The AUStralian MEDiterranean Diet Heart Trial (AUSMED Heart Trial): A randomized clinical trial in secondary prevention of coronary heart disease in a multiethnic Australian population: Study protocol.

The Mediterranean diet was first characterized as a heart-protective diet in the 1960s. The significant cardioprotective effects of the Mediterranean diet in comparison to the standard-care low-fat diet have been established in the primary prevention of cardiovascular disease (CVD); however, there is insufficient evidence in secondary prevention research to influence the current standard of care. Opportunity exists to assess the Mediterranean diet as a therapeutic target for secondary CVD prevention within Australia's ethnoculturally diverse communities. The AUSMED Heart Trial is a multisite randomized controlled trial that will evaluate the efficacy of the Mediterranean diet for secondary prevention of CVD in the Australian health care setting. This trial aims to evaluate the effect of a 6-month Mediterranean diet intervention (delivered by dietitians) versus a "standard-care" low-fat diet in reducing the composite incidence of cardiovascular events at 12 months and at trial end in participants with documented evidence of a previous acute myocardial infarction at trial entry. The quality of the diet at baseline and follow-up will be assessed using comprehensive dietary questionnaires and diaries as well as relevant dietary biomarkers (such as urinary polyphenols and erythrocyte fatty acids). Cardiovascular risk markers, including novel measures of immune and inflammatory status, endothelial function, vascular compliance, platelet activity, and body composition, will be collected to explore possible mechanisms for treatment effect. Cost-effectiveness will also be estimated to support policy translation. We plan to recruit 1,032 participants (516 per arm) from cardiology clinics in major Australian hospitals in Melbourne, Adelaide, and Brisbane.

N-terminal pro-B-type Natriuretic Peptides' Prognostic Utility Is Overestimated in Meta-analyses Using Study-specific Optimal Diagnostic Thresholds.

BACKGROUND: N-terminal fragment B-type natriuretic peptide (NT-proBNP) prognostic utility is commonly determined post hoc by identifying a single optimal discrimination threshold tailored to the individual study population. The authors aimed to determine how using these study-specific post hoc thresholds impacts meta-analysis results. METHODS: The authors conducted a systematic review of studies reporting the ability of preoperative NT-proBNP measurements to predict the composite outcome of all-cause mortality and nonfatal myocardial infarction at 30 days after noncardiac surgery. Individual patient-level data NT-proBNP thresholds were determined using two different methodologies. First, a single combined NT-proBNP threshold was determined for the entire cohort of patients, and a meta-analysis conducted using this single threshold. Second, study-specific thresholds were determined for each individual study, with meta-analysis being conducted using these study-specific thresholds. RESULTS: The authors obtained individual patient data from 14 studies (n = 2,196). Using a single NT-proBNP cohort threshold, the odds ratio (OR) associated with an increased NT-proBNP measurement was 3.43 (95% CI, 2.08 to 5.64). Using individual study-specific thresholds, the OR associated with an increased NT-proBNP measurement was 6.45 (95% CI, 3.98 to 10.46). In smaller studies (<100 patients) a single cohort threshold was associated with an OR of 5.4 (95% CI, 2.27 to 12.84) as compared with an OR of 14.38 (95% CI, 6.08 to 34.01) for study-specific thresholds. CONCLUSIONS: Post hoc identification of study-specific prognostic biomarker thresholds artificially maximizes biomarker predictive power, resulting in an amplification or overestimation during meta-analysis of these results. This effect is accentuated in small studies.

Synchronous cardiac arrest in monozygotic twins with hypertrophic cardiomyopathy--is sudden cardiac death genetically pre-programmed?

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is a myocardial disorder characterised by left ventricular hypertrophy (LVH) in the absence of another cardiac or systemic disease capable of producing the magnitude of LVH evident. HCM causes variable symptoms and is one of the leading causes of sudden cardiac death (SCD) in young adults. While various phenotypic features of HCM among monozygotic twin pairs are not uncommonly reported, occurrence of synchronous cardiac arrest among them is not known from literature. CASE PRESENTATION: We present a case of monozygotic twins with HCM who both had a cardiac arrest post physical exertion in 63rd year of their lives. CONCLUSION: This case highlights potential genetics predisposition of cardiac arrest in patients with HCM despite having different phenotypic expression. SCD may be the only manifestation of patients with HCM. Decision of implantable cardioverter-defibrillator (ICD) placement for primary prevention of SCD should be based on the recommended guidelines, clinical judgment and patient's preference.

Radiation exposure with the radial approach for diagnostic coronary angiography in a centre previously performing purely the femoral approach.

INTRODUCTION: Use of the radial approach for coronary angiography and percutaneous coronary intervention (PCI) is known to improve many patient outcome measures. However, there is some concern that it may be associated with increased patient radiation exposure. This study explores radiation exposure with the radial approach compared with the femoral approach in a centre previously performing purely femoral approach. PATIENTS AND METHODS: Data was collected retrospectively for all patients undergoing diagnostic coronary angiography over a six month period. PCIs and procedures with inherent technical difficulty or use of additional techniques (graft studies, optical coherence tomography, fractional flow reserve) were excluded. Dose area product (DAP) and fluoroscopy time (FT) were analysed for all remaining procedures (n=389), comparing radial (n=109) and femoral (n=280) approaches. RESULTS: The overall mean FT for transradial cases (7.45 mins) was significantly higher than for transfemoral cases (4.59 mins; p<0.001). The overall mean DAP for transradial cases (95.64 G Gycm(2)) was significantly higher than for transfemoral cases (70.25 Gycm(2), p<0.05)). Neither the FT nor the DAP decreased over the six month period. CONCLUSION: The radial approach was associated with significantly higher DAP and FT compared to the femoral approach during an initial introductory phase which was likely insufficient to develop radial proficiency. The results of this study are consistent with previous studies and may influence choice of access for non-emergent diagnostic coronary angiography before radial proficiency has been established, particularly for patients more susceptible to radiation risks.

A case of acute stent thrombosis during treatment with the thrombopoietin receptor agonist peptide--romiplostim.

Romiplostim is a thrombopoietin receptor agonist that increases platelet counts and restores platelet function in patients with chronic immune thrombocytopenia (ITP). Increase in platelet count and platelet activation has been associated with increased thromboembolic risk. The present case report describes an interesting case of acute stent thrombosis in a patient with chronic immune thrombocytopenic purpura (ITP) being treated with romiplostim.

Non-Newtonian Endothelial Shear Stress Simulation: Does It Matter?

Patient-specific coronary endothelial shear stress (ESS) calculations using Newtonian and non-Newtonian rheological models were performed to assess whether the common assumption of Newtonian blood behavior offers similar results to a more realistic but computationally expensive non-Newtonian model. 16 coronary arteries (from 16 patients) were reconstructed from optical coherence tomographic (OCT) imaging. Pulsatile CFD simulations using Newtonian and the Quemada non-Newtonian model were performed. Endothelial shear stress (ESS) and other indices were compared. Exploratory indices including local blood viscosity (LBV) were calculated from non-Newtonian simulation data. Compared to the Newtonian results, the non-Newtonian model estimates significantly higher time-averaged ESS (1.69 (IQR 1.36)Pa versus 1.28 (1.16)Pa, p < 0.001) and ESS gradient (0.90 (1.20)Pa/mm versus 0.74 (1.03)Pa/mm, p < 0.001) throughout the cardiac cycle, under-estimating the low ESS (<1Pa) area (37.20 ± 13.57% versus 50.43 ± 14.16%, 95% CI 11.28-15.18, p < 0.001). Similar results were also found in the idealized artery simulations with non-Newtonian median ESS being higher than the Newtonian median ESS (healthy segments: 0.8238Pa versus 0.6618Pa, p < 0.001 proximal; 0.8179Pa versus 0.6610Pa, p < 0.001 distal; stenotic segments: 0.8196Pa versus 0.6611Pa, p < 0.001 proximal; 0.2546Pa versus 0.2245Pa, p < 0.001 distal) On average, the non-Newtonian model has a LBV of 1.45 times above the Newtonian model with an average peak LBV of 40-fold. Non-Newtonian blood model estimates higher quantitative ESS values than the Newtonian model. Incorporation of non-Newtonian blood behavior may improve the accuracy of ESS measurements. The non-Newtonian model also allows calculation of exploratory viscosity-based hemodynamic indices, such as local blood viscosity, which may offer additional information to detect underlying atherosclerosis.

Incidence, predictors and clinical implications of new renal impairment following percutaneous coronary intervention.

BACKGROUND: Renal impairment post-percutaneous coronary intervention (post-PCI) is a well-described adverse effect following the administration of contrast media. Within a large cohort of registry patients, we aimed to explore the incidence, predictors and clinical outcomes of renal impairment post-PCI. METHODS: The Victorian Cardiac Outcomes Registry is an Australian state-based clinical quality registry focusing on collecting data from all PCI capable centres. Data from 36 970 consecutive PCI cases performed between 2014 and 2018 were analysed. Patients were separated into three groups based on post-procedure creatinine levels (new renal impairment (NRI), defined as an absolute rise in serum creatinine>44.2 µmol/L or>25% of baseline creatinine; new renal impairment requiring dialysis (NDR), defined as worsening renal failure that necessitated a new requirement for renal dialysis; no NRI). Multivariate logistic regression analysis was performed to investigate the impact of NRI and NDR on clinical outcomes. RESULTS: 3.1% (n=1134) of patients developed NRI, with an additional 0.6% (n=225) requiring dialysis. 96.3% (n=35 611) of patients did not develop NRI. Those who developed renal impairment were more comorbid, with higher rates of diabetes (22% vs 38% vs 38%, p<0.001), peripheral vascular disease (3.4% vs 8.2% vs 11%, p<0.001), chronic kidney disease (19% vs 49.7% vs 54.2%) and severe left ventricular dysfunction (5% vs 22% vs 40%, p<0.001). Multivariable analysis found that when compared with the no NRI group, those in the combined NRI/NDR group were at a greater risk of 30-day mortality (OR 4.77; 95% CI 3.89 to 5.86, p<0.001) and 30-day major adverse cardiac events (OR 3.72; 95% CI 3.15 to 4.39, p<0.001). CONCLUSIONS: NRI post-PCI remains a common occurrence, especially among comorbid patients, and is associated with a significantly increased morbidity and mortality risk.

Single centre experience with GORE-HELEX septal occluder for closure of PFO.

Several devices are available for percutaneous patent foramen ovale (PFO) closure. Over the past 3 years our planned treatment strategy of PFO closure has been routine use of the GORE-HELEX septal occluder device, followed by 6 months of aspirin therapy. We present the safety and feasibility of routinely using this device for all patients undergoing percutaneous PFO closure, with 3-month transthoracic echocardiogram (TTE) follow up. In total, 75 adult patients (44.0+/-11.7 years; 45.3% male) were referred for PFO closure during the study period. All patients underwent echocardiography prior to PFO closure. In 5 patients no PFO was found, and 1 patient had an atrial secundum defect closed using the Amplatzer septal occluder. Of the 69 remaining patients with PFO, 68/69 (98.6%) underwent closure with the GORE-HELEX device. Six of 69 cases required device retrieval and 5 of 6 were replaced successfully with a second GORE-HELEX device. One of the 6, a large PFO associated with atrial septal aneurysm, was replaced using the Amplatzer septal occluder. There were no major complications. At 3-month follow up, 65/68 (95.6%) had no residual shunt on TTE, and 3 patients had small residual shunts thought to be related to incomplete endothelialisation at 3 months. In conclusion, percutaneous PFO closure using the GORE-HELEX septal occluder device is safe and feasible, with no major peri-procedural complications and excellent short-term results at 3-month follow up.

Prospective evaluation of the impact of diabetes and left ventricular hypertrophy on the relationship between ischemia and transient ischemic dilation of the left ventricle on single-day adenosine Tc-99m myocardial perfusion imaging.

BACKGROUND: Diabetes and left ventricular hypertrophy (LVH) can cause coronary flow reserve abnormalities in the absence of coronary artery disease (CAD). We sought to evaluate the impact of LVH and diabetes on the relationship between ischemia, severe CAD, and transient ischemic dilation (TID) on adenosine myocardial perfusion imaging (MPI). METHODS AND RESULTS: We prospectively recruited 157 patients referred for routine single-day adenosine technetium 99m MPI. LVH was assessed by use of transthoracic echocardiography. A ratio of 1.19 or greater on MPI defined TID in men and 1.31 or greater in women. Summed difference scores were determined by use of a 17-segment 5-point scoring system. TID was present in 22 of 157 patients (14%), diabetes in 54 of 157 (34%), and LVH in 42 of 157 (27%). By multivariate logistic regression, LVH, ischemia (summed difference score >2), and diabetes were independently predictive of TID. The incidence of TID was stratified by the presence or absence of diabetes and/or LVH in those with ischemia on MPI (8/8 [100%] vs 0/11 [0%], P < .002) or severe CAD on angiography (5/7 [71%] vs 0/8 [0%], P < .01). All those with TID (22/22 [100%]) had either diabetes or LVH (or both). CONCLUSION: Although this study confirms the association between TID and both ischemia and severe CAD, all patients with TID had diabetes, LVH, or frequently, both, suggesting that the pathophysiology of these disease processes may play an integral role in the manifestation of TID on adenosine MPI.

The role of intravascular ultrasound in the management of spontaneous coronary artery dissection.

Primary or spontaneous coronary artery dissection (SCAD) is an unusual but increasingly recognized cause of acute myocardial ischemia and sudden cardiac death. Typically, SCAD presents in younger patients without conventional risk factors for coronary artery disease. It occurs more commonly in women than in men, and frequently during pregnancy or the postpartum period. Its pathophysiology is poorly understood, and there is considerable controversy regarding the optimal management of patients with SCAD-related myocardial ischemia. Therapeutic approaches include conservative medical therapy, coronary artery bypass graft surgery and percutaneous coronary intervention (PCI). We present four cases of SCAD to illustrate specific aspects of the presentation and management of this condition, with particular reference to the importance of intravascular ultrasound (IVUS) to aid diagnosis and guide subsequent PCI.

Plaque volume and occurrence and location of periprocedural myocardial necrosis after percutaneous coronary intervention: insights from delayed-enhancement magnetic resonance imaging, thrombolysis in myocardial infarction myocardial perfusion grade analysis, and intravascular ultrasound.

BACKGROUND: Myocardial necrosis can occur during percutaneous coronary intervention (PCI) despite optimal adjunctive pharmacology and careful technique. We investigated the mechanisms of procedural infarction using angiographic analysis, intravascular ultrasound, and delayed-enhancement magnetic resonance imaging. METHODS AND RESULTS: Fifty-two patients (64 vessels) who underwent complex PCI were studied. All patients were preloaded with clopidogrel and received glycoprotein IIb/IIIa inhibitors. "Adjacent" myonecrosis was defined as the presence of an area of new gadolinium hyperenhancement close to the stent. "Distal" myonecrosis was defined as situated at least 10 mm downstream from the stent. Fifteen vessels (23%) had evidence of new hyperenhancement after PCI. Of these, 8 (12%) had the distal type, and 7 (11%) had the adjacent type. Intravascular ultrasound showed a significantly greater reduction in plaque volume (91.6+/-51.5 versus 8+/-14 versus 20+/-35 mm3; P < 0.001) in the group with distal hyperenhancement compared with patients without new hyperenhancement or adjacent hyperenhancement. In the entire sample, a significant correlation was seen between changes in plaque volume (rho = 0.58, P < 0.001) after PCI and the mass of new necrosis measured by magnetic resonance imaging. Thrombolysis in Myocardial Infarction perfusion grade assessment of a closed microvasculature after PCI carried an odds ratio of 8.0 (95% confidence interval, 1.4 to 46.1; P = 0.02) for the occurrence of hyperenhancement, whereas side-branch occlusion was associated with an odds ratio of 16.2 (95% confidence interval, 2.6 to 102.5; P = 0.03). However, a closed microvasculature was associated with distal hyperenhancement (P = 0.02), and side-branch occlusion was associated with adjacent hyperenhancement (P < 0.001). CONCLUSIONS: These data suggest that distal embolization of plaque material occurs in contemporary PCI of native coronary arteries. Efforts to minimize procedural necrosis may require careful review of side branch anatomy and/or use of distal protection during extensive coronary stenting.

A bleeding kiss: intramural haematoma secondary to balloon angioplasty.

BACKGROUND: Intramural coronary haematoma following percutaneous coronary intervention in the absence of coronary dissection is a rare phenomenon. CASE PRESENTATION: A 69 year old lady with previous prosthetic aortic valve replacement underwent percutaneous coronary intervention (PCI) from the left mainstem to the left anterior descending artery (LAD) and kissing balloon inflations to the LAD and circumflex (Cx) arteries. Although intravascular ultrasound examination (IVUS) of both the LAD and Cx showed both vessels to be widely patent at the end of the procedure, she developed ischaemic chest pain six hours later. Repeat coronary angiography revealed a significant stenosis in the proximal Cx vessel, which was confirmed on IVUS to be intramural haematoma. CONCLUSION: In patients taking warfarin in addition to standard antiplatelet therapy, kissing balloon inflations should be carried out with caution.

Prevalence and outcomes of trans-radial access for percutaneous coronary intervention in contemporary practise.

BACKGROUND: Trans-radial access for percutaneous coronary intervention (PCI) has been associated with lower vascular complication rates and improved outcomes. We assessed the current uptake of trans-radial PCI in Victoria, Australia, and evaluated if patients were selected according to baseline bleeding risk in contemporary clinical practise, and compared selected clinical outcomes. METHODS: PCI data of all patients between 1st January 2013 and 31st December 2014 were analysed using The Victorian Cardiac Outcomes Registry (VCOR). Propensity-matched analysis was performed to compare the clinical outcomes. RESULTS: 11,711 procedures were analysed. The femoral route was the predominant access site (66%). Patients undergoing trans-radial access PCI were younger (63.9±11.6 vs. 67.2±11.8; p<0.001), had a higher BMI (28.9±5.5 vs. 28.5±5.2; p<0.001), more likely to be male (80.0 vs. 74.9%;p<0.001), less likely to have presented with cardiogenic shock (0.9 vs. 2.8%; p<0.001) or have the following comorbidities: diabetes (19.8 vs. 23.1%; p<0.001), peripheral vascular disease (2.9 vs. 4.3%; p=0.005) or renal impairment (13.6 vs. 22.1%; p<0.001). The radial group had less bleeding events (3.2 vs. 4.6%; p<0.001) and shorter hospital length of stay (3.1±4.7 vs. 3.3±3.9; p=0.006). There was no significant difference in mortality (1.0 vs. 1.4%; p=0.095). CONCLUSIONS: Trans-femoral approach remains the dominant access site for PCI in Victoria. The choice of route does not appear to be selected by consideration of bleeding risk. The radial route is associated with improved clinical outcomes of reduced bleeding and length of stay consistent with previous findings, and this supports the efficacy and safety of trans-radial PCI in real-world clinical practise.

Platypnea-orthodeoxia associated with a fenestrated atrial septal aneurysm: case report.

BACKGROUND: Platypnea-orthodeoxia describes the condition of combined dyspnea and hypoxia respectively, whilst in the upright position, which improves in the recumbent position. CASE REPORT: We present a case of platypnea-orthodeoxia due to a fenestrated atrial septal defect associated with an atrial septal aneurysm. Due to the fenestrated nature of the atrial septal defect, surgical rather than percutaneous correction was performed. CONCLUSION: A high index of suspicion is required to diagnose the syndrome of platypnea-orthodeoxia. Careful echocardiographic evaluation is required to identify the syndrome, and to determine suitability for percutaneous repair.

What is the best contemporary treatment for in-stent restenosis?

In-stent restenosis (ISR) remains a challenging problem in percutaneous coronary intervention and the optimal treatment strategy remains unclear. The aim of this study was to compare the 18 month clinical outcomes in patients receiving sirolimus-eluting stents (SES) with vascular brachytherapy (VBT) for the treatment of ISR. Twenty-five consecutive patients treated with VBT were compared with 29 patients who had SES deployment for ISR. Major adverse cardiac events (MACE) were defined as a combination of death from cardiac causes, nonfatal myocardial infarction, or repeat TVR. At 18 month follow-up, the MACE rate was significantly lower in the SES compared with the VBT group (14% vs 40%, P=.03). One patient in the VBT group developed late stent thrombosis (at 10 months) and died; there was no stent thrombosis in the SES group. This observational study, taken with other recent reports, offers further credence to the use of SES for ISR. The results of randomized comparisons with VBT are awaited with interest.

Practical experience with ticagrelor: an Australian and New Zealand perspective.

OBJECTIVE: Ticagrelor is recommended in local and international guidelines as first-line therapy in combination with aspirin in patients presenting with acute coronary syndromes (ACS). The purpose of this article is to provide practical guidance regarding the use of ticagrelor in this setting. METHODS AND RESULTS: Ticagrelor, a direct-acting, reversible P2Y12 receptor antagonist, has a faster onset, and a more potent and predictable antiplatelet effect compared with clopidogrel. The authors recommend considering the use of ticagrelor in moderate-to-high risk ACS patients treated with an invasive approach and those managed non-invasively who have elevated troponin levels. Consistent with outcomes observed in the PLATO trial overall, ticagrelor was superior to clopidogrel treatment in patients with chronic kidney disease, a history of stroke or transient ischemic attack, the elderly, and patients requiring surgical revascularization. CONCLUSIONS: When switching from clopidogrel to ticagrelor, patients established on clopidogrel therapy can be switched directly without loading; patients not loaded with clopidogrel and not taking maintenance dose clopidogrel for at least 5 days should first be loaded with ticagrelor. Guidelines recommend discontinuing ticagrelor 5 days before surgery if antiplatelet effects are not desired and recommencing therapy as soon as safe following surgery. Ticagrelor should be avoided in individuals with a history of intracranial hemorrhage, moderate-to-severe hepatic impairment, high bleeding risk, within 24 hours of thrombolytic therapy, and in those treated with oral anticoagulants. Local, real-world experience suggests low bleeding rates with ticagrelor therapy. Dyspnoea is a common symptom in patients with ACS and is also a side-effect of ticagrelor therapy. Discontinuation of ticagrelor due to dyspnoea has been uncommon in clinical trials. However, local registry data suggest higher discontinuation rates (2-9%) related to dyspnoea in the real-world setting, indicating that clinicians may need to consider other potential causes of dyspnoea before discontinuing ticagrelor.

Rivaroxaban in acute coronary syndromes--is it prime time?

Arterial thrombosis in acute coronary syndrome (ACS) is associated with activation of platelets and the coagulation cascade. Persistent thrombin levels have been reported after ACS in such patients. Novel oral anticoagulants without a need of close monitoring and frequent blood tests such as warfarin can provide a chronic beneficial effect on recurrent ischaemic events in such a population. Rivaroxaban, a new oral factor Xa inhibitor, has been tried for this indication in the 'Anti-Xa Therapy to Lower Cardiovascular Events in Addition to Standard Therapy in Subjects With Acute Coronary Syndrome ACS 2-Thrombolysis In Myocardial Infarction 51' (ATLAS ACS 2-TIMI 51) trial using a low dose regimen in an attempt to balance the adverse effects of bleeding related to chronic anticoagulation on background of dual antiplatelet therapy for ACS, and the beneficial effects on recurrent coronary ischemia. The role of rivaroxaban in this context has been discussed in detail in this review.

Effects of intravenous caffeine on fractional flow reserve measurements in coronary artery disease.

BACKGROUND: Intravenous adenosine is used to minimise the coronary micro-resistance to achieve maximal hyperaemia along with nitrates for optimal fractional flow reserve (FFR) measurements. We hypothesise that caffeine, being a competitive inhibitor of adenosine, would influence adenosine-mediated FFR readings. METHODS: Consecutive patients undergoing angiogram and FFR measurements were enrolled after abstaining from caffeine for 24 h. Patients with any contraindications to intravenous adenosine or caffeine were excluded. FFR measurements were taken using nitrates and adenosine pre and post 4 mg/kg intravenous caffeine administration and results were compared. RESULTS: 10 patients were analysed (80% men, age 59.9±9.4, weight 87.5±15.6). Baseline caffeine levels were undetectable in all patients and increased significantly postintravenous caffeine administration (16.4±5.5 µg/mL). Baseline preadenosine FFR values were similar before and after caffeine administration (0.91±0.06 vs 0.91±0.07; p=0.41). Postadenosine FFR readings were 0.79±0.07, which increased non-significantly to 0.82±0.11 postcaffeine (p=0.15). Two significant FFR readings (≤0.8) changed to non-significant after caffeine administration (0.77-0.93 and 0.8-0.91). CONCLUSIONS: Caffeine may affect FFR results in some patients. Larger studies are warranted to clarify the extent and magnitude of caffeine/adenosine interaction particularly due to ubiquitous nature of caffeine and increasing importance of FFR in clinical practice.