Screening for cardiac amyloidosis in patients with tenosynovial red flags: A collaboration between family medicine and cardiology.

BACKGROUND: Amyloid deposition in tenosynovial structures precedes cardiac involvement up to 20 years. Therefore, a cardiological screening in patients with a history of tenosynovial manifestations of cardiac amyloidosis (CA) could lead to an increased number of early diagnoses. METHODS: Patients with tenosynovial manifestations of CA (carpal tunnel syndrome, atraumatic biceps tendon rupture, lumbar spinal stenosis) have been identified by general practitioners and evaluated in a Referral Center for CA. Patients with a high suspicion of CA underwent the CA diagnostic pathway. RESULTS: Among 50 General Practitioners (GP) contacted, 10 (20%) agreed to participate in the study for a total of 5615 patients ≥60 years. One hundred forty-five patients met the inclusion criteria, 2 of them already had a diagnosis of CA, and 57 agreed to undergo a cardiological evaluation (electrocardiography, echocardiography, NTproBNP assay). The median age was 73 [67-80] years and 31 (54%) were women. Eight patients were suggested to start the CA diagnostic pathway, five of them underwent a complete diagnostic evaluation for CA, three refused to complete the diagnostic exams and no new diagnoses were made. CONCLUSION: A screening program for CA in patients with tenosynovial manifestations identified by general practitioners is feasible, but may not yield a high rate of new diagnosis. In this study, we identified two patients who already had a diagnosis of CA, and among patients at high risk for CA, 37% refused to complete the diagnostic pathway. Increased awareness of CA among patients might increase participation and diagnostic yield in screening studies. Further validation of this protocol is needed to evaluate its diagnostic performance.

Italian contributions to the history of acute myocardial infarction treatment.

The reduction in mortality from cardiovascular disease has been one of the crowning achievements of medicine over the past century. The evolution in management of acute myocardial infarction (AMI) has played a key role. Yet, the epidemiology of patients with STEMI continues to evolve. The Global Registry of Acute Coronary Events (GRACE) documented that STEMI accounted for ~36% of ACS cases. According to an analysis of a large USA database, the age-adjusted and sex-adjusted incidence of hospitalizations for STEMI significantly decreased from 133 per 100,000 person-years in 1999 to 50 per 100,000 person-years in 2008. Despite advances in both the early management and longer-term treatment of AMI, this condition still represents a leading cause of morbidity and mortality in western countries, making essential understanding its determinants. Early mortality gains noted in all AMI patients may not be sustained over the longer term and reciprocal trends of decreasing mortality after AMI accompanied by an increasing incidence of heart failure have been demonstrated in more recent years. Greater salvage of high-risk MI patients in recent periods may contribute to these trends. Over the past century, insights into the pathophysiology of AMI revolutionized approaches to management through different historical phases. This review provides a historic perspective on the underlying discoveries and pivotal trials that have been the foundation of the key changes of pharmacological and interventional treatment of AMI leading to the dramatic improvement of prognosis during the last tre decades, with special emphasis to the Italian contributions to the field.

Optimal timing of follow-up cardiac magnetic resonance in patients with uncomplicated acute myocarditis.

BACKGROUND: Cardiac magnetic resonance (CMR) is central in the diagnosis and prognostic stratification of acute myocarditis (AM) but the timing of repeated CMR scans to assess edema resolution and late gadolinium enhancement (LGE) stabilization remain unclear. We assessed edema and LGE evolution over 12 months to identify the optimal timing of repeat CMR evaluation in AM. METHODS AND RESULTS: Thirty-three consecutive patients with AM underwent CMR at clinical presentation (CMR-1), after 3 months (CMR-2) and after 12-months (CMR-3). CMR included assessment of edema and LGE, left ventricular ejection fraction (LVEF) and left ventricular mass index (LVMi). After CMR-3 patients were followed-up every three-months by clinical evaluation, Holter-monitoring, and echocardiography. All patients had edema and LGE at CMR-1. At CMR-2 edema-positive segments (0.42 ± 0.34 vs. 3.18 ± 2.33, p < 0.005), LGE (4.98 ± 4.56 vs. 9.60 ± 8.58 g, and 4.22 ± 3.97% vs 7.50 ± 5.61%) and LVMi (69.82 ± 11.83 vs 76.06 ± 13.13 g/m2) (all p < 0.0001) significantly reduced, while LVEF (63.12 ± 5.47% vs.61.15 ± 6.87% p < 0.05) significantly improved, compared to CMR-1. At CMR-2 edema persisted in 7 patients (21%) but resolved at CMR-3 with no further changes of LVMi, LVEF and LGE. During follow-up (85 ± 15 months), 5 (15%) patients showed persistent ventricular arrhythmias. Univariate predictors of arrhythmic persistence were LGE extension at CMR-2 and CMR-3 (both p < 0.05), but not at CMR-1 (p = 0.07). CONCLUSIONS: Most patients with uncomplicated AM show edema resolution with LGE stabilization after 3 months. Further CMR evaluations should be limited to patients with persisting edema at this time. LGE extent measured after edema resolution is associated with persistent ventricular arrhythmias.

Safety of cangrelor and transition to oral P2Y12 inhibitors in patients undergoing percutaneous coronary intervention: the ARCANGELO study.

Aims: Cangrelor is the only intravenous P2Y12 inhibitor available. Safety, efficacy, and transitioning from cangrelor to oral P2Y12 inhibitors were recorded in patients with acute coronary syndrome (ACS). The ARCANGELO study aims to assess the safety of cangrelor on bleeding and the effects of the transition to oral P2Y12 inhibitors in a real-world setting according to the European Medical Agency's requirement. Methods and results: Adult patients with ACS undergoing percutaneous coronary intervention (PCI) receiving cangrelor were included in the study. Patients were followed for 30 days. Incidence of bleeding events, major adverse cardiac events, and transition strategy to oral P2Y12 were recorded. Among 1004 ACS patients undergoing PCI, 995 (99.1%) were eligible for the analysis; 597 (60.0%) of them had ST-segment elevation myocardial infarction. A total of 925 (93.1%) patients underwent PCI by radial catheter access, and 972 (97.2%) received drug-eluting stents. All eligible patients received bolus and cangrelor infusion between 2 and 4 h in 95% of the cases. A total of 730 patients (73.4%) received ticagrelor, 127 (12.8%) prasugrel, and 138 (13.9%) clopidogrel as transition therapy. Bleeding, according to Bleeding Academic Research Consortium (BARC) criteria, within 30 days post-PCI occurred in 5.2% of patients (95% confidence interval: 3.9-6.8%); 0.5% experienced a moderate (BARC 3), and all others mild (BARC 1-2) bleeding events. Major adverse cardiac events occurred in 14 (1.4%) patients, principally all-cause mortality (n = 6 patients) and myocardial infarction (n = 7 patients). Conclusion: The use of cangrelor in ACS patients undergoing PCI and the transition strategy to P2Y12 inhibitors are confirmed as safe and effective in daily practice.

[Ischemic burden or anatomic burden: which non-invasive testing in stable patients with suspected coronary artery disease?] / Valutazione anatomica o ricerca di ischemia: quale esame non invasivo preferire?

Guidance on the diagnostic approach to coronary artery disease has diverged as the increasing complexity of atherosclerotic clinicopathologic correlations has been revealed. Foundational concepts linking stenosis, the ischaemic cascade and prognosis have been re-evaluated in light of the underwhelming results from the percutaneous revascularization of stenotic vessels. These studies have revealed ischaemia to be an important marker for cardiovascular outcomes, but likely separate from the causal pathway of hard clinical events. Instead, observations from non-invasive anatomical imaging have redefined risk, shifting the focus away from discrete lesions towards total atherosclerotic burden, and with it elevating the role of computed tomography in contemporary diagnostic pathways. As it currently stands, functional and anatomical approaches provide complementary information; stress testing continues to provide guidance for potential revascularization in current guidelines, yet anatomical testing may additionally identify individuals likely to benefit from preventive therapy. While guidelines attempt to keep pace with the advancing technology and expanding literature, clinicians are left to apply clinical acumen to decide on a vast and confusing array of investigative options. This review will deal with strenghts and limitations of the current approach to the diagnosis of coronary artery disease, providing the rationale for both functional and anatomical approaches.

Long-term follow-up after invasive or conservative management of stable coronary disease: the ISCHEMIA-EXTEND study.

The ISCHEMIA trial found no statistical difference in the primary endpoint between initial invasive and conservative management of patients with chronic coronary disease and moderate-to-severe ischaemia on stress testing. However, an invasive strategy increased peri-procedural myocardial infarction (MI) but decreased spontaneous MI with continued separation of curves over time. Thus, in order to assess the long-term effect of invasive management strategy on mortality, the ISCHEMIA-EXTEND observational study was planned including surviving participants from the initial phase of the ISCHEMIA trial with a projected median follow-up of nearly 10 years. Recently, an interim report of 7-year all-cause, cardiovascular (CV), and non-CV mortality rates has been published showing no difference in all-cause mortality between the two strategies, but with a lower risk of CV mortality and higher risk of non-CV mortality with an initial invasive strategy over a median follow-up of 5.7 years. The trade-offs in CV and non-CV mortality observed in ISCHEMIA-EXTEND raise many important questions regarding the heterogeneity of treatment effect, the drivers of mortality, and the relative importance and reliability of CV vs. all-cause mortality. Overall, findings from ISCHEMIA and ISCHEMIA-EXTEND trials might help physicians in shared decision-making as to whether to add invasive management to guideline-directed medical management in selected patients with chronic coronary artery disease and moderate or severe ischaemia.

Myocarditis and COVID-19 related issues.

The recent COVID-19 (Coronavirus Disease 2019) pandemic by SARS-CoV2 infection has caused millions of deaths and hospitalizations across the globe. In the early pandemic phases, the infection had been initially considered a primary pulmonary disease. However, increasing evidence has demonstrated a wide range of possible cardiac involvement. Most of systemic and cardiac damage is likely sustained by a complex interplay between inflammatory, immune-related and thrombotic mechanisms. Biventricular failure and myocardial damage with elevation of cardiac biomarkers have been reported in COVID-19 patients, although histological demonstration of acute myocarditis has been rarely documented. Indeed while cardiac magnetic resonance findings include different patterns of myocardial involvement in terms of late gadolinium enhancement, histological data from necropsy and endomyocardial biopsy showed peculiar inflammatory patterns, mostly composed by macrophages. On the other hand COVID-19 vaccines based on mRN technology have been also associated with increased risk of myocarditis. COVID-19 and mRNA vaccine-related myocarditis present different clinical and imaging presentations and recent data suggest the presence of distinctive immunological mechanisms involved.

Computed tomography to replace invasive coronary angiography? The DISCHARGE trial.

Ongoing advancements of coronary computed tomographic angiography (CTA) continue to challenge the role of invasive coronary angiography (ICA) as the gold standard for the evaluation of coronary artery disease (CAD). To investigate the comparative effectiveness of ICA when compared with CTA as an initial diagnostic imaging strategy the DISCHARGE Trial enrolled 3561 patients with stable chest pain and an intermediate pre-test probability of obstructive CAD. The study showed no difference between CTA and ICA in the incidence of the primary composite outcome of cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke during 3.5 years of follow up. As with many trials that advance a field, this trial raises several additional questions of interest that will be discussed. Furthermore, recent studies focused on the discrepancies of CTA vs. ICA indicate that the status of CTA remains unchanged in its ability to rule out disease but at present cannot be considered a substitute for ICA when coronary lesions are documented. Thus, a change in clinical practice patterns likely requires evidence from clinical studies demonstrating equivalence of CT to ICA for guiding medical management. Developments, however, are swift, and CT technology is catching up on its invasive counterpart.

Beyond Sarcomeric Hypertrophic Cardiomyopathy: How to Diagnose and Manage Phenocopies.

PURPOSE OF REVIEW: We describe the most common phenocopies of hypertrophic cardiomyopathy, their pathogenesis, and clinical presentation highlighting similarities and differences. We also suggest a step-by-step diagnostic work-up that can guide in differential diagnosis and management. RECENT FINDINGS: In the last years, a wider application of genetic testing and the advances in cardiac imaging have significantly changed the diagnostic approach to HCM phenocopies. Different prognosis and management, with an increasing availability of disease-specific therapies, make differential diagnosis mandatory. The HCM phenotype can be the cardiac manifestation of different inherited and acquired disorders presenting different etiology, prognosis, and treatment. Differential diagnosis requires a cardiomyopathic mindset allowing to recognize red flags throughout the diagnostic work-up starting from clinical and family history and ending with advanced imaging and genetic testing. Different prognosis and management, with an increasing availability of disease-specific therapies make differential diagnosis mandatory.

Use of cangrelor in patients with acute coronary syndromes undergoing percutaneous coronary intervention: Study design and interim analysis of the ARCANGELO study.

BACKGROUND: The itAlian pRospective Study on CANGrELOr (ARCANGELO) was aimed to assess the safety of using cangrelor during percutaneous coronary intervention (PCI) in patients with acute coronary syndromes (ACS) in the daily practice. HYPOTHESIS: The safety of cangrelor after the transition to oral P2Y12 inhibitors was evaluated as the incidence of bleeding outcomes in the 30 days following PCI according to postauthorization safety study guidelines. METHODS: Adults with ACS who were treated with cangrelor in one of the 28 centers involved in the study. Patients who consented to participate were followed in the 30 days following their PCI. Bleedings (Bleeding Academic Research Consortium [BARC] classification), major adverse cardiac events (MACEs), and adverse events were recorded. The interim results at two-thirds of the enrollment period are presented. RESULTS: A total of 17 bleedings were observed in the 320 patients who completed the study at this stage. All bleedings were classified as BARC Type 1-2, except for one case of Type 3a (vessel puncture site hematoma). Four patients experienced MACEs (2 acute myocardial infarctions, 1 sudden cardiac death, 1 noncardiovascular death due to respiratory distress, and multiorgan failure). None of the bleedings was rated as related to cangrelor. CONCLUSIONS: The interim results of the ARCANGELO study provide a preliminary confirmation that the use of cangrelor on patients with ACS undergoing PCI is not associated with severe bleedings.

Drug-Eluting Balloon for Below the Knee Angioplasty: Five-Year Outcome of the DEBATE-BTK Randomized Clinical Trial.

BACKGROUND: The aim of this study is to evaluate the 5-year clinical outcome of the DEBATE-BTK (Drug-eluting balloon for below-the-knee angioplasty evaluation) trial. METHODS: The DEBATE-BTK was a single-center, randomized trial that enrolled 132 diabetic patients with critical limb ischemia. Subjects were randomized 1:1 to DCB or plain old balloon angioplasty (POBA). Major clinical endpoints were, freedom from all-cause death, freedom from clinically driven target lesion revascularization (CDTLR) and the occurrence of major amputation. Additional analysis were conducted to assess overall survival in patients treated with DCB compared to those treated with only POBA in the entire 5-years period and to test the correlation between paclitaxel dose exposure (in terciles) and overall survival. RESULTS: Freedom from all-cause death at 5 years was 63.1% (41/65) in DCB vs. 53.7%(35/67) POBA patients (p = 0.4). Freedom from CDTLR was 82% in DCB and 63% in POBA patients (p = 0.002) at 1 year and 63 versus 54% at 5 years respectively P = 0.07. One patient in DCB and 2 patients in POBA underwent a major amputation of the target limb. During the 5-year follow-up, 24 patients originally randomized to POBA received DCB treatment for additional limb revascularization. According to DCB treatment in all the 5 years period, overall survival was 66.3.% (30/89) in DCB versus 40%(26/43) in POBA patients, p = 0.003. CONCLUSIONS: Overall survival at 5-year was similar in DCB treated patients compared to POBA. Moreover, survival was higher in patients that received DCB angioplasty at any time of the 5 years period. LEVEL OF EVIDENCE: Level 1b, Individual inception cohort study with > 80% follow-up.

Could the PARIS Risk Scores Be Useful for the Choice of Triple versus Dual Antithrombotic Therapy in Patients with Atrial Fibrillation Undergoing Percutaneous Coronary Intervention?

INTRODUCTION: Current guidelines recommend dual antithrombotic therapy (DAT) for the majority of patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) and suggest a short course of triple antithrombotic therapy (TAT) for those at very high thrombotic risk (TR) but low bleeding risk (BR). METHODS: We analyze if the PARIS ischemic-hemorrhagic scale could be useful for the choice of antithrombotic strategy in patients with acute coronary syndromes and AF treated with coronary stenting enrolled in the prospective, observational, nationwide MATADOR-PCI study. RESULTS: Among the 588 patients discharged alive, a TAT was prescribed in 381 (64.8%) and DAT in 52 (8.8%) patients. According to the PARIS scoring system, 142 (24.2%) were classified as low, 244 (41.5%) as intermediate, and 292 (34.3%) as high TR. In parallel, 87 (14.8%) were categorized in the low, 260 (44.2%) in the intermediate, and 241 (41.0%) in the high-risk stratum for major bleedings. Crossing the various strata of the two PARIS risk scores, the largest group of patients consisted of those at high TR and BR (n = 130, 22%), followed by those at intermediate risk according to both scores (n = 122, 21%). At discharge, TAT was mainly used in patients at intermediate to high BR, while DAT in those at intermediate to high TR but low BR, according to the PARIS score. CONCLUSION: Our data suggest that some variables associated with increased TR or BR are poorly considered in the daily practice, while the use of PARIS scales could help in the implementation of guidelines' recommendations.

PRECISE-DAPT score for bleeding risk prediction in patients on dual or single antiplatelet regimens: insights from the GLOBAL LEADERS and GLASSY.

AIMS: The five-item PRECISE-DAPT, integrating age, haemoglobin, white-blood-cell count, creatinine clearance, and prior bleeding, predicts bleeding risk in patients on dual antiplatelet therapy (DAPT) after stent implantation. We sought to assess whether the bleeding risk prediction offered by the PRECISE-DAPT remains valid among patients receiving ticagrelor monotherapy from 1 month onwards after coronary stenting instead of standard DAPT and having or not having centrally adjudicated bleeding endpoints. METHODS AND RESULTS: The PRECISE-DAPT was calculated in 14 928 and 7134 patients from GLOBAL LEADERS and GLASSY trials, respectively. The ability of the score to predict Bleeding Academic Research Consortium 3 or 5 bleeding was assessed and compared among patients on ticagrelor monotherapy (experimental strategy) or standard DAPT (reference strategy) from 1 month after drug-eluting stent implantation. Bleeding endpoints were investigator-reported or centrally adjudicated in GLOBAL LEADERS and GLASSY, respectively. At 2 years, the c-indexes for the score among patients treated with the experimental or reference strategy were 0.67 [95% confidence interval (CI): 0.63-0.71] vs. 0.63 (95% CI: 0.59-0.67) in GLOBAL LEADERS (P = 0.27), and 0.67 (95% CI: 0.61-0.73) vs. 0.66 (95% CI: 0.61-0.72) in GLASSY (P = 0.88). Decision curve analysis showed net benefit using the PRECISE-DAPT to guide bleeding risk assessment under both treatment strategies. Results were consistent between investigator-reported and adjudicated endpoints and using the simplified four-item PRECISE-DAPT. CONCLUSION: The PRECISE-DAPT offers a prediction model that proved similarly effective to predict clinically relevant bleeding among patients on ticagrelor monotherapy from 1 month after coronary stenting compared with standard DAPT and appears to be unaffected by the presence or absence of adjudicated bleeding endpoints.