A Novel Approach to Cardiac Magnetic Resonance Scar Characterization in Patients Affected by Cardiac Amyloidosis: A Pilot Study.

Background and Objectives: Cardiac magnetic resonance (CMR) imaging has become an essential instrument in the study of cardiomyopathies; it has recently been integrated into the diagnostic workflow for cardiac amyloidosis (CA) with remarkable results. An additional emerging role is the stratification of the arrhythmogenic risk by scar analysis and the possibility of merging these data with electro-anatomical maps. This is made possible by using a software (ADAS 3D, Galgo Medical, Barcelona, Spain) able to provide 3D heart models by detecting fibrosis along the whole thickness of the myocardial walls. Little is known regarding the applications of this software in the wide spectrum of cardiomyopathies and the potential benefits have yet to be discovered. In this study, we tried to apply the ADAS 3D in the context of CA. Materials and Methods: This study was a retrospectively analysis of consecutive CMR imaging of patients affected by CA that were treated in our center (Marche University Hospital). Wherever possible, the data were processed with the ADAS 3D software and analyzed for a correlation between the morphometric parameters and follow-up events. The outcome was a composite of all-cause mortality, unplanned cardiovascular hospitalizations, sustained ventricular arrhythmias (VAs), permanent reduction in left ventricular ejection fraction, and pacemaker implantation. The secondary outcomes were the need for a pacemaker implantation and sustained VAs. Results: A total of 14 patients were deemed eligible for the software analysis: 8 patients with wild type transthyretin CA, 5 with light chain CA, and 1 with transthyretin hereditary CA. The vast majority of imaging features was not related to the composite outcome, but atrial wall thickening displayed a significant association with both the primary (p = 0.003) and the secondary outcome of pacemaker implantation (p = 0.003). The software was able to differentiate between core zones and border zones of scars, with the latter being the most extensively represented in all patients. Interestingly, in a huge percentage of CMR images, the software identified the highest degree of core zone fibrosis among the epicardial layers and, in those patients, we found a higher incidence of the primary outcome, without reaching statistical significance (p = 0.18). Channels were found in the scar zones in a substantial percentage of patients without a clear correlation with follow-up events. Conclusions: CMR imaging plays a pivotal role in cardiovascular diagnostics. Our analysis shows the feasibility and applicability of such instrument for all types of CA. We could not only differentiate between different layers of scars, but we were also able to identify the presence of fibrosis channels among the different scar zones. None of the data derived from the ADAS 3D software seemed to be related to cardiac events in the follow-up, but this might be imputable to the restricted number of patients enrolled in the study.

Characteristics and Clinical Value of Electroanatomic Voltage Mapping in Cardiac Amyloidosis.

BACKGROUND: Cardiac amyloidoses (CAs) are an increasingly recognised group of infiltrative cardiomyopathies associated with high risk of adverse cardiac events. We sought to characterise the characteristics and clinical value of right ventricular (RV) electroanatomic voltage mapping (EVM) in CA. METHODS: Fifteen consecutive patients undergoing endomyocardial biopsy (EMB) for suspected CA (median age 75 years, 1st-3rd quartiles 64-78 years], 67% male) were enrolled in an observational prospective study. Each patient underwent RV high-density EVM using a multipolar catheter and EMB. The primary outcome was death or heart failure hospitalisation at 1-year follow-up. We recorded electrographic features at EMB sampling sites and electroanatomic data in the overall RV, and explored their correlations with histopathologic findings and primary outcomes events. RESULTS: A final EMB-proven diagnosis of immunoglobulin light chain or transthyretin CA was formulated in 6 and 9 patients, respectively. Electrogram amplitudes in the bipolar and unipolar configurations averaged 1.55 ± 0.44 mV and 5.14 ± 1.50 mV, respectively, in the overall RV, with lower values in AL CA patients. We found a significant inverse correlation between both bipolar and unipolar electrogram amplitude and amyloid burden according to EMB (P = 0.001 and P = 0.025, respectively). At 1-year follow-up, 7 patients (47%) experienced a primary outcome event; the extent of bipolar dense scar area at RV EVM was an independent predictor of primary outcome events at multivariable analysis (odds ratio 2.40; P = 0.037). CONCLUSIONS: In CA, electrogram amplitudes are around the lower limit of normal yet disproportionately low compared with the increased wall thickness. Out data suggest that RV electrogram amplitude may be a quantitative marker of amyloid burden, and that RV EVM may have prognostic value.

Stress-rest dynamic-CT myocardial perfusion imaging in the management of myocardial bridging: A "one-stop shop" exam.

Myocardial bridging (MB) is a congenital anomaly characterized by the intramyocardial coronary course that can cause coronary compression during systole leading to myocardial ischemia, often with the concomitant presence of endothelial dysfunction.Improvements in computed tomography (CT) technology have increased the burden of MB detection during coronary-CT (cCT) but their anatomical and functional assessment is often challenging. A stress-rest myocardial perfusion imaging (MPI) by single-photon emission CT (SPECT) is usually required to decide the correct patient management. However, SPECT has long acquisition protocols, poor spatial resolution, and significant radiation doses for the patient. The recent advances in CT scan technology have allowed the evaluation of stress-rest MPI, representing a promising alternative to SPECT.In this paper, we report six cases of MBs assessed with cCT examination and further evaluated with a stress-rest dynamic-CT MPI and SPECT. A reversible perfusion defect in the left anterior descending (LAD) territory segments potentially due to MB was detected in two of six patients, and they were referred for heart team evaluation.In conclusion, cCT and stress-rest dynamic-CT MPI allowed to detect MBs, evaluate their functional significance, and decide the patients' management in a "one-stop shop" examination. Learning objective: Improvements in computed tomography (CT) technology have increased the burden of myocardial bridging (MB) detection during coronary-CT but their anatomical and functional assessment is often challenging.A stress-rest myocardial perfusion imaging (MPI) by single-photon emission CT (SPECT) is then usually required to decide the correct patient management.Recent advances in CT scan technology have allowed the evaluation of stress-rest MPI, that represent a promising alternative to SPECT.

Characteristics of patients with recurrent acute myocardial infarction after MINOCA.

BACKGROUND: Myocardial infarction (MI) with non-obstructed coronary arteries (MINOCA) is an increasingly recognized condition with challenging management. Some MINOCA patients ultimately experience recurrent acute MI (re-AMI) during follow-up; however, clinical and angiographic factors predisposing to re-AMI are still poorly defined. METHODS: In this retrospective multicenter cohort study we enrolled consecutive patients fulfilling diagnostic criteria of MINOCA according to the IV universal definition of myocardial infarction; characteristics of patients experiencing re-AMI during the follow-up were compared to a group of MINOCA patients without re-AMI. RESULTS: 54 patients (mean age 66 ± 13) experienced a subsequent re-AMI after MINOCA and follow-up was available in 44 (81%). Compared to MINOCA patients without re-AMI (n = 695), on first invasive coronary angiography (ICA) MINOCA patients with re-AMI showed less frequent angiographically normal coronaries (37 versus 53%, p = 0.032) and had a higher prevalence of atherosclerosis involving 3 vessels or left main stem (17% versus 8%, p = 0.049). Twenty-four patients (44%) with re-AMI underwent a new ICA: 25% had normal coronary arteries, 12.5% had mild luminal irregularities (<30%), 20.8% had moderate coronary atherosclerosis (30-49%), and 41.7% showed obstructive coronary atherosclerosis (≥50% stenosis). Among patients undergoing new ICA, atherosclerosis progression was observed in 11 (45.8%), 37.5% received revascularization, only 4.5% had low-density lipoprotein cholesterol (LDL_C) under 55 mg/dL and 33% experienced a new cardiovascular disease (CVD) event (death, AMI, heart failure, stroke) at subsequent follow-up. CONCLUSIONS: In the present study, only a minority of MINOCA patients with re-AMI underwent a repeated ICA, nearly one out of two showed atherosclerosis progression, often requiring revascularization. Recommended LDL-C levels were achieved only in a minority of the cases, indicating a possible underestimation of CVD risk in this population.

Persistence to rivaroxaban therapy for stroke prevention in clinical practice in Italy: Rationale and design of the RITMUS-AF prospective observational cohort study.

Background: Non-valvular atrial fibrillation (NVAF) is a cardiac rhythm disturbance that increases the risk of stroke and is highly prevalent in Europe and Italy, increasingly with advancing age. Oral anticoagulation is a key component of stroke prevention in patients with NVAF, yet withdrawal or interruption of anticoagulation may transiently increase the risk of embolic events. Treatment persistence to anticoagulation is an important metric but one that is not well studied in patients with NVAF in Italy. The RITMUS-AF study aims to evaluate the persistence with rivaroxaban treatment for stroke prevention in patients with NVAF in Italy. Methods: RITMUS-AF is a prospective, observational cohort study of patients with NVAF in hospital cardiology departments with a non-vitamin K antagonist oral anticoagulant surveillance program across all 20 regions of Italy. The study population comprises consecutively screened, consenting patients with NVAF naïve to and newly treated with rivaroxaban for stroke prevention in routine clinical practice. The target enrollment is 800 patients; each patient will be followed for a maximum duration of 24 months. The primary endpoint is the proportion of patients who discontinue rivaroxaban treatment. Secondary endpoints are reasons for rivaroxaban discontinuation, dose changes and reasons for changes, switches to alternative therapies and the reasons for these decisions, and self-reported adherence. Data analyses will be exploratory and descriptive. Conclusion: RITMUS-AF will help to address the limited data in Italian clinical practice on treatment persistence and reasons for drug interruptions in patients with NVAF on rivaroxaban.

Acute heart failure: differential diagnosis and treatment.

Acute heart failure is a heterogeneous clinical syndrome and is the first cause of unplanned hospitalization in people >65 years. Patients with heart failure may have different clinical presentations according to clinical history, pre-existing heart disease, and pattern of intravascular congestion. A comprehensive assessment of clinical, echocardiographic, and laboratory data should aid in clinical decision-making and treatment. In some cases, a more accurate evaluation of patient haemodynamics via a pulmonary artery catheter may be necessary to undertake and guide escalation and de-escalation of therapy, especially when clinical, echo, and laboratory data are inconclusive or in the presence of right ventricular dysfunction. Similarly, a pulmonary artery catheter may be useful in patients with cardiogenic shock undergoing mechanical circulatory support. With the subsequent de-escalation of therapy and haemodynamic stabilization, the implementation of guideline-directed medical therapy should be pursued to reduce the risk of subsequent heart failure hospitalization and death, paying particular attention to the recognition and treatment of residual congestion.

Health status and clinical outcomes in older adults with chronic coronary disease: the ISCHEMIA trial

BACKGROUND: Whether initial invasive management in older vs younger adults with chronic coronary disease and moderate or severe ischemia improves health status or clinical outcomes is unknown. OBJECTIVES: The goal of this study was to examine the impact of age on health status and clinical outcomes with invasive vs conservative management in the ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) trial. METHODS: One-year angina-specific health status was assessed with the 7-item Seattle Angina Questionnaire (SAQ) (score range 0-100; higher scores indicate better health status). Cox proportional hazards models estimated the treatment effect of invasive vs conservative management as a function of age on the composite clinical outcome of cardiovascular death, myocardial infarction, or hospitalization for resuscitated cardiac arrest, unstable angina, or heart failure. RESULTS: Among 4,617 participants, 2,239 (48.5%) were aged <65 years, 1,713 (37.1%) were aged 65 to 74 years, and 665 (14.4%) were aged ≥75 years. Baseline SAQ summary scores were lower in participants aged <65 years. Fully adjusted differences in 1-year SAQ summary scores (invasive minus conservative) were 4.90 (95% CI: 3.56-6.24) at age 55 years, 3.48 (95% CI: 2.40-4.57) at age 65 years, and 2.13 (95% CI: 0.75-3.51) at age 75 years (Pinteraction = 0.008). Improvement in SAQ Angina Frequency was less dependent on age (Pinteraction = 0.08). There were no age differences between invasive vs conservative management on the composite clinical outcome (Pinteraction = 0.29). CONCLUSIONS: Older patients with chronic coronary disease and moderate or severe ischemia had consistent improvement in angina frequency but less improvement in angina-related health status with invasive management compared with younger patients. Invasive management was not associated with improved clinical outcomes in older or younger patients. (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches [ISCHEMIA]; NCT01471522).

Health Status and Clinical Outcomes in Older Adults With Chronic Coronary Disease: The ISCHEMIA Trial.

BACKGROUND: Whether initial invasive management in older vs younger adults with chronic coronary disease and moderate or severe ischemia improves health status or clinical outcomes is unknown. OBJECTIVES: The goal of this study was to examine the impact of age on health status and clinical outcomes with invasive vs conservative management in the ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) trial. METHODS: One-year angina-specific health status was assessed with the 7-item Seattle Angina Questionnaire (SAQ) (score range 0-100; higher scores indicate better health status). Cox proportional hazards models estimated the treatment effect of invasive vs conservative management as a function of age on the composite clinical outcome of cardiovascular death, myocardial infarction, or hospitalization for resuscitated cardiac arrest, unstable angina, or heart failure. RESULTS: Among 4,617 participants, 2,239 (48.5%) were aged <65 years, 1,713 (37.1%) were aged 65 to 74 years, and 665 (14.4%) were aged ≥75 years. Baseline SAQ summary scores were lower in participants aged <65 years. Fully adjusted differences in 1-year SAQ summary scores (invasive minus conservative) were 4.90 (95% CI: 3.56-6.24) at age 55 years, 3.48 (95% CI: 2.40-4.57) at age 65 years, and 2.13 (95% CI: 0.75-3.51) at age 75 years (Pinteraction = 0.008). Improvement in SAQ Angina Frequency was less dependent on age (Pinteraction = 0.08). There were no age differences between invasive vs conservative management on the composite clinical outcome (Pinteraction = 0.29). CONCLUSIONS: Older patients with chronic coronary disease and moderate or severe ischemia had consistent improvement in angina frequency but less improvement in angina-related health status with invasive management compared with younger patients. Invasive management was not associated with improved clinical outcomes in older or younger patients. (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches [ISCHEMIA]; NCT01471522).

SARS-COV-2 Infection, Vaccination, and Immune-Mediated Diseases: Results of a Single-Center Retrospective Study.

Objectives: The relationship between infections or vaccine antigens and exacerbations or new onset of immune-mediated diseases (IMDs) has long been known. In this observational study, conducted during the COVID-19 pandemic, we evaluated the onset of clinical and laboratory immune manifestations related to COVID-19 or SARS-CoV-2 vaccination. Methods: Four groups of patients were evaluated: A) 584 COVID-19 inpatients hospitalized from March 2020 to June 2020 and from November 2020 to May 2021; B) 135 outpatients with previous SARS-CoV-2 infection, assessed within 6 months of recovery; C) outpatients with IMDs in remission and flared after SARS-COV-2 infection; D) outpatients with symptoms of probable immune-mediated origin after SARS-CoV-2 vaccination. Results: In cohort A we observed n. 28 (4.8%) arthralgia/myalgia, n. 2 (0.3%) arthritis, n. 3 (0.5%) pericarditis, n. 1 (0.2%) myocarditis, n. 11 (1.9%) thrombocytopenia or pancytopenia, and in the follow up cohort B we identified 9 (6.7%) cases of newly diagnosed IMDs after the recovery from COVID-19. In all cases, serological alterations were not observed.In cohort C we observed n.5 flares of pre-existing IMD after SARS-COV2 infection, and in the cohort D n. 13 IMD temporally close with SARS-CoV-2 vaccination in 8 healthy subjects (with clinical classifiable IMD-like presentation) and in 5 patients affected by an anamnestic IMD. Also in these latter cases, except in 2 healthy subjects, there were not found serological alterations specific of a classifiable IMD. Conclusions: This study suggests that the interplay between SARS-CoV-2 and the host may induce complex immune-mediated reactions, probably induced by the anti-spike antibodies, in healthy people and IMD patients without specific serological autoimmunity. Moreover, our data suggest that the anti-SARS-CoV-2 antibodies generated by the vaccination may cause in healthy subjects' clinical manifestations similar to well-definite IMDs. These findings support the hypothesis that SARS-Cov2 infection in COVID-19 induce an innate and adaptive immune response that may be both responsible of the symptoms correlated with the occurrence of the IMDs described in our study. And, in this context, the IMDs observed in healthy people in close temporal correlation with the vaccination suggest that the anti-Spike antibodies may play a key role in the induction of an abnormal and deregulated immune response.

Statins and age: is there a limit beyond which primary prevention is futile?

Hypercholesterolaemic patients at an advanced age (>75 years) with and without known cardiovascular disease are at higher cardiovascular risk than younger subjects, and the frequency of vascular events in this group of the patient increases with increasing age. However, in clinical practice, these subjects are undertreated for various reasons: conservative cultural attitude, fear of side effects, doubts about efficacy, lack of specific trials. Two recent meta-analyses have shown that the use of lipid-lowering drugs is as safe and effective in this age group as in younger subjects. Subjects aged >75 years in primary prevention are poorly represented in trials but should be considered for treatment in daily clinical practice, because, in the risk assessment (SCORE algorithm), they are very often classified as intermediate or high risk but can also be reclassified at increased risk if an additional assessment step with clinical markers (diabetes and reduced glomerular filtrate) or cardiovascular imaging is used for the detection of subclinical atherosclerosis. Greater attention to treatment methods and monitoring of possible side effects is recommended, but the only limit to the treatment is its 'futility' in the fragile patient.

Updated antithrombotic strategies to reduce the burden of cardiovascular recurrences in patients with chronic coronary syndrome.

Despite recent achievements in secondary cardiovascular prevention, the risk of further events in patients with chronic coronary syndromes (CCS) remains elevated. Highest risk is seen in patients with recurrent events, comorbidities or multisite atherosclerosis. Optimising antithrombotic strategies in this setting may significantly improve outcomes. The higher the baseline risk, the higher the absolute event reduction with approaches using combined antithrombotic treatments. Tailoring such strategies to the individual patient risk appears crucial to achieve net benefit (i.e., substantial ischaemic event prevention at a limited cost in terms of bleeding). This paper focuses on antithrombotic and non-pharmacological approaches to secondary cardiovascular disease prevention in CCS. In particular, we critically review current evidence on the use of dual antithrombotic therapy, including the newest approach of aspirin plus low-dose anticoagulation and its net clinical outcome according to baseline risk.

Intensive cardiac care unit admission trends during the COVID-19 outbreak in Italy: a multi-center study.

A significant decline in the admission to intensive cardiac care unit (ICCU) has been noted in Italy during the COVID-19 outbreak. Previous studies have provided data on clinical features and outcome of these patients, but information is still incomplete. In this multicenter study conducted in six ICCUs, we enrolled consecutive adult patients admitted to ICCU in three specific time intervals: from February 8 to March 9, 2020 [before national lockdown (pre-LD)], from March 10 to April 9, 2020 [during the first period of national lockdown (in-LD)] and from May 18 to June 17, 2020 [soon after the end of all containment measures (after-LD)]. Compared to pre-LD, in-LD was associated with a significant drop in the admission to ICCU for all causes (- 35%) and acute coronary syndrome (ACS; - 49%), with a rebound soon after-LD. The in-LD reduction was greater for women (- 49%) and NSTEMI (- 61%) compared to men (- 28%) and STEMI (- 33%). Length-of-stay, and in-hospital mortality did not show any significant change from to pre-LD to in-LD in the whole population as well as in the ACS group. This study confirms a notable reduction in the admissions to ICCUs from pre-LD to in-LD followed by an increment in the admission rates after-LD. These data strongly suggest that people, particularly women and patients with NSTEMI, are reluctant to seek medical care during lockdown, possibly due to the fear of viral infection. Such a phenomenon, however, was not associated with a rise in mortality among patients who get hospitalization.

Myocardial Infarction in the ISCHEMIA Trial: Impact of Different Definitions on Incidence, Prognosis, and Treatment Comparisons.

BACKGROUND: In the ISCHEMIA trial (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches), an initial invasive strategy did not significantly reduce rates of cardiovascular events or all-cause mortality in comparison with a conservative strategy in patients with stable ischemic heart disease and moderate/severe myocardial ischemia. The most frequent component of composite cardiovascular end points was myocardial infarction (MI). METHODS: ISCHEMIA prespecified that the primary and major secondary composite end points of the trial be analyzed using 2 MI definitions. For procedural MI, the primary MI definition used creatine kinase-MB as the preferred biomarker, whereas the secondary definition used cardiac troponin. Procedural thresholds were >5 times the upper reference level for percutaneous coronary intervention and >10 times for coronary artery bypass grafting. Procedural MI definitions included (1) a category of elevated biomarker only events with much higher biomarker thresholds, (2) new ST-segment depression of ≥1 mm for the primary and ≥0.5 mm for the secondary definition, and (3) new coronary dissections >National Heart, Lung, and Blood Institute grade 3. We compared MI type, frequency, and prognosis by treatment assignment using both MI definitions. RESULTS: Procedural MIs accounted for 20.1% of all MI events with the primary definition and 40.6% of all MI events with the secondary definition. Four-year MI rates in patients undergoing revascularization were more frequent with the invasive versus conservative strategy using the primary (2.7% versus 1.1%; adjusted hazard ratio [HR], 2.98 [95% CI, 1.87-4.73]) and secondary (8.2% versus 2.0%; adjusted HR, 5.04 [95% CI, 3.64-6.97]) MI definitions. Type 1 MIs were less frequent with the invasive versus conservative strategy using the primary (3.40% versus 6.89%; adjusted HR, 0.53 [95% CI, 0.41-0.69]; P<0.0001) and secondary (3.48% versus 6.89%; adjusted HR, 0.53 [95% CI, 0.41-0.69]; P<0.0001) definitions. The risk of subsequent cardiovascular death was higher after a type 1 MI than after no MI using the primary (adjusted HR, 3.38 [95% CI, 2.03-5.61]; P<0.001) or secondary MI definition (adjusted HR, 3.52 [2.11-5.88]; P<0.001). CONCLUSIONS: In ISCHEMIA, type 1 MI events using the primary and secondary definitions during 5-year follow-up were more frequent with an initial conservative strategy and associated with subsequent cardiovascular death. Procedural MI rates were greater in the invasive strategy and with the use of the secondary MI definition. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01471522.

External applicability of the ISCHEMIA trial: an analysis of a prospective, nationwide registry of patients with stable coronary artery disease.

AIMS: We sought to assess the proportion of patients eligible for the ISCHEMIA trial and to compare the characteristics and outcomes of these patients with those without ISCHEMIA inclusion or with ISCHEMIA exclusion criteria in a contemporary, nationwide cohort of patients with stable coronary artery disease (CAD). METHODS AND RESULTS: Among the 5,070 consecutive patients enrolled in the START registry, 4,295 (84.7%) did not fulfil the inclusion criteria (ISCHEMIA-Not Included or ISCHEMIA-Unclassifiable), 582 (11.5%) had exclusion criteria (ISCHEMIA-Excluded), and the remaining 193 (3.8%) were classified as ISCHEMIA-Like. At one year, the incidence of the primary outcome, a composite of death from cardiovascular (CV) causes, myocardial infarction (MI), or hospitalisation for unstable angina and heart failure, was 0.5% in the ISCHEMIA-Like versus 3.3% in other patients (p=0.03). The composite secondary outcome of CV mortality and MI occurred in 0.5% of the ISCHEMIA-Like patients and in 1.4% of the remaining patients (p=0.1). CONCLUSIONS: In a contemporary real-world cohort of stable CAD patients, only 4% resulted in being eligible for the ISCHEMIA trial. These patients presented an extremely low annual risk of adverse events, especially when compared with other groups of stable CAD patients.

SARS-CoV-2 infection in kidney transplant recipients: Experience of the italian marche region.

BACKGROUND: Infection related to Coronavirus-19 (CoV-2) is pandemic affecting more than 4 million people in 187 countries worldwide. By May 10, 2020, it caused more than 280 000 deaths all over the world. Preliminary data reported a high prevalence of CoV-2 infection and mortality due to severe acute respiratory syndrome related CoV-2 (SARS-CoV-2) in kidney-transplanted patients (KTRs). Nevertheless, the outcomes and the best treatments for SARS-CoV-2-affected KTRs remain unclear. METHODS: In this report, we describe the clinical data, the treatments, and the outcomes of 5 KTRs with SARS-CoV-2 admitted to our hospital in Ancona, Marche region, Italy, from March 17 to present. Due to the severity of SARS-CoV-2, immunosuppression with calcineurin inhibitors, antimetabolites, and mTOR-inhibitors were stopped at the admission. All KTRs were treated with low-dose steroids. 4/5 KTRs were treated with hydroxychloroquine. All KTRs received tocilizumab up to one dose. RESULTS: Overall, the incidence of SARS-CoV-2 in KTRs in the Marche region was 0.85%. 3/5 were admitted in ICU and intubated. One developed AKI with the need of CRRT with Cytosorb. At present, two patients died, two patients were discharged, and one is still inpatient in ICU. CONCLUSIONS: The critical evaluation of all cases suggests that the timing of the administration of tocilizumab, an interleukin-6 receptor antagonist, could be associated with a better efficacy when administered in concomitance to the drop of the oxygen saturation. Thus, in SARS-CoV-2-affected KTRs, a close biochemical and clinical monitoring should be set up to allow physicians to hit the virus in the right moment such as a sudden reduction of the oxygen saturation and/or a significant increase in the laboratory values such as D-dimer.

Preventing myocardial infarction: use and limitation of non-invasive imaging modalities.

Identifying patients at high risk of coronary events is the main focus of cardiovascular prevention. For primary prevention score and risk cards are very low cost solutions, but only of limited efficacy, thus justifying the use of non-invasive imaging testing for the purpose of increasing the 'diagnostic gain'. Considering all the diagnostic tests employed, only few demonstrated significant additional contribution to the risk score stratification. Coronary imaging with high speed volumetric computed tomography can provide essential information in ruling out and/or definition of coronary artery disease but also has limitations as far as the biological risk, the costs, and the difficulties of putting into perspective the results obtained in asymptomatic patients.

Renal effects of Sacubitril/Valsartan in heart failure with reduced ejection fraction: a real life 1-year follow-up study.

Real-life data confirming the favourable renal outcome in patients with heart failure (HF) treated with Sacubitril/Valsartan, previously found in several trials (RCTs), are still scant. We evaluated the renal effects of Sacubitril/Valsartan in a real-life sample of HF patients. Observational analysis of 54 consecutive outpatients affected by HF with reduced ejection fraction (HFrEF) and clinical indication for Sacubitril/Valsartan. Patients were evaluated at baseline (T0) and after six (T6) and twelve (T12) months after initiating Sacubitril/Valsartan and compared with a group of 30 historical controls. Mean age: 65.5 ± 11.7 years. Older patients: 29 (53.7%). Mean baseline estimated glomerular filtration rate (eGFR): 59.4 ± 19.2 ml/min/1.73 m2. Patients with chronic kidney disease (CKD), defined by an eGFR < 60 ml/min/1.73 m2, were 29 (53.7%). Sacubitril/Valsartan was less titrated in both older patients and patients with CKD. There were no changes in diuretics during follow-up. Systolic blood pressure (BP) decreased during follow-up (p = 0.014), while left ventricular ejection fraction (LVEF) slighly increased (p < 0.001). Renal function improved after 12 months compared to historical controls (p for interaction < 0.001) and a greater benefit was found in subjects aged < 65 years (p for interaction = 0.002) and patients with CKD (p for interaction = 0.009). A statistically (p = 0.009), but not clinically significant increase in serum potassium was also found, regardless of age and CKD. This is the first study focused on the renal effects of Sacubitril/Valsartan in HFrEF patients followed for 12 months in a real-life clinical context. The improved eGFR, despite lower BP, represents an important confirmation outside the peculiar world of RCTs.

Available oral lipid-lowering agents could bring most high-risk patients to target: an estimate based on the Dyslipidemia International Study II-Italy.

AIMS: The analysis evaluated the contemporary percentage of patients with established coronary heart disease (CHD) reaching the European guidelines recommended LDL-cholesterol (LDL-C) levels of less than 70 mg/dl and the threshold required for proprotein convertase subtlisin/kexin type 9 reimbursement in Italy (100 mg/dl). It also assessed how these percentages would change in case of diffuse use of ezetimibe. METHODS: The Dyslipidemia International Study II enrolled CHD patients aged at least 18 either on lipid-lowering therapy (LLT) for at least 3 months or not on LLT at the time of the lipid profile. Distribution of LLTs and LDL-C target attainment were assessed. Multivariate logistic regression evaluated predictors of LDL-C target attainment. A 24% LDL-C lowering was modeled in patients not taking ezetimibe to assess its potential effects. RESULTS: Among 676 Italian CHD patients enrolled, LDL-C concentrations were lower among the 631 patients (93.3%) who were on LLT (82 versus 118 mg/dl; P < 0.001). The LDL-C target was attained by 35.4% of patients. Statin dose (median atorvastatin dose 40 mg/day) was the sole significant predictor of LDL-C target attainment. The simple addition of ezetimibe in the model reduced the percentage of patients more than 70 and 100 mg/dl from 64.6 to 37.9% and from 25.1 to 11.8%, respectively. CONCLUSION: Despite treatment in more than 90%, only one-third of Italian stable CHD patients attained the recommended LDL-C target. Statin dose was the sole predictor of the target achievement. The addition of ezetimibe would almost double patients at target and halve the potential candidates for reimbursement of more expensive agents such as proprotein convertase subtlisin/kexin type 9 inhibitors.