Myocardial Ischemic Syndromes: A New Nomenclature to Harmonize Evolving International Clinical Practice Guidelines.

Since the 1960s, cardiologists have adopted several binary classification systems for acute myocardial infarction (MI) that facilitated improved patient management. Conversely, for chronic stable manifestations of myocardial ischemia, various classifications have emerged over time, often with conflicting terminology-eg, "stable coronary artery disease" (CAD), "stable ischemic heart disease," and "chronic coronary syndromes" (CCS). While the 2019 European guidelines introduced CCS to impart symmetry with "acute coronary syndromes" (ACS), the 2023 American guidelines endorsed the alternative term "chronic coronary disease." An unintended consequence of these competing classifications is perpetuation of the restrictive terms "coronary" and 'disease', often connoting only a singular obstructive CAD mechanism. It is now important to advance a more broadly inclusive terminology for both obstructive and non-obstructive causes of angina and myocardial ischemia that fosters conceptual clarity and unifies dyssynchronous nomenclatures across guidelines. We, therefore, propose a new binary classification of "acute myocardial ischemic syndromes" and "non-acute myocardial ischemic syndromes," which comprises both obstructive epicardial and non-obstructive pathogenetic mechanisms, including microvascular dysfunction, vasospastic disorders, and non-coronary causes. We herein retain accepted categories of ACS, ST-segment elevation MI, and non-ST segment elevation MI, as important subsets for which revascularization is of proven clinical benefit, as well as new terms like ischemia and MI with non-obstructive coronary arteries. Overall, such a more encompassing nomenclature better aligns, unifies, and harmonizes different pathophysiologic causes of myocardial ischemia and should result in more refined diagnostic and therapeutic approaches targeted to the multiple pathobiological precipitants of angina pectoris, ischemia, and infarction.

Myocardial ischaemic syndromes: a new nomenclature to harmonize evolving international clinical practice guidelines.

Since the 1960s, cardiologists have adopted several binary classification systems for acute myocardial infarction (MI) that facilitated improved patient management. Conversely, for chronic stable manifestations of myocardial ischaemia, various classifications have emerged over time, often with conflicting terminology-e.g. 'stable coronary artery disease' (CAD), 'stable ischaemic heart disease', and 'chronic coronary syndromes' (CCS). While the 2019 European guidelines introduced CCS to impart symmetry with 'acute coronary syndromes' (ACS), the 2023 American guidelines endorsed the alternative term 'chronic coronary disease'. An unintended consequence of these competing classifications is perpetuation of the restrictive terms 'coronary' and 'disease', often connoting only a singular obstructive CAD mechanism. It is now important to advance a more broadly inclusive terminology for both obstructive and non-obstructive causes of angina and myocardial ischaemia that fosters conceptual clarity and unifies dyssynchronous nomenclatures across guidelines. We, therefore, propose a new binary classification of 'acute myocardial ischaemic syndromes' and 'non-acute myocardial ischaemic syndromes', which comprises both obstructive epicardial and non-obstructive pathogenetic mechanisms, including microvascular dysfunction, vasospastic disorders, and non-coronary causes. We herein retain accepted categories of ACS, ST-segment elevation MI, and non-ST-segment elevation MI, as important subsets for which revascularization is of proven clinical benefit, as well as new terms like ischaemia and MI with non-obstructive coronary arteries. Overall, such a more encompassing nomenclature better aligns, unifies, and harmonizes different pathophysiologic causes of myocardial ischaemia and should result in more refined diagnostic and therapeutic approaches targeted to the multiple pathobiological precipitants of angina pectoris, ischaemia and infarction.

Echocardiographic and clinical features of patients developing prosthesis-patient mismatch after transcatheter aortic valve replacement: Insights from the Recovery-TAVR registry.

BACKGROUND: The impact of prosthesis-patient mismatch (PPM) on major endpoints after transcatheter aortic valve replacement (TAVR) is controversial and the effects on progression of heart damage are poorly investigated. Therefore, our study aims to evaluate the prevalence and predictors of PPM in a "real world" cohort of patients at intermediate and low surgical risk, its impact on mortality and the clinical-echocardiographic progression of heart damage. METHODS: 963 patients who underwent TAVR procedure between 2017 and 2021, from the RECOVERY-TAVR international multicenter observational registry, were included in this analysis. Multiparametric echocardiographic data of these patients were analyzed at 1-year follow-up (FU). Clinical and echocardiographic features were stratified by presence of PPM and PPM severity, as per the most current international recommendations, using VARC-3 criteria. RESULTS: 18% of patients developed post-TAVR. PPM, and 7.7% of the whole cohort had severe PPM. At baseline, 50.3% of patients with PPM were male (vs 46.2% in the cohort without PPM, P = .33), aged 82 (IQR 79-85y) years vs 82 (IQR 78-86 P = .46), and 55.6% had Balloon-Expandable valves implanted (vs 46.8% of patients without PPM, P = .04); they had smaller left ventricular outflow tract (LVOT) diameter (20 mm, IQR 19-21 vs 20 mm, IQR 20-22, P = .02), reduced SVi (34.2 vs 38 mL/m2, P < .01) and transaortic flow rate (190.6 vs 211 mL/s, P < .01). At predischarge FU patients with PPM had more paravalvular aortic regurgitation (moderate-severe AR 15.8% vs 9.2%, P < .01). At 1-year FU, maladaptive alterations of left ventricular parameters were found in patients with PPM, with a significant increase in end-systolic diameter (33 mm vs 28 mm, P = .03) and a significant increase in left ventricle end systolic indexed volume in those with moderate and severe PPM (52 IQR 42-64 and 52, IQR 41-64 vs 44 IQR 35-59 in those without, P = .02)). No evidence of a significant impact of PPM on overall (P = .71) and CV (P = .70) mortality was observed. Patients with moderate/severe PPM had worse NYHA functional class at 1 year (NYHA III-IV 13% vs 7.8%, P = .03). Prosthesis size≤23 mm (OR 11.6, 1.68-80.1) was an independent predictor of PPM, while SVi (OR 0.87, 0.83-0.91, P < .001) and LVOT diameter (OR 0.79, 0.65-0.95, P = .01) had protective effect. CONCLUSIONS: PPM was observed in 18% of patients undergoing TAVR. Echocardiographic evaluations demonstrated a PPM-related pattern of early ventricular maladaptive alterations, possibly precursor to a reduction in cardiac function, associated with a significant deterioration in NYHA class at 1 year. These findings emphasize the importance of prevention of PPM of any grade in patients undergoing TAVR procedure, especially in populations at risk.

Sirolimus-coated balloon in all-comer population of coronary artery disease patients: the EASTBOURNE DIABETES prospective registry.

BACKGROUND: The outcomes of percutaneous coronary intervention (PCI) in diabetic patients are still suboptimal, and it is unclear if diabetic patients might derive a benefit from the use of drug-coated balloons. AIMS: To evaluate the impact of diabetes mellitus on the outcomes of patients undergoing PCI with sirolimus-coated balloon (SCB) MagicTouch (Concept Medical, India). METHODS: We conducted a subgroup analysis of the prospective, multicenter, investigator-initiated EASTBOURNE registry, evaluating the performance of MagicTouch SCB in patients with and without diabetes. The study primary endpoint was target lesion revascularization (TLR) at 12-month follow-up. Secondary clinical endpoints were major adverse clinical events (MACE), death, myocardial infarction (MI), and BARC 2-5 bleedings. RESULTS: Among 2,083 enrolled patients, a total of 864 suffered from diabetes (41.5%). Patients with diabetes had a numerically higher occurrence of TLR (6.5% vs. 4.7% HR 1.38, 95%CI 0.91-2.08), all-cause death (3.8% vs. 2.6%, HR 1.81, 95%CI 0.95-3.46), and MACE (12.2% vs. 8.9%; HR 1.26 95%CI 0.92-1.74). The incidence of spontaneous MI was significantly higher among diabetic patients (3.4% vs. 1.5%, HR 2.15 95%CI 1.09-4.25); bleeding events did not significantly differ. The overall incidence of TLR was higher among in-stent restenosis (ISR) as compared to de-novo coronary lesions, irrespectively from diabetes status. CONCLUSIONS: In the EASTBOURNE DIABETES registry, diabetic patients treated with the MagicTouch SCB did not have a significant increase in TLR when compared to non-diabetic patients; moreover, diabetic status did not affect the study device performance in terms of TLR, in both de-novo lesions and ISR.

One-month DAPT after biodegradable-polymer everolimus-eluting stent implantation in women at high-bleeding risk: Insights from the POEM trial.

AIMS: We conducted a prespecified subanalysis of the POEM trial to assess the association between sex and clinical outcomes following a short 1-month dual-antiplatelet-therapy (DAPT) period after percutaneous coronary intervention (PCI) with bioresorbable polymer everolimus-eluting stent (BP-EES) among patients at high bleeding risk (HBR). BACKGROUND: Shortening the DAPT period after PCI is an effective bleeding avoidance strategy with contemporary drug-eluting stents. Whether sex affects the risk of adverse events following PCI is still debated. METHODS: Patients at HBR undergoing PCI with BP-EES were enrolled and treated with 1-month DAPT. If anticoagulation was needed, study participants received an oral anticoagulant (OAC) in addition to a P2Y12 inhibitor for 1 month, followed by OAC only thereafter. The primary endpoint was a composite of cardiac death, myocardial infarction, or definite/probable stent thrombosis at 12 months. We report sex-based outcomes of patients included in the POEM study. RESULTS: We enrolled 129 (29.1%) women and 314 (70.9%) men. Women were older, with lower hemoglobin levels, and worse renal function. Accordingly, they had a trend for a greater number of HBR criteria fulfilled and a higher PARIS bleeding score. However, they were not at a significantly higher risk for the primary endpoint (men vs. women: 5.17% vs. 3.94%; HR 1.30; 95% CI: 0.48-3.54, p = 0.61), or any of the hemorrhagic and ischemic secondary endpoints. CONCLUSIONS: This prespecified subanalysis of the POEM trial suggests that 1-month DAPT following PCI with BP-EES may be a safe and effective therapeutic strategy for women at HBR.

Management strategies for heavily calcified coronary stenoses: an EAPCI clinical consensus statement in collaboration with the EURO4C-PCR group.

Since the publication of the 2015 EAPCI consensus on rotational atherectomy, the number of percutaneous coronary interventions (PCI) performed in patients with severely calcified coronary artery disease has grown substantially. This has been prompted on one side by the clinical demand for the continuous increase in life expectancy, the sustained expansion of the primary PCI networks worldwide, and the routine performance of revascularization procedures in elderly patients; on the other side, the availability of new and dedicated technologies such as orbital atherectomy and intravascular lithotripsy, as well as the optimization of the rotational atherectomy system, has increased operators' confidence in attempting more challenging PCI. This current EAPCI clinical consensus statement prepared in collaboration with the EURO4C-PCR group describes the comprehensive management of patients with heavily calcified coronary stenoses, starting with how to use non-invasive and invasive imaging to assess calcium burden and inform procedural planning. Objective and practical guidance is provided on the selection of the optimal interventional tool and technique based on the specific calcium morphology and anatomic location. Finally, the specific clinical implications of treating these patients are considered, including the prevention and management of complications and the importance of adequate training and education.

Prognostic value of stress CMR and SPECT-MPI in patients undergoing intermediate-to-high-risk non-cardiac surgery.

PURPOSE: The objective of this study was to investigate the role of myocardial perfusion imaging (MPI) stress tests using stress cardiac magnetic resonance (sCMR) and single-photon emission computed tomography myocardial perfusion imaging (SPECT-MPI) in non-cardiac surgery (NCS) pre-operatory management. MATERIALS AND METHODS: This monocentric retrospective study enrolled patients with coronary artery disease or a minimum of two cardiovascular risk factors undergoing intermediate-to-high-risk non-cardiac surgeries. The primary composite endpoint comprised cardiac death, cardiogenic shock, acute coronary syndromes (ACS), and cardiogenic pulmonary edema occurring within 30 days after surgery, while the secondary endpoint was ACS. RESULTS: A total of 1590 patients were enrolled; among them, 669 underwent a MPI stress test strategy (sCMR: 287, SPECT-MPI: 382). The incidence of 30-day cardiac events was lower in the stress-tested group compared to the non-stress-tested group (1.2% vs. 3.4%; p 0.006). Adopting a stress test strategy showed a significant reduction in the risk of the composite endpoint (OR: 0.33, 95% CI: 0.15-0.76, p 0.009) and ACS (OR: 0.41, 95% CI: 0.17-0.98, p 0.046) at multivariable analysis, with similar cardiac events rate between stress CMR and SPECT (1.1% vs. 1.3%, p 0.756). Stress CMR showed a greater accuracy to predict coronary artery revascularizations (sCMR c-statistic: 0.95, ischemic cut-point: 5.5%; SPECT c-statistic: 0.85, ischemic cut-point: 7.5%). CONCLUSION: Stress test strategy is related to a lower occurrence of cardiac events in high-risk patients scheduled for intermediate-to-high-risk non-cardiac surgeries. Both sCMR and SPECT-MPI comparably reduce the likelihood of cardiac complications, albeit sCMR offers greater accuracy in predicting coronary artery revascularization.

Multiparametric Mapping via Cardiovascular Magnetic Resonance in the Risk Stratification of Ventricular Arrhythmias and Sudden Cardiac Death.

Risk stratification for malignant ventricular arrhythmias and sudden cardiac death is a daunting task for physicians in daily practice. Multiparametric mapping sequences obtained via cardiovascular magnetic resonance imaging can improve the risk stratification for malignant ventricular arrhythmias by unveiling the presence of pathophysiological pro-arrhythmogenic processes. However, their employment in clinical practice is still restricted. The present review explores the current evidence supporting the association between mapping abnormalities and the risk of ventricular arrhythmias in several cardiovascular diseases. The key message is that further clinical studies are needed to test the additional value of mapping techniques beyond conventional cardiovascular magnetic resonance imaging for selecting patients eligible for an implantable cardioverter defibrillator.

P2Y12 Inhibitors Monotherapy in Patients Undergoing Complex vs Non-Complex Percutaneous Coronary Intervention: A Meta-Analysis of Randomized Trials.

BACKGROUND: Monotherapy with P2Y12 inhibitors (P2Y12i) is emerging as alternative strategy to dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI). However, early withdrawal of aspirin as part of P2Y12i monotherapy regimens may pose concerns in high-risk patients, such as those undergoing complex PCI. Our aim was to evaluate the efficacy and safety of P2Y12i monotherapy after a short course of DAPT (1-3-month) compared with standard DAPT (≥12-month) according to PCI complexity. METHODS: We performed a meta-analysis of randomized trials using random effects models to combine hazard ratios (HRs) with 95% confidence intervals (CIs). Within-trial interactions were pooled to estimate heterogeneity between complex and noncomplex PCI strata. The study protocol was registered in the PROSPERO (CRD42021291027). RESULTS: We identified 5 trials including 31,627 patients, of whom 8,328 (26.3%) underwent complex PCI. P2Y12i monotherapy compared with standard DAPT was associated with a similar risk of all-cause death, stent thrombosis, and stroke, with no evidence for interaction between complex and noncomplex PCI. We found heterogeneity in the treatment effect of P2Y12i monotherapy vs standard DAPT with respect to myocardial infarction (P-interaction = 0.027). Compared with standard DAPT, P2Y12i monotherapy decreased the risk of myocardial infarction in complex PCI (HR 0.77, 95%CI 0.60-0.99, P = .042), but not in noncomplex PCI patients (HR 1.09, 95%CI 0.90-1.30, P = .382). The risk of major bleeding was significantly reduced by P2Y12i monotherapy with a consistent treatment effect (P-interaction = 0.699) in both complex and noncomplex PCI strata. CONCLUSIONS: Patients undergoing complex PCI may derive more benefit and less harm from P2Y12i monotherapy after early aspirin withdrawal compared with standard DAPT.

Rationale and design of the PARTHENOPE trial: A two-by-two factorial comparison of polymer-free vs biodegradable-polymer drug-eluting stents and personalized vs standard duration of dual antiplatelet therapy in all-comers undergoing PCI.

BACKGROUND: Over the past few decades, percutaneous coronary intervention (PCI) has undergone significant advancements as a result of the combination of device-based and drug-based therapies. These iterations have led to the development of polymer-free drug-eluting stents. However, there is a scarcity of data regarding their clinical performance. Furthermore, while various risk scores have been proposed to determine the optimal duration of dual antiplatelet therapy (DAPT), none of them have undergone prospective validation within the context of randomized trials. DESIGN: The PARTHENOPE trial is a phase IV, prospective, randomized, multicenter, investigator-initiated, assessor-blind study being conducted at 14 centers in Italy (NCT04135989). It includes 2,107 all-comers patients with minimal exclusion criteria, randomly assigned in a 2-by-2 design to receive either the Cre8 amphilimus-eluting stent or the SYNERGY everolimus-eluting stent, along with either a personalized or standard duration of DAPT. Personalized DAPT duration is determined by the DAPT score, which accounts for both bleeding and ischemic risks. Patients with a DAPT score <2 (indicating higher bleeding than ischemic risk) receive DAPT for 3 or 6 months for chronic or acute coronary syndrome, respectively, while patients with a DAPT score ≥2 (indicating higher ischemic than bleeding risk) receive DAPT for 24 months. Patients in the standard DAPT group receive DAPT for 12 months. The trial aims to establish the noninferiority between stents with respect to a device-oriented composite end point of cardiovascular death, target-vessel myocardial infarction, or clinically-driven target-lesion revascularization at 12 months after PCI. Additionally, the trial aims to demonstrate the superiority of personalized DAPT compared to a standard approach with respect to a net clinical composite of all-cause death, any myocardial infarction, stroke, urgent target-vessel revascularization, or type 2 to 5 bleeding according to the Bleeding Academic Research Consortium criteria at 24-months after PCI. SUMMARY: The PARTHENOPE trial is the largest randomized trial investigating the efficacy and safety of a polymer-free DES with a reservoir technology for drug-release and the first trial evaluating a personalized duration of DAPT based on the DAPT score. The study results will provide novel insights into the optimizing the use of drug-eluting stents and DAPT in patients undergoing PCI.

Safety of metformin continuation in diabetic patients undergoing invasive coronary angiography: the NO-STOP single arm trial.

BACKGROUND: Despite paucity of data, it is common practice to discontinue metformin before invasive coronary angiography due to an alleged risk of Metformin-Associated Lactic Acidosis (M-ALA). We aimed at assessing the safety of metformin continuation in diabetic patients undergoing coronary angiography in terms of significant increase in lactate levels. METHODS: In this open-label, prospective, multicentre, single-arm trial, all diabetic patients undergoing coronary angiography with or without percutaneous coronary intervention at 3 European centers were screened for enrolment. The primary endpoint was the increase in lactate levels from preprocedural levels at 72-h after the procedure. Secondary endpoints included contrast associated-acute kidney injury (CA-AKI), M-ALA, and all-cause mortality. RESULTS: 142 diabetic patients on metformin therapy were included. Median preprocedural lactate level was 1.8 mmol/l [interquartile range (IQR) 1.3-2.3]. Lactate levels at 72 h after coronary angiography were 1.7 mmol/l (IQR 1.3-2.3), with no significant differences as compared to preprocedural levels (p = 0.91; median difference = 0; IQR - 0.5 to 0.4 mmol/l). One patient had 72-h levels ≥ 5 mmol/l (5.3 mmol/l), but no cases of M-ALA were reported. CA-AKI occurred in 9 patients (6.1%) and median serum creatinine and estimated glomerular filtration rate remained similar throughout the periprocedural period. At a median follow-up of 90 days (43-150), no patients required hemodialysis and 2 patients died due to non-cardiac causes. CONCLUSIONS: In diabetic patients undergoing invasive coronary angiography, metformin continuation throughout the periprocedural period does not increase lactate levels and was not associated with any decline in renal function. TRIAL REGISTRATION: The study was registered at Clinicaltrials.gov (NCT04766008).

Clinical and procedural outcomes of percutaneous coronary intervention for de novo lesions involving the ostial left circumflex coronary artery.

BACKGROUND: Percutaneous treatment for ostial left circumflex artery (LCx) lesions is known to be associated with suboptimal results. AIMS: The present study aims to assess the procedural and long-term clinical outcomes of percutaneous coronary intervention (PCI) for de novo ostial LCx lesions overall and according to the coronary revascularization strategy. METHODS: Consecutive patients undergoing PCI with second generation drug eluting stents or drug coated balloons for de novo ostial LCx lesions in three high-volume Italian centers between 2012 and 2021 were retrospectively evaluated. The primary endpoint was target-vessel revascularization (TVR) at 2 years. Secondary endpoints included major adverse cardiovascular and cerebrovascular events (MACCE), target lesion revascularization, myocardial infarction, stroke, all-cause death, and repeat revascularization. RESULTS: A total of 366 patients were included in the analysis with a median follow-up of 901 (IQR: 450-1728) days. 79.5% of the patients were male, 33.6% were diabetic, 49.7% had a previous PCI, and 23.1% a prior surgical revascularization. Very ostial LCx stenting was performed in 34.1%, crossover from left main to LCx in 17.3%, and a two-stent strategy in 48.6% of cases, respectively. In the overall population, the incidence of TVR at 2 years was 19.0% while MACCE rate was 25.7%. No major differences in clinical outcomes were found according to the stenting strategy. Use of intracoronary imaging was associated with fewer MACCE (HR: 0.47, 95% CI: 0.25-1.13, p = 0.01), while the diameter of the stent implanted in the ostial LCx was associated with less TVR (HR: 0.43, 95% CI: 0.25-0.75, p = 0.002). CONCLUSIONS: Percutaneous revascularization of the ostial LCx is associated with a high rate of TVR, regardless of the stenting strategy. Intracoronary imaging and proper stent sizing may reduce the failure rates.

Atrial arrhythmias and heart failure: A "modern view" of an old paradox.

BACKGROUND: Heart failure (HF) and atrial arrhythmias (AAs) are two clinical conditions that characterize the daily clinical practice of cardiologists. In this perspective review, we analyze the shared etiopathogenetic pathways of atrial arrhythmias, which are the most common cause of atrial arrhythmias-induced cardiomyopathy (AACM) and HF. HYPOTHESIS: The aim is to explore the pathophysiology of these two conditions considering them as a "unicum", allowing the definition of a cardiovascular continuum where it is possible to predict the factors and to identify the patient phenotype most at risk to develop HF due to atrial arrhythmias. METHODS: Potentially eligible articles, identified from the Electronic database (PubMed), and related references were used for a literature search that was conducted between January 2022 and January 2023. Search strategies were designed to identify articles that reported atrial arrhythmias in association with heart failure and vice versa. For the search we used the following keywords: atrial arrhythmias, atrial fibrillation, heart failure, arrhythmia-induced cardiomyopathy, tachycardiomyopathy. We identified 620 articles through the electronic database search. Out of the 620 total articles we removed 320 duplicates, thus selecting 300 eligible articles. About 150 titles/abstracts were excluded for the following reasons: no original available data, no mention of atrial arrhythmias and heart failure crosstalk, very low quality analysis or evidence. We excluded also non-English articles. When multiple articles were published on the same topic, the articles with the most complete set of data were considered. We preferentially included all papers that could provide the best evidence in the field. As a result, the present review article is based on a final number of 104 references. RESULTS: While the pathophysiology of AACM and Heart Failure with reduced ejection fraction (HFrEF) has been studied in detail over the years, the causal link between atrial arrhythmias and heart failure with Preserved Ejection Fraction (HFpEF) has been often subject of interest. HFpEF is strictly related to AAs, which has always been considered significant risk factor. In this review we described the pathophysiological links between atrial fibrillation and heart failure. Furthermore, we illustrated and discussed the preclinical and clinical predicting factors of AF and HFpEF, and the corresponding targets of the available therapeutic agents. Finally, we outlined the patient phenotype at risk of developing AF and HFpEF (Central Illustration). CONCLUSIONS: In this review, we underline how these two clinical conditions (AF and HFpEF) represent a "unicum" and, therefore, should be considered as a single disease that can manifest itself in the same phenotype of patients but at different times. Furthermore, considering that today we have few therapeutic strategies to treat these patients, it would be good to make an early diagnosis in the initial stages of the disease or intervene even before the development of signs and symptoms of HF. This is possible only by paying greater attention to patients with predisposing factors and carrying out a targeted screening with the correct diagnostic methods. A systemic approach aimed at improving the immuno-metabolic profile of these patients by lowering the body mass index, threatening the predisposing factors, lowering the mean heart rate and reducing the sympathetic nervous system activation is the key strategy to reduce the clinical impact of this disease.

Effects of two-month treatment with a mixture of natural activators of autophagy on oxidative stress and arterial stiffness in patients with essential hypertension: A pilot study.

BACKGROUND AND AIMS: Trehalose, spermidine, nicotinamide, and polyphenols are natural substances that exert pro-autophagic and antioxidant properties. Their role in blood pressure (BP) regulation and preservation of vascular function in essential hypertension is unknown. The aim of this study was to evaluate the effect of a mixture of these agents on BP level, markers of oxidative stress, autophagy, endothelial function, and vascular stiffness in outpatients with grade 1 uncomplicated essential hypertension. METHODS AND RESULTS: A single-centre, open-label, case-control, pilot study was conducted in adult outpatients (aged ≥18 years) receiving or not the mixture for two months along with the standard therapies. Both at baseline and at the end of the treatment the following clinical parameters were evaluated: brachial seated office BP level, central aortic pressure, pulse wave velocity, augmentation index (AI@75). Both at baseline and at the end of the treatment, a blood sample was drawn for the measurement of: H2O2, HBA%, levels of sNOX2-dp, Atg 5, P62, endothelin 1, and NO bioavailability. The mixture of nutraceuticals did not influence BP levels. Patients receiving the mixture showed a significant decrease of oxidative stress, stimulation of autophagy, increased NO bioavailability and no increase of the AI@75, in contrast to what observed in hypertensive patients not receiving the mixture. CONCLUSIONS: The supplementation of the trehalose, spermidine, nicotinamide, and polyphenols mixture counteracted hypertension-related arterial stiffness through mechanisms likely dependent on oxidative stress downregulation and autophagy stimulation. These natural activators of autophagy may represent favourable adjuvants for prevention of the hypertensive cardiovascular damage.

Long-term prognostic impact of subclinical myocardial dysfunction in patients recovered from COVID-19.

BACKGROUND: Cardiovascular sequelae may occur in patients recovered from coronavirus disease 2019 (COVID-19). Recent studies have detected a considerable incidence of subclinical myocardial dysfunction-assessed with speckle-tracking echocardiography-and of long-COVID symptoms in these patients. This study aimed to define the long-term prognostic role of subclinical myocardial dysfunction and long-COVID condition in patients recovered from COVID-19 pneumonia. METHODS: We prospectively followed up 110 patients hospitalized at our institution due to COVID-19 pneumonia in April 2020 and then recovered from SARS-CoV-2 infection. A 7-month clinical and echocardiographic evaluation was performed, followed by a 21-month clinical follow-up. The primary outcome was major adverse cardiovascular events (MACE), a composite of myocardial infarction, stroke, heart failure hospitalization, and all-cause mortality. RESULTS: A subclinical myocardial dysfunction-defined as an impairment of left ventricular global longitudinal strain (≥-18%)-was identified at a 7-month follow-up in 37 patients (34%), was associated with an increased risk of long-term MACE with a good discriminative power (area under the curve: .73) and resulted in a strong independent predictor of extended MACE in multivariate regression analyses. Long-COVID condition was not associated with a worse long-term prognosis, instead. CONCLUSIONS: In patients recovered from COVID-19 pneumonia, a subclinical myocardial dysfunction is present in one-third of the whole population at 7-month follow-up and is associated with a higher risk of MACE at long-term follow-up. Speckle-tracking echocardiography is a promising tool to optimize the risk-stratification in patients recovered from COVID-19 pneumonia, while the definition of a long-COVID condition has no prognostic relevance.

Prognostic value of tricuspid regurgitation.

Tricuspid regurgitation (TR) has a considerable prevalence in the overall population, that further increases in selected categories of patients. Three morphologic types of TR prevail, namely primary, secondary and atrial TR, mostly, but not always, occurring in different subsets of patients. Recent evidences demonstrate a negative impact of TR on outcomes, irrespective of etiology and even when less than severe in grading. Unfortunately, current surgical standards are void of strong prospective evidence of positive impact on clinical outcomes. While on one hand recent advances in diagnosis and risk stratification of patients with TR are shedding light onto the population that may benefit from intervention and its appropriate timing, on the other hand the arrival on stage of percutaneous treatment options is widening even more the therapeutic options for such population. In this review we will address and discuss the available evidence on the prognostic impact of TR in different clinical contexts encountered in practice.

Long term follow-up after balloon expandable covered stents implantation for management of transcatheter aortic valve replacement related vascular access complications.

OBJECTIVES: To report the experience of a high-volume center with balloon-expandable (BE) stents implantation to manage vascular complications after transcatheter aortic valve replacement (TAVR). BACKGROUND: Despite increased operator experience and better devices, vascular complications after TAVR are still a major issue and covered stent implantation is often required. METHODS: We retrospectively collected baseline and procedural data about 78 consecutive patients who underwent BE stent implantation to manage a vascular complication after transfemoral TAVR. Primary endpoints were technical success, incidence of new-onset claudication and need for vascular interventions during long-term follow-up. Secondary endpoints included length of hospitalization, in-hospital and 30-day mortality, and major postoperative complications. RESULTS: BE stents implantation to manage vascular complications after TAVR was successfully performed in 96.2% of the cases, with bailout surgery required in two cases. One patient suffered in-hospital death. Predischarge Doppler Ultrasound revealed no cases of in-stent occlusion or fracture. At a median follow-up of 429 days (interquartile range, 89-994 days), no cases of symptomatic leg ischemia were reported and only one patient experienced new-onset claudication. CONCLUSIONS: Our experience showed good periprocedural and long-term results of BE covered stent implantation to manage vascular complication after TAVR. Their great radial outward force may guarantee effective hemostasis without necessarily being associated with stent deformation/fracture resulting in restenosis or further interventions. More research is needed to define the role of BE covered stents in this setting.

Left atrial appendage closure with the II generation Ultraseal device: An international registry. The LIGATE study.

OBJECTIVES: To assess feasibility and safety of second-generation left atrial appendage closure (LAAC) Ultraseal device in patients with nonvalvular atrial fibrillation (NVAF). BACKGROUND: LAAC with first-generation Ultraseal device (Cardia, Eagan, Minnesota) has been shown to be a feasible therapeutic option in patients with NVAF. However, there is a paucity of data regarding the novel second-generation Ultraseal device. METHODS: All patients with NVAF undergoing second-generation Ultraseal device implantation between February 2018 and September 2020 were included in a multicenter international registry. Periprocedural and post-discharge events were collected through 6-month follow-up. Co-primary efficacy endpoints were device success and technical success while primary safety endpoint was in-hospital major adverse event (MAE) occurrence. RESULTS: A total of 52 patients were included: mean age 75 ± 8, 30.8% women, mean HAS-BLED 3 ± 1. The device was successfully implanted in all patients. Technical success was achieved in 50 patients (96.1%). In-hospital MAEs occurred in three patients (5.8%). The incidence of 6-month all-cause death and major bleeding was 11.6% and 2.1%, respectively. No strokes, transient ischemic attacks, systemic embolisms, or device embolization were reported after discharge. CONCLUSIONS: Second-generation Ultraseal device implantation was associated with high success rates and a low incidence of peri-procedural complications. Larger studies with longer follow-up are warranted to further evaluate the safety and the efficacy of this device, especially at long-term follow-up.

Biochemical Efficacy of Sodium-Glucose Cotransporter 2 Inhibitors by Cardiovascular Risk Profile and Volume Status in a Real-World Diabetic Population.

ABSTRACT: Despite large-scale randomized clinical trials (RCTs) highlighting a consistent prognostic benefit of sodium-glucose cotransporter 2 inhibitors (SGLT2is) both in diabetic patients at high cardiovascular risk and in those with heart failure, there is relative paucity of data on their biochemical effects in a real-world setting. We performed a retrospective analysis on consecutive diabetic patients who were prescribed a SGLT2i in a tertiary referral center and completed at least 1 year of treatment. Changes in glycated hemoglobin, weight, and hematocrit were compared across 2 cardiovascular risk categories, defined through the inclusion criteria of 3 large RCTs. Of the 459 patients screened, 312 completed 1 year of treatment (68.0%), 92 interrupted the treatment prematurely (20.0%), and 55 were lost to follow-up (12.0%). The most common cause of drug discontinuation was genital or urinary tract infections (9.4%). At 1 year, reduction in glycated hemoglobin concentration (-0.7 ± 1.5%, P < 0.001) and body weight (2.4 ± 4.6 kg, P < 0.001) was comparable between patients at high versus low cardiovascular risk, while hematocrit increase (2.3 ± 3.3%, P < 0.001) was more marked in patients with high cardiovascular risk and low baseline hematocrit. In a real-world population of diabetic patients, SGLT2is were well-tolerated at 1 year and led to improved glycemic control and weight loss. Hematocrit increase was more consistent in patients with high cardiovascular risk and signs of fluid overload, indicating euvolemic restoration as a potential cardioprotective mechanism mediated by these compounds.

Left Ventricular Thrombus Management After Acute Myocardial Infarction in Clinical Practice: Results from LEVITATION Survey and Narrative Review.

PURPOSE: Left ventricular thrombus (LVT) after ST-elevation myocardial infarction still presents diagnostic and therapeutic challenges. The LEVITATION survey was designed to take a picture of LVT management in current clinical practice. METHODS: The survey covered diagnostic, therapeutic, and prophylactic issues and was completed by 104 European cardiac centers. Most of them (59%) were university or tertiary centers. RESULTS: The survey showed anterior apical a-/dyskinesia, large MI, spontaneous echo-contrast, late presentation with delayed PCI, and TIMI flow 0-1 as the most important perceived risk factors for LVT formation. Serial ultrasound imaging is the most used tool to diagnose LVT (88% of the centers), with contrast-enhanced ultrasound and cardiac MR performed in case of poor apex visualization or spontaneous echo-contrast. One third (34%) of the centers uses prophylactic anticoagulation to prevent LVT formation. In the presence of LVT, low molecular weight heparin is the most used in-hospital therapy. At discharge, vitamin K antagonist and direct oral anticoagulants are used in 67 and 32% of the cases, respectively. Triple antithrombotic therapy with aspirin plus clopidogrel and VKA is the most used strategy at discharge (55%), whereas a single antiplatelet therapy is preferred only in the case of moderate-to-high risk of bleeding. To assess LVT total regression, half of the centers use contrast-enhanced ultrasound and/or cardiac-MR. The duration of anticoagulation is usually 3-6 months (55%), with long-term prolongation in case of LVT persistence or recurrence. CONCLUSION: The survey has depicted for the first time the current real-world management of this neglected topic and has highlighted several grey zones that are still present and not supported by evidence.