Percutaneous extraction of a Micra AV transcatheter pacing system due to a rare sudden battery failure after 19 months from implantation: A first experience worldwide.

INTRODUCTION: Micra AV Transcatheter Pacing System (TPS) represents an innovative second-generation leadless pacemaker which represents an effective alternative to conventional devices in selected cases. Intrinsic malfunctions of these devices are rare, requiring sometimes their retrieval. When performed in experienced centers, this procedure is safe. CASE PRESENTATION: We describe a case of sudden battery malfunction of a Micra AV TPS, which required the extraction and the placement of a new pacing system in the right ventricle. DISCUSSION: This case, which has never been reported, highlights the need to a careful fluoroscopic evaluation and the usefulness of remote monitoring.

Performance of a multisensor implantable defibrillator algorithm for heart failure monitoring related to co-morbidities.

AIMS: The HeartLogic algorithm combines multiple implantable defibrillator (ICD) sensor data and has proved to be a sensitive and timely predictor of impending heart failure (HF) decompensation in cardiac resynchronization therapy (CRT-D) patients. We evaluated the performance of this algorithm in non-CRT ICD patients and in the presence of co-morbidities. METHODS AND RESULTS: The HeartLogic feature was activated in 568 ICD patients (410 with CRT-D) from 26 centres. The median follow-up was 26 months [25th-75th percentile: 16-37]. During follow-up, 97 hospitalizations were reported (53 cardiovascular) and 55 patients died. We recorded 1200 HeartLogic alerts in 370 patients. Overall, the time IN the alert state was 13% of the total observation period. The rate of cardiovascular hospitalizations or death was 0.48/patient-year (95% CI: 0.37-0.60) with the HeartLogic IN the alert state and 0.04/patient-year (95% CI: 0.03-0.05) OUT of the alert state, with an incidence rate ratio of 13.35 (95% CI: 8.83-20.51, P < 0.001). Among patient characteristics, atrial fibrillation (AF) on implantation (HR: 1.62, 95% CI: 1.27-2.07, P < 0.001) and chronic kidney disease (CKD) (HR: 1.53, 95% CI: 1.21-1.93, P < 0.001) independently predicted alerts. HeartLogic alerts were not associated with CRT-D versus ICD implantation (HR: 1.03, 95% CI: 0.82-1.30, P = 0.775). Comparisons of the clinical event rates in the IN alert state with those in the OUT of alert state yielded incidence rate ratios ranging from 9.72 to 14.54 (all P < 0.001) in all groups of patients stratified by: CRT-D/ICD, AF/non-AF, and CKD/non-CKD. After multivariate correction, the occurrence of alerts was associated with cardiovascular hospitalization or death (HR: 1.92, 95% CI: 1.05-3.51, P = 0.036). CONCLUSIONS: The burden of HeartLogic alerts was similar between CRT-D and ICD patients, while patients with AF and CKD seemed more exposed to alerts. Nonetheless, the ability of the HeartLogic algorithm to identify periods of significantly increased risk of clinical events was confirmed, regardless of the type of device and the presence of AF or CKD.

The impact of UEFA Euro 2020 football championship on Takotsubo Syndrome: Results of a multicenter national registry.

Objectives: The UEFA 2020 European Football Championship held in multiple cities across Europe from June 11 to July 11, 2021, was won by Italy, providing an opportunity to examine the relationship between emotional stress and the incidence of acute cardiovascular events (ACE). Methods and results: Cardiovascular hospitalizations in the Cardiac Care Units of 49 hospital networks in Italy were assessed by emergency physicians during the UEFA Euro 2020 Football Championship. We compared the events that occurred during matches involving Italy with events that occurred during the remaining days of the championship as the control period. ACE was assessed in 1,235 patients. ACE during the UEFA Euro 2020 Football Championship semifinal and final, the most stressful matches ended with penalties and victory of the Italian team, were assessed. A significant increase in the incidence of Takotsubo Syndrome (TTS) by a factor of 11.41 (1.6-495.1, P < 0.003), as compared with the control period, was demonstrated during the semifinal and final, whereas no differences were found in the incidence of ACS [IRR 0.93(0.74-1.18), P = 0.57]. No differences in the incidence of ACS [IRR 0.98 (0.87-1.11; P = 0.80)] or TTS [IRR 1.66(0.80-3.4), P = 0.14] were found in the entire period including all matches of the UEFA Euro 2020 compared to the control period. Conclusions: The data of this national registry demonstrated an association between the semifinal and final of UEFA Euro 2020 and TTS suggesting that it can be triggered by also positive emotions such as the victory in the European Football Championship finals.

Coronary-specific quantification of myocardial deformation by strain echocardiography may disclose the culprit vessel in patients with non-ST-segment elevation acute coronary syndrome.

Aims: To compare the diagnostic accuracy of speckle tracking echocardiography technique using territorial longitudinal strain (TLS) for the detection of culprit vessel vs. vessel-specific wall motion score index (WMSI) in non-ST-segment elevation-acute coronary syndrome (NSTE-ACS) patients scheduled for invasive coronary angiography (ICA). Methods and results: One hundred and eighty-three patients (mean age: 66 ± 12 years, male: 71%) diagnosed with NSTE-ACS underwent echocardiography evaluation at hospital admission and ICA within 24 h. Culprit vessels were left anterior descending (LAD), left circumflex (CX), and right coronary arteries (RCAs) in 38.5%, 39.6%, and 21.4%, respectively. An increase of affected vessels [1-, 2-, and 3-vessel coronary artery disease (CAD)] was associated with increased WMSI and TLS values. There was a statistically significant difference of both WMSI-LAD, WMSI-CX, WMSI-RCA and TLS-LAD, TLS-CX, TLS-RCA of myocardial segments with underlying severe CAD compared to no CAD (P = 0.001 and P < 0.001, respectively). Moreover, a significant difference of TLS-LAD, TLS-CX, TLS-RCA, and WMSI-CX of myocardial segments with an underlying culprit vessel compared to non-culprit vessels (P < 0.001, P < 0.001, P = 0.022, and P < 0.001, respectively) was identified. WMSI-LAD and WMSI-RCA did not show statistical significant differences. A regression model revealed that the combination of WMSI + TLS was more accurate compared to WMSI alone in detecting the culprit vessel (LAD, P = 0.001; CX, P < 0.001; and RCA, P = 0.019). Conclusion: Territorial longitudinal strain allows an accurate identification of the culprit vessel in NSTE-ACS patients. In addition to WMSI, TLS may be considered as part of routine echocardiography for better clinical assessment in this subset of patients.

Role of Nuclear Lamin A/C in the Regulation of Nav1.5 Channel and Microtubules: Lesson From the Pathogenic Lamin A/C Variant Q517X.

In this work, we studied an lmna nonsense mutation encoding for the C-terminally truncated Lamin A/C (LMNA) variant Q517X, which was described in patients affected by a severe arrhythmogenic cardiomyopathy with history of sudden death. We found that LMNA Q517X stably expressed in HL-1 cardiomyocytes abnormally aggregates at the nuclear envelope and within the nucleoplasm. Whole-cell patch clamp experiments showed that LMNA Q517X-expressing cardiomyocytes generated action potentials with reduced amplitude, overshoot, upstroke velocity and diastolic potential compared with LMNA WT-expressing cardiomyocytes. Moreover, the unique features of these cardiomyocytes were 1) hyper-polymerized tubulin network, 2) upregulated acetylated α-tubulin, and 3) cell surface Nav1.5 downregulation. These findings pointed the light on the role of tubulin and Nav1.5 channel in the abnormal electrical properties of LMNA Q517X-expressing cardiomyocytes. When expressed in HEK293 with Nav1.5 and its ß1 subunit, LMNA Q517X reduced the peak Na+ current (INa) up to 63% with a shift toward positive potentials in the activation curve of the channel. Of note, both AP properties in cardiomyocytes and Nav1.5 kinetics in HEK293 cells were rescued in LMNA Q517X-expressing cells upon treatment with colchicine, an FDA-approved inhibitor of tubulin assembly. In conclusion, LMNA Q517X expression is associated with hyper-polymerization and hyper-acetylation of tubulin network with concomitant downregulation of Nav1.5 cell expression and activity, thus revealing 1) new mechanisms by which LMNA may regulate channels at the cell surface in cardiomyocytes and 2) new pathomechanisms and therapeutic targets in cardiac laminopathies.

Wellens' Syndrome from COVID-19 Infection Assessed by Enhanced Transthoracic Coronary Echo Doppler: A Case Report.

Wellens' syndrome (WS) is a preinfarction state caused by a sub-occlusion of the proximal left anterior descending coronary artery (LAD). In this case report, for the first time, we describe how this syndrome can be caused by COVID-19 infection and, most importantly, that it can be assessed bedside by enhanced transthoracic coronary echo Doppler (E-Doppler TTE). This seasoned technique allows blood flow Doppler to be recorded in the coronaries and at the stenosis site but has never been tested in an acute setting. Two weeks after clinical recovery from bronchitis allegedly caused by COVID-19 infection on the basis of epidemiologic criteria (no swab performed during the acute phase but only during recovery, at which time it was negative), our patient developed typical angina for the first time, mainly during effort but also at rest. He was admitted to our tertiary center, where pharyngeal swabs tested positive for COVID-19. A typical EKG finding supporting WS prompted an assessment of the left main coronary artery (LMCA) and the whole LAD blood flow velocity by E-Doppler TTE. Localized high velocity (transtenotic velocity) (100 cm/s) was recorded in the proximal LAD, with the reference velocity being 20 cm/s. This indicated severe stenosis with 90% area narrowing according to the continuity equation, as confirmed by coronary angiography. During follow-up after successful stenting, E-Doppler TTE showed a decrease in the transtenotic acceleration, confirming stent patency and a normal coronary flow reserve (3.2) and illustrating a normal microcirculatory function. Conclusion: COVID infection can trigger a coronary syndrome like WS. E-Doppler TTE, an ionizing radiation-free method, allows safe and rapid bedside management of the syndrome. This new strategy can be pivotal in distinguishing true WS from pseudo-WS. In cases of pseudo-WS, coronary angiography can be avoided. If E-Doppler TTE confirms the stenosis and PCI (percutaneous coronary intervention) is performed, the same method can allow assessment over time of the precise residual stenosis after stenting and verify the microvasculature status by evaluating coronary flow reserve.

Unmasking the prevalence of amyloid cardiomyopathy in the real world: results from Phase 2 of the AC-TIVE study, an Italian nationwide survey.

AIM: To investigate the prevalence of amyloid cardiomyopathy (AC) and the diagnostic accuracy of echocardiographic red flags of AC among consecutive adult patients undergoing transthoracic echocardiogram for reason other than AC in 13 Italian institutions. METHODS AND RESULTS: This is an Italian prospective multicentre study, involving a clinical and instrumental work-up to assess AC prevalence among patients ≥55 years old with an echocardiogram suggestive of AC (i.e. at least one echocardiographic red flag of AC in hypertrophic, non-dilated left ventricles with preserved ejection fraction). The study was registered at ClinicalTrials.gov (NCT04738266). Overall, 381 patients with an echocardiogram suggestive of AC were identified among a cohort of 5315 screened subjects, and 217 patients completed the investigations. A final diagnosis of AC was made in 62 patients with an estimated prevalence of 29% (95% confidence interval 23%-35%). Transthyretin-related AC (ATTR-AC) was diagnosed in 51 and light chain-related AC (AL-AC) in 11 patients. Either apical sparing or a combination of ≥2 other echocardiographic red flags, excluding interatrial septum thickness, provided a diagnostic accuracy >70%. CONCLUSION: In a cohort of consecutive adults with echocardiographic findings suggestive of AC and preserved left ventricular ejection fraction, the prevalence of AC (either ATTR or AL) was 29%. Easily available echocardiographic red flags, when combined together, demonstrated good diagnostic accuracy.

Cardiorenal Syndrome Triggered by Slowly Progressive Drugs Toxicity-Induced Renal Failure along with Minimal Mitral Disease: A Case Report.

BACKGROUND: We report the case of a 93-year-old patient with normal left ventricular function and severe mitral annulus calcification, with mild mitral steno-insufficiency. CASE PRESENTATION: She had developed creeping drugs-induced renal toxicity that is generally totally overlooked, due mainly to statins, a proton pump inhibitor, and aspirin. The Na and fluid retention, along with hypertension that ensued, although not severe, caused acute heart failure (sub-pulmonary edema) by worsening the mitral insufficiency. This occurred due to a less efficient calcific mitral annulus contraction during systole and an increasing mitral transvalvular gradient, as the transvalvular mitral gradient has an exponential relation to flow. After the suspension of the nephrotoxic drugs and starting intravenous furosemide, she rapidly improved. At 6 months follow-up, she is stable, in an NYHA 1-2 functional class, despite the only partial recovery of the renal function. CONCLUSION: Progressive renal failure can functionally worsen even minimal mitral valvulopathy. Drug-induced nephrotoxicity can always be suspected in case of renal failure of unknown etiology. The suspension of the culprit drugs can improve renal function and dramatically improve the clinical symptoms even in a nonagenarian.

Conduction delays after transcatheter aortic valve implantation with balloon-expandable prosthesis and high implantation technique.

Performing transcatheter aortic valve implantation with high implantation technique, i.e. with an aorto-ventricular ratio > 60/40, reduces the need of permanent pacemaker implantation. Valve calcification and prosthesis oversizing are predictors of permanent pacemaker implantation, but there are no available data on their role when transcatheter aortic valve implantation is performed with an aorto-ventricular ratio > 60/40. The aim of this study was to evaluate the effect of leaflets/annulus calcification and prosthesis oversizing on the incidence of permanent pacemaker implantation after transcatheter aortic valve implantation with a high implantation technique. Transcatheter aortic valve implantation was performed in 48 patients implanting a balloon-expandable transcatheter heart valve with an aorto-ventricular ratio > 60/40. Calcium burden was assessed by preprocedural multidetector computed tomography. An invasive electrophysiological study was performed before and after transcatheter aortic valve implantation. Five patients (10.4%) needed permanent pacemaker implantation. At univariate analysis, baseline right bundle branch block and postprocedural PR, QRS and His-ventricular interval elongation significantly predicted permanent pacemaker implantation (p < 0.05). Receiver-operating characteristic curve analysis showed a correlation between transcatheter heart valve oversizing and permanent pacemaker implantation need, with the best cut-off being 17% (AUC = 0.72, p = 0.033). Linear regression analysis demonstrated that QRS complex elongation was related to total, left and non-coronary leaflet calcification (p < 0.05). This study demonstrates that, when transcatheter aortic valve implantation is performed using a balloon-expandable transcatheter heart valve deployed with an aorto-ventricular ratio > 60/40, the presence of leaflets/annulus calcification or the need to oversize the prosthesis correlate with the occurrence of pathological cardiac conduction delays.

Clinical use of cangrelor: a real-world multicenter experience from South Italy.

BACKGROUND: Dual antiplatelet therapy (DAPT) with acetylsalicylic acid and oral P2Y12 inhibitor (P2Y12-I) represents the standard of care for patients with acute coronary syndromes (ACS) or with chronic coronary syndromes (CCS) treated with percutaneous coronary intervention (PCI). Cangrelor, the first intravenous P2Y12-I, is deemed to overcome the drawbacks of the oral administration; nevertheless, real world data on this new drug are scanty. We sought to investigate routine clinical use of cangrelor in four interventional centers of Italy. METHODS: We enrolled 241 consecutive patients (196 ACS, 45 CCS) treated with cangrelor during PCI. Drug administration modalities and in-hospital clinical outcomes were evaluated. A subanalysis in patients selected based on the CHAMPION Phoenix trial inclusion/exclusion criteria (CHAMPION-like subpopulation) was also performed. RESULTS: Cangrelor was mainly utilized in ACS patients, who presented poorer clinical conditions and higher bleeding risk. Cangrelor was given only in P2Y12-I naïve patients; switch to clopidogrel was always done at the end of the infusion, while ticagrelor or prasugrel were prevalently given 30 minutes before. In-hospital mortality was 10.0% and GUSTO moderate/severe bleeding was 2.5%. Bleeding data showed nevertheless to be in line with the CHAMPION Phoenix results in the "CHAMPION-like" subpopulation. CONCLUSIONS: Cangrelor was predominantly used in ACS with modalities substantially in accord with the label indications. Poor clinical outcomes are due to the prevalent utilization in highly challenging clinical settings, nevertheless the rate of bleeding and stent thrombosis are in line with the randomized trials if analyzed in a subpopulation of comparable risk profile.

Prognostic value of 12-leads admission electrocardiogram in low-risk patients hospitalized for COVID-19.

BACKGROUND: Cardiac involvement significantly contributes to coronavirus disease 2019 (COVID-19) mortality.12-lead electrocardiogram (ECG) represents a fast, cheap, and easy to perform exam with the adjunctive advantage of the remote reporting possibility. In this study, we sought to investigate if electrocardiographic parameters can identify patients, deemed at low-risk at admission, who will face in-hospital unfavorable course. METHODS: From March 1, 2020, through March 30, 2021, 384 consecutive patients with confirmed low-risk COVID-19 were hospitalized at the University Hospital of Bari (Italy). Criteria for low risk were: admission to the division of Pneumology or Infectious Diseases, no need for immediate (within 24 hours from admission) transfer to Intensive Care Unit or for respiratory support with invasive mechanical ventilation (IMV) or for circulation support (either mechanical or pharmacological). Admission ECGs were reviewed and interpreted by two expert cardiologists. The primary outcomes were in-hospital death and the composite outcome of in-hospital death and IMV. RESULTS: In low-risk COVID-19 patients, atrial fibrillation (AF), poor R wave progression (PRWP), tachycardia, and right bundle branch block (RBBB) resulted as statistically significant and independent predictors of in-hospital all-cause mortality; AF, PRWP, Tachycardia, RBBB, and corrected QT interval showed to be statistically significant and independent risk factors for the occurrence of the composite endpoint of death and IMV. CONCLUSIONS: Our study demonstrated for the first time that RBBB and PRWP, assessed upon admission with ECG, are associated with unfavorable clinical course in a baseline low-risk population hospitalized for COVID-19.

Mid-Diastolic Events (L Events): A Critical Review.

Mid-diastolic events (L events) include three phenomena appreciable on echocardiography occurring during diastasis: mid-diastolic transmitral flow velocity (L wave), mid-diastolic mitral valve motion (L motion), and mid-diastolic mitral annular velocity (L' wave). L wave is a known marker of advanced diastolic dysfunction in different pathological clinical settings such as left ventricle and atrial remodeling, overloaded states, and cardiomyopathies. Patients with L events have poor outcomes with a higher risk of developing heart failure symptoms and arrhythmic complications, including sudden cardiac death. The exact mechanism underlying the genesis of mid-diastolic events is not fully understood, just as the significance of these events in healthy young people or their presence at the tricuspid valve level. We also report an explicative case of a patient with L events studied using speckle tracking imaging of the left atrium and ventricle at the same reference heartbeat supporting the hypothesis of a post-early diastolic relaxation or a "two-step" ventricular relaxation for L wave genesis. Our paper seeks to extend knowledge about the pathophysiological mechanisms on mid-diastolic events and summarizes the current knowledge.

Predictors of Exercise Capacity in Dilated Cardiomyopathy with Focus on Pulmonary Venous Flow Recorded with Transesophageal Eco-Doppler.

The aim of this study was to clarify the relative contribution of elevated left ventricle (LV) filling pressure (FP) estimated by pulmonary venous (PV) and mitral flow, transesophageal Doppler recording (TEE), and other extracardiac factors like obesity and renal insufficiency (KI) to exercise capacity (ExC) evaluated by cardiopulmonary exercise testing (CPX) in patients with dilated cardiomyopathy (DCM). During the CPX test, 119 patients (pts) with DCM underwent both peak VO2 consumption and then TEE with color-guided pulsed-wave Doppler recording of PVF and transmitral flow. In 78 patients (65%), peak VO2 was normal or mildly reduced (>14 mL/kg/min) (group 1) while it was markedly reduced (≤14 mL/kg/min) in 41 (group 2). In univariate analysis, systolic fraction (S Fract), a predictor of elevated pre-a LV diastolic FP, appeared to be the best diastolic parameter predicting a significantly reduced peak VO2. Logistic regression analysis identified five parameters yielding a unique, statistically significant contribution in predicting reduced ExC: creatinine clearance < 52 mL/min (odds ratio (OR) = 7.4, p = 0.007); female gender (OR = 7.1, p = 0.004); BMI > 28 (OR = 5.8, p = 0.029), age > 62 years (OR = 5.5, p = 0.03), S Fract < 59% (OR = 4.9, p = 0.02). Conclusion: KI was the strongest predictor of reduced ExC. The other modifiable factors were obesity and severe LV diastolic dysfunction expressed by blunted systolic venous flow. Contrarily, LV ejection fraction was not predictive, confirming other previous studies. This has important clinical implications.

Pro-inflammatory cytokines as emerging molecular determinants in cardiolaminopathies.

Mutations in Lamin A/C gene (lmna) cause a wide spectrum of cardiolaminopathies strictly associated with significant deterioration of the electrical and contractile function of the heart. Despite the continuous flow of biomedical evidence, linking cardiac inflammation to heart remodelling in patients harbouring lmna mutations is puzzling. Therefore, we profiled 30 serum cytokines/chemokines in patients belonging to four different families carrying pathogenic lmna mutations segregating with cardiac phenotypes at different stages of severity (n = 19) and in healthy subjects (n = 11). Regardless lmna mutation subtype, high levels of circulating granulocyte colony-stimulating factor (G-CSF) and interleukin 6 (IL-6) were found in all affected patients' sera. In addition, elevated levels of Interleukins (IL) IL-1Ra, IL-1ß IL-4, IL-5 and IL-8 and the granulocyte-macrophage colony-stimulating factor (GM-CSF) were measured in a large subset of patients associated with more aggressive clinical manifestations. Finally, the expression of the pro-inflammatory 70 kDa heat shock protein (Hsp70) was significantly increased in serum exosomes of patients harbouring the lmna mutation associated with the more severe phenotype. Overall, the identification of patient subsets with overactive or dysregulated myocardial inflammatory responses could represent an innovative diagnostic, prognostic and therapeutic tool against Lamin A/C cardiomyopathies.

Importance of clinical suspicion and multidisciplinary management for early diagnosis of a cardiac laminopathy patient: A case report.

BACKGROUND: Laminopathies are rare diseases, whose cardiac manifestations are heterogeneous and, especially in their initial stage, similar to those of more common conditions, such as ischemic heart disease. Early diagnosis is essential, as these conditions can first manifest themselves with sudden cardiac death. Electrical complications usually appear before structural complications; therefore, it is important to take into consideration these rare genetic disorders for the differential diagnosis of brady and tachyarrhythmias, even when left ventricle systolic function is still preserved. CASE SUMMARY: A 60-year-old man, without history of previous disorders, presented in September 2019 to the emergency department because of the onset of syncope associated with hypotension. The patient was diagnosed with a high-grade atrioventricular block. A dual chamber pacemaker was implanted, but after the onset of a sustained ventricular tachycardia during physical exertion, a drug eluting stent was implanted on an intermediate stenosis on the left anterior descending artery, which had previously been considered non-haemodynamically significant. During the follow-up, the treating cardiologist, suspicious of the overall clinical picture, recommended a genetic test for the diagnosis of cardiomyopathies, which tested positive for a pathogenetic mutation of the lamin A/C gene. While awaiting the result of the genetic test and, later, the pacemaker to be upgraded to a biventricular defibrillator, a remote monitoring device was given to the patient in order to minimize in-person clinical evaluations during the coronavirus disease 2019-related lockdown. CONCLUSION: This case aims to raise awareness of the cardiological manifestations of laminopathies, which can be dangerously misdiagnosed as other, more common conditions.

Autoimmune diseases in patients undergoing percutaneous coronary intervention: A risk factor for in-stent restenosis?

BACKGROUND AND AIMS: Despite the relation between autoimmune diseases and increased atherosclerotic risk is established, the influence of autoimmune disorders on in-stent restenosis (ISR) after percutaneous coronary intervention (PCI) is only partly known. ISR is an aberrant reparative process mainly characterized by an increased number of vascular smooth muscle cells and excessive deposition of extracellular proteoglycans and type III collagen. Chronic inflammation, always present in autoimmune diseases, modulates the endothelial response to PCI. Aim of this review is to resume the current evidence on the association between ISR and autoimmune diseases, focusing on pathogenic mechanisms and therapeutic targets. METHODS: We conducted a comprehensive review of the literature on the relationship between ISR and insulin-dependent diabetes mellitus (IDDM), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), antiphospholipid-antibodies syndrome (APS), inflammatory bowel diseases (IBD), and Hashimoto's thyroiditis (HT). RESULTS: Patients affected with IDDM, RA, SLE, APS, IBD and HT proved to face higher rates of ISR compared to the general population. The endothelial dysfunction seems the principal common pathogenic pathway for ISR and is attributed to both the immune system disorder and the systemic inflammation. Some evidence suggested that methotrexate and anti-tumor necrosis factor treatments can be effective in reducing ISR, while antibodies against vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 showed to reduce neointimal hyperplasia in animal models. CONCLUSIONS: Autoimmune diseases are a risk factor for ISR. The study of the potential cardiovascular benefits of the current therapies, mainly anti-inflammatory drugs, and the pursuit of innovative treatments appear of paramount interest.

Dalbavancin Efficacy and Impact on Hospital Length-of-Stay and Treatment Costs in Different Gram-Positive Bacterial Infections.

BACKGROUND AND OBJECTIVES: The study aimed to evaluate the impact of dalbavancin therapy on both hospital length-of-stay (LOS) and treatment-related costs, as well as to describe the clinical outcome, in a retrospective cohort of patients with diverse Gram-positive bacterial infections, hospitalized in different specialty Units. METHODS: From July 2017 to July 2019, clinical and sociodemographic data were collected for all hospitalized patients switched to dalbavancin for the treatment of Gram-positive infections. LOS and treatment-related costs were assessed and compared to a hypothetical scenario where the initial standard antimicrobial therapy would have been administered in hospital for the same duration as dalbavancin. RESULTS: A total of 50 patients were enrolled. The observed infections were: acute bacterial skin and skin structure infections (ABSSSIs, 12 patients), complicated ABSSSIs (eight patients), osteoarticular infections (18 patients), vascular graft or cardiovascular implantable electronic devices (CIED) infections (12 patients). After a median of 14 [interquartile range (IQR) 7-28] days, the in-hospital antimicrobial therapy was switched to dalbavancin 1500 mg. When appropriate, considering the site and the clinical course of the infection, 1500 mg doses were repeated every 14 days until recovery. Overall, 49/50 (98%) patients reported clinical success at the end of therapy. No relapses were observed in 37 patients for whom a median follow-up of 150 (IQR 30-180) days was available. By switching to dalbavancin, a median of €8,259 (IQR 5644-17,270) and 14 hospital days (IQR 22-47) per patient were saved. CONCLUSIONS: In this experience, the use of dalbavancin contributed to shorten LOS and treatment-related costs, especially in difficult Gram-positive infections requiring prolonged therapy.

Coronary Flow and Reserve by Enhanced Transthoracic Doppler Trumps Coronary Anatomy by Computed Tomography in Assessing Coronary Artery Stenosis.

We report the case of a 71-year-old patient with many risk factors for coronary atherosclerosis, who underwent computed coronary angiography (CTA), in accordance with the guidelines, for recent onset atypical chest pain. CTA revealed critical (>50% lumen diameter narrowing) stenosis of the proximal anterior descending coronary, and the patient was scheduled for invasive coronary angiography (ICA). Before ICA he underwent enhanced transthoracic echo-Doppler (E-Doppler TTE) for coronary flow detection by color-guided pulsed-wave Doppler recording of the left main (LMCA) and whole left anterior descending coronary artery (LAD,) along with coronary flow reserve (CFR) in the distal LAD calculated as the ratio, of peak flow velocity during i.v. adenosine (140 mcg/Kg/m) to resting flow velocity. E-Doppler TTE mapping revealed only mild stenosis (28% area narrowing) of the mid LAD and a CFR of 3.20, in perfect agreement with the color mapping showing no flow limiting stenosis in the LMCA and LAD. ICA revealed only a very mild stenosis in the mid LAD and mild atherosclerosis in the other coronaries (intimal irregularities). Thus, coronary stenosis was better predicted by E-Doppler TTE than by CTA. Coronary flow and reserve as assessed by E-Doppler TTE trumps coronary anatomy as assessed by CTA, without exposing the patient to harmful radiation and iodinated contrast medium.

Inflammatory Bowel Disease and Acute Coronary Syndromes: From Pathogenesis to the Fine Line Between Bleeding and Ischemic Risk.

Inflammatory bowel disease (IBD) is a pathological condition that first involves the gastrointestinal wall but can also trigger a systemic inflammatory state and thus extraintestinal manifestations. Systemic inflammation is probably secondary to the passage of bacterial products into the bloodstream because of altered intestinal permeability and the consequent release of proinflammatory mediators. Inflammation, through several diverse pathophysiological pathways, determines both a procoagulative state and systemic endothelial dysfunction, which are both deemed to be responsible for venous and arterial thromboembolic adverse events. The management of systemic thrombotic complications is particularly challenging in this category of patients, who also present a high bleeding risk; what is more, both bleeding and thrombotic risks peak during the active phases of the disease. The literature suggests that treating physicians have been, so far, more heavily influenced by concerns about bleeding than by the thrombotic risk. Despite the absence of data provided by large cohorts or randomized studies, the high risk of arterial and venous atherothrombosis in patients with IBD seems unquestionable. Moreover, several reports suggest that when arterial thromboembolism involves the coronary vessels, causing acute coronary syndromes, ischemic complications from antithrombotic drug undertreatment are frequent and severe. This review aims to shed light on the tricky balance between the ischemic and hemorrhagic risks of patients with IBD and to highlight how difficult it is for clinicians to define a tailored therapy based on a case-by-case, careful, and unprejudiced clinical evaluation.