[Contemporary diagnosis and treatment of tricuspid regurgitation: from neglected valve to primetime]. / Diagnosi e trattamento contemporaneo dell'insufficienza tricuspidale: da valvola dimenticata a primetime.

Tricuspid insufficiency has long been considered an entity with low prognostic importance and associated with symptoms and signs only secondarily to left heart pathology. Scientific research in recent years has debunked this myth, demonstrating a key role in determining symptoms and signs of right heart failure, even in advanced stages. In parallel, advances in transcatheter technologies have opened up treatment options even for patients with increased surgical risk, who were previously excluded from traditional surgical options, with increasingly convincing results in reducing symptoms and improving the quality of life of our patients. The contemporary challenge is to translate these messages into everyday clinical practice and to encourage the centralization of patients in centers that currently have the expertise for feasibility evaluation and subsequent treatment. In this Review, we will analyze the most recent evidence on the pathophysiology and diagnosis of tricuspid insufficiency, the latest recommendations from European guidelines, and we will try to illustrate the most common technologies for percutaneous treatment and the abundant evidence supporting them.

Use of cangrelor for complex percutaneous coronary intervention in the context of concomitant severe aortic stenosis: a case series.

Background: There is a growing need for percutaneous coronary intervention (PCI) to be performed within the same transcatheter aortic valve implantation (TAVI) procedure. In such cases, cangrelor, a fast-acting intravenous P2Y12-inhibitor with a short offset, is potential clinical utility to minimize bleeding and vascular complications during large-bore arterial access (LBAA) as well as the thrombotic risk associated with concomitant PCI. Case summary: We report two cases of TAVI with an indication to concomitant, high-risk PCI. In the first one, cangrelor was started only after LBAA was secured and TAVI completed, just before the initiation of complex PCI. In the second case, due to predicted complex coronary cannulation after TAVI, complex PCI was performed before TAVI and cangrelor started just after LBAA. In both cases, use of cangrelor (vs. pre-treatment with oral P2Y12-i) allowed for a tailored minimization of the risk of bleeding and vascular complications during LBAA while offering full platelet inhibition during a complex/high-risk PCI. Discussion: In this case series, we illustrate a possible approach to the use of cangrelor for patients undergoing TAVI and complex/high-risk PCI. In such complex cases, thorough pre-procedural planning might include a cangrelor to minimize vascular, bleeding, and ischaemic complications.

Atrial fibrillation and ischemic heart disease: (un)solved therapeutic dilemma?

Concomitant presence of atrial fibrillation and coronary artery disease requiring percutaneous coronary intervention is a frequent occurrence. The choice of optimal antithrombotic therapy, in this context, is still challenging. To offer the best protection both in terms of stroke and stent thrombosis, triple therapy with oral anticoagulation and dual antiplatelet therapy would be required. Several drug combinations have been tested in recent years, including direct oral anticoagulants, with the aim of balancing ischemic and bleeding risk. Both pharmacokinetic aspects of the molecules and patient's characteristics should be analyzed in choosing oral anticoagulation. Then, as suggested by guidelines, triple therapy should start with a seven-day duration and the aim to prolong to thirty days in high thrombotic risk patients. Dual therapy should follow to reach twelve months after coronary intervention. Even not fully discussed by the guidelines, in order to balance ischemic and bleeding risk it should also be considered: 1) integrated assessment of coronary artery disease and procedural complexity of coronary intervention; 2) appropriateness to maintain the anticoagulant drug dosage indicated in technical data sheet; the lack of data on the suspension of antiplatelet drugs one year after percutaneous intervention; 3) the possibility of combination therapy with ticagrelor; and 4) the need to treat the occurrence of paroxysmal atrial fibrillation during acute coronary syndrome. With data provided clinician should pursue a therapy as personalized as possible, both in terms of drug choice and treatment duration, in order to balance ischemic and bleeding risk.

Transcatheter aortic valve replacement with the self-expanding ACURATE Neo2 in patients with horizontal aorta: Insights from the ITAL-neo registry.

BACKGROUND: Horizontal aorta (HA), defined by an aortic angulation (AA) ≥48°, is associated with worse outcomes particularly after self-expanding (SE) trans-catheter heart valve (THV) implantation. Although the SE ACURATE Neo THV demonstrated favorable procedural success rates in patients with HA, it remains associated with a non-negligible rate of moderate or greater paravalvular leak (PVL). OBJECTIVES: Aim of the study was to assess the performance of ACURATE Neo2 in the setting of HA. METHODS: We performed a multicenter cohort analysis on patients with severe aortic valve stenosis and HA undergoing transcatheter aortic valve replacement (TAVR) with the Neo or Neo2 THV enrolled in the ITAL-neo registry. The primary endpoint was a composite of early safety and clinical efficacy at 30 days according to the Valve Academic Research Consortium-3 (VARC-3). Secondary endpoints included the occurrence of moderate or severe PVL and 90-day clinical outcomes. RESULTS: Among 900 patients included in the ITAL-neo registry, 407 exhibited HA; of these, 300 received a Neo THV and 107 a Neo2 THV. HA, irrespective of the THV implanted, emerged as an independent risk factor for developing ≥ moderate PVL. Technical and device success at 30-day follow-up was comparable between groups. However, Neo2 was associated with a significantly lower rate of ≥moderate PVL vs. Neo: (5% vs. 15%; p < 0.001), which was confirmed also at 90-day follow-up. Additionally, no correlation was found between ≥moderate PVL and AA in the Neo2 group, while PVL degree increased proportionally to the AA in the Neo cohort. CONCLUSION: In patients with HA, the new generation Acurate Neo2 THV was associated with a comparable device success rate and a significantly lower rate of ≥moderate PVL, when compared with its predecessor.

Natural history and clinical burden of moderate aortic stenosis: a systematic review and explorative meta-analysis.

AIMS: The mortality risk of patients with moderate aortic stenosis is not well known, but recent studies suggested that it might negatively affect prognosis. We aimed to assess the natural history and clinical burden of moderate aortic stenosis and to investigate the interaction of patients' baseline characteristics with prognosis. METHODS: Systematic research was conducted on PubMed. The inclusion criteria were inclusion of patients with moderate aortic stenosis; and report of the survival at 1-year follow-up (minimum). Incidence ratios related to all-cause mortality in patients and controls of each study were estimated and then pooled using a fixed effects model. All patients with mild aortic stenosis or without aortic stenosis were considered controls. Meta-regression analysis was performed to assess the impact of left ventricular ejection fraction and age on the prognosis of patients with moderate aortic stenosis. RESULTS: Fifteen studies and 11 596 patients with moderate aortic stenosis were included. All-cause mortality was significantly higher among patients with moderate aortic stenosis than in controls in all timeframes analysed (all P  < 0.0001). Left ventricular ejection fraction and sex did not significantly impact on the prognosis of patients with moderate aortic stenosis ( P  = 0.4584 and P  = 0.5792), while increasing age showed a significant interaction with mortality (estimate = 0.0067; 95% confidence interval: 0.0007-0.0127; P  = 0.0323). CONCLUSION: Moderate aortic stenosis is associated with reduced survival. Further studies are necessary to confirm the prognostic impact of this valvulopathy and the possible benefit of aortic valve replacement.

Bi-Caval Valve Implantation to Palliate Symptoms in a Case of Massive Tricuspid Regurgitation.

Severe tricuspid regurgitation is associated with the occurrence of right failure and increased morbidity and mortality. Transcatheter heterotopic bi-caval valve implantation might offer symptom relief in these patients that are often at prohibitive surgical risk.

Transcatheter treatment of severe aortic stenosis in patients with complex coronary artery disease: case series and proposed therapeutic algorithm.

Background: Patients with severe aortic stenosis (AS) and complex coronary artery disease with a clinical indication to both transcatheter aortic valve implantation (TAVI) and percutaneous coronary intervention (PCI) pose a clinical dilemma since it is unclear which lesion should be treated first and careful planning is required. Case summary: We report two cases of AS with complex PCI (ASCoP) features. In the first one, easy coronary cannulation with an Acurate Neo2 valve and commissural alignment was predicted; therefore, TAVI was performed first, and subsequently complex high-risk PCI of the left main was performed in the same procedure but without the burden of ongoing severe AS. In the second case, complex coronary cannulation after TAVI with an Evolut PRO valve was predicted; therefore, balloon aortic valvuloplasty and Impella placement were performed first to allow for complex, high-risk multivessel PCI and subsequent TAVI. In both cases, a single-stage approach was preferred to reduce the use of large-bore arterial access with possible consequent adverse events. Discussion: In this case series, we illustrate a possible approach to the treatment of ASCoP patients. In such complex cases, a thorough preprocedural planning is mandatory, and clinical decision-making should be centred upon the predicted chance of cannulation of coronary arteries after TAVI.

Acute Kidney Injury After Transcatheter Aortic Valve Replacement Mediates the Effect of Chronic Kidney Disease.

Background Acute kidney injury (AKI) after transcatheter aortic valve replacement (TAVR) is associated with increased mortality. However, it is controversial whether AKI affects prognosis per se, being linked to baseline chronic kidney disease (CKD) and bleeding complications. The aim of this study was to disentangle, applying mediation analysis, the association between AKI and clinical outcome, considering CKD and bleedings. Methods and Results Consecutive patients undergoing TAVR were prospectively enrolled at 5 high-volume centers in Italy. AKI was defined according to Valve Academic Research Consortium-3 consensus, whereas bleeding with Bleeding Academic Research Consortium. Primary outcome was all-cause mortality after 1-year follow-up. Among 2621 patients undergoing TAVR, AKI occurrence was associated with 1-year mortality. This association of AKI with the primary end points remained significant after adjusting for baseline risk estimators, either Society of Thoracic Surgeons score (hazard ratio [HR], 2.78 [95% CI, 1.95-3.80], P<0.001) or EuroSCORE-II (HR, 1.85 [95% CI, 1.35-2.56], P<0.001). Both AKI and CKD significantly and independently affected primary outcome (HR, 3.06 [95% CI, 2.01-4.64], P<0.001 and HR, 1.82 [95% CI 1.27-2.65], P<0.01, respectively). The estimated proportion of the total effect of CKD mediated via AKI was, on average, 15%, 95% CI, 4%-29%, P<0.001. The significant effect of Bleeding Academic Research Consortium 2-5 bleedings on the primary outcome was not mediated by AKI. Conclusions AKI occurs in 1 out of 6 patients and significantly mediates one fifth of the effect of baseline CKD on all-cause mortality after TAVR. Our analysis supports a systematic effort to prevent AKI during TAVR, which may potentially translate into improved patients' 1-year survival.

Large-bore arterial access closure after transcatheter aortic valve replacement: a systematic review and network meta-analysis.

Aims: As the indications to transcatheter aortic valve replacement (TAVR) expand to patients at increasingly lower risk, procedure-related vascular and bleeding complications events must be minimized. We aimed to evaluate the impact of different large-bore arterial access closure devices on clinical outcomes after TAVR. Methods and results: We searched for papers that reported outcomes according to the type of vascular closure device/technique used after TAVR and performed a Bayesian network meta-analysis (NMA). Fifteen studies involving 9259 patients who underwent access site closure using PROSTAR™ XL percutaneous vascular surgical system (Abbott Vascular, Santa Clara, CA, USA), Perclose ProGlide™ suture-mediated closure system (Abbott), or MANTATM vascular closure device (Teleflex, Morrisville, NC, USA) were included. NMA showed MANTA to have the highest likelihood of reducing a primary composite endpoint of intra-hospital death, major vascular complications, and major or life-threatening bleedings [surface under the cumulative ranking curve analysis (SUCRA) 94.8%], but this was mitigated when only randomized clinical trials and propensity-matched cohorts were included (SUCRA 56.1%). The ProGlide showed the highest likelihood to reduce major or life-threatening bleedings, especially with increasing procedural complexity, and the MANTA device to reduce major and minor vascular complications. The ProStar XL device performed poorly in all explored endpoints. Conclusion: Available evidence summarized through a NMA shows that ProGlide and MANTA devices appear to be both valid vascular closure devices globally and to be the best options to minimize vascular complications and reduce bleeding in patients undergoing TAVR, respectively.

Transcatheter Aortic Valve Replacement With Self-Expanding ACURATE neo2: Postprocedural Hemodynamic and Short-Term Clinical Outcomes.

BACKGROUND: The first-generation ACURATE neo transcatheter heart valve (THV) (Boston Scientific) was associated with a non-negligible occurrence of moderate or greater paravalvular aortic regurgitation (AR) following transcatheter aortic valve replacement. To overcome this issue, the ACURATE neo2 iteration, which incorporates a taller outer skirt aimed at reducing the occurrence of paravalvular AR, has recently been developed. OBJECTIVES: The aim of this study was to assess the efficacy and safety of the ACURATE neo2 (Boston Scientific) THV in patients with severe aortic valve stenosis. METHODS: ITAL-neo was an observational, retrospective, multicenter registry enrolling consecutive patients with severe aortic valve stenosis, treated with first- and second-generation ACURATE neo THVs, via transfemoral and trans-subclavian access, in 13 Italian centers. One-to-one propensity score matching was applied to account for baseline characteristics unbalance. The primary endpoint was the occurrence of moderate or greater paravalvular AR on predischarge echocardiographic assessment. Secondary endpoints included postprocedural technical success and 90-day device success and safety. RESULTS: Among 900 patients included in the registry, 220 received the ACURATE neo2 THV, whereas 680 were treated with the first-generation device. A total of 410 patients were compared after 1:1 propensity score matching. The ACURATE neo2 THV was associated with a 3-fold lower frequency of postprocedural moderate or greater paravalvular AR (11.2% vs 3.5%; P < 0.001). No other hemodynamic differences were observed. Postprocedural technical success was similar between the 2 cohorts. Fewer adverse events were observed in patients treated with the ACURATE neo2 at 90 days. CONCLUSIONS: Transfemoral transcatheter aortic valve replacement using the ACURATE neo2 was associated with a significant lower frequency of moderate or greater paravalvular AR compared with the earlier generation ACURATE neo device, with encouraging short-term safety and efficacy.

Uso de anticoagulantes orales directos en pacientes con fibrilación auricular post implante de TAVI: resultados de una encuesta internacional / Use of anticoagulants in patients with atrial fibrillation undergoing transcatheter aortic valve implantation

BACKGROUND: Transcatheter Aortic Valve Implantation (TAVI) is beneficial in patients with symptomatic severe Aortic Stenosis (AS). There is no consensus about the best anticoagulation strategy for patients with a recent TAVI and with atrial fibrillation (AF). Direct oral anticoagulants (DOACs) are effective to prevent embolic events with a significant lower incidence of bleeding. There is scarce evidence about the use of these drugs in patients undergoing TAVI. AIM: To assess the management of anticoagulation at the moment of discharge of patients with AF and TAVI. Material and Methods: A four question survey was sent to cardiologists involved in TAVI programs in different international centers. Results: The survey was answered by 72 interventional cardiologists. Even with the lack of randomized evidence, in most of the scenarios DOACs are prescribed at discharge in patients with indication for anticoagulation. Also, in patients with high bleeding risk, most cardiologists would perform a left atrial appendage closure. In patients with concomitant coronary artery disease, if a stent was recently implanted, prescription of the combination of a DOAC and one antiplatelet drug was the most common answer. In patients with a former coronary angioplasty, DOAC or Warfarin was the therapy of choice. CONCLUSIONS: In the absence of randomized data, interventional cardiologists prescribe DOACs at discharge to patients with AF and TAVI, without following current guidelines in most cases.

Prevalence, Characteristics, and Outcomes of COVID-19-Associated Acute Myocarditis.

BACKGROUND: Acute myocarditis (AM) is thought to be a rare cardiovascular complication of COVID-19, although minimal data are available beyond case reports. We aim to report the prevalence, baseline characteristics, in-hospital management, and outcomes for patients with COVID-19-associated AM on the basis of a retrospective cohort from 23 hospitals in the United States and Europe. METHODS: A total of 112 patients with suspected AM from 56 963 hospitalized patients with COVID-19 were evaluated between February 1, 2020, and April 30, 2021. Inclusion criteria were hospitalization for COVID-19 and a diagnosis of AM on the basis of endomyocardial biopsy or increased troponin level plus typical signs of AM on cardiac magnetic resonance imaging. We identified 97 patients with possible AM, and among them, 54 patients with definite/probable AM supported by endomyocardial biopsy in 17 (31.5%) patients or magnetic resonance imaging in 50 (92.6%). We analyzed patient characteristics, treatments, and outcomes among all COVID-19-associated AM. RESULTS: AM prevalence among hospitalized patients with COVID-19 was 2.4 per 1000 hospitalizations considering definite/probable and 4.1 per 1000 considering also possible AM. The median age of definite/probable cases was 38 years, and 38.9% were female. On admission, chest pain and dyspnea were the most frequent symptoms (55.5% and 53.7%, respectively). Thirty-one cases (57.4%) occurred in the absence of COVID-19-associated pneumonia. Twenty-one (38.9%) had a fulminant presentation requiring inotropic support or temporary mechanical circulatory support. The composite of in-hospital mortality or temporary mechanical circulatory support occurred in 20.4%. At 120 days, estimated mortality was 6.6%, 15.1% in patients with associated pneumonia versus 0% in patients without pneumonia (P=0.044). During hospitalization, left ventricular ejection fraction, assessed by echocardiography, improved from a median of 40% on admission to 55% at discharge (n=47; P<0.0001) similarly in patients with or without pneumonia. Corticosteroids were frequently administered (55.5%). CONCLUSIONS: AM occurrence is estimated between 2.4 and 4.1 out of 1000 patients hospitalized for COVID-19. The majority of AM occurs in the absence of pneumonia and is often complicated by hemodynamic instability. AM is a rare complication in patients hospitalized for COVID-19, with an outcome that differs on the basis of the presence of concomitant pneumonia.

[Use of anticoagulants in patients with atrial fibrillation undergoing transcatheter aortic valve implantation]. / Uso de anticoagulantes orales directos en pacientes con fibrilación auricular post implante de TAVI: resultados de una encuesta internacional.

BACKGROUND: Transcatheter Aortic Valve Implantation (TAVI) is beneficial in patients with symptomatic severe Aortic Stenosis (AS). There is no consensus about the best anticoagulation strategy for patients with a recent TAVI and with atrial fibrillation (AF). Direct oral anticoagulants (DOACs) are effective to prevent embolic events with a significant lower incidence of bleeding. There is scarce evidence about the use of these drugs in patients undergoing TAVI. AIM: To assess the management of anticoagulation at the moment of discharge of patients with AF and TAVI. MATERIAL AND METHODS: A four question survey was sent to cardiologists involved in TAVI programs in different international centers. RESULTS: The survey was answered by 72 interventional cardiologists. Even with the lack of randomized evidence, in most of the scenarios DOACs are prescribed at discharge in patients with indication for anticoagulation. Also, in patients with high bleeding risk, most cardiologists would perform a left atrial appendage closure. In patients with concomitant coronary artery disease, if a stent was recently implanted, prescription of the combination of a DOAC and one antiplatelet drug was the most common answer. In patients with a former coronary angioplasty, DOAC or Warfarin was the therapy of choice. CONCLUSIONS: In the absence of randomized data, interventional cardiologists prescribe DOACs at discharge to patients with AF and TAVI, without following current guidelines in most cases.

The Role of Uric Acid in Acute and Chronic Coronary Syndromes.

Uric acid (UA) is the final product of the catabolism of endogenous and exogenous purine nucleotides. While its association with articular gout and kidney disease has been known for a long time, new data have demonstrated that UA is also related to cardiovascular (CV) diseases. UA has been identified as a significant determinant of many different outcomes, such as all-cause and CV mortality, and also of CV events (mainly Acute Coronary Syndromes (ACS) and even strokes). Furthermore, UA has been related to the development of Heart Failure, and to a higher mortality in decompensated patients, as well as to the onset of atrial fibrillation. After a brief introduction on the general role of UA in CV disorders, this review will be focused on UA's relationship with CV outcomes, as well as on the specific features of patients with ACS and Chronic Coronary Syndrome. Finally, two issues which remain open will be discussed: the first is about the identification of a CV UA cut-off value, while the second concerns the possibility that the pharmacological reduction of UA is able to lower the incidence of CV events.

Emergency cardiac imaging for coronavirus disease 2019 (COVID-19) in practice: a case of takotsubo stress cardiomyopathy.

BACKGROUND: Cardiovascular complications of severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV2) are known to be associated with poor outcome. A small number of case series and reports have described cases of myocarditis and ischaemic events, however, knowledge on the aetiology of acute cardiac failure in SARS-CoV2 remains limited. We describe the occurrence and risk stratification imaging correlates of 'takotsubo' stress cardiomyopathy presenting in a patient with Coronavirus Disease 2019 (COVID-19) in the intensive care unit. An intubated 53-year old patient with COVID19 suffered acute haemodynamic collapse in the intensive care unit, and was thus investigated with transthoracic echocardiography (TTE), 12-lead electrocardiograms (ECG) and serial troponins and blood tests, and eventually coronary angiography due to clinical suspicion of ischaemic aetiology. Echocardiography revealed a reduced ejection fraction, with evident extensive apical akinesia spanning multiple coronary territories. Troponins and NT-proBNP were elevated, and ECG revealed ST elevation: coronary angiography was thus performed. This revealed no significant coronary stenosis. Repeat echocardiography performed within the following week revealed a substantial recovery of ejection fraction and wall motion abnormalities. Despite requirement of a prolonged ICU stay, the patient now remains clinically stable, and is on spontaneous breathing. CONCLUSION: This case report presents a case of takotsubo stress cardiomyopathy occurring in a critically unwell patient with COVID19 in the intensive care setting. Stress cardiomyopathy may be an acute cardiovascular complication of COVID-19 infection. In the COVID19 critical care setting, urgent bedside echocardiography is an important tool for initial clinical assessment of patients suffering haemodynamic compromise.

Uric acid in chronic coronary syndromes: Relationship with coronary artery disease severity and left ventricular diastolic parameter.

BACKGROUND AND AIMS: Uric Acid (UA) has been related to the development of Cardio-Vascular (CV) events in patients affected by Chronic Coronary Syndromes (CCS). Among various hypothesis, two arise: UA may negatively act on coronary artery determining a higher degree of atherosclerotic disease, and/or on heart determining a higher prevalence of diastolic dysfunction. Both the above hypothesized effects are object of our investigation. METHODS AND RESULTS: 231 patients who were admitted to the cardiological department of the Niguarda Hospital (Milan, Italy) for CCS from January 2017 to June 2018 were enrolled. Coronary atherosclerotic burden was evaluated from coronary angiography as the number and type of involved vessels, as well as with both Gensini and Syntax scores. All subjects underwent a complete echocardiogram. At unadjusted and adjusted/multivariable analysis, UA levels were not significantly associated with variables analysed from the coronary angiography (number and type of vessels involved, neither the Gensini and Syntax scores) as well as with echocardiographic parameters regarding systolic and diastolic function. CONCLUSIONS: In conclusion, the main finding of our work is the absence of a role for UA in determining coronary arteries disease as well as LV diastolic dysfunction in CCS subjects. Taking together the results of previous studies with ours, we hypothesize that UA could act on heart (both on coronary arteries and on LV function) in an early phase of the disease, whereas while in the advanced stages other factors (previous myocardial infarction, previous myocardial revascularization and so on) may overshadow its effects.