography (2014-2018). Outcomes were ascertained by anonymised linkage to national datasets. RESULTS: Of 26,869 patients, 1,791 (6.7%) had prior CABG and 25,078 (93.3%) had no prior CABG. Prior CABG patients were older (mean age 71 years vs 65 years), more comorbid and less likely to be revascularised than those without CABG (49.8% vs 73.0%). Compared to patients without CABG, at a mean follow-up of 2.1 years, patients with prior CABG had higher all-cause mortality (HR 2.03 (1.80-2.29)), and were more likely to have recurrent myocardial infarction (HR 2.70 (2.40-3.04)), rehospitalisation with congestive cardiac failure (HR 2.36 (2.10-2.66)) and stroke (HR 1.82 (1.41-2.34)). CONCLUSION: In contemporary real-world practice, despite half of the patients with ACS and prior CABG receiving PCI, the outcomes remain poor compared with those without prior CABG.

Randomized evaluation of beta blocker and ACE-inhibitor/angiotensin receptor blocker treatment in patients with myocardial infarction with non-obstructive coronary arteries (MINOCA-BAT): Rationale and design.

Myocardial infarction with non-obstructive coronary arteries (MINOCA) is common and occurs in 6-8% of all patients fulfilling the diagnostic criteria for acute myocardial infarction (AMI). This paper describes the rationale behind the trial 'Randomized Evaluation of Beta Blocker and ACE-Inhibitor/Angiotensin Receptor Blocker Treatment (ACEI/ARB) of MINOCA patients' (MINOCA-BAT) and the need to improve the secondary preventive treatment of MINOCA patients. METHODS: MINOCA-BAT 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 the composite endpoint of death of any cause, readmission because of AMI, ischemic stroke or heart failure in patients discharged after MINOCA without clinical signs of heart failure and with left ventricular ejection fraction ≥40%. A total of 3500 patients will be randomized into four groups; e.g. ACEI/ARB and beta blocker, beta blocker only, ACEI/ARB only and neither ACEI/ARB nor beta blocker, and followed for a mean of 4 years. SUMMARY: While patients with MINOCA have an increased risk of serious cardiovascular events and death, whether conventional secondary preventive therapies are beneficial has not been assessed in randomized trials. There is a limited basis for guideline recommendations in MINOCA. Furthermore, studies of routine clinical practice suggest that use of secondary prevention therapies in MINOCA varies considerably. Thus results from this trial may influence future treatment strategies and guidelines specific to MINOCA patients.

Left ventricular thrombus after ST segment elevation myocardial infarction: a single-centre observational study.

AIMS: The incidence of left ventricular (LV) thrombus following ST segment elevation myocardial infarction (STEMI) has reduced with modern reperfusion therapies. There is scant local data on the incidence and outcomes of LV thrombus in the contemporary era of rapid reperfusion. METHODS: Patients with STEMI admitted to Auckland City Hospital between January 2014 and December 2015 were identified using the All New Zealand Acute Coronary Syndrome Quality Improvement (ANZACS-QI) registry and their clinical notes were retrospectively reviewed. RESULTS: Among the 997 patients admitted with STEMI, 53 patients (5%) had LV thrombus. Most patients with LV thrombus had an anterior STEMI (87%). The median time from admission to echocardiography was 48 hours (range 6-552 hours); the median LV ejection fraction was 38% (range 15-53%). Oral anticoagulation was initiated in 44 (83%) patients. LV thrombus resolved in 81% by six months in 42 patients given warfarin. Total mortality at 12 months was 13%. Bleeding occurred in 11% and was the most common treatment-related morbidity. CONCLUSIONS: The incidence of LV thrombus following STEMI was low and it was associated with a low rate of stroke and systemic embolism but high mortality. Randomised studies are needed to evaluate the efficacy of NOAC's in this context.

A pragmatic diagnostic approach to myocardial infarction with non-obstructive coronary arteries.

Myocardial infarction with non-obstructive coronary arteries (MINOCA) is an increasingly recognised condition and it accounts for approximately 10% of all cases of MI. Despite the absence of obstructive coronary artery disease, patients with MINOCA are at increased risk of morbidity and mortality compared to the general population. While many well recognised conditions can present as MINOCA, it can be difficult to reach a final diagnosis with certainty due to the relative infrequency of these conditions in the general population and the lack of diagnostic gold-standard tests. The most common causes of MINOCA are myocarditis, coronary vasospasm, coronary plaque disruption and coronary thrombus or embolism. These can be assessed by way of cardiac magnetic resonance imaging, intra-coronary imaging modalities and clinically relevant diagnostic blood tests, respectively. There are less common and rarer aetiologies which should be considered in the absence of an apparent cause, each with a unique diagnostic standard. By following a systematic approach of diagnostic tests, an underlying cause of MINOCA can be found in the majority of cases, allowing a directed management strategy to be pursued.

Diagnostic coronary angiography and percutaneous coronary intervention practices in New Zealand: The All New Zealand Acute Coronary Syndrome-Quality Improvement CathPCI registry 3-year study (ANZACS-QI 37).

BACKGROUND: Coronary heart disease remains one of the leading causes of mortality and morbidity in New Zealand (NZ) and globally. The All New Zealand Acute Coronary Syndrome Quality Improvement (ANZACS-QI) programme includes the CathPCI registry which records all those referred for diagnostic coronary angiography (DCA) and percutaneous coronary intervention (PCI) in NZ. We present the methods and three-years of data from the ANZACS-QI CathPCI registry. METHODS: The data was extracted from the ANZACS QI CathPCI registry from 01/09/2014 to 24/09/2017. The ANZACS-QI data dictionary defines all the clinical, procedural and outcomes variables collected, and standard statistical analyses were applied. RESULTS: 40,870 patients underwent cardiac catheterisation, with a mean age of 65 years, and males making up 67% of the cohort. Indications included acute coronary syndrome 55%, angina with suspected stable coronary disease 28%, valve surgery workup 8%, planned PCI 3%, heart failure/cardiomyopathy 3%, arrhythmia 1% and other 2%. For those undergoing DCA alone, radial access was used in 85% and two-thirds had at least one major artery with >50% stenosis. PCI was performed in 39% of patients. Drug-eluting stents were used in 97%. CONCLUSION: The CathPCI registry records the characteristics and outcomes of all patients undergoing DCA and PCI in NZ hospitals. As part of the ANZACS-QI programme the registry provides an important platform for quality improvement, research and to inform clinical practice.

Fasting prior to cardiac catheterisation: a single-centre observational study.

AIM: Previous generation contrast agents were associated with high rates of nausea, vomiting and risk of aspiration leading to recommendations to fast prior to the procedure. However, modern contrast agents are well tolerated with a low risk of aspiration. Our current guidelines recommend fasting four to six hours before elective and semi-urgent cardiac catheterisation despite a lack of evidence to support this. We sought to determine the duration and effects of fasting at our centre. METHODS: A single-centre prospective observational study in patients undergoing elective cardiac catheterisation over a six-month period between 7 August 2017 to 7 February 2018 at Auckland City Hospital, New Zealand. RESULTS: One thousand and thirty patients with a mean age of 66±12 years underwent catheterisation. Sixty-seven percent were male, 26% had diabetes, 72% had hypertension and 23% had stage 3 or worse chronic kidney disease. The mean duration of fasting was 11.6±4.9 hours with 80% fasting longer than recommended. One hundred and eight (48%) patients with documented chronic kidney disease did not receive recommended pre-hydration. The most common symptoms related to fasting were hunger (47 %), nausea (3.9%) and vomiting (0.8%). Hypertension (4.1%) and hyperglycaemia (0.8%) occurred due to missed medication. There were no reports of aspiration. CONCLUSION: Most patients were fasted for significantly longer than recommended and pre-hydration was underutilised in patients at high risk of contrast-induced nephropathy. There were no episodes of aspiration with modern contrast agents. Further studies are required to evaluate the need for fasting prior to non-emergency cardiac catheterisation.

The impact of a national COVID-19 lockdown on acute coronary syndrome hospitalisations in New Zealand (ANZACS-QI 55).

BACKGROUND: Countries with a high incidence of coronavirus 2019 (COVID-19) reported reduced hospitalisations for acute coronary syndromes (ACS) during the pandemic. This study describes the impact of a nationwide lockdown on ACS hospitalisations in New Zealand (NZ), a country with a low incidence of COVID-19. METHODS: All patients admitted to a NZ Hospital with ACS who underwent coronary angiography in the All NZ ACS Quality Improvement registry during the lockdown (23 March - 26 April 2020) were compared with equivalent weeks in 2015-2019. Ambulance attendances and regional community troponin-I testing were compared for lockdown and non-lockdown (1 July 2019 to 16 February 2020) periods. FINDINGS: Hospitalisation for ACS was lower during the 5-week lockdown (105 vs. 146 per-week, rate ratio 0•72 [95% CI 0•61-0•83], p = 0.003). This was explained by fewer admissions for non-ST-segment elevation ACS (NSTE-ACS; p = 0•002) but not ST-segment elevation myocardial infarction (STEMI; p = 0•31). Patient characteristics and in-hospital mortality were similar. For STEMI, door-to-balloon times were similar (70 vs. 72 min, p = 0•52). For NSTE-ACS, there was an increase in percutaneous revascularisation (59% vs. 49%, p<0•001) and reduction in surgical revascularisation (9% vs. 15%, p = 0•005). There were fewer ambulance attendances for cardiac arrests (98 vs. 110 per-week, p = 0•04) but no difference for suspected ACS (408 vs. 420 per-week, p = 0•44). Community troponin testing was lower throughout the lockdown (182 vs. 394 per-week, p<0•001). INTERPRETATION: Despite the low incidence of COVID-19, there was a nationwide decrease in ACS hospitalisations during the lockdown. These findings have important implications for future pandemic planning. FUNDING: The ANZACS-QI registry receives funding from the New Zealand Ministry of Health.

Percutaneous Coronary Intervention for Left Main Coronary Disease in New Zealand: National Linkage Study of Characteristics and In-Hospital Outcomes (ANZACS-QI 38).

BACKGROUND: Approximately 5% of coronary angiographies detect LMS disease >50%. Recent randomized trials showed PCI has comparable outcomes to coronary artery bypass grafting (CABG) in low or intermediate risk candidates. In clinical practice, PCI is frequently utilized in those with prohibitive surgical risk. We reviewed contemporary national results of percutaneous coronary intervention (PCI) for left main coronary disease (LMS) disease in New Zealand. METHODS: All patients undergoing PCI for LMS disease from 01/09/2014-24/09/2017 were extracted from the All New Zealand Acute Coronary Syndrome-Quality Improvement registry with national dataset linkage, analyzing characteristics and in-hospital outcomes. RESULTS: The cohort included 469 patients, mean age 70.8 ±â€¯10.7 years, male 331 (71%), and the majority 339 (72%) were unprotected LMS. Indications include ST-elevation myocardial infarction (STEMI) 83 (18%) and NSTEMI or unstable angina 229 (49%). Compared with protected LMS, unprotected LMS were more likely to present with an acute coronary syndrome (73% versus 48%, P < 0.001), and to die in-hospital (9.4% versus 3.9%, P = 0.045). In those with unprotected LMS, in-hospital mortality after acute STEMI PCI was higher than for other indications (21.1% versus 6.1%, P < 0.001). Independent predictors of in-hospital death and major adverse cardiovascular events included STEMI, femoral access and worse renal function. CONCLUSION: Our LMS PCI cohort had high mortality rates, especially those presenting with STEMI and an unprotected LMS. This reflects the contemporary real-world practice of LMS PCI being predominantly performed in high risk patients which differs from randomized trial populations, and this should be considered before comparing with CABG outcomes.

Evolving management and improving outcomes of pregnancy-associated spontaneous coronary artery dissection (P-SCAD): a systematic review.

BACKGROUND: Pregnancy-associated spontaneous coronary artery dissection (P-SCAD) is defined as SCAD occurring during pregnancy or within 3 months post-partum. Earlier systematic reviews have suggested a high maternal and foetal mortality rate. We undertook a structured systematic review of P-SCAD demographics, management and maternal and foetal outcomes. METHODS: Case study identification was conducted according to PRISMA guidelines, with screening of all published P-SCAD cases not meeting pre-defined exclusion criteria. Of two hundred and seventy-three publications screened, one hundred and thirty-eight cases met inclusion criteria. Cases were allocated to one of three time periods; 1960-85 (twenty cases) reflecting early management of P-SCAD, 1986-2005 (forty-two cases) reflecting recent management, and 2006-16 (seventy-six cases), reflecting contemporary management. RESULTS: The only significant demographic change in women experiencing P-SCAD over the last 50 years was an increasing proportion of primigravidas (p = 0.02). Management and outcomes, however, have altered significantly. Emergent angiography (p < 0.0001), reduced thrombolysis (p = 0.006) and increasingly conservative or percutaneous management (p < 0.0001) are associated with dramatic reductions in maternal mortality (85% in earliest reports to 4% in the last decade, p < 0.0001) and foetal mortality (50% in earliest reports to 0.0% in the last decade, p = 0.023). CONCLUSION: This systematic review of temporal changes in presentation, management and outcomes of P-SCAD represents the widest range of variables analysed in the largest cohort of P-SCAD patients to date. In the setting of earlier coronary angiography and increasingly conservative management, maternal and foetal survival rates continue to improve.

Different patients, different outcomes: A case-control study of spontaneous coronary artery dissection versus acute coronary syndrome.

INTRODUCTION: There is progressive interest worldwide in spontaneous coronary artery dissection (SCAD). To identify a SCAD cohort and compare risk factors, presentation, and management outcomes compared to acute coronary syndrome (ACS) matched controls. METHODS: Retrospective analysis was performed from 2000 to 2015. Clinical data included a neuropsychiatric history, with management and clinical outcomes assessed at 12 months. Patients were matched on a 1:3 case-control basis according to type of ACS. Twenty-two SCAD patients were matched to 66 controls by ACS type (ST-elevation myocardial infarction 45%, Non-ST-elevation myocardial infarction 41%, unstable angina 14%). RESULTS: The SCAD group were more likely female (77.3% vs 19.7%, P < 0.0001), of younger age (48.7 ± 10.7 years vs 61.3 ± 10.6 years, P < 0.0001) with no cases of diabetes (0% vs 33.3%, P = 0.002), compared to controls. SCAD patients had a high prevalence of anxiety, depression or previous neuropsychiatric history (52.4% SCAD vs 1.5% ACS, P < 0.0001). A conservative revascularization strategy with stenting was performed in a minority of SCAD patients (13.6% SCAD vs 83.3% ACS, P < 0.0001), with no significant difference in cumulative major adverse cardiac or cerebrovascular events (MACCE) of death, stroke, re-admission, or repeat angiography rates between both groups (13.6% SCAD vs 27.3% ACS P = NS). CONCLUSION: SCAD affects young females with a paucity of cardiovascular risk factors. The major risk factor for SCAD was a history of anxiety, depression, or neuropsychiatric illness. A conservative approach to SCAD revascularization led to similar MACCE when compared to ACS controls undergoing guideline revascularization at 12 months.

Calibrated integrated backscatter and myocardial fibrosis in patients undergoing cardiac surgery.

OBJECTIVE: The reported association between calibrated integrated backscatter (cIB) and myocardial fibrosis is based on study of patients with dilated or hypertrophic cardiomyopathy and extensive (mean 15-34%) fibrosis. Its association with lesser degrees of fibrosis is unknown. We examined the relationship between cIB and myocardial fibrosis in patients with coronary artery disease. METHODS: Myocardial histology was examined in left ventricular epicardial biopsies from 40 patients (29 men and 11 women) undergoing coronary artery bypass graft surgery, who had preoperative echocardiography with cIB measurement. RESULTS: Total fibrosis (picrosirius red staining) varied from 0.7% to 4%, and in contrast to previous reports, cIB showed weak inverse associations with total fibrosis (r=-0.32, p=0.047) and interstitial fibrosis (r=-0.34, p=0.03). However, cIB was not significantly associated with other histological parameters, including immunostaining for collagens I and III, the advanced glycation end product (AGE) N(ε)-(carboxymethyl)lysine (CML) and the receptor for AGEs (RAGE). When biomarkers were examined, cIB was weakly associated with log plasma levels of amino-terminal pro-B-type natriuretic peptide (r=0.34, p=0.03), creatinine (r=0.33, p=0.04) and glomerular filtration rate (r=-0.33, p=0.04), and was more strongly associated with log plasma levels of soluble vascular endothelial growth factor receptor-1 (sVEGFR-1) (r=0.44, p=0.01) and soluble RAGE (r=0.53, p=0.002). CONCLUSIONS: Higher cIB was not a marker of increased myocardial fibrosis in patients with coronary artery disease, but was associated with higher plasma levels of sVEGFR-1 and soluble RAGE. The role of cIB as a non-invasive index of fibrosis in clinical studies of patients without extensive fibrosis is, therefore, questionable.

Obesity is associated with lower coronary microvascular density.

BACKGROUND: Obesity is associated with diastolic dysfunction, lower maximal myocardial blood flow, impaired myocardial metabolism and increased risk of heart failure. We examined the association between obesity, left ventricular filling pressure and myocardial structure. METHODS: We performed histological analysis of non-ischemic myocardium from 57 patients (46 men and 11 women) undergoing coronary artery bypass graft surgery who did not have previous cardiac surgery, myocardial infarction, heart failure, atrial fibrillation or loop diuretic therapy. RESULTS: Non-obese (body mass index, BMI, ≤ 30 kg/m(2), n=33) and obese patients (BMI >30 kg/m(2), n=24) did not differ with respect to myocardial total, interstitial or perivascular fibrosis, arteriolar dimensions, or cardiomyocyte width. Obese patients had lower capillary length density (1145 ± 239, mean ± SD, vs. 1371 ± 333 mm/mm(3), P=0.007) and higher diffusion radius (16.9 ± 1.5 vs. 15.6 ± 2.0 µm, P=0.012), in comparison with non-obese patients. However, the diffusion radius/cardiomyocyte width ratio of obese patients (0.73 ± 0.11 µm/µm) was not significantly different from that of non-obese patients (0.71 ± 0.11 µm/µm), suggesting that differences in cardiomyocyte width explained in part the differences in capillary length density and diffusion radius between non-obese and obese patients. Increased BMI was associated with increased pulmonary capillary wedge pressure (PCWP, P<0.0001), and lower capillary length density was associated with both increased BMI (P=0.043) and increased PCWP (P=0.016). CONCLUSIONS: Obesity and its accompanying increase in left ventricular filling pressure were associated with lower coronary microvascular density, which may contribute to the lower maximal myocardial blood flow, impaired myocardial metabolism, diastolic dysfunction and higher risk of heart failure in obese individuals.

Impact of right atrial pressure on decision-making using fractional flow reserve (FFR) in elective percutaneous intervention.

BACKGROUND: We undertook a prospective study to assess the impact of routine incorporation of right atrial pressure into the calculation of FFR in a real world elective PCI cohort. METHODS: 42 patients with stenoses in 2 separate epicardial vessels at coronary angiography were studied. Using a temperature and pressure sensing guidewire (TPSG) FFR and FFRRAP were performed in the target vessel pre and post PCI and in a non-target vessel. FFR was defined as Pd/Pa, FFRRAP as Pd-Pv/Pa-Pv where Pv was right atrial pressure and Pd/Pa were the hyperemic distal and proximal arterial pressures respectively. RESULTS: Mean RAP was 9.1 ± 0.7 mmHg. Mean FFR was significantly lower when RAP was included in the calculation (FFRRAP 0.77 ± 0.19 vs. FFR 0.80 ± 0.16, p<0.001). In the target vessel pre PCI, incorporating RAP into the calculation of FFR resulted in a significant difference in the FFR value (FFR Pre-PCI 0.69 ± 0.02 vs. FFRRAP Pre-PCI 0.63 ± 0.03, p<0.0001). 21 patients had an FFR ≤ 0.8 in the group. If right atrial pressure were utilized to calculate FFR prior to PCI, an additional 9 patients would have been re-categorised to an FFR ≤ 0.8. Following PCI, mean FFR was lower when RAP was incorporated (Post PCI FFRRAP 0.93±0.05 vs. Post PCI FFR 0.95 ± 0.06, p<0.001). CONCLUSION: Incorporation of right atrial pressure into the calculation of FFR significantly alters FFR values and may potentially reclassify lesions below ischaemic thresholds.

Reduced microvascular density in non-ischemic myocardium of patients with recent non-ST-segment-elevation myocardial infarction.

BACKGROUND: Myocardial microvascular dysfunction has been implicated in the pathogenesis of myocardial infarction (MI). We tested the hypothesis that patients with MI have lower microvasculature density in myocardium remote from the site of infarction than patients with similar extent of coronary artery disease (CAD) without MI and examined the relationship between myocardial capillary length density and plasma levels of angiogenesis-related biomarkers. METHODS: We analyzed biopsies from non-ischemic left ventricular (LV) myocardium and measured plasma levels of angiogenesis-related biomarkers in patients undergoing coronary artery bypass graft surgery, 57 without previous MI (no-MI) and 27 with recent non-ST-segment-elevation MI (NSTEMI). Comparison was made with biopsies from 31 aortic stenosis (AS) patients and 6 patients with "normal" LV without CAD. RESULTS: Myocardial microvascular density of NSTEMI patients was approximately half the density of no-MI patients, and similar to AS patients. Whereas the reduced microvascular density of AS patients was accounted for by their cardiomyocyte hypertrophy, this was not the case for NSTEMI patients, who had higher diffusion radius/cardiomyocyte width ratio than no-MI, "normal" LV, and AS patients. NSTEMI patients had lower plasma levels of carboxymethyl lysine and low molecular weight fluorophores, higher vascular endothelial growth factor (VEGF) receptor-1/VEGF-A ratio, and higher endostatin and hepatocyte growth factor levels than no-MI patients. CONCLUSIONS: Recent MI was associated with reduced microvasculature density in myocardium remote from the site of infarction and alteration in plasma levels of angiogenesis-related biomarkers.

Diastolic dysfunction of aging is independent of myocardial structure but associated with plasma advanced glycation end-product levels.

BACKGROUND: Heart failure is associated with abnormalities of myocardial structure, and plasma levels of the advanced glycation end-product (AGE) N(ε)-(carboxymethyl)lysine (CML) correlate with the severity and prognosis of heart failure. Aging is associated with diastolic dysfunction and increased risk of heart failure, and we investigated the hypothesis that diastolic dysfunction of aging humans is associated with altered myocardial structure and plasma AGE levels. METHODS: We performed histological analysis of non-ischemic left ventricular myocardial biopsies and measured plasma levels of the AGEs CML and low molecular weight fluorophores (LMWFs) in 26 men undergoing coronary artery bypass graft surgery who had transthoracic echocardiography before surgery. None had previous cardiac surgery, myocardial infarction, atrial fibrillation, or heart failure. RESULTS: The patients were aged 43-78 years and increasing age was associated with echocardiographic indices of diastolic dysfunction, with higher mitral Doppler flow velocity A wave (r = 0.50, P = 0.02), lower mitral E/A wave ratio (r = 0.64, P = 0.001), longer mitral valve deceleration time (r = 0.42, P = 0.03) and lower early diastolic peak velocity of the mitral septal annulus, e' (r = 0.55, P = 0.008). However, neither mitral E/A ratio nor mitral septal e' was correlated with myocardial total, interstitial or perivascular fibrosis (picrosirius red), immunostaining for collagens I and III, CML, and receptor for AGEs (RAGE), cardiomyocyte width, capillary length density, diffusion radius or arteriolar dimensions. Plasma AGE levels were not associated with age. However, plasma CML levels were associated with E/A ratio (r = 0.44, P = 0.04) and e' (r = 0.51, P = 0.02) and LMWF levels were associated with E/A ratio (r = 0.49, P = 0.02). Moreover, the mitral E/A ratio remained correlated with plasma LMWF levels in all patients (P = 0.04) and the mitral septal e' remained correlated with plasma CML levels in non-diabetic patients (P = 0.007) when age was a covariate. CONCLUSIONS: Diastolic dysfunction of aging was independent of myocardial structure but was associated with plasma AGE levels.

The index of microvascular resistance identifies patients with periprocedural myocardial infarction in elective percutaneous coronary intervention.

BACKGROUND: This study was designed to assess whether measurement of the index of microvascular resistance (IMR) could help prospectively identify patients who develop periprocedural myocardial infarction (PPMI). METHODS AND RESULTS: IMR was measured in 54 patients before and following percutaneous coronary intervention (PCI) in a culprit vessel with a PressureWire using the equation IMR = Pa(Hyp) × Tmn(Hyp) (Pd(Hyp)-Pw/Pa(Hyp)-Pw). IMR was also measured in an angiographically normal reference vessel. The relative pre-IMR ratio (rPIMR) defined as IMR Culprit divided by IMR Non-Culprit was also calculated. Troponin was sequentially sampled up to 24 h following PCI. Mean troponin post-PCI was 0.37±0.8 ng/ml. 33 (61%) patients fulfilled the criteria for PPMI. IMR pre-PCI was the most significant correlate of post-PCI troponin (r=0.43 p=0.001), however, the number of balloon inflations (r=0.3, p=0.02) and rPIMR (r=0.33 p=0.017) were also correlated. IMR pre-PCI was higher in patients with periprocedural myocardial infarction compared with patients without PPMI (IMR pre-PCI 21.2±2.1 PPMI vs 15.6±1.8 No PPMI, p=0.02). The strongest predictor of troponin post-PCI was IMR pre-PCI (ß 0.7, p=0.02). Both IMR pre- and rPIMR were predictive of PPMI (OR 11 (1.3 to 90.5) p=0.026, OR 1.09 (1 to 1.19) p=0.03, respectively). CONCLUSION: Microvascular function prior to PCI is an important determinant of PPMI. Measuring IMR pre-PCI and rPIMR may allow prospective identification of patients at risk of periprocedural myocardial infarction. Future studies in a larger cohort are required to establish the predictive ability of IMR in PPMI.