Management of vulnerable patient phenotypes and acute coronary syndrome mechanisms.

Atherosclerosis is a chronic vascular disease. Its prevalence increases with aging. However, atherosclerosis may also affect young subjects without significant exposure to the classical risk factors. Recent evidence indicates clonal hematopoiesis of indeterminate potential (CHIP) as a novel cardiovascular risk factor that should be suspected in young patients. CHIP represents a link between impaired bone marrow and atherosclerosis. Atherosclerosis may present with an acute symptomatic manifestation or subclinical events that favor plaque growth. The outcome of a plaque relies on a balance of innate and environmental factors. These factors can influence the processes that initiate and propagate acute plaque destabilization leading to intraluminal thrombus formation or subclinical vessel healing. Thirty years ago, the first autopsy study revealed that coronary plaques can undergo rupture even in subjects without a known cardiovascular history. Nowadays, cardiac magnetic resonance studies demonstrate that this phenomenon is not rare. Myocardial infarction is mainly due to plaque rupture and plaque erosion that have different pathophysiological mechanisms. Plaque erosion carries a better prognosis as compared to plaque rupture. Thus, a tailored conservative treatment has been proposed and some studies demonstrated it to be safe. On the contrary, plaque rupture is typically associated with inflammation and anti-inflammatory treatments have been proposed in response to persistently elevate biomarkers of systemic inflammation. In conclusion, atherosclerosis may present in different forms or phenotypes. Vulnerable patient phenotypes, identified by using intravascular imaging techniques, biomarkers, or even genetic analyses, are characterized by distinctive pathophysiological mechanisms. These different phenotypes merit tailored management.

Novel Medical Treatments and Devices for the Management of Heart Failure with Reduced Ejection Fraction.

Heart failure (HF) is a growing issue in developed countries; it is often the result of underlying processes such as ischemia, hypertension, infiltrative diseases or even genetic abnormalities. The great majority of the affected patients present a reduced ejection fraction (≤40%), thereby falling under the name of "heart failure with reduced ejection fraction" (HFrEF). This condition represents a major threat for patients: it significantly affects life quality and carries an enormous burden on the whole healthcare system due to its high management costs. In the last decade, new medical treatments and devices have been developed in order to reduce HF hospitalizations and improve prognosis while reducing the overall mortality rate. Pharmacological therapy has significantly changed our perspective of this disease thanks to its ability of restoring ventricular function and reducing symptom severity, even in some dramatic contexts with an extensively diseased myocardium. Notably, medical therapy can sometimes be ineffective, and a tailored integration with device technologies is of pivotal importance. Not by chance, in recent years, cardiac implantable devices witnessed a significant improvement, thereby providing an irreplaceable resource for the management of HF. Some devices have the ability of assessing (CardioMEMS) or treating (ultrafiltration) fluid retention, while others recognize and treat life-threatening arrhythmias, even for a limited time frame (wearable cardioverter defibrillator). The present review article gives a comprehensive overview of the most recent and important findings that need to be considered in patients affected by HFrEF. Both novel medical treatments and devices are presented and discussed.

Recurrent events after acute ST-segment elevation myocardial infarction: predictors and features of plaque progression and stent failure.

OBJECTIVES: Patients with acute ST-segment elevation myocardial infarction (STEMI) are at high risk for recurrent coronary events (RCE). Non-culprit plaque progression and stent failure are the main causes of RCEs. We sought to identify the incidence and predictors of RCEs. METHODS: Eight hundred thirty patients with STEMI were enrolled and followed up for 5 years. All patients underwent blood test analysis at hospital admission, at 1-month and at 12-month follow-up times. Patients were divided into RCE group and control group. RCE group was further categorized into non-culprit plaque progression and stent failure subgroups. RESULTS: Among 830 patients with STEMI, 63 patients had a RCE (7.6%). At hospital admission, HDL was numerically lower in RCE group, while LDL at both 1-month and 12-month follow-up times were significantly higher in RCE group. Both HDL at hospital admission and LDL at 12-month follow-up were independently associated with RCEs (OR 0.90, 95% CI 0.81-0.99 and OR 1.041, 95% CI 1.01-1.07, respectively). RCEs were due to non-culprit plaque progression in 47.6% of cases, while in 36.5% due to stent failure. The mean time frame between pPCI and RCE was significantly greater for non-culprit plaque progression subgroup as compared to stent failure subgroup (27 ±â€…18 months and 16 ±â€…14 months, P  = 0.032). CONCLUSION: RCEs still affect patients after pPCI. Low levels of HDL at admission and high levels of LDL at 12 months after pPCI significantly predicted RCEs. A RCE results in non-culprit plaque progression presents much later than an event due to stent failure.

Cardiac Contractility Modulation Therapy in Patients with Amyloid Cardiomyopathy and Heart Failure, Case Report, Review of the Biophysics of CCM Function, and AMY-CCM Registry Presentation.

Cardiac amyloidosis may result in an aggressive form of heart failure (HF). Cardiac contractility modulation (CCM) has been shown to be a concrete therapeutic option in patients with symptomatic HF, but there is no evidence of its application in patients with cardiac amyloidosis. We present the case of TTR amyloidosis, where CCM therapy proved to be effective. The patient had a history of multiple HF hospitalizations due to an established diagnosis of wild type TTR-Amyloidosis with significant cardiac involvement. Since he was highly symptomatic, except during continuous dobutamine and diuretic infusion, it was opted to pursue CCM therapy device implantation. At follow up, a significant improvement in clinical status was reported with an increase of EF, functional status (6 min walk test improved from zero meters at baseline, to 270 m at 1 month and to 460 m at 12 months), and a reduction in pulmonary pressures. One year after device implantation, no other HF hospital admission was needed. CCM therapy may be effective in this difficult clinical setting. The AMY-CCM Registry, which has just begun, will evaluate the efficacy of CCM in patients with HF and diagnosed TTR amyloidosis to bring new evidence on its potential impact as a therapeutic option.

Long-term Results of Perfusion-Balloon Valvuloplasty, Without Rapid Pacing, in High-Risk Elderly Patients With Severe Aortic Stenosis: A New Space Oddity.

BACKGROUND: Percutaneous balloon aortic valvuloplasty (BAV) is actually recommended as a bridge to surgery or transcatheter aortic valve replacement in patients with severe aortic stenosis (AS) in particular clinical settings. In this pilot study, for the first time, we report our experience utilizing a nonocclusive balloon for BAV, which does not require rapid ventricular pacing (RVP), in high-risk symptomatic elderly patients with severe AS. METHODS AND RESULTS: From 2018 to 2020, a total of 30 high-risk elderly patients with heart failure due to severe AS were treated with BAV and were all prospectively included in the study. We used a perfusion-balloon valvuloplasty without RVP (True Flow; BD/Bard). Hemodynamic parameters were invasively evaluated during catheterization, before and immediately after BAV. All patients were regularly followed to detect the rate of mortality. The patients were 87.56 ± 4.10 years old and 23% were males. In the catheterization laboratory, the peak left ventricular to aortic pressure gradient significantly decreased from 55 mm Hg (interquartile range [IQR], 48.75-66.25) to 26 mm Hg (IQR, 15.7-30) immediately after balloon inflation (P<.001). The median value of percentage decrease of transaortic gradient was 56% (IQR, 50-74). At a median of 12 months (IQR, 5-27) follow-up, 12 patients (40%) died. The median time between BAV and mortality was 10.5 months (IQR, 1.75-15.5). At multivariable analysis, the only predictor of mortality was the New York Heart Association class at admission (odds ratio, 3.29; 95% confidence interval, 2.4-298.4; P<.01). CONCLUSION: This single-center pilot study represents the first evidence that perfusion-balloon valvuloplasty without RVP is a safe, valid, and durable option in high-risk, symptomatic, elderly patients with severe AS.

Coronary Plaque Rupture in Stable Coronary Artery Disease and Non-ST Segment Elevation Myocardial Infarction: An Optical Coherence Tomography Study.

BACKGROUND: Plaque rupture (PR) is the main cause of coronary thrombosis in non-ST segment elevation myocardial infarction (NSTEMI), but can be found in stable coronary artery disease (CAD). Our study compared the morphology and local inflammatory activity of ruptured plaques between stable CAD and NSTEMI patients using frequency-domain optical coherence tomography (FD-OCT). METHODS: We retrospectively evaluated 70 plaques with PR at the FD-OCT (25 in stable CAD patients and 45 in NSTEMI patients). Main clinical, angiographic, and morphological features were compared. RESULTS: Besides an overall equivalence in clinical and angiographic features (except for more smokers among NSTEMI patients), some important FD-OCT differences in plaque morphology emerged: PR in NSTEMI was characterized by more macrophage infiltrates (78% in NSTEMI patients vs 20% in stable CAD patients; P<.001) and intraluminal thrombosis (84% in NSTEMI patients vs 48% in stable CAD patients; P<.01). Quantitative analysis showed a higher density of macrophages in NSTEMI than in stable CAD patients: median max normalized standard deviation (NSD) was 0.0934 (IQR, 0.0796-0.1022) vs 0.0689 (IQR, 0.0598-0.0787); P<.01 and mean NSD was 0.062 (IQR, 0.060-0.065) vs 0.053 (IQR, 0.051-0.060); P<.001. Other morphological features did not differ between stable CAD and NSTEMI patients. Main FD-OCT quantitative parameters like minimal lumen area and plaque length were also equivalent between the 2 groups. CONCLUSIONS: Differences in morphological features of PR between stable CAD and NSTEMI patients suggest that local inflammation contributes to the unstable fate of the atherosclerotic plaque.

Reduction in acute coronary syndromes during coronavirus disease 2019 global pandemic: data from the Marche region of Italy.

AIMS: During the novel severe acute respiratory syndrome coronavirus 2 (coronavirus disease 2019) pandemic, a worldwide reduction in total acute coronary syndrome (ACS) has been reported. In early 2020, Italy became the most affected country and national lockdown was declared early on in March. We described trends in ACS from all the Marche coronary catheterization laboratories (CCL) during the global pandemic. METHODS: Retrospective study of all consecutive patients admitted to the four regional CCL. The coronavirus disease 2019 period (20 February 2020 to 15 April 2020) was compared with the interyear control period (1 January 2020 to 19 February 2020) and to the intrayear control period (20 February 2019 to 15 April 2019). All patients with an initial diagnosis of ACS were included in the analysis, and further stratified into ST-segment elevation myocardial infarction (STEMI) and non-STEMI (NSTEMI)/unstable angina. RESULTS: A total of 1239 patients were enrolled. Daily incidence of ACS was 6.1, 6.3 and 4.5 for the interyear control period, the intrayear control period and the case period, respectively. There was no difference in overall STEMI daily incidence while NSTEMI/unstable angina fell from 3.6 and 3.3-1.8 during the case period (P = 0.01). Incidence rate ratios were significantly lower when the case period was compared with the intrayear control period (incidence rate ratios: 0.49, 95% confidence interval 0.41-0.59, P = 0.001) and the interyear control period (incidence rate ratios: 0.67, 95% confidence interval 0.50-0.90, P = 0.008). CONCLUSION: During the global pandemic there was a significant reduction in total ACS and NSTEMI in the Marche region. Unlike previous reports, there was no difference in overall access to CCL for STEMI during the same period.

Appropriate use criteria for coronary angiography: a single centre experience.

BACKGROUND: Increasing attention is being given to the rational use of invasive procedures. In this study, we aimed to evaluate, among patients referred for coronary angiography, the appropriateness of cardiac catheterization according to the Appropriate Use Criteria (AUC) for diagnostic catheterization and to examine the relationship between the appropriateness and the presence of obstructive coronary artery disease (CAD) and revascularization. METHODS: From November 2017 to December 2018, 1188 consecutive patients referred to undergo a diagnostic catheterization were included. They were categorized as having appropriate, uncertain or inappropriate indication, using a database (Melograno System). We restricted our analysis to 9 appropriate indications including acute coronary syndromes, suspected CAD, valvular heart disease, arrhythmias and cardiomyopathy. We restricted the analysis to the subgroup of patients with suspected or known CAD and, among them, we evaluate the rate of CAD and the need for revascularization. RESULTS: The indications were appropriate in 1017 patients (85.6%), of uncertain appropriateness in 134 (11.3%), and inappropriate in 37 (3.1%). Restricting the analysis to the CAD subgroup, the indications were appropriate in 848 patients (83.3%), of uncertain appropriateness in 133 (13.1%) and inappropriate in 37 (3.6%). The proportion of patients with critical CAD were 75.9%, 44.3% and 29.7% in the appropriate, uncertain and inappropriate categories respectively (p < 0.001). The revascularization rate was 63.1%, 32.2% and 21.6% in the appropriate, uncertain and inappropriate categories respectively (p < 0.001). CONCLUSIONS: Application of AUC is feasible in a community setting. Melograno system is useful to improve patient care.

Optical coherence tomography and C-reactive protein in risk stratification of acute coronary syndromes.

BACKGROUND: Patients with acute coronary syndrome (ACS) associated to high C-reactive protein (CRP) levels exhibit a higher risk of future acute ischemic events. Yet, the positive predictive value of CRP is too low to guide a specific treatment. Our study aims to identify a high-risk patient subset who might mostly benefit from anti-inflammatory treatment on the basis of the combination of optical coherence tomography (OCT) assessment of the culprit vessel and CRP serum levels. METHODS: Patients admitted for ACS and undergoing pre-interventional OCT assessment of the culprit vessel were selected from "Agostino Gemelli" Hospital OCT Registry. The primary end-point was recurrent ACS (re-ACS). CRP levels ≥2 mg/L were considered abnormal. RESULTS: The overall study population consisted of 178 patients. Among these, 156 patients were included in the primary end-point analysis. The re-ACS rate was 23% at 3-year follow-up. High CRP (2.587, 95% CI:1.345-10.325, p = 0.031), plaque rupture (3.985, 95% CI:1.698-8.754, p = 0.009), macrophage infiltration (3.145, 95% CI:1.458-9.587, p = 0.012) and multifocal atherosclerosis (2.734, 95% CI:1.748-11.875, p = 0.042) were independent predictors of re-ACS. All patients (14/14) with high CRP and with all OCT high-risk features had re-ACS. At the other extreme, only 4 of the 82 patients with low CRP levels and lack of high-risk features at OCT examination exhibited re-ACS at follow-up. CONCLUSIONS: The combination of systemic evidence of inflammation and OCT findings in the culprit plaque identifies very high-risk ACS. Future studies are warranted to confirm these findings and to test an anti-inflammatory treatment in this patient subset.

Intracoronary imaging to guide percutaneous coronary intervention: Clinical implications.

BACKGROUND: Over the last decade, the intra-coronary imaging (ICI) has emerged to guide percutaneous coronary intervention (PCI), thus overcoming the limitations of "luminology" offered by angiography. METHODS: In this review, we aim at purely focusing on the clinical implications of the employment of ICI in the routine practice, thus providing suggestions for future applications. In particular, we will describe the principal contributions and implications of ICI in the following different clinical settings: 1) assessment of clinical and imaging outcomes of PCI; 2) guiding PCI before and after stent implantation; 3) identification of mechanisms of stent failure. RESULTS: Several studies showed the capability of ICI in assessing the clinical and imaging outcomes of PCI. In particular, they have compared the ICI-guided PCI with the angiography-guided procedures, emphasizing the advantages of using imaging. Indeed, ICI can characterize the coronary plaque, provide a precise estimation of the coronary stenosis, select the appropriate method of intervention, and optimize stent deployment and lesion coverage. Finally, ICI has been shown to be useful to point out the mechanisms of stent failure. CONCLUSIONS: ICI can facilitate decision-making in patients with unclear angiographic findings, guide-selected interventions and optimize the final PCI results in complex lesions or. in high-risk patients. Finally, by the identification of specific mechanisms of stent failure, the ICI can allow to adopt a tailored therapy for the singles cases.

Editor's Choice- Pathophysiology, diagnosis and management of MINOCA: an update.

Myocardial infarction with non-obstructive coronary arteries (MINOCA) is a syndrome with different causes, characterised by clinical evidence of myocardial infarction with normal or near-normal coronary arteries on angiography. Its prevalence ranges between 5% and 25% of all myocardial infarction. The prognosis is extremely variable, depending on the cause of MINOCA. The key principle in the management of this syndrome is to clarify the underlying individual mechanisms to achieve patient-specific treatments. Clinical history, electrocardiogram, cardiac enzymes, echocardiography, coronary angiography and left ventricular angiography represent the first level diagnostic investigations to identify the causes of MINOCA. Regional wall motion abnormalities at left ventricular angiography limited to a single epicardial coronary artery territory identify an 'epicardial pattern'whereas regional wall motion abnormalities extended beyond a single epicardial coronary artery territory identify a 'microvascular pattern'. The most common causes of MINOCA are represented by coronary plaque disease, coronary dissection, coronary artery spasm, coronary microvascular spasm, Takotsubo cardiomyopathy, myocarditis, coronary thromboembolism, other forms of type 2 myocardial infarction and MINOCA of uncertain aetiology. This review aims at summarising the diagnosis and management of MINOCA, according to the underlying physiopathology.

Role of ST-Segment Resolution in Patients With ST-Segment Elevation Myocardial Infarction Treated With Primary Percutaneous Coronary Intervention (from the 5-Year Outcomes of the EXAMINATION [Evaluation of the Xience-V Stent in Acute Myocardial Infarction] Trial).

In patients with ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (pPCI), lack of ST-segment resolution (STR) is associated with poor prognosis at short- and long-term follow-up. The aim of this study was to evaluate the role of STR on very long-term outcomes in patients with STEMI treated with pPCI included in the EXAMINATION (Evaluation of the Xience-V Stent in Acute Myocardial Infarction) trial. Patients were stratified according to the presence of STR < 50% and STR < 70% at the 30-minute post-pPCI electrocardiogram. Primary end point was the patient-oriented composite endpoint (POCE) of all-cause death, any myocardial infarction, or any revascularization at 5-year follow-up. Both baseline and post-PCI 30-minute electrocardiograms were available for STR assessment in 1,351 patients. Of these patients, 228 (16.9%) and 500 (37.0%) exhibited STR < 50% and STR < 70%, respectively. At 5-year follow-up, the POCE was observed more frequently in patients with STR < 50% (hazard ratio [HR] 1.556; 95% confidence interval [CI] 1.194 to 2.027; p <0.001) and in patients with STR < 70% (HR 1.460, 95% CI 1.169 to 1.824, p <0.001) compared with patients with STR > 50% and STR ≥ 70%, respectively. In both cases, this difference was mainly driven by a significant increase in the rate of all-cause death and any revascularization. After multivariable adjustment, STR < 70%, but not STR < 50%, resulted as a 5-year independent predictor of POCE (adjusted HR 1.338, 95% CI 1.008 to 1.778, p = 0.044). In conclusion, in patients with STEMI, the evaluation of 70% STR after pPCI provides independent prognostic information at 5-year follow-up and it can be used to identify patients at high risk of very long-term cardiovascular events.

First-in-human experience of left atrial appendage occlusion with the steerable FuStar sheath.

BACKGROUND: Due the wide variability of left atrial appendage morphology left atrial appendage occlusion (LAAO) remains a challenging procedure. The steerable FuStar delivery sheath was designed to allow both, transseptal access and delivery of percutaneous devices. We here report the first-in-human experience of LAAO with the FuStar sheath. METHODS: Twenty patients (76.6 ± 8.4 years; 12 (60%) males; CHA2 DS2 -VASc score: 5.0 ± 2) with non-valvular fibrillation and contraindications to oral anticoagulation underwent LAAO with the LAmbre device using the FuStar steerable sheath (Lifetech Scientific Corp., Shenzhen, China) at two german centers. RESULTS: Successful device implantation was achieved in all patients (100%). No periprocedural complications were observed. Procedure time, fluoroscopy time, contrast media, and radiation dose were 23.4 min ± 9.2, 11.9 min ± 4.1, 96.2 mL ± 45.7, and 2718.4 cG*cm2 ± 3835.3, respectively. CONCLUSION: This study demonstrates the feasibility and safety of the steerable FuStar sheath for LAAO.

Perilipin 2 levels are increased in patients with in-stent neoatherosclerosis: A clue to mechanisms of accelerated plaque formation after drug-eluting stent implantation.

BACKGROUND: Perilipin 2 (PLIN2) is a protein that potentially facilitates atherogenesis in native coronary arteries or arteries with an implanted drug-eluting stent (DES). The aim of the study was to determine PLIN2 protein levels in peripheral monocytes of enrolled subjects and compare them between patients with native coronary artery disease (CAD) and those with an in-stent restenosis (ISR) due to neoatherosclerosis occurring >1 year after DES implantation. METHODS: Forty-two patients were prospectively enrolled in the study in 3:1 fashion and underwent coronary catheterization. Both groups were angiographically matched for CAD burden with respect to the number of diseased vessels. Neoatherosclerosis was determined by intracoronary optical coherence tomography (OCT) among patients with ISR. RESULTS: Patients with ISR due to neoatherosclerosis had significantly higher PLIN2 protein levels in peripheral blood monocytes compared to patients with native CAD (342.47 ±â€¯75.63[SE] versus 119.51 ±â€¯20.95, p < 0.001). PLIN2 protein levels did not significantly differ between unstable and stable disease phenotype (125.59 ±â€¯131.02 vs. 146.14 ±â€¯111.87, p = 0.109). CONCLUSIONS: In this explorative study, PLIN2 protein levels are significantly increased in patients with neoatherosclerosis, irrespective of clinical presentation, implicating that it might play a pathogenetic role in accelerated atherosclerosis after DES implantation. Further larger clinical studies are warranted to confirm these initial findings.

Effects of statins on plaque rupture assessed by optical coherence tomography in patients presenting with acute coronary syndromes: insights from the optical coherence tomography (OCT)-FORMIDABLE registry.

Aims: Chronic pre-treatment with statins may reduce mortality and morbidity in patients experiencing acute coronary syndromes (ACS), but mechanisms accounting for these findings are not completely understood. Methods and results: The optical coherence tomography (OCT)-Formidable registry retrospectively enrolled 285 consecutive patients with ACS undergoing OCT in 9 European centres. Mean age was 60.4 ± 12.8 years, 148 (51.9%) patients had hyperlipemia, 45 (15.8%) diabetes mellitus and 142 (49.8%) presented with ST Segment Elevation Myocardial Infarction (STEMI). Patients were stratified according to statin prescription: 150 (52.6%) were on chronic pre-treatment with statins before ACS and were more likely to present with non-ST segment elevation acute coronary syndromes (NSTE-ACS) at admission (111, 74%) rather than STEMI, while the opposite was observed for patients not on statins. The primary end-point of ruptured plaque at OCT occurred significantly less frequently in the patients on chronic pre-treatment with statins [odds ratio (OR) 0.375, 95% confidence interval (CI) 0.185-0.759, P = 0.006]. The secondary end-point of thin-cap fibro-atheroma (TCFA) at any site was significantly less frequent in the statin group (OR 0.423, 95%CI 0.213-0.840, P = 0.014). No differences were observed for the secondary end-point of not-ruptured TCFA as the culprit lesion. Pre-specified sensitivity analysis was conducted according to the pattern of ACS: the reported differences were confirmed for NSTE-ACS patients, with a trend towards less plaque rupture and a significant reduction of TCFA at any site with statins, but not for STEMI. Conclusions: Chronic pre-treatment with statins is associated with a reduced prevalence of ruptured plaques in patients presenting with ACS, particularly in those with NSTE-ACS. Statins bear hence the potential to reduce morbidity during the acute phase of ACS.