Impact of coronary disease patterns, anatomical factors, micro-vascular disease and non-coronary cardiac factors on invasive coronary physiology.

Invasive coronary physiology has been applied by interventional cardiologists to guide the management of coronary artery disease (CAD), with well-defined thresholds applied to determine whether CAD should be managed with optimal medical therapy (OMT) alone or OMT and percutaneous coronary intervention (PCI). There are multiple modalities in clinical use, including hyperaemic and non-hyperaemic indices. Despite endorsement in the major guidelines, there are various factors which impact and confound the readings of invasive coronary physiology, both within the coronary tree and beyond. This review article aims to summarise the mechanisms by which these factors impact invasive coronary physiology, and distinguish factors that contribute to ischaemia from confounding factors. The potential for mis-classification of ischaemic status is highlighted. Lastly, the authors identify targets for future research to improve the precision of physiology-guided management of CAD.

Outcomes of deferred revascularisation following negative fractional flow reserve in diabetic and non-diabetic patients: a meta-analysis.

BACKGROUND: Fractional Flow Reserve (FFR) is a widely applied invasive physiological assessment, endorsed by major guidelines to aid in the decision to perform or defer revascularisation. While a threshold of > 0.8 has been applied universally, clinical outcomes may be affected by numerous factors, including the presence of diabetes. This meta-analysis aims to investigate the outcomes of diabetic versus non-diabetic patients in whom revascularisation was deferred based on negative FFR. METHODS: We performed a meta-analysis investigating the outcomes of diabetic and non-diabetic patients in whom revascularisation was deferred based on negative FFR. A search was performed on MEDLINE, PubMed and EMBASE, and peer-reviewed studies that reported MACE for diabetic and non-diabetic patients with deferred revascularisation based on FFR > 0.8 were included. The primary end point was MACE. RESULTS: The meta-analysis included 7 studies in which 4275 patients had revascularisation deferred based on FFR > 0.8 (1250 diabetic). Follow up occurred over a mean of 3.2 years. Diabetes was associated with a higher odds of MACE (OR = 1.66, 95% CI 1.35-2.04, p = < 0.001), unplanned revascularisation (OR = 1.48, 95% CI 1.06-2.06, p = 0.02), all-cause mortality (OR = 1.74, 95% CI 1.20-2.52, p = 0.004) and cardiovascular mortality (OR = 2.08, 95% CI 1.07-4.05, p = 0.03). CONCLUSIONS: For patients with stable coronary syndromes and deferred revascularisation based on FFR > 0.8, the presence of diabetes portends an increased long-term risk of MACE compared to non-diabetic patients. Trail registration URL:  https://www.crd.york.ac.uk/PROSPERO/ ; Unique identifier: CRD42022367312.

Both surgical and percutaneous revascularization improve prognosis in patients with a coronary chronic total occlusion (CTO) irrespective of collateral robustness.

The impact of surgical or percutaneous coronary revascularization on prognosis in patients with a chronic total occlusion (CTO) remains uncertain. Particularly, whether revascularization of those with robust coronary collaterals improves prognosis is unknown. The objective of this study was to determine the predictors and prognostic impact of revascularization of a CTO, and to determine the clinical impact of robust coronary collaterals. Patients with a CTO diagnosed on coronary angiography between Jul 2010 and Dec 2019 were included in this study. Management strategy of the CTO was defined as percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG) or medical management. The degree of collateral robustness was determined by the Rentrop grading classification. Demographic, angiographic and clinical outcomes were recorded. A total of 954 patients were included in the study, of which 186 (19.5%) patients underwent CTO PCI, 296 (31.0%) patients underwent CABG and 472 (49.5%) patients underwent medical management of the CTO. 166 patients (17.4%) had Rentrop grade zero or one collaterals, 577 (60.5%) patients had Rentrop grade two and 211 (22.1%) had Rentrop grade three collaterals. The independent predictors of medical management of the CTO were older age, greater stenosis in the donor vessel, an emergent indication for angiography, a non-LAD CTO and female sex. The degree of collateral robustness was not associated with long-term mortality, while patients who were revascularized either through CABG or PCI had a significantly lower mortality compared to medical management alone (p < 0.0001). In patients with a CTO, the presence of robust collaterals is not associated with prognosis, while both surgical and percutaneous revascularization is associated with improved prognosis. Further research into the optimal revascularization strategy for a CTO is required.

Safety and efficacy of ulnar artery approach for percutaneous cardiac catheterization: Systematic review and meta-analysis.

BACKGROUND: Trans-radial access has rapidly become the standard for percutaneous coronary procedures in the last decade. As proceduralists overcome the learning curve and become more competent in trans-radial access, alternative safe access sites such as the ulnar artery have been increasingly used for emergent and elective procedures. The aim of this study was to synthesize the best available evidence of the impact on major adverse cardiac events (MACE) of ulnar artery compared to radial artery cardiac catheterization. METHODS: This review considered randomized controlled trials that included adult patients who had a percutaneous coronary procedure via the radial or ulnar artery. The intervention of interest was the use of ulnar compared to radial artery for cardiac catheterization. An extensive search was undertaken for published and unpublished trials up to May 2017. Methodological quality was assessed independently by two reviewers using the Joanna Briggs Institute Meta-Analysis of Statistics Assessment and Review Instrument (JBI-MAStARI) checklist. Data were analyzed using Review Manager. RESULTS: A total of six trials were included in the review. There was no statistically significant difference in the incidence of MACE between patients who underwent trans-ulnar or trans-radial artery catheterization (OR 0.90; 95% CI 0.65-1.25). Complications associated with access including hematoma formation, (n = 6 trials) pseudo-aneurysm, and arterio-venous fistulae formation (n = 5 trials), were investigated in a total of 5,276 patients, with no difference in these complications noted between the two groups. There were no differences in arterial access time, fluoroscopy time, and contrast load between the two groups. CONCLUSIONS: There is evidence to support safe use of the ulnar artery as an alternative to the radial artery for access for cardiac catheterization.

Multidisciplinary Assessment in Optimising Results of Percutaneous Patent Foramen Ovale Closure.

BACKGROUND: Percutaneous patent foramen ovale (PFO) closure is a therapeutic option to prevent recurrent cerebral ischaemia in patients with cryptogenic stroke and transient cerebral ischaemia (TIA). The apparent lack of benefit seen in previous randomised trials has, in part, reflected inclusion of patients with alternate mechanisms of stroke. The role of formal neurology involvement in accurately delineating the likely aetiology of stroke or TIA is crucial in appropriate identification of patients for device closure. Furthermore, as the benefits of device closure may accrue over time, long-term follow-up is essential to define the role of device closure in management of presumed cryptogenic stroke. METHODS: We retrospectively reviewed our experience with percutaneous PFO device closure since 2005. All subjects who underwent PFO closure at John Hunter and Lake Macquarie Private Hospitals were included in the study. All patients referred for device closure following cryptogenic stroke or TIA had first undergone formal neurology review with appropriate imaging and exclusion of paroxysmal atrial arrhythmia. Patients with a history of transient ischaemic attack (TIA) are frequently referred to a specialised clinic, aimed to identify patients with conditions not referable to cerebral ischaemia, with investigations initiated by the specialist clinic to elucidate an underlying aetiology. Outcome data was derived from the Hunter New England Area Local Health District Cardiac and Stroke Outcomes Unit, in addition to review of the medical record. The Cardiac and Stroke Outcomes Unit prospectively identified all patients presenting with stroke, TIA and atrial fibrillation. RESULTS: One hundred and twelve consecutive patients undergoing percutaneous patent foramen ovale closure between 2005 and 2015 were identified. The average age was 42.7 years and 57 (50.9%) patients were male. Cryptogenic stroke (68.8%) and transient cerebral ischaemia (23.2%) were the most common indications for PFO closure, with the Amplatzer device used in 83 cases (74.1%). Early residual shunting was visible in seven patients (6.3%), however on follow-up agitated saline study only two patients had residual shunt (1.8%). The annual risk of recurrent stroke or TIA was 0.21%. CONCLUSIONS: Percutaneous patent foramen ovale closure can be performed safely and effectively in patients with paradoxical embolism. In selected patients, following appropriate multidisciplinary specialist pre-procedural assessment, excellent long-term results with low incidence of recurrent events may be achieved.

Association between vessel-specific coronary Aggregated plaque burden, Agatston score and hemodynamic significance of coronary disease (The CAPTivAte study).

Background: CT coronary angiography (CTCA) is a guideline-endorsed assessment for patients with stable angina and suspected coronary disease. Although associated with excellent negative predictive value in ruling out obstructive coronary disease, there are limitations in the ability of CTCA to predict hemodynamically significant coronary disease. The CAPTivAte study aims to assess the utility of Aggregated Plaque Burden (APB) in predicting ischemia based on Fractional Flow Reserve (FFR). Methods: In this retrospective study, patients who had a CTCA and invasive FFR of the LAD were included. The entire length of the LAD was analyzed using semi-automated software which characterized total plaque burden and plaque morphological subtype (including Low Attenuation Plaque (LAP), Non-calcific plaque (NCP) and Calcific Plaque (CP). Aggregated Plaque Burden (APB) was calculated. Univariate and multivariate analysis were performed to assess the association between these CT-derived parameters and invasive FFR. Results: There were 145 patients included in this study. 84.8 % of patients were referred with stable angina. There was a significant linear association between APB and FFR in both univariate and multivariate analysis (Adjusted R-squared = 0.0469; p = 0.035). Mean Agatston scores are higher in FFR positive vessels compared to FFR negative vessels (371.6 (±443.8) vs 251.9 (±283.5, p = 0.0493). Conclusion: CTCA-derived APB is a reliable predictor of ischemia assessed using invasive FFR and may aid clinicians in rationalizing invasive vs non-invasive management strategies. Vessel-specific Agatston scores are significantly higher in FFR-positive vessels than in FFR-negative vessels. Associations between HU-derived plaque subtype and invasive FFR were inconclusive in this study.

Advances in the Computational Assessment of Disturbed Coronary Flow and Wall Shear Stress: A Contemporary Review.

Coronary artery blood flow is influenced by various factors including vessel geometry, hemodynamic conditions, timing in the cardiac cycle, and rheological conditions. Multiple patterns of disturbed coronary flow may occur when blood flow separates from the laminar plane, associated with inefficient blood transit, and pathological processes modulated by the vascular endothelium in response to abnormal wall shear stress. Current simulation techniques, including computational fluid dynamics and fluid-structure interaction, can provide substantial detail on disturbed coronary flow and have advanced the contemporary understanding of the natural history of coronary disease. However, the clinical application of these techniques has been limited to hemodynamic assessment of coronary disease severity, with the potential to refine the assessment and management of coronary disease. Improved computational efficiency and large clinical trials are required to provide an incremental clinical benefit of these techniques beyond existing tools. This contemporary review is a clinically relevant overview of the disturbed coronary flow and its associated pathological consequences. The contemporary methods to assess disturbed flow are reviewed, including clinical applications of these techniques. Current limitations and future opportunities in the field are also discussed.

Vessel-Specific Outcomes of Deferred Revascularization Following Negative Fractional Flow Reserve.

Variations in myocardial supply area and hydrostatic pressure gradients result in greater likelihood of positive fractional flow reserve (FFR) in the left anterior descending (LAD) compared with the circumflex (Cx) and right coronary artery (RCA). However, the same FFR threshold for deferral of revascularization is applied to all arteries, without evidence that this results in equivalent outcomes. We assessed vessel-specific outcomes of deferred revascularization for the 3 major coronary arteries based on FFR > 0.8. In this retrospective study, data were obtained on consecutive patients who underwent indicated FFR assessment across 2 tertiary institutions. Patients with deferred revascularization were followed for 36 months for the primary end point of vessel-specific target lesion failure (TLF). Of 1,916 major coronary arteries (1,579 patients), the odds ratio of positive FFR was highest in the LAD (odds ratio 3.36, p <0.001). In total, 867 vessels (733 patients) with FFR > 0.8 had complete 3-year medical record follow-ups. The TLF rate for deferred vessels was 10.21%, 11.52%, and 10.96% for the LAD, Cx, and RCA respectively. In a multivariate analysis, there was no significant difference in the odds of TLF for the 0.84 (0.53 to 1.33, p = 0.459), 1.17 (0.68 to 2.01, p = 0.582), and 1.11 (0.62 to 2.00, p = 0.715) in the LAD, Cx, and RCA, respectively. In a multivariate analysis, diabetes mellitus was the only baseline characteristic significantly associated at risk of TLF (1.43 [1.01 to 2.02], p = 0.043). In conclusion, despite greater likelihood of positive FFR in the LAD, the FFR threshold for deferred revascularization resulted in equivalent outcomes in all 3 major coronary arteries, and patients with diabetes mellitus may represent a group that requires aggressive surveillance and risk factor modification after deferred revascularization.

Impact of coronary artery bypass grafting (CABG) on coronary collaterals in patients with a chronic total occlusion (CTO).

Chronic total occlusions (CTO) are found commonly in patients with prior coronary artery bypass grafting (CABG). We sought to determine the effect of CABG on collateral robustness in patients with a CTO. Patients with a CTO diagnosed on coronary angiography between July 2010 and December 2019 were included in this study. Patients were classified as either CTO supplied by a functional graft, CTO supplied by collaterals from a non-grafted donor vessel (non-grafted) or a CTO supplied by collaterals from a grafted donor vessel (grafted). The degree of collateral robustness was determined by the Rentrop classification and collateral connection (CC) grade. Demographic, angiographic and clinical outcomes were recorded. A total of 2088 CTO lesions were identified, of which 878 (42.0%) were supplied by a functional graft, 994 (47.6%) CTOs were supplied by a non-grafted donor vessel and 216 (10.3%) CTOs were supplied by a grafted donor vessel. CTOs supplied by a grafted donor vessel had lower rates of robust collaterals (37.0% vs 83.0%, p < 0.0001) with less mature collaterals as determined by the Rentrop grade (p < 0.0001) and CC grade (p < 0.0001) as compared to CTOs supplied by a non-grafted donor vessel. In patients with a previous CABG, a grafted donor vessel results in less robust coronary collaterals with lower Rentrop and CC grade compared to an ungrafted donor vessel. This may be attributable to changes in coronary blood flow and shear stress, and may be a factor in the lower procedural success rates for CTO intervention in patients with prior CABG.

No-reflow phenomenon in ST-segment elevation myocardial infarction: still the Achilles' heel of the interventionalist.

Improvements in systems, technology and pharmacotherapy have significantly changed the prognosis over recent decades in patients presenting with ST-segment elevation myocardial infarction. These clinical achievements have, however, begun to plateau and it is becoming increasingly necessary to consider novel strategies to further improve outcomes. Approximately a third of patients treated by primary percutaneous coronary intervention for ST-segment elevation myocardial infarction will suffer from coronary no-reflow (NR), a condition characterized by poor myocardial perfusion despite patent epicardial arteries. The presence of NR impacts significantly on clinical outcomes including left ventricular dysfunction, heart failure and death, yet conventional management algorithms neither assess the risk of NR nor treat NR. This review will provide a contemporary overview on the pathogenesis, diagnosis and treatment of NR.

Relation of Obstructive Sleep Apnea in Patients With a Coronary Chronic Total Occlusion to Coronary Collaterals and Mortality.

A chronic total occlusion (CTO) is frequently identified in patients undergoing coronary angiography. The prognostic implications of intermittent hypoxia from obstructive sleep apnea (OSA) on patients with a CTO, and effects on collateral recruitment are unknown. The aim of this study was to determine the prevalence, vascular effects, and prognostic implications of the presence of OSA in patients with a CTO. Patients with a CTO between July 2010 and December 2019 were reviewed. Electronic medical records were accessed to determine documented patient history of OSA, demographics, and clinical course. Patients with robust collateral recruitment were defined as Rentrop grade 2 or 3. A total of 948 patients were included in the study, of which 127 (13.4%) had a documented history of OSA. These patients were younger (67.0 years vs 70.6 years, p < 0.01), had a higher body mass index (29.6 kg/m2 vs 26.7 kg/m2, p < 0.0001), higher rates of hypertension (91.3% vs 83.2%, p < 0.05), higher rates of smokers (63.3% vs 49.0%, p < 0.01) and more use of ß-blockers (79% vs 68.5%, p < 0.05) and statins (92.7% vs 82.1%, p < 0.01). A documented history of OSA was independently associated with robust collaterals (OR 3.0 95%CI 1.5 to 5.8, p < 0.01) and lower mortality (HR 0.3 95% CI 0.1 to 0.7, p < 0.01) with a mean survival of 10.8 years, as compared to 8.1 years (log rank p < 0.0001). In conclusion, in patients with a CTO, documented OSA is independently associated with more robust coronary collaterals and lower mortality. The possible cardioprotective implications of intermittent hypoxia in OSA, as well as treatment effect requires further investigation.

Echocardiographic assessment of pulmonary artery systolic pressure following treadmill stress testing.

AIMS: The use of treadmill stress echocardiography (SE) for the diagnosis of nascent pulmonary hypertension (PH) has been hampered by a lack of well-defined, post-exercise pulmonary artery systolic pressure (PASP) values across representative age groups in a normal cohort. METHODS AND RESULTS: Five hundred and eleven subjects (mean age: 53 ±14, 68% female) with normal resting PASP were included in the study. All participants performed treadmill exercise using the Bruce protocol to a high level of perceived exertion. PASP was calculated before and immediately after exercise using Doppler assessment of tricuspid regurgitation. For the cohort, post-exercise PASP was 39 ± 7 mmHg (range: 23-64 mmHg) representing an increase of 11 ± 6 mmHg (44%) from resting values (P < 0.001). The 95th centile values for post-exercise PASP were calculated for the following age cohorts: <30 years; 46 mmHg, 31-50 years; 50 mmHg, 51-70 years; 52 mmHg, >70 years; 53 mmHg. There was a modest independent correlation between post-exercise PASP and (i) increasing age and (ii) resting PASP (r2 = 0.35 and 0.49, respectively, P = 0.01). CONCLUSION: An increase of post-exercise PASP was seen in all patients undergoing SE in this study. Age was directly correlated with post-exercise PASP. Using normative data from healthy controls, treadmill SE-derived post-exercise PASP may be a useful adjunct in the diagnosis of PH.

Clozapine and incidence of myocarditis and sudden death - Long term Australian experience.

BACKGROUND: Clozapine is the cornerstone of therapy for refractory schizophrenia; however, the potential for cardiotoxicity is an important limitation in its use. In the current analysis we sought to evaluate the long term cardiac outcomes of clozapine therapy. METHODS: All-cause mortality, incidence of sudden death and time to myocarditis were assessed in a cohort of patients maintained on clozapine between January 2009 and December 2015. All patients had regular electrocardiograms, complete blood count, clozapine levels and echocardiography as part of a formal protocol. RESULTS: A total of 503 patients with treatment-resistant schizophrenia were maintained on clozapine during the study period of which 93 patients (18%) discontinued therapy with 29 (6%) deaths. The incidence of sudden death and myocarditis were 2% (n=10) and 3% (n=14) respectively. Amongst patients with sudden death, 7 out of 10 (70%) were documented to have used illicit drugs prior to death, with a tendency to weight gain also noted. The mean time to myocarditis post clozapine commencement was 15±7days. The reduction in left ventricular ejection fraction in those with myocarditis was 11±2%. CONCLUSION: Myocarditis and sudden cardiac death are uncommon but clinically important complications in a cohort of patients followed while maintained on clozapine undergoing regular cardiac assessment. Further studies are required to document the role of preventive measures for left ventricular dysfunction and sudden cardiac death in this population.