The Role of Multimodality Imaging (CT & MR) as a Guide to the Management of Chronic Coronary Syndromes.

Chronic coronary syndrome (CCS) is one of the leading cardiovascular causes of morbidity, mortality, and use of medical resources. After the introduction by international guidelines of the same level of recommendation to non-invasive imaging techniques in CCS evaluation, a large debate arose about the dilemma of choosing anatomical (with coronary computed tomography angiography (CCTA)) or functional imaging (with stress echocardiography (SE), cardiovascular magnetic resonance (CMR), or nuclear imaging techniques) as a first diagnostic evaluation. The determinant role of the atherosclerotic burden in defining cardiovascular risk and prognosis more than myocardial inducible ischemia has progressively increased the use of a first anatomical evaluation with CCTA in a wide range of pre-test probability in CCS patients. Functional testing holds importance, both because the role of revascularization in symptomatic patients with proven ischemia is well defined and because functional imaging, particularly with stress cardiac magnetic resonance (s-CMR), gives further prognostic information regarding LV function, detection of myocardial viability, and tissue characterization. Emerging techniques such as stress computed tomography perfusion (s-CTP) and fractional flow reserve derived from CT (FFRCT), combining anatomical and functional evaluation, appear capable of addressing the need for a single non-invasive examination, especially in patients with high risk or previous revascularization. Furthermore, CCTA in peri-procedural planning is promising to acquire greater importance in the non-invasive planning and guiding of complex coronary revascularization procedures, both by defining the correct strategy of interventional procedure and by improving patient selection. This review explores the different roles of non-invasive imaging techniques in managing CCS patients, also providing insights into preoperative planning for percutaneous or surgical myocardial revascularization.

Prognostic value of hypochloremia on mortality in patients with heart failure: a systematic review and meta-analysis.

AIMS: Electrolyte imbalances are common in patients with heart failure. Several studies have shown that a low serum chloride level is associated with adverse outcomes in hospitalized patients with acute heart failure and in outpatients with chronic heart failure. We performed a systematic review and meta-analysis to assess the association of hypochloremia with all-cause mortality in patients with heart failure. METHODS: Data search was conducted from inception through 1 February 2023, using the following MeSH terms: ('chloride' OR 'hypochloremia') AND 'heart failure'. Studies evaluating the association between serum chloride and all-cause mortality in patients with heart failure were included. The predefined primary outcome was all-cause mortality. Pooled hazard ratios and 95% confidence intervals (CIs) were used as effect estimates and calculated with a random-effects model; fixed-effects model and leave-one-out sensitivity analyses were also performed. RESULTS: A total of 15 studies, involving 25 848 patients, were included. The prevalence of hypochloremia ranged from 8.6 to 31.5%. Follow-up time ranged from 6 to 67 months. Hypochloremia as a categorical variable was associated with an increased risk of all-cause mortality [hazard ratio 1.56; 95% confidence interval (CI) 1.38-1.75; P  < 0.001]. As a continuous variable, serum chloride was associated with all-cause mortality (hazard ratio per mmol/l decrease in serum chloride: 1.06; 95% CI 1.05-1.07; P  < 0.001). Results were confirmed by using several sensitivity analyses. CONCLUSION: Hypochloremia exhibits a significant prognostic value in patients with heart failure. Serum chloride can be used as an effective tool for risk stratifying in patients with heart failure.

DEep LearnIng-based QuaNtification of epicardial adipose tissue predicts MACE in patients undergoing stress CMR.

BACKGROUND AND AIMS: This study investigated the additional prognostic value of epicardial adipose tissue (EAT) volume for major adverse cardiovascular events (MACE) in patients undergoing stress cardiac magnetic resonance (CMR) imaging. METHODS: 730 consecutive patients [mean age: 63 ± 10 years; 616 men] who underwent stress CMR for known or suspected coronary artery disease were randomly divided into derivation (n = 365) and validation (n = 365) cohorts. MACE was defined as non-fatal myocardial infarction and cardiac deaths. A deep learning algorithm was developed and trained to quantify EAT volume from CMR. EAT volume was adjusted for height (EAT volume index). A composite CMR-based risk score by Cox analysis of the risk of MACE was created. RESULTS: In the derivation cohort, 32 patients (8.7 %) developed MACE during a follow-up of 2103 days. Left ventricular ejection fraction (LVEF) < 35 % (HR 4.407 [95 % CI 1.903-10.202]; p<0.001), stress perfusion defect (HR 3.550 [95 % CI 1.765-7.138]; p<0.001), late gadolinium enhancement (LGE) (HR 4.428 [95%CI 1.822-10.759]; p = 0.001) and EAT volume index (HR 1.082 [95 % CI 1.045-1.120]; p<0.001) were independent predictors of MACE. In a multivariate Cox regression analysis, adding EAT volume index to a composite risk score including LVEF, stress perfusion defect and LGE provided additional value in MACE prediction, with a net reclassification improvement of 0.683 (95%CI, 0.336-1.03; p<0.001). The combined evaluation of risk score and EAT volume index showed a higher Harrel C statistic as compared to risk score (0.85 vs. 0.76; p<0.001) and EAT volume index alone (0.85 vs.0.74; p<0.001). These findings were confirmed in the validation cohort. CONCLUSIONS: In patients with clinically indicated stress CMR, fully automated EAT volume measured by deep learning can provide additional prognostic information on top of standard clinical and imaging parameters.

Bileaflet Tethering With Preserved LV Geometry and Function: An Unusual Mechanism of Functional Mitral Regurgitation.

An 81-year-old woman presented with acute pulmonary edema. Echocardiography revealed severe functional mitral regurgitation, the mechanism of which was unusual. An atypical bileaflet tethering caused by disharmonic annular remodeling, concomitant aortic dilatation, and reduced aorto-mitral angle without left ventricular dysfunction or dilatation was found. A transcatheter edge-to-edge repair was nonetheless successfully performed.

GLP-1-ra and heart failure-related outcomes in patients with and without history of heart failure: an updated systematic review and meta-analysis.

AIMS: Glucagon-like peptide-1 receptor agonists (GLP1-ra) have shown to reduce cardiovascular (CV) events in patients with diabetes, including heart failure (HF) hospitalizations. However, whether such benefit consistently occurs in patients with history of HF remains uncertain. We performed a systematic review and meta-analysis to assess the impact of GLP1-ra on CV outcomes in patients with and without HF history. METHODS AND RESULTS: All randomized, placebo-controlled trials evaluating GLP1-ra and reporting CV outcomes stratified by HF history were searched in Pubmed from inception to November 12th, 2023. The primary outcome was HF hospitalizations. Secondary outcomes included CV death, the composite of CV death and hospitalizations for HF, and major adverse cardiovascular events (MACE). Hazard ratio (HR) and 95% confidence interval (CIs) were used as effect estimates and calculated with a random-effects model. 68,653 patients (GLP1-ra = 34,301, placebo = 34,352) from 10 trials were included. GLP1-ra reduced HF hospitalization (no HF: HR = 0.79, 95% CI 0.63-0.98; HF: HR = 1.00, 95% CI 0.82-1.24, pinteraction = 0.12), CV death (no HF: HR = 0.81, 95% CI 0.71-0.92; HF: HR = 0.97, 95% CI 0.81-1.15, pinteraction = 0.11), and the composite of HF hospitalizations and CV death (no HF: HR = 0.80, 95% CI 0.72-0.89; HF: HR = 1.00 95% CI 0.88-1.15, pinteraction = 0.010) only in patients without history of HF, despite a significant interaction between HF history and treatment effect was detected only for the latter. MACE were reduced in both subgroups without significant interaction between HF history and treatment effect (no HF: HR = 0.86, 95% CI 0.78-0.96; HF: HR = 0.83, 95% CI 0.72-0.95, pinteraction = 0.69). CONCLUSION: GLP1-ra do not decrease HF-hospitalization risk, despite a potential benefit in patients without history of HF, but are effective in reducing ischemic events irrespective of the presence of HF. PROSPERO-registered (CRD42022371264).

Real-world data of patients affected by advanced heart failure treated with implantable cardioverter defibrillator and left ventricular assist device: Results of a multicenter observational study.

BACKGROUND: Left ventricular assist device (L-VAD) implantation is increasingly used in patients with heart failure (HF) and most patients also have an implantable cardioverter defibrillator (ICD). Limited data are available on the incidence of ICD therapies and complications in this special setting. The aim of this study was to analyze the real-world incidence and predictors of ICD therapies, complications and interactions between ICD and L-VAD. METHODS: We conducted a multicenter retrospective observational study in patients with advanced HF implanted with ICD and a continuous-flow L-VAD, followed-up in five advanced HF centers in Northern Italy. RESULTS: A total of 234 patients (89.7% male, median age 59, 48.3% with ischemic etiology) were enrolled. After a median follow-up of 21 months, 66 patients (28.2%) experienced an appropriate ICD therapy, 22 patients (9.4%) an inappropriate ICD therapy, and 17 patients (7.3%) suffered from an interaction between ICD and L-VAD. The composite outcome of all ICD-related complications was reported in 41 patients (17.5%), and 121 (51.7%) experienced an L-VAD-related complication. At multivariable analysis, an active ventricular tachycardia (VT) zone and a prior ICD generator replacement were independent predictors of ICD therapies and of total ICD-related complications, respectively. CONCLUSIONS: Real-world patients with both L-VAD and ICD experience a high rate of ICD therapies and complications. Our findings suggest the importance of tailoring device programming in order to minimize the incidence of unnecessary ICD therapies, thus sparing the need for ICD generator replacement, a procedure associated to a high risk of complications.

Percutaneous suture-based patent foramen ovale closure: A state-of-the-art review.

Percutaneous closure of a patent foramen ovale (PFO), a common variation of interatrial septum anatomy, is a commonly performed procedure in the catheterization laboratory to reduce the risk of recurrent stroke in selected patients and to treat other PFO-related syndromes. In the last twenty years, disc-based devices have represented the armamentarium of the interventional cardiologist; recently, suture-based devices have become an attractive alternative, despite limited data regarding their long-term performance. The present review gives an overview of the current evidence regarding suture-based PFO closure, the device's characteristics, the echocardiographic evaluation of the PFO anatomy, and recommendations for patient selection. A detailed procedural guide is then provided, and potential complications and future developments in the field are discussed.

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.

Nebivolol versus placebo in patients undergoing anthracyclines (CONTROL Trial): rationale and study design.

AIMS: Anthracyclines are the chemotherapeutic agents most frequently associated with cardiotoxicity, while remaining widely used. Different neurohormonal blockers have been tested as a primary prevention strategy to prevent or attenuate the onset of cardiotoxicity, with mixed results. However, prior studies were often limited by a nonblinded design and an assessment of cardiac function based only on echocardiographic imaging. Moreover, on the basis of an improved mechanistic understanding of anthracycline cardiotoxicity mechanisms, new therapeutic strategies have been proposed. Among cardioprotective drugs, nebivolol might be able to prevent the cardiotoxic effects of anthracyclines, through its protective properties towards the myocardium, endothelium, and cardiac mitochondria. This study aims to evaluate the cardioprotective effects of the beta blocker nebivolol in a prospective, placebo-controlled, superiority randomized trial in patients with breast cancer or diffuse large B cell lymphoma (DLBCL) who have a normal cardiac function and will receive anthracyclines as part of their first-line chemotherapy programme. METHODS: The CONTROL trial is a randomized, placebo-controlled, double-blinded, superiority trial. Patients with breast cancer or a DLBCL, with a normal cardiac function as assessed by echocardiography, scheduled for treatment with anthracyclines as part of their first-line chemotherapy programme will be randomized 1 : 1 to nebivolol 5 mg once daily (o.d.) or placebo. Patients will be examined with cardiological assessment, echocardiography and cardiac biomarkers at baseline, 1 month, 6 months and 12 months. A cardiac magnetic resonance (CMR) assessment will be performed at baseline and at 12 months. The primary end point is defined as left ventricular ejection fraction reduction assessed by CMR at 12 months of follow-up. CONCLUSION: The CONTROL trial is designed to provide evidence to assess the cardioprotective role of nebivolol in patients undergoing chemotherapy with anthracyclines. CLINICAL TRIAL REGISTRATION: The study is registered in the EudraCT registry (number: 2017-004618-24) and in the ClinicalTrials.gov registry (identifier: NCT05728632).

Solving the Riddle of Sudden Cardiac Death in Hypertrophic Cardiomyopathy: The Added Role of Cardiac Magnetic Resonance.

Cardiac magnetic resonance (CMR) has been recently implemented in clinical practice to refine the daunting task of establishing the risk of sudden cardiac death (SCD) in patients with hypertrophic cardiomyopathy (HCM). We present an exemplificative case highlighting the practical clinical utility of this imaging modality in a 24-year-old man newly diagnosed with an apical HCM. CMR was essential in unmasking a high risk of SCD, which appeared low-intermediate after traditional risk assessment. A discussion examines the essential role of CMR in guiding the patient's therapy and underlines the added value of CMR, including novel and potential CMR parameters, compared to traditional imaging assessment for SCD risk stratification.

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.

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.

Implantation of contemporary transcatheter aortic valves in small aortic annuli: the international multicentre TAVI-SMALL 2 registry.

BACKGROUND: Treatment of aortic stenosis in patients with small annuli is challenging and can result in prosthesis-patient mismatch (PPM). AIMS: We aimed to compare the forward flow haemodynamics and clinical outcomes of contemporary transcatheter valves in patients with small annuli. METHODS: The TAVI-SMALL 2 international retrospective registry included 1,378 patients with severe aortic stenosis and small annuli (annular perimeter <72 mm or area <400 mm2) treated with transfemoral self-expanding (SEV; n=1,092) and balloon-expandable valves (BEV; n=286) in 16 high-volume centres between 2011 and 2020. Analyses comparing SEV versus BEV and supra-annular (SAV; n=920) versus intra-annular valves (IAV; n=458) included inverse probability of treatment weighting (IPTW). The primary endpoints were the predischarge mean aortic gradient and incidence of severe PPM. The secondary endpoint was the incidence of more than mild paravalvular leak (PVL). RESULTS: The predischarge mean aortic gradient was lower after SAV versus IAV (7.8±3.9 vs 12.0±5.1; p<0.001) and SEV versus BEV implantation (8.0±4.1 vs 13.6±4.7; p<0.001). Severe PPM was more common with IAV and BEV when compared to SAV and SEV implantation, respectively, (8.8% vs 3.6%; p=0.007 and 8.7% vs 4.6%; p=0.041). At multivariable logistic regression weighted by IPTW, SAV protected from severe PPM regardless of its definition. More than mild PVL occurred more often with SEV versus BEV (11.6% vs 2.6%; p<0.001). CONCLUSIONS: In small aortic annuli, implantation of SAV and SEV was associated with a more favourable forward haemodynamic profile than after IAV and BEV implantation, respectively. More than mild PVL was more common after SEV than BEV implantation.

Edge-to-edge percutaneous mitral repair for functional ischaemic and non-ischaemic mitral regurgitation: a systematic review and meta-analysis.

AIM: Randomized controlled trials comparing the use of the MitraClip device in addition to guideline directed medical therapy (GDMT) to GDMT alone in patients with secondary mitral regurgitation (MR) have shown conflicting results. However, if these differences could be due to the underlying MR aetiology is still unknown. Therefore, we aimed to evaluate if the effects of percutaneous edge-to-edge repair with MitraClip implantation could differ in patients with ischaemic (I-MR) and non-ischaemic mitral regurgitation (NI-MR). METHODS AND RESULTS: PubMed, Embase, BioMed Central, and the Cochrane Central Register of Controlled Trials were searched for all studies including patients with secondary MR treated with the MitraClip device. Data were pooled using a random-effects model. Primary endpoint was the composite of all-cause death and heart failure-related hospitalization. Secondary endpoints were the single components of the primary endpoint, New York Heart Association functional Classes III and IV, and mitral valve re-intervention. Seven studies enrolling 2501 patients were included. Patients with I-MR compared with patients with NI-MR had a similar risk of the primary endpoint (odds ratio: 1.17; 95% confidence interval: 0.93 to 1.46; I2 : 0%). The risk of all-cause death was increased in patients with I-MR (odds ratio: 1.31; 95% confidence interval: 1.07 to 1.62; I2 : 0%), while no differences were observed between the two groups in terms of the other secondary endpoints. CONCLUSIONS: The risk of mortality after MitraClip implantation is lower in patients with NI-MR than in those with I-MR. No absolute differences in the risk of heart failure related hospitalization were observed between groups.

Transcatheter aortic valve replacement in aortic stenosis and cardiac amyloidosis: a systematic review and meta-analysis.

AIMS: Aortic stenosis (AS) and cardiac amyloidosis (CA) are typical diseases of the elderly. Up to 16% of older adults with severe AS referred to transcatheter aortic valve replacement (TAVR) have a concomitant diagnosis of CA. CA-AS population suffers from reduced functional capacity and worse prognosis than AS patients. As the prognostic impact of TAVR in patients with CA-AS has been historically questioned and in light of recently published evidence, we aim to provide a comprehensive synthesis of the efficacy and safety of TAVR in CA-AS patients. METHODS AND RESULTS: We performed a systematic review and meta-analysis of studies: (i) evaluating mortality with TAVR as compared with medical therapy in CA-AS patients and (ii) reporting complications and clinical outcomes of TAVR in CA-AS patients as compared with patients with AS alone. A total of seven observational studies were identified: four reported mortality with TAVR, and four reported complications and clinical outcomes after TAVR of patients with CA-AS compared with AS alone patients. In patients with CA-AS, the risk of mortality was lower with TAVR (n = 44) as compared with medical therapy (n = 36) [odds ratio (OR) 0.23, 95% confidence interval (CI) 0.07-0.73, I2  = 0%, P = 0.001, number needed to treat = 3]. The safety profile of TAVR seems to be similar in patients with CA-AS (n = 75) as compared with those with AS alone (n = 536), with comparable risks of stroke, vascular complications, life-threatening bleeding, acute kidney injury, and 30 day mortality, although CA-AS was associated with a trend towards an increased risk of permanent pacemaker implantation (OR 1.76, 95% CI 0.91-4.09, I2  = 0%, P = 0.085). CA is associated with a numerically higher rate of long-term mortality and rehospitalizations following TAVR in patients with CA-AS as compared with those with AS alone. CONCLUSIONS: TAVR is an effective and safe procedure in CA-AS patients, with a substantial survival benefit as compared with medical therapy, and a safety profile comparable with patients with AS alone except for a trend towards higher risk of permanent pacemaker implantation.

Direct oral anticoagulants versus vitamin K antagonists in the treatment of left ventricular thrombosis: a systematic review and meta-analysis.

INTRODUCTION: Evidence about the use of direct oral anticoagulants (DOACs) in patients with left ventricular thrombosis (LVT) are emerging. The aim of our study was to provide a comprehensive synthesis of the available evidence concerning the clinical effects of DOACs versus vitamin K antagonists (VKAs) in LVT treatment. EVIDENCE ACQUISITION: Systematic search of studies evaluating DOACs versus VKAs use in patients with LVT was performed on May 11th, 2021. Data were pooled by meta-analysis using a random-effects model. Odds ratios (OR) with relative 95% confidence intervals (CI) were used as measures of effect estimates. The primary efficacy and safety endpoint were ischemic stroke and any bleeding, respectively. Secondary endpoints were LVT resolution, systemic embolism, major bleeding, hemorrhagic stroke, and all cause death. EVIDENCE SYNTHESIS: Twenty studies were included in the meta-analysis: 1,391 patients were treated with DOACs and 1,534 with VKAs. A significant reduction in the risk of ischemic stroke (OR 0.67, 95% CI, 0.45-0.98, P=0.048, number needed to treat to benefit [NNTB] 22 [95% CI 15-43]) and any bleeding (OR 0.64, 95% CI 0.46-0.89, P=0.009, NNTB 26 [95% CI 16-80]) was observed with DOACs compared to VKAs. No statistically significant difference was observed among the two treatment arms for the secondary endpoints. CONCLUSIONS: Compared to VKAs, DOACs are associated with a reduced risk of ischemic stroke and bleeding. In light of these findings, and the practical advantages of DOACs, additional large scale randomized controlled trials are needed to confirm the benefits of DOACs in patients with LVT.

Subclinical myocardial dysfunction in patients recovered from COVID-19.

BACKGROUND: Myocardial injury (MI) can be detected during the acute phase of Coronavirus disease 19 (COVID-19) and is associated with a dismal prognosis. Recent imaging studies described the persistence of cardiac abnormalities after the recovery. The aim of the study was to investigate the spectrum of cardiac abnormalities at mid-term follow-up in patients recovered from COVID-19 using clinical assessment, laboratory tests, and imaging evaluation with comprehensive echocardiography. METHODS: This is an observational, cross-sectional study assessing an unselected cohort of consecutive patients recovered from COVID-19. MI was defined by elevated plasma levels of high sensitive troponin T (hsTnT). At the follow-up, a complete examination including echocardiography was performed. RESULTS: The 123 patients included were divided into two groups according to the presence of MI during hospitalization: group A (without MI) and group B (with MI). After a median of 85 days, group B patients were more frequently symptomatic for dyspnea and had significantly higher values of hsTnT and N-Terminal prohormone of Brain Natriuretic Peptide (NT-proBNP), compared to Group A. No differences between the two groups in left nor right ventricle dimension and ejection fraction were found. However, in group B a significant reduction of mean left ventricle global longitudinal strain was observed (-15.7±.7 vs -18.1± .3 in group A, p < 0.001), together with higher frequency of impaired diastolic function and higher values of pulmonary pressure. CONCLUSIONS: In patients recovered from COVID-19, echocardiography with speckle-tracking analysis may be an useful imaging tool to identify subclinical myocardial dysfunction and potentially guide management strategies.

Disentangling the Association of Hydroxychloroquine Treatment with Mortality in Covid-19 Hospitalized Patients through Hierarchical Clustering.

The efficacy of hydroxychloroquine (HCQ) in treating SARS-CoV-2 infection is harshly debated, with observational and experimental studies reporting contrasting results. To clarify the role of HCQ in Covid-19 patients, we carried out a retrospective observational study of 4,396 unselected patients hospitalized for Covid-19 in Italy (February-May 2020). Patients' characteristics were collected at entry, including age, sex, obesity, smoking status, blood parameters, history of diabetes, cancer, cardiovascular and chronic pulmonary diseases, and medications in use. These were used to identify subtypes of patients with similar characteristics through hierarchical clustering based on Gower distance. Using multivariable Cox regressions, these clusters were then tested for association with mortality and modification of effect by treatment with HCQ. We identified two clusters, one of 3,913 younger patients with lower circulating inflammation levels and better renal function, and one of 483 generally older and more comorbid subjects, more prevalently men and smokers. The latter group was at increased death risk adjusted by HCQ (HR[CI95%] = 3.80[3.08-4.67]), while HCQ showed an independent inverse association (0.51[0.43-0.61]), as well as a significant influence of cluster∗HCQ interaction (p < 0.001). This was driven by a differential association of HCQ with mortality between the high (0.89[0.65-1.22]) and the low risk cluster (0.46[0.39-0.54]). These effects survived adjustments for additional medications in use and were concordant with associations with disease severity and outcome. These findings suggest a particularly beneficial effect of HCQ within low risk Covid-19 patients and may contribute to clarifying the current controversy on HCQ efficacy in Covid-19 treatment.