Autonomic responses in young females with typical vasovagal syncope.

To determine whether young women who have experienced typical vasovagal syncope (tVVS) have altered autonomic response parameters, based on a battery of autonomic tests and maneuvers. Notably, previous studies including small cohorts and a partial list of tests yielded conflicting results. A total of 91 otherwise healthy women were included and divided according to those who had experienced tVVS (39 patients) or not (52 patients). Heart rate variability was evaluated at rest, under strict conditions, during 5 min of standing and during a deep breathing test. Response to Valsalva maneuver and Ewing maneuver were also quantified and compared. Both groups had similar clinical characteristics at baseline. No significant differences were found between the two groups in any of the autonomic parameters evaluated. Autonomic responses in young women who experienced typical vasovagal syncope at baseline were indistinguishable from those who did not. Thus, using non-tilt test autonomic screening tests does not seem to provide diagnostic benefits, and may not be useful in predicting recurrence in this patient population.

Normal baseline cardiac autonomic function and increased pupillary parasympathetic tone in patients with vasovagal syncope.

It is controversial whether people with vasovagal syncope (VVS) have abnormal autonomic responses at baseline and whether specific diagnostic manoeuvres have a diagnostic value. We investigated whether the pupillary light reflex and cardiac autonomic tests can be used to identify autonomic dysfunction in volunteers with a medical history of VVS. The study groups included 128 healthy volunteers, of whom 31 reported a history of typical VVS. The right pupil was evaluated using an automated, commercial infra-red pupillometer under strict conditions. In addition to miosis and mydriasis kinetics, pupil diameters were measured. Heart rate variability at rest and heart rate changes to standing were quantified with high-resolution electrocardiography and designated software. The demographic and clinical characteristics of both groups were statistically similar. Average constriction velocity (ACV) was significantly higher in VVS patients following a univariate analysis (3.83 ± 0.59 vs. 3.56 ± 0.73 mm/s, p = 0.042) and after correcting for potential confounders (p = 0.049). All other pupillometric and heart rate indices were comparable between groups. Patients with a history of VVS depict pupillary parasympathetic overactivity in response to light stimuli, manifested as increased ACV. The prognostic implications of this finding and the significance of using this simple clinical tool to identify patients who are at risk for developing frequent episodes of VVS or physical injuries following a syncope merits further study.

Percutaneous coronary intervention with ridaforolimus eluting-stents in small vessel coronary artery disease.

INTRODUCTION: The ridaforolimus-eluting stent (RES) system uses a novel cobalt alloy-based coronary stent with a durable elastomeric polymer eluting ridaforolimus. AIM OF STUDY: To assess the safety and efficacy of small diameter (2.25 mm) RES (EluNIR) in small coronary artery disease. METHODS: A prospective, multicenter, single-arm, open-label clinical trial. Clinical follow-up was performed at 30 days, 6 months, and 1 year after the procedure. Target lesions were located in native coronary arteries or bypass graft conduits, with visually estimated diameter of ≥2.25 mm to ≤2.5 mm. The primary endpoint was combined device success, defined as final in-stent residual diameter stenosis <30%, without 30-day major adverse cardiovascular events (MACE). RESULTS: A total of 81 patients were enrolled in the study. Twenty-three patients (28%) had acute coronary syndrome (ACS) at presentation and 37 (46%) had prior myocardial infarction (MI). Most of the target lesions were located in the circumflex coronary artery (44%) and were classified as B2/C grade according to the American Heart Association/American College of Cardiology classification. The final mean minimal lumen diameter, mean reference vessel diameter, and mean residual percent diameter stenosis were 2.0 ± 0.2 mm, 2.3 ± 0.1 mm, and 14 + 6.6%, respectively. The primary endpoint of device success without 30-day MACE was achieved in 98.8% of the patients. Target lesion failure (TLF) at 6 months was 1.2%. Thirty-day and 1-year MACE rates were 1.2% and 2.5%, respectively. CONCLUSION: The EluNIR 2.25 mm stent shows excellent results in small coronary artery disease and adds another tool in the treatment of this complex lesion type.

First-in-human study of the CAPTIS embolic protection system during transcatheter aortic valve replacement.

BACKGROUND: Stroke and other clinically significant embolic complications are well documented in the early period following transcatheter aortic valve replacement (TAVR). The CAPTIS device is an embolic protection system, designed to provide neurovascular and systemic protection by deflecting debris away from the brain's circulation, capturing the debris and thus avoiding systemic embolisation. AIMS: We aimed to study the safety and feasibility study of the CAPTIS complete cerebral and full-body embolic protection system during TAVR. METHODS: A first-in-human study investigated the safety, feasibility and debris capturing ability of CAPTIS during TAVR. Patients were followed for 30 days. The primary endpoints were device safety and cerebrovascular events at 72 hours. RESULTS: Twenty patients underwent TAVR using balloon-expandable or self-expanding valve systems. CAPTIS was successfully delivered, positioned, deployed, and retrieved in all cases, and TAVR was successfully completed without device-related complications. No cerebrovascular events were observed. High numbers of debris particles were captured in all patients. CONCLUSIONS: The use of the CAPTIS full-body embolic protection system during TAVR was safe, and it captured a substantial number of debris particles. No patient suffered from a cerebrovascular event. A randomised clinical trial is warranted to prove its efficacy.

The impact of on-site cardiac surgical backup on clinical outcomes of acute coronary syndrome-analysis of the ACSIS national registry.

Background: The availability of advanced technologies for mechanical support in hospitals with on-site cardiac surgery (CS), along with the ability to perform urgent coronary artery bypass graft (CABG) surgery, may result in improved clinical outcomes in patients with acute coronary syndrome (ACS). Methods: We conducted a retrospective analysis of the bi-annually Acute Coronary Syndrome Israeli Survey (ACSIS) registry from the year 2000 to 2020, performed in hospitals with and without CS. Mortality rates and major adverse cardiac and cerebrovascular events (MACCE) rates are reported. We evaluated two periods of the study-early (2000-2010) vs. late (2011-2020). Propensity score matching was performed to reduce bias between the two groups. Results: The study included 16,979 patients (52.3% in the on-site CS group). Patients in the on-site CS group were more likely to undergo percutaneous coronary intervention (PCI), (odds ratio [OR], 1.26 [95% CI, 1.18-1.35]; p < 0.001) and CABG [OR, 1.91 (95%CI, 1.63-2.24); P < 0.001], and patients in hospitals without on-site CS had higher 30-day MACCE [OR, 1.17 (95% CI, 1.07-1.27); p < 0.0005]. Overall, there was no difference in 1-year mortality (hazard ratio [HR], 0.98 [95% CI, 0.89-1.08]; p = 0.71) between the groups. During the late period of the study, patients in the group without on-site CS had lower 30-day mortality [OR, 0.69 (95% CI, 0.49-0.97); P = 0.04], yet with no difference in 1-year mortality [HR, 0.81 (95% CI, 0.65-1.01); p = 0.07]. Conclusions: The availability of on-site CS resulted in variations in treatment modality, yet it did not affect the clinical outcomes of ACS. A trend to a better short-term outcomes was noted in hospitals without CS during the late period of the study, which warrants further investigation.

Coronary Embolism After Transcatheter Aortic Valve Replacement-Case Series and Review of Literature.

Periprocedural systemic embolism is a well-documented complication of transcatheter aortic valve replacement (TAVR). Although the most focus was given to cerebral embolism (which remains unpredictable, difficult to prevent, and a source of increased morbidity and mortality after TAVR), coronary embolism remains less investigated and potentially overlooked. This study provides a case series of 3 patients diagnosed with coronary embolism after TAVR in our institution over a 2-year period (3 of 297 cases, 1%) and a systematic literature review (4 studies; 19 case reports). Overall, coronary embolism associated with TAVR is frequently characterized by proximal vessel occlusion causing ST-elevation myocardial infarction and hemodynamic instability with lower mortality in the acute phase as compared with late coronary embolism. However, it often presents with distal vessel occlusion and minor symptoms that may be overlooked in the periprocedural period. In conclusion, we suggest that TAVR-associated coronary embolism has a much higher prevalence than previously documented. Further studies are warranted to properly assess the prevalence and impact of this phenomenon.

Assessing the use of a noninvasive monitoring system providing multiple cardio-pulmonary parameters following revascularization in STEMI patients.

Background: Continuous monitoring of ECG, respiratory rate, systolic and diastolic blood pressure, pulse rate, cardiac output, and cardiac index is important in patients with ST-elevation myocardial infarction (STEMI) admitted to the intensive cardiac care unit (ICCU). However, monitoring these parameters in this setting and in these patients using noninvasive, wireless devices has not been conducted so far. We aimed to assess the use of a novel noninvasive continuous monitoring device in STEMI patients admitted to the ICCU. Methods: Participants included STEMI patients that were admitted to the ICCU after primary percutaneous coronary intervention (PPCI). Patients were continuously monitored using a novel wearable chest patch monitor. Results: Fifteen patients with STEMI who underwent PPCI were included in this study. The median age was 52.8 years, the majority were males, and the median body mass index (BMI) was 25.7. Monitoring lasted for 66 ± 16 hours, and included the automatic collection and recording of all vitals, freeing the nursing staff to focus on other tasks. The user experience of nurses as reflected in filled questionnaires showed high satisfaction rates in all aspects. Conclusion: A novel noninvasive, wireless device showed high feasibility in continuously monitoring multiple crucial parameters in STEMI patients admitted to the ICCU after PPCI.

When Does a Calcium Score Equate to Secondary Prevention?: Insights From the Multinational CONFIRM Registry.

BACKGROUND: Elevated coronary artery calcium (CAC) scores in subjects without prior atherosclerotic cardiovascular disease (ASCVD) have been shown to be associated with increased cardiovascular risk. OBJECTIVES: The authors sought to determine at what level individuals with elevated CAC scores who have not had an ASCVD event should be treated as aggressively for cardiovascular risk factors as patients who have already survived an ASCVD event. METHODS: The authors performed a cohort study comparing event rates of patients with established ASVCD to event rates in persons with no history of ASCVD and known calcium scores to ascertain at what level elevated CAC scores equate to risk associated with existing ASCVD. In the multinational CONFIRM (Coronary CT Angiography Evaluation for Clinical Outcomes: An International Multicenter) registry, the authors compared ASCVD event rates in persons without a history of myocardial infarction (MI) or revascularization (as categorized on CAC scores) to event rates in those with established ASCVD. They identified 4,511 individuals without known coronary artery disease (CAC) who were compared to 438 individuals with established ASCVD. CAC was categorized as 0, 1 to 100, 101 to 300, and >300. Cumulative major adverse cardiovascular events (MACE), MACE plus late revascularization, MI, and all-cause mortality incidence was assessed using the Kaplan-Meier method for persons with no ASCVD history by CAC level and persons with established ASCVD. Cox proportional hazards regression analysis was used to calculate HRs with 95% CIs, which were adjusted for traditional cardiovascular risk factors. RESULTS: The mean age was 57.6 ± 12.4 years (56% male). In total, 442 of 4,949 (9%) patients experienced MACEs over a median follow-up of 4 years (IQR: 1.7-5.7 years). Incident MACEs increased with higher CAC scores, with the highest rates observed with CAC score >300 and in those with prior ASCVD. All-cause mortality, MACEs, MACE + late revascularization, and MI event rates were not statistically significantly different in those with CAC >300 compared with established ASCVD (all P > 0.05). Persons with a CAC score <300 had substantially lower event rates. CONCLUSIONS: Patients with CAC scores >300 are at an equivalent risk of MACE and its components as those treated for established ASCVD. This observation, that those with CAC >300 have event rates comparable to those with established ASCVD, supplies important background for further study related to secondary prevention treatment targets in subjects without prior ASCVD with elevated CAC. Understanding the CAC scores that are associated with ASCVD risk equivalent to stable secondary prevention populations may be important for guiding the intensity of preventive approaches more broadly.

Clustering of clinical and echocardiographic phenotypes of covid-19 patients.

We sought to divide COVID-19 patients into distinct phenotypical subgroups using echocardiography and clinical markers to elucidate the pathogenesis of the disease and its heterogeneous cardiac involvement. A total of 506 consecutive patients hospitalized with COVID-19 infection underwent complete evaluation, including echocardiography, at admission. A k-prototypes algorithm applied to patients' clinical and imaging data at admission partitioned the patients into four phenotypical clusters: Clusters 0 and 1 were younger and healthier, 2 and 3 were older with worse cardiac indexes, and clusters 1 and 3 had a stronger inflammatory response. The clusters manifested very distinct survival patterns (C-index for the Cox proportional hazard model 0.77), with survival best for cluster 0, intermediate for 1-2 and worst for 3. Interestingly, cluster 1 showed a harsher disease course than cluster 2 but with similar survival. Clusters obtained with echocardiography were more predictive of mortality than clusters obtained without echocardiography. Additionally, several echocardiography variables (E' lat, E' sept, E/e average) showed high discriminative power among the clusters. The results suggested that older infected males have a higher chance to deteriorate than older infected females. In conclusion, COVID-19 manifests differently for distinctive clusters of patients. These clusters reflect different disease manifestations and prognoses. Although including echocardiography improved the predictive power, its marginal contribution over clustering using clinical parameters only does not justify the burden of echocardiography data collection.

Sex and age-specific interactions of coronary atherosclerotic plaque onset and prognosis from coronary computed tomography.

AIMS: The totality of atherosclerotic plaque derived from coronary computed tomography angiography (CCTA) emerges as a comprehensive measure to assess the intensity of medical treatment that patients need. This study examines the differences in age onset and prognostic significance of atherosclerotic plaque burden between sexes. METHODS AND RESULTS: From a large multi-center CCTA registry the Leiden CCTA score was calculated in 24 950 individuals. A total of 11 678 women (58.5 ± 12.4 years) and 13 272 men (55.6 ± 12.5 years) were followed for 3.7 years for major adverse cardiovascular events (MACE) (death or myocardial infarction). The age where the median risk score was above zero was 12 years higher in women vs. men (64-68 years vs. 52-56 years, respectively, P < 0.001). The Leiden CCTA risk score was independently associated with MACE: score 6-20: HR 2.29 (1.69-3.10); score > 20: HR 6.71 (4.36-10.32) in women, and score 6-20: HR 1.64 (1.29-2.08); score > 20: HR 2.38 (1.73-3.29) in men. The risk was significantly higher for women within the highest score group (adjusted P-interaction = 0.003). In pre-menopausal women, the risk score was equally predictive and comparable with men. In post-menopausal women, the prognostic value was higher for women [score 6-20: HR 2.21 (1.57-3.11); score > 20: HR 6.11 (3.84-9.70) in women; score 6-20: HR 1.57 (1.19-2.09); score > 20: HR 2.25 (1.58-3.22) in men], with a significant interaction for the highest risk group (adjusted P-interaction = 0.004). CONCLUSION: Women developed coronary atherosclerosis approximately 12 years later than men. Post-menopausal women within the highest atherosclerotic burden group were at significantly higher risk for MACE than their male counterparts, which may have implications for the medical treatment intensity.

Treatment of late paravalvular regurgitation after transcatheter aortic valve implantation: prognostic implications.

AIMS: Paravalvular regurgitation (PVR) after transcatheter aortic valve implantation (TAVI) is associated with increased morbidity and mortality. The effect of transcatheter interventions to treat PVR after the index TAVI was investigated. METHODS AND RESULTS: A registry of consecutive patients who underwent transcatheter intervention for ≥ moderate PVR after the index TAVI at 22 centers. The principal outcomes were residual aortic regurgitation (AR) and mortality at 1 year after PVR treatment. A total of 201 patients were identified: 87 (43%) underwent redo-TAVI, 79 (39%) plug closure, and 35 (18%) balloon valvuloplasty. Median TAVI-to-re-intervention time was 207 (35; 765) days. The failed valve was self-expanding in 129 (63.9%) patients. The most frequent devices utilized were a Sapien 3 valve for redo-TAVI (55, 64%), an AVP II as plug (33, 42%), and a True balloon for valvuloplasty (20, 56%). At 30 days, AR ≥ moderate persisted in 33 (17.4%) patients: 8 (9.9%) after redo-TAVI, 18 (25.9%) after plug, and 7 (21.9%) after valvuloplasty (P = 0.036). Overall mortality was 10 (5.0%) at 30 days and 29 (14.4%) at 1 year: 0, 8 (10.1%), and 2 (5.7%) at 30 days (P = 0.010) and 11 (12.6%), 14 (17.7%), and 4 (11.4%) at 1 year (P = 0.418), after redo-TAVI, plug, and valvuloplasty, respectively. Regardless of treatment strategy, patients in whom AR was reduced to ≤ mild had lower mortality at 1 year compared with those with AR persisting ≥ moderate [11 (8.0%) vs. 6 (21.4%); P = 0.007]. CONCLUSION: This study describes the efficacy of transcatheter treatments for PVR after TAVI. Patients in whom PVR was successfully reduced had better prognosis. The selection of patients and the optimal PVR treatment modality require further investigation.

Thoracic Aorta Perforation Treated Conservatively After TAVR in a Patient With Extremely Tortuous Aorta.

Aortic perforation is a rare complication of transcatheter aortic valve replacement associated with grim outcomes. Tortuous and calcified aortas increase the risk of aortic trauma and perforation. We report a case in which, despite massive thoracic bleeding, avoidance of thoracic aortic surgery resulted in clinical recovery. (Level of Difficulty: Intermediate.).

Prognostic Significance of Nonobstructive Left Main Coronary Artery Disease in Patients With and Without Diabetes: Long-Term Outcomes From the CONFIRM Registry.

BACKGROUND: Prognostic significance of non-obstructive left main (LM) disease was recently reported. However, the influence of diabetes mellitus (DM) on event rates in patients with and without non-obstructive LM disease is not well-known. METHODS: We evaluated 27,252 patients undergoing coronary computed tomographic angiography from the COroNary CT Angiography Evaluation For Clinical Outcomes: An InteRnational Multicenter (CONFIRM) Registry. Cumulative long-term incidence of all-cause mortality (ACM) was assessed between DM and non-DM patients by normal or non-obstructive LM disease (1-49% stenosis). RESULTS: The mean age of the study population was 57.6±12.6 years. Of the 27,252 patients, 4,434 (16%) patients had DM. A total of 899 (3%) deaths occurred during the follow-up of 3.6±1.9. years. Compared to patients with normal LM, those with non-obstructive LM had more pronounced overall coronary atherosclerosis and more cardiovascular risk factors. After clinical risk factors, segment involvement score, and stenosis severity adjustment, compared to patients without DM and normal LM, patients with DM were associated with increased ACM regardless of normal (HR 1.48, 95% CI 1.22-1.78, p<0.001) or non-obstructive LM (HR 1.46, 95% CI 1.04-2.04, p=0.029), while nonobstructive LM disease was not associated with increased ACM in patients without DM (HR 0.85, 95% CI 0.67-1.07, p=0.165) and there was no significant interaction between DM and LM status (HR 1.03, 95% CI 0.69-1.54, p=0.879). CONCLUSION: From the CONFIRM registry, we demonstrated that DM was associated with increased ACM. However, the presence of non-obstructive LM was not an independent risk marker of ACM, and there was no significant interaction between DM and non-obstructive LM disease for ACM.

A validated score to predict one-year and long-term mortality in patients with significant tricuspid regurgitation.

Aims: Most patients with significant (defined as ≥ moderate) tricuspid regurgitation (TR) are treated conservatively. Individual mortality rates are markedly variable. We developed a risk score based on comprehensive clinical and echocardiographic evaluation, predicting mortality on an individual patient level. Methods and results: The cohort included 1701 consecutive patients with significant TR, half with isolated TR, admitted to a single hospital, treated conservatively. We derived a scoring system predicting 1-year mortality and validated it using k-fold cross-validation and with external validation on another cohort of 5141 patients. Score utility was compared with matched patients without significant TR. One-year mortality rate was 31.3%. The risk score ranged 0-17 points and included 11 parameters: age (0-3), body mass index ≤ 25 (0-1), history of liver disease (0-2), history of chronic lung disease (0-2), estimated glomerular filtration rate (0-5), haemoglobin (0-2), left-ventricular ejection fraction (0-1), right-ventricular dysfunction (0-1), right atrial pressure (0-2), stroke volume index (SVI) (0-1) and left-ventricular end-diastolic diameter (0-1). One-year mortality rates increased from 0 to 100%, as the score increased up to ≥16. Areas under the receiver operating curves were 0.78, 0.70, and 0.73, for the original, external validation, and external validation with SVI measured cohorts. The score remained valid in subpopulations of patients with quantified RV function, quantified TR and isolated TR. Significant TR compared to no TR, affected 1-year mortality stronger with higher scores, with a significantly positive interaction term. Conclusion: We suggest a robust risk score for inpatients with significant TR, assisting risk stratification and decision-making. Our findings underscore the burden of TR providing benchmarks for clinical trial design.

Extent of subclinical atherosclerosis on coronary computed tomography and impact of statins in patients with diabetes without known coronary artery disease: Results from CONFIRM registry.

BACKGROUND: Absence of subclinical atherosclerosis is considered safe to defer statin therapy in general population. However, impact of statins on atherosclerotic cardiovascular disease in patients with diabetes stratified by coronary artery calcium (CAC) scores and extent of non-obstructive CAD on coronary computed tomography angiography (CCTA) has not been evaluated. METHODS: CONFIRM (Coronary CT Angiography EvaluatioN For Clinical Outcomes: An InteRnational Multi-center Registry) study enrolled consecutive adults 18 years of age between 2005 and 2009 who underwent 364-detector row CCTA for suspected CAD. The long-term registry includes data on 12,086 subjects who underwent CCTA at 17 centers in 9 countries. In this sub-study of CONFIRM registry, patients with diabetes mellitus (DM) and without diabetes mellitus with normal CCTA or non-obstructive plaque (<50 % diameter stenosis) for whom data on baseline statin use was available were included. CAC score was calculated using Agatston score. The magnitude of non-obstructive coronary artery disease on CCTA was quantified using segment involvement score (SIS). Primary outcome was major cardiovascular events (MACE) which included all-cause mortality, myocardial infarction, and target vessel re-vascularization. RESULTS: A total of 7247 patients (Mean age 56.8 years) with a median follow up of 5 years were included. For DM patients, baseline statin therapy significantly reduced MACE for patients with CAC ≥100 (HR: 0.24; 95 % CI 0.07-0.87; p = 0.03) and SIS≥3 (HR: 0.23; 95 % CI 0.06-0.83; p = 0.024) compared to those not on statin therapy. Among Diabetics with lower CAC (<100) and SIS (≤3) scores, MACE was similar in statin and non-statin groups. In contrast, among non-DM patients, MACE was similar in statin and no statin groups irrespective of baseline CAC (1-99 or ≥100) and SIS. CONCLUSION: In this large multicenter cohort of patients, the presence and extent of subclinical atherosclerosis as assessed by CAC and SIS identified patients most likely to derive benefit from statin therapy.

Outcomes among patients admitted for non-ST-segment myocardial infarction in the pre-pandemic and pandemic COVID-19 era: Israel Nationwide study.

BACKGROUND: Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic in 2019, several countries have reported a substantial drop in the number of patients admitted with non-ST-segment myocardial infarction (NSTEMI). OBJECTIVE: We aimed to evaluate the changes in admissions, in-hospital management and outcomes of patients with NSTEMI in the COVID-19 era in a nationwide survey. METHOD: A prospective, multicenter, observational, nationwide study involving 13 medical centers across Israel aimed to evaluate consecutive patients with NSTEMI admitted to intensive cardiac care units over an 8-week period during the COVID-19 outbreak and to compare them with NSTEMI patients admitted at the same period 2 years earlier (control period). RESULTS: There were 624 (43%) NSTEMI patients, of whom 349 (56%) were hospitalized during the COVID-19 era and 275 (44%) during the control period. There were no significant differences in age, gender and other baseline characteristics between the two study periods. During the COVID-19 era, more patients arrived at the hospital via an emergency medical system compared with the control period (P = 0.05). Time from symptom onset to hospital admission was longer in the COVID-19 era as compared with the control period [11.5 h (interquartile range, IQR, 2.5-46.7) vs. 2.9 h (IQR 1.7-6.8), respectively, P < 0.001]. Nevertheless, the time from hospital admission to reperfusion was similar in both groups. The rate of coronary angiography was also similar in both groups. The in-hospital mortality rate was similar in both the COVID-19 era and the control period groups (2.3% vs. 4.7%, respectively, P = 0.149) as was the 30-day mortality rate (3.7% vs. 5.1%, respectively, P = 0.238). CONCLUSION: In contrast to previous reports, admission rates of NSTEMI were similar in this nationwide survey during the COVID-19 era. With longer time from symptoms to admission, but with the same time from hospital admission to reperfusion therapy and with similar in-hospital and 30-day mortality rates. Even in times of crisis, adherence of medical systems to clinical practice guidelines ensures the preservation of good clinical outcomes.

Aspirin and Statin Therapy for Nonobstructive Coronary Artery Disease: Five-year Outcomes from the CONFIRM Registry.

Purpose: In this cohort study, 5-year data from the Coronary CT Angiography Evaluation for Clinical Outcomes: An International Multicenter Registry (ie, CONFIRM) were examined to identify associations of baseline aspirin and statin use with mortality, major adverse cardiovascular events (MACE), and myocardial infarction (MI) in individuals without substantial (≥50%) stenosis. Materials and Methods: In this prospective cohort study, all participants in the registry underwent coronary CT angiography and were classified as having no detectable coronary plaque or having nonobstructive coronary artery disease (CAD) (1%-49% stenosis). Participants with obstructive (≥50%) stenosis were excluded from analysis. The study commenced in June 2003 and was completed in March 2016. All unadjusted and risk-adjusted analyses utilized the Cox proportional hazard model with hospital sites modeled using shared frailty. Results: A total of 6386 participants with no detectable plaque or with nonobstructive CAD were included (mean age, 56.0 years ± 13.3 [SD], 52% men). The mean follow-up period was 5.66 years ± 1.10. Nonobstructive CAD (n = 2815, 44% of all participants included in the study) was associated with a greater risk of all-cause mortality (10.6% [298 of 2815] vs 4.8% [170 of 3571], P < .001) compared to those without CAD (n = 3571, 56%). Baseline aspirin and statin use was documented for 1415 and 1429 participants, respectively, with nonobstructive CAD, and for 1560 and 1565 participants without detectable plaque, respectively. In individuals with nonobstructive CAD, baseline aspirin use was not associated with a reduction in MACE (10.9% [102 of 936] vs 14.7% [52 of 355], P = .06), all-cause mortality (9.6% [95 of 991] vs 10.9% [46 of 424], P = .468), or MI (4.4% [41 of 936] vs 6.2% [22 of 355], P = .18). On multivariate risk-adjusted analysis, baseline statin use was associated with a lower rate of MACE (hazard ratio, 0.59; 95% CI: 0.40, 0.87; P = .007). Neither therapy improved clinical outcomes for participants with no detectable plaque. Conclusion: In participants with nonobstructive CAD, baseline use of statins, but not of aspirin, was associated with improved clinical outcomes. Neither therapy was associated with benefit in participants without plaque.Keywords: Aspirin, Statin, Coronary Artery Disease, CT Angiography, Nonobstructive Coronary Artery DiseaseClinical trial registration no. NCT01443637 Supplemental material is available for this article. © RSNA, 2022See also the commentary by Canan and Navar in this issue.

Associations between dyspnoea, coronary atherosclerosis, and cardiovascular outcomes: results from the long-term follow-up CONFIRM registry.

AIMS: The relationship between dyspnoea, coronary artery disease (CAD), and major cardiovascular events (MACE) is poorly understood. This study evaluated (i) the association of dyspnoea with the severity of anatomical CAD by coronary computed tomography angiography (CCTA) and (ii) to which extent CAD explains MACE in patients with dyspnoea. METHODS AND RESULTS: From the international COronary CT Angiography EvaluatioN for Clinical Outcomes: An InteRnational Multicenter (CONFIRM) registry, 4425 patients (750 with dyspnoea) with suspected but without known CAD were included and prospectively followed for ≥5 years. First, the association of dyspnoea with CAD severity was assessed using logistic regression analysis. Second, the prognostic value of dyspnoea for MACE (myocardial infarction and death), and specifically, the interaction between dyspnoea and CAD severity was investigated using Cox proportional-hazard analysis. Mean patient age was 60.3 ± 11.9 years, 63% of patients were male and 592 MACE events occurred during a median follow-up duration of 5.4 (IQR 5.1-6.0) years. On uni- and multivariable analysis (adjusting for age, sex, body mass index, chest pain typicality, and risk factors), dyspnoea was associated with two- and three-vessel/left main (LM) obstructive CAD. The presence of dyspnoea increased the risk for MACE [hazard ratio (HR) 1.57, 95% confidence interval (CI): 1.29-1.90], which was modified after adjusting for clinical predictors and CAD severity (HR 1.26, 95% CI: 1.02-1.55). Conversely, when stratified by CAD severity, dyspnoea did not provide incremental prognostic value in one-, two-, or three-vessel/LM obstructive CAD, but dyspnoea did provide incremental prognostic value in non-obstructive CAD. CONCLUSION: In patients with suspected CAD, dyspnoea was independently associated with severe obstructive CAD on CCTA. The severity of obstructive CAD explained the elevated MACE rates in patients presenting with dyspnoea, but in patients with non-obstructive CAD, dyspnoea portended additional risk.

Prognostic significance of plaque location in non-obstructive coronary artery disease: from the CONFIRM registry.

AIM: Obstructive coronary artery disease (CAD) in proximal coronary segments is associated with a poor prognosis. However, the relative importance of plaque location regarding the risk for major adverse cardiovascular events (MACE) in patients with non-obstructive CAD has not been well defined. METHODS AND RESULTS: From the Coronary CT Angiography Evaluation for Clinical Outcomes: An International Multicenter (CONFIRM) registry, 4644 patients without obstructive CAD were included in this study. The degree of stenosis was classified as 0 (no) and 1-49% (non-obstructive). Proximal involvement was defined as any plaque present in the left main or the proximal segment of the left anterior descending artery, left circumflex artery, and right coronary artery. Extensive CAD was defined as segment involvement score of >4. During a median follow-up of 5.2 years (interquartile range 4.1-6.0), 340 (7.3%) MACE occurred. Within the non-obstructive CAD group (n = 2065), proximal involvement was observed in 1767 (85.6%) cases. When compared to non-obstructive CAD patients without proximal involvement, those with proximal involvement had an increased MACE risk (log-rank P = 0.033). Multivariate Cox analysis showed when compared to patients with no CAD, proximal non-obstructive CAD was associated with increased MACE risk [hazard ratio (HR) 1.90, 95% confidence interval (CI) 1.47-2.45, P < 0.001] after adjusting for extensive CAD and conventional cardiovascular risk factors; however, non-proximal non-obstructive CAD did not increase MACE risk (HR 1.26, 95% CI 0.79-2.01, P = 0.339). CONCLUSIONS: Independent of plaque extent, proximal coronary involvement was associated with increased MACE risk in patients with non-obstructive CAD. The plaque location information by coronary computed tomography angiography may provide additional risk prediction over CAD extent in patients with non-obstructive CAD.