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One of the most common complications of tricuspid valve replacement is atrioventricular block (AVB), often requiring permanent pacing. The endocardial pacemaker lead, placed in the right ventricle, may sometimes interfere with the implanted prosthesis, causing its early dysfunction and the need for alternative sites of pacing. To the best of our knowledge, we present the first case of a successful combined percutaneous procedure consisting of the implantation of two leads in the coronary sinus for univentricular bifocal pacing and a transcatheter tricuspid valve-in-valve implantation in a young patient with severe dysfunction of the tricuspid bioprosthesis, requiring permanent pacing for a postsurgical complete atrioventricular block. Tricuspid valve replacement with surgery can often lead to cardiac rhythm disorders requiring a permanent pacemaker. This device may occasionally damage the tricuspid prosthesis. We present the first case of a combined procedure of tricuspid valve replacement and device implantation distant from the prosthesis without the need for a surgical approach in a young patient with severe tricuspid prosthesis malfunctioning and permanent pacing. Article highlights Right-sided infective endocarditis in young patients may be caused by intravenous drug use, leading to tricuspid valve injury and the need for valve replacement with a prosthesis. Complete atrioventricular block represents an important postoperative complication of valve surgery requiring, frequently, the implantation of a permanent pacemaker. The endocardial pacemaker lead in the right ventricle may sometimes interfere with the implanted bioprosthesis, causing its early degeneration with the need for prosthesis replacement and research of other sites of pacing. Surgical replacement of a malfunctioning tricuspid prosthesis is among the highest-risk procedures. A combined percutaneous implantation of two pacing leads in the coronary sinus for univentricular bifocal pacing and a transcatheter tricuspid valve-in-valve may be a safe and effective alternative to surgery in patients requiring a permanent pacing site. In the case of pacemaker dependency, the use of actively fixating leads should be preferable to passive ones in order to minimize the risk of lead dislocation. Other strategies such as pacing with epicardial leads, the use of his-bundle pacing, or leadless pacemakers were taken into account but not deemed suitable. The Heart Team plays a critical role in decision-making in these particular conditions. [ABSTRACT FROM AUTHOR]

Long-COVID-19 refers to the signs and symptoms that continue or develop after the "acute COVID-19" phase. These patients have an increased risk of multiorgan dysfunction, readmission, and mortality. In Long-COVID-19 patients, it is possible to detect a persistent increase in D-Dimer, NT-ProBNP, and autonomic nervous system dysfunction. To verify the dysautonomia hypothesis in Long-COVID-19 patients, we studied heart rate variability using 12-lead 24-h ECG monitoring in 30 Long-COVID-19 patients and 20 No-COVID patients. Power spectral analysis of heart rate variability was lower in Long-COVID-19 patients both for total power (7.46 ± 0.5 vs. 8.08 ± 0.6; p < 0.0001; Cohens-d = 1.12) and for the VLF (6.84 ± 0.8 vs. 7.66 ± 0.6; p < 0.0001; Cohens-d = 1.16) and HF (4.65 ± 0.9 vs. 5.33 ± 0.9; p = 0.015; Cohens-d = 0.76) components. The LF/HF ratio was significantly higher in Long-COVID-19 patients (1.46 ± 0.27 vs. 1.23 ± 0.13; p = 0.001; Cohens-d = 1.09). On multivariable analysis, Long-COVID-19 is significantly correlated with D-dimer (standardized β-coefficient = 0.259), NT-ProBNP (standardized β-coefficient = 0.281), HF component of spectral analysis (standardized β-coefficient = 0.696), and LF/HF ratio (standardized β-coefficient = 0.820). Dysautonomia may explain the persistent symptoms in Long COVID-19 patients. The persistence of a procoagulative state and an elevated myocardial strain could explain vagal impairment in these patients. In Long-COVID-19 patients, impaired vagal activity, persistent increases of NT-ProBNP, and a prothrombotic state require careful monitoring and appropriate intervention. [ABSTRACT FROM AUTHOR]

Background and Objective: Sacubitril/valsartan improved the prognosis of patients with heart failure with reduced ejection fraction in the PARADIGM-HF study. Recently, the TRANSITION and PIONEER-HF studies demonstrated the safety and efficacy of sacubitril/valsartan in patients hospitalized for acute decompensated heart failure, with treatment initiated after hemodynamic and clinical stabilization. In this case series study, we assessed the short-term effects of sacubitril/valsartan on exercise capacity, inflammation, and biomarkers in patients with acute decompensated heart failure. Methods: Patients admitted for acute decompensated heart failure to the Department of Internal Medicine of Telese Terme Hospital and Cardiovascular Department, University of Bari, from 9 March, 2017 to 9 June, 2018 were enrolled. Following hemodynamic stabilization, patients initiated sacubitril/valsartan 24/26 mg twice a day for 4 weeks, with up-titration to 49/51 mg twice a day based on tolerability after 1 week. Efficacy outcomes included the 6-min walking test, N-terminal pro-B-type natriuretic peptide, high-sensitivity C-reactive protein, and lymphocyte count. Safety outcomes included renal function, hyperkalemia, and symptomatic hypotension. Results: In total, 40 patients completed the study and 27 (67.5%) patients were up-titrated. Compared with baseline, exercise capacity and relative lymphocyte count increased significantly after 4 weeks of treatment, while N-terminal pro-B-type natriuretic peptide and high-sensitivity C-reactive protein decreased significantly. N-terminal pro-B-type natriuretic peptide and relative lymphocyte count independently predicted the 6-min walking test distance (p = 0.021). No patients experienced any relevant side effects. Conclusions: Early initiation of sacubitril/valsartan in patients with heart failure with reduced ejection fraction after acute decompensated heart failure may be safe and effective in terms of functional capacity and biomarkers. [ABSTRACT FROM AUTHOR]

Purpose of Review: To summarize epidemiology, pathophysiology, prognostic relevance, and treatment options of coronary artery disease (CAD) when coupled with severe aortic stenosis (SAS). In regard to treatment options, we focused on the most recently adopted therapeutic approaches and on the future perspectives in light of the latest percutaneous and surgical technical improvements in the field of both CAD and SAS management. Recent Findings: Nowadays, SAS is the most common valve disease requiring intervention, either surgical or percutaneous. On the other side, CAD is one of the leading causes of death in the developed countries. CAD and degenerative SAS share several predisposing factors and are often concurrently found in clinical practice. Despite in the last years the transcatheter aortic valve replacement (TAVR) has been deeply changing the therapeutic approach to SAS, the correct management of patients with concomitant CAD remains controversial due to limited and heterogeneous data in the literature. Summary: Coronary revascularization is often performed in patients with concomitant CAD and SAS. Complete surgical approach is still the standard of care according to international guidelines. However, in light of the recent results of TAVR trials, the therapeutic approach is expected to change. To date, percutaneous coronary intervention performed before TAVR is safe and feasible even if the optimal timing for revascularization remains debated. Due to the great complexity of the patients affected by SAS and CAD and until unquestionable truths will come from large randomized trials, the role of the Heart Team in the decision-making process is of primary importance to guarantee the best tailored therapeutic strategy for the single patient. [ABSTRACT FROM AUTHOR]

Percutaneous closure of atrial septal defect (ASD)/patent foramen ovale (PFO) can influence systemic hemodynamics. The aim of this research was to evaluate the influence of the closure procedure on morphological and functional characteristics of systemic vascular walls. Fourteen ASD (mean age 40 ± 16 years) and 14 PFO (45 ± 8 years) patients were enrolled in this retrospective study. All underwent percutaneous closure procedure; physical, clinical and biochemical evaluations; echocardiography; carotid evaluation; and brachial artery flow-mediated vasodilatation (FMD). All the evaluations were performed at the time of enrollment, 24 h post-procedure, at 1–6–12-month follow-up. FMD at enrollment was higher in PFO patients as compared to ASD (8.5% [7.6–10.7%] versus 6.5% [5.6–7.6%], p < 0.0001). FMD values in ASD patients significantly increased during follow-up (enrollment: 6.5% [5.6–7.6%], 12-month follow-up: 8.8% [7.2–10.3%], p < 0.01). PFO patients showed reduced FMD values 24 h after the procedure (enrollment: 8.5% [7.6–10.7%], 24 h post-procedure: 7% [6.3–9%], p < 0.001), while recovering endothelial function during follow-up period to baseline values (FMD at 12-month follow-up: 8.2% [7.6–10.5%]). At one-year follow-up, FMD remained inversely related to systolic pulmonary arterial pressure and right and left atrial/ventricle chambers dimensions (RV proximal diameter efflux tract, right atrium [RA] longitudinal diameter, RA transverse diameter, RA area, left ventricle [LV] end-diastolic diameter, left atrium [LA] anteroposterior diameter, LA area; p < 0.01) in ASD patients. Endothelial function improved after percutaneous closure of ASD, while remaining stable after PFO closure. Therefore, ASD patients seem to improve their cardiovascular risk profile after percutaneous closure of their defect. [ABSTRACT FROM AUTHOR]

Inflammatory bowel diseases have been recognized as predisposing factors to atherosclerosis and thrombotic events, involving both the venous and the arterial circulatory systems. We report the case of a 70-year-old man who presented with ST elevation myocardial infarction during the active phase of ulcerative colitis (UC). Because of the ongoing hematochezia, after successful revascularization of the culprit vessel, the patient was medicated with Clopidogrel, in place of one of the more powerful new oral P2Y12 inhibitors that currently represent the gold standard therapy. Few days later a second elective percutaneous coronary intervention (PCI) on a non-culprit vessel ensued in a life-threatening early massive stent thrombosis involving the left main. During and after emergency PCI antiplatelet therapy was upgraded to Abciximab and Ticagrelor; this therapy proved successful in handling the massive stent thrombosis in the absence of severe bleeding complications. This case is unique and paradigmatic of the complex management of patients with coexisting active UC and acute coronary syndromes; it demonstrates as in this setting the balance between hemorrhagic and ischemic risk is labile and tricky to assess. [ABSTRACT FROM AUTHOR]

Takotsubo cardiomyopathy (TTC) is characterized by transient systolic ventricular dysfunction. It is supposed to be caused by a cathecolaminergic wave which leads to myocardial stunning through a massive action on beta2-adrenoreceptor. Moreover, beta2-receptor hyperactivity negatively influences endothelial function. It can be detected by brachial flow mediated dilation (b-FMD) which assesses endothelium regulated vasomotility. The study aim is to analyze the b-FMD variability during hospitalization in 50 patients admitted with TTC. In addition, we investigated a possible correlation between b-FMD at admission and both length of hospital stay (LOHS) and troponin I peak. We detected b-FMD by measuring the hypoxic induced vasoreactivity through assessing brachial artery dilation after 5 min of iatrogenic ischemia obtained by inflating a sphygmomanometer cuff. Artery diameter modifications were assessed by high-resolution ultrasound, and a dedicated software calculated accurately the percentage of dilation after ischemia by comparing it to the basal. These values were measured at admission and on discharge. The obtained values were compared for each patient to explore their variability during hospitalization. Moreover, the correlation between the b-FMD at admission and both the troponin I peak and the LOHS was investigated. There was a statistical significant difference between mean FMD measured at admission and at discharge (respectively 1.54 ± 0.34 and 8.92 ± 2.48%; p < 0.001). Moreover, we found a significant negative correlation between troponin I peak and FMD values at admission (r = − 0.7645; p < 0.001) and a significant inverse correlation between FMD at admission and LOHS (r = − 0.7543; p < 0.001). There is a significant improvement of b-FMD during hospitalization in patients admitted for Tako-Tsubo Cardiomyopathy. Moreover, for the first time, a direct correlation among b-FMD, troponin I peak and LOHS has been detected. [ABSTRACT FROM AUTHOR]

Aims: Preliminary data on Sapien 3 valve (S3-THV) use for transcatheter aortic valve implantation have shown an increased permanent pacemaker implantation (PPMI) rate with respect to Sapien XT valve. Aim of this study was to investigate the role of S3-THV position in the left ventricular outflow tract (LVOT) on electrocardiographic changes suggestive of atrioventricular (ΔPR) and/or intraventricular (ΔQRS) conduction abnormalities and 30 days PPMI rate.Methods and results: Eighty-six consecutive patients treated with S3-THV were included in the study. All patients underwent clinical and electrocardiogram evaluation. Left ventricular outflow tract prosthesis depth was assessed by fluoroscopy and expressed quantitatively (mm) and as aorto-ventricular ratio (AVR). Eight patients (9.3%) needed PPMI at 30 days. A low AVR (≤60/40) predicted PPMI (OR = 6.09, 95% CI 1.19-31.01, P = 0.030) and resulted into higher PPMI rate, compared with higher AVR (30.0 vs. 6.6%, P = 0.017). For each millimetre increase in the LVOT prosthesis depth PPMI risk increased by 1.41 times (95% CI 1.06-1.87, P = 0.017). In patients with low AVR, ΔPR was higher than in those with higher AVR (33.4 ± 56.7 vs. 12.1 ± 19.4 ms, P = 0.021) and ΔPR was associated to LVOT prosthesis depth (β = 0.286, P = 0.009). Furthermore, ΔPR was associated with risk of PPMI (OR = 1.03, 95% CI 1.01-1.06, P = 0.024).Conclusions: A low AVR is associated to higher ΔPR and PPMI rates. The correlation between LVOT prosthesis depth with ΔPR and higher PPMI rate suggests the need of a careful S3-THV implantation. [ABSTRACT FROM AUTHOR]

Background: There is an increasing trend towards shorter hospital stays after transcatheter aortic valve implantation (TAVI), in particular for patients undergoing the procedure via transfemoral (TF) access. Preliminary data suggest that there exists a population of patients that can be discharged safely very early after TF-TAVI. However, current evidence is limited to few retrospective studies, encompassing relatively small sample sizes.Methods: The Feasibility And Safety of early discharge after Transfemoral TAVI (FAST-TAVI) registry is a prospective observational registry that will be conducted at 10 sites across Italy, the Netherlands and the UK. Patients will be included if they have been scheduled to undergo TF-TAVI with the balloon-expandable SAPIEN 3 transcatheter heart valve (THV; Edwards Lifesciences, Irvine, CA). The primary endpoint is a composite of all-cause mortality, vascular-access-related complications, permanent pacemaker implantation, stroke, re-hospitalisation due to cardiac reasons, kidney failure and major bleeding, occurring during the first 30 days after hospital discharge. Patients will be stratified according to whether they were high or low risk for early discharge (≤3 days) (following pre-specified criteria), and according to whether or not they were discharged early. Secondary endpoints will include time-to-event (Kaplan-Meier) analysis for the primary outcome and its individual components, analysis of the relative costs of early and late discharge, and changes in short- and long-term quality of life. Multivariate logistic regression will be used to identify factors that indicate that a patient may be suitable for early discharge.Discussion: The data gathered in the FAST-TAVI registry should help to clarify the safety of early discharge after TF-TAVI and to identify patient and procedural characteristics that make early discharge from hospital a safe and cost-effective strategy.Trial Registration: ClinicalTrials.gov Identifier: NCT02404467 (registration first received March 23rd 2015). [ABSTRACT FROM AUTHOR]

Left ventricular noncompaction (LVNC) is a myocardial disorder probably due to the arrest of normal embryogenesis of the left ventricle. It could be isolated or associated with other extracardiac and cardiac abnormalities, including coronary artery anomalies. Despite the continuous improvement of imaging resolution quality, this cardiomyopathy still remains frequently misdiagnosed, especially if associated with other heart diseases. We report a case of LVNC association with both malposition of the great arteries and a very original coronary artery pattern. [ABSTRACT FROM AUTHOR]

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) commonly complicates with coagulopathy. A syndrome called Long-COVID-19 is emerging recently in COVID-19 survivors, characterized, in addition to the persistence of symptoms typical of the acute phase, by alterations in inflammatory and coagulation parameters due to endothelial damage. The related disseminated intravascular coagulation (DIC) can be associated with high death rates in COVID-19 patients. It is possible to find a prothrombotic state also in Long-COVID-19. Early administration of anticoagulants in COVID-19 was suggested in order to improve patient outcomes, although exact criteria for their application were not well-established. Low-molecular-weight heparin (LMWH) was commonly adopted for counteracting DIC and venous thromboembolism (VTE), due to its pharmacodynamics and anti-inflammatory properties. However, the efficacy of anticoagulant therapy for COVID-19-associated DIC is still a matter of debate. Thrombin and Factor Xa (FXa) are well-known components of the coagulation cascade. The FXa is known to strongly promote inflammation as the consequence of increased cytokine expression. Endothelial cells and mononuclear leucocytes release cytokines, growth factors, and adhesion molecules due to thrombin activation. On the other hand, cytokines can activate coagulation. The cross-talk between coagulation and inflammation is mediated via protease-activated receptors (PARs). These receptors might become potential targets to be considered for counteracting the clinical expressions of COVID-19. SARS-CoV-2 is effectively able to activate local and circulating coagulation factors, thus inducing the generation of disseminated coagula. LMWH may be considered as the new frontier in the treatment of COVID-19 and Long-COVID-19. Indeed, direct oral anticoagulants (DOACs) may be an alternative option for both early and later treatment of COVID-19 patients due to their ability to inhibit PARs. The aim of this report was to evaluate the role of anticoagulants—and DOACs in particular in COVID-19 and Long-COVID-19 patients. We report the case of a COVID-19 patient who, after administration of enoxaparin developed DIC secondary to virosis and positivity for platelet factor 4 (PF4) and a case of Long-COVID with high residual cardiovascular risk and persistence of blood chemistry of inflammation and procoagulative state. [ABSTRACT FROM AUTHOR]

Diabetes mellitus (DM) represents an independent risk factor for chronic AF and is associated with unfavorable outcomes. We aimed to evaluate the efficacy and safety of direct oral anticoagulants (DOACs) in patients with atrial fibrillation (AF), with and without diabetes mellitus (DM), using a new risk index (RI) defined as: RI = Rate   of   Events Rate   of   Patients   at   Risk . In particular, an RI lower than 1 suggests a favorable treatment effect. We searched MEDLINE, MEDLINE In-Process, EMBASE, PubMed, and the Cochrane Central Register of Controlled Trials. The risk index (RI) was calculated in terms of efficacy (rate of stroke/systemic embolism (stroke SEE)/rate of patients with and without DM; rate of cardiovascular death/rate of patients with and without DM) and safety (rate of major bleeding/rate of patients with and without DM) outcomes. AF patients with DM (n = 22,057) and 49,596 without DM were considered from pivotal trials. DM doubles the risk index for stroke/SEE, major bleeding (MB), and cardiovascular (CV) death. The RI for stroke/SEE, MB, and CV death was comparable in patients treated with warfarin or DOACs. The lowest RI was in DM patients treated with Rivaroxaban (stroke/SEE, RI = 0.08; CV death, RI = 0.13). The RIs for bleeding were higher in DM patients treated with Dabigatran (RI110 = 0.32; RI150 = 0.40). Our study is the first to use RI to homogenize the efficacy and safety data reported in the DOACs pivotal studies against warfarin in patients with and without DM. Anticoagulation therapy is effective and safe in DM patients. DOACs appear to have a better efficacy and safety profile than warfarin. The use of DOACs is a reasonable alternative to vitamin-K antagonists in AF patients with DM. The RI can be a reasonable tool to help clinicians choose between DOACs or warfarin in the peculiar set of AF patients with DM. [ABSTRACT FROM AUTHOR]

We explored the significance of the L-Arginine/asymmetric dimethylarginine (L-Arg/ADMA) ratio as a biomarker of endothelial dysfunction in stroke patients. To this aim, we evaluated the correlation, in terms of severity, between the degree of endothelial dysfunction (by L-Arg/ADMA ratio), the methylene tetrahydrofolate reductase (MTHFR) genotype, and the interatrial septum (IAS) phenotype in subject with a history of stroke. Methods and Results: L-Arg, ADMA, and MTHFR genotypes were evaluated; the IAS phenotype was assessed by transesophageal echocardiography. Patients were grouped according to the severity of IAS defects and the residual enzymatic activity of MTHFR-mutated variants, and values of L-Arg/ADMA ratio were measured in each subgroup. Of 57 patients, 10 had a septum integrum (SI), 38 a patent foramen ovale (PFO), and 9 an ostium secundum (OS). The L-Arg/ADMA ratio differed across septum phenotypes (p ≤ 0.01), and was higher in SI than in PFO or OS patients (p ≤ 0.05, p ≤ 0.01, respectively). In the PFO subgroup a negative correlation was found between the L-Arg/ADMA ratio and PFO tunnel length/height ratio (p ≤ 0.05; r = − 0.37; R2 = 0.14). Interestingly, the L-Arg/ADMA ratio varied across MTHFR genotypes (p ≤ 0.0001) and was lower in subgroups carrying the most impaired enzyme with respect to patients carrying the conservative MTHFR (p ≤ 0.0001, p ≤ 0.05, respectively). Consistently, OS patients carried the most dysfunctional MTHFR genotypes, whereas SI patients the least ones. Conclusions: A low L-Arg/ADMA ratio correlates with impaired activity of MTHFR and with the jeopardized IAS phenotype along a severity spectrum encompassing OS, PFO with long/tight tunnel, PFO with short/large tunnel, and SI. This infers that genetic MTHFR defects may underlie endothelial dysfunction-related IAS abnormalities, and predispose to a cryptogenic stroke. Our findings emphasize the role of the L-Arg/ADMA ratio as a reliable marker of stroke susceptibility in carriers of IAS abnormalities, and suggest its potential use both as a diagnostic tool and as a decision aid for therapy. [ABSTRACT FROM AUTHOR]