Cardiovascular risk factors and mortality in hospitalized patients with COVID-19: systematic review and meta-analysis of 45 studies and 18,300 patients.

BACKGROUND: A high prevalence of cardiovascular risk factors including age, male sex, hypertension, diabetes, and tobacco use, has been reported in patients with Coronavirus disease 2019 (COVID-19) who experienced adverse outcome. The aim of this study was to investigate the relationship between cardiovascular risk factors and in-hospital mortality in patients with COVID-19. METHODS: MEDLINE, Cochrane, Web of Sciences, and SCOPUS were searched for retrospective or prospective observational studies reporting data on cardiovascular risk factors and in-hospital mortality in patients with COVID-19. Univariable and multivariable age-adjusted analyses were conducted to evaluate the association between cardiovascular risk factors and the occurrence of in-hospital death. RESULTS: The analysis included 45 studies enrolling 18,300 patients. The pooled estimate of in-hospital mortality was 12% (95% CI 9-15%). The univariable meta-regression analysis showed a significant association between age (coefficient: 1.06; 95% CI 1.04-1.09; p < 0.001), diabetes (coefficient: 1.04; 95% CI 1.02-1.07; p < 0.001) and hypertension (coefficient: 1.01; 95% CI 1.01-1.03; p = 0.013) with in-hospital death. Male sex and smoking did not significantly affect mortality. At multivariable age-adjusted meta-regression analysis, diabetes was significantly associated with in-hospital mortality (coefficient: 1.02; 95% CI 1.01-1.05; p = 0.043); conversely, hypertension was no longer significant after adjustment for age (coefficient: 1.00; 95% CI 0.99-1.01; p = 0.820). A significant association between age and in-hospital mortality was confirmed in all multivariable models. CONCLUSIONS: This meta-analysis suggests that older age and diabetes are associated with higher risk of in-hospital mortality in patients infected by SARS-CoV-2. Conversely, male sex, hypertension, and smoking did not independently correlate with fatal outcome.

Multimodality Imaging Approach for Planning and Guiding Direct Transcatheter Tricuspid Valve Annuloplasty.

Interest in transcatheter treatment of tricuspid regurgitation (TR) has grown significantly in recent years due to increasing evidence correlating TR severity with mortality and to limited availability of surgical options often considered high-risk in these patients. Although edge-to-edge repair is currently the main transcatheter therapeutic strategy, tricuspid valve direct annuloplasty can also be performed safely and effectively to reduce TR and improve heart failure symptoms and quality of life. In the annuloplasty procedure, an adjustable band is implanted around the tricuspid annulus to reduce valvular size and improve TR. Patient selection and careful preoperative imaging, including transthoracic echocardiography, transesophageal echocardiography, and computed tomography, are critical for procedural success and proper device implantation. Compared to edge-to-edge repair, perioperative imaging with transesophageal echocardiography and fluoroscopy is particularly challenging. Alignment and insertion of the anchors are demanding but essential to achieve good results and avoid damaging the surrounding structures. The presence of shadowing artifacts due to cardiac devices makes the acquisition of good-quality images even more challenging. In this review, we discuss the current role of multimodality imaging in planning direct transcatheter tricuspid valve annuloplasty and describe all procedural steps focusing on echocardiographic monitoring.

Arterial hypertension in patients with takotsubo syndrome: prevalence, long-term outcome, and secondary preventive strategies: a report from the Takotsubo Italian Network register.

AIMS: The aim of this study was to investigate the long-term outcome of takotsubo syndrome (TTS) patients with and without hypertension (HT) and to evaluate the effectiveness of treatment with beta-blockers (BBs) and/or renin-angiotensin-aldosterone system inhibitors (RAASi). METHODS AND RESULTS: The study population includes a register-based, multicentre cohort of consecutive patients with TTS, divided into two groups according to the history of HT. Further stratification was performed for BB/RAASi prescription at discharge. The primary outcome was the composite of all-cause death and TTS recurrence at the longest available follow-up. The propensity score weighting technique was used to account for potential confounding. In the overall population (903 patients, mean age 70 ± 11 years), HT was reported in 66% of cases. At a median 2-year follow-up, there was no difference in the risk of the primary composite outcome between patients with and without HT. The adjusted Cox regression analysis showed a significantly lower risk for the primary outcome [adjusted hazard ratio (aHR): 0.69; 95% confidence interval (CI): 0.49-0.99] in patients who received BB vs. those who did not. Renin-angiotensin-aldosterone system inhibitors treatment was not associated with the primary study outcome. The lower risk for the primary outcome with BB treatment was confirmed in patients with HT (aHR: 0.37; 95% CI: 0.24-0.56) but not in patients without (aHR: 1.83; 95% CI: 0.92-3.64; Pinteraction < 0.001). CONCLUSION: In this TTS study, HT did not affect the long-term risk of adverse events but increased the probability of benefit from BB treatment after discharge. Owing to the favourable outcome impact of BB prescription in TTS patients with HT, a tailored pharmacological therapy should be considered in this cohort.

Although not associated with clinical outcomes, hypertension (HT) seems to modify the long-term effectiveness of pharmacological treatment in patients with takotsubo syndrome (TTS). Beta-blockers improved the overall survival of TTS patients with HT and should be considered as first-line therapy in this patient population. The effectiveness of renin­angiotensin­aldosterone system inhibitors on long-term outcome was not significant regardless of the history of HT.

Importance of Echocardiography and Clinical "Red Flags" in Guiding Genetic Screening for Fabry Disease.

Introduction: Aim of this study was to evaluate, in a metropolitan area not already explored, the prevalence of Anderson-Fabry disease, by genetic screening, in patients with echocardiographic evidence of left ventricular hypertrophy (LVH) of unknown origin and "clinical red flags". Methods: From August 2016 to October 2017, all consecutive patients referring to our echo-lab for daily hospital practices with echocardiographic evidence of LVH of unknown origin in association with history of at least one of the classical signs and symptoms related to Fabry disease (FD) (neuropathic pain, anhidrosis/hypohidrosis, angiokeratomas, gastrointestinal problems, chronic kidney disease, or cerebrovascular complications) were considered eligible for the FD genetic screening program. Through dried blood spot testing, α-Galactosidase A (α-Gal A) activity and analysis of the GLA gene were performed. Results: Among 3,360 patients who underwent transthoracic echocardiography in our echo-lab during the study period, 30 patients (0.89%; 19 men, mean age 58 ± 18.2 years) were selected. FD was diagnosed in 3 (10%) unrelated patients. Three different GLA gene mutations were detected, one of them [mutation c.388A > G (p.Lys130Glu) in exon 3] never described before. Moreover, probands' familiar genetic screening allowed the identification of 5 other subjects affected by FD. Conclusion: In a metropolitan area not previously investigated, among patients with LVH of unknown origin associated with other "red flags," undergoing genetic screening, the prevalence of FD was very high (10%). Our results highlight the importance of an echocardiographic- and clinical-oriented genetic screening for FD in patients with uncommon cause of LVH.

Sacubitril/valsartan reduces indications for arrhythmic primary prevention in heart failure with reduced ejection fraction: insights from DISCOVER-ARNI, a multicenter Italian register.

Aims: This sub-study deriving from a multicentre Italian register [Deformation Imaging by Strain in Chronic Heart Failure Over Sacubitril-Valsartan: A Multicenter Echocardiographic Registry (DISCOVER)-ARNI] investigated whether sacubitril/valsartan in addition to optimal medical therapy (OMT) could reduce the rate of implantable cardioverter-defibrillator (ICD) indications for primary prevention in heart failure with reduced ejection fraction (HFrEF) according to European guidelines indications, and its potential predictors. Methods and results: In this observational study, consecutive patients with HFrEF eligible for sacubitril/valsartan from 13 Italian centres were included. Lack of follow-up or speckle tracking data represented exclusion criteria. Demographic, clinical, biochemical, and echocardiographic data were collected at baseline and after 6 months from sacubitril/valsartan initiation. Of 351 patients, 225 (64%) were ICD carriers and 126 (36%) were not ICD carriers (of whom 13 had no indication) at baseline. After 6 months of sacubitril/valsartan, among 113 non-ICD carriers despite having baseline left ventricular (LV) ejection fraction (EF) ≤ 35% and New York Heart Association (NYHA) class = II-III, 69 (60%) did not show ICD indications; 44 (40%) still fulfilled ICD criteria. Age, atrial fibrillation, mitral regurgitation > moderate, left atrial volume index (LAVi), and LV global longitudinal strain (GLS) significantly varied between the groups. With receiver operating characteristic curves, age ≥ 75 years, LAVi ≥ 42 mL/m2 and LV GLS ≥-8.3% were associated with ICD indications persistence (area under the curve = 0.65, 0.68, 0.68, respectively). With univariate and multivariate analysis, only LV GLS emerged as significant predictor of ICD indications at follow-up in different predictive models. Conclusions: Sacubitril/valsartan may provide early improvement of NYHA class and LVEF, reducing the possible number of implanted ICD for primary prevention in HFrEF. Baseline reduced LV GLS was a strong marker of ICD indication despite OMT. Early therapy with sacubitril/valsartan may save infective/haemorrhagic risks and unnecessary costs deriving from ICDs.

A case report of takotsubo syndrome complicated by ischaemic stroke: the clinical dilemma of anticoagulation.

BACKGROUND: Takotsubo syndrome (TTS) is an acute and transient heart failure syndrome due to reversible myocardial dysfunction characterized by a wide spectrum of possible clinical scenarios. About one-fifth of TTS patients experience adverse in-hospital events. Thromboembolic complications, especially stroke, have been reported, albeit in a minority of patients. CASE SUMMARY: A 69-year-old woman presented to our emergency department for dyspnoea after a family quarrel. Electrocardiogram revealed ST-segment elevation in anterolateral leads and laboratory exams showed a slight elevation of high-sensitivity cardiac troponin. The patient was treated according to current guidelines on ST-elevation myocardial infarction and referred to the cath lab. Urgent coronary angiography revealed normal coronary arteries. Based on the patient profile and instrumental findings, a diagnosis of TTS was hypothesized. After 6 days, the patient developed dysarthria and right hemiparesis under therapy with aspirin, whilst low molecular weight heparin had been previously withdrawn. Transthoracic echocardiography (TTE) revealed persisting apical akinesia and a subtle intraventricular thrombus. Head computed tomography and magnetic resonance imaging detected focal areas of ischaemic necrosis resembling diffuse cardioembolic lesions. Anticoagulation therapy was started and regular TTE showed complete recovery of myocardial systolic function and absence of ventricular thrombi at 1-month follow-up. The patient fully recovered speech after 5 months. DISCUSSION: This challenging case reinforces current recommendations to administer antithrombotic therapy in TTS patients with extensive apical dysfunction up to complete or near-complete recovery of myocardial contractility, regardless of the presence of atrial fibrillation, and highlights the importance of close TTE monitoring during the acute phase.

Cardiovascular Involvement in COVID-19: What Sequelae Should We Expect?

Several forms of cardiovascular involvement have been described in patients with Coronavirus disease 19 (COVID-19): myocardial injury, acute coronary syndrome, acute heart failure, myocarditis, pericardial diseases, arrhythmias, takotsubo syndrome, and arterial and venous atherothrombotic and thromboembolic events. Data on long-term outcome of these patients are still sparse, and the type and real incidence of cardiovascular sequelae are poorly known. It is plausible that myocardial injury may be the initiator of an inflammatory cascade, edema, and subsequent fibrosis, but also a consequence of systemic inflammation. The extent and distribution of ongoing inflammation may be the basis for ventricular dysfunction and malignant arrhythmias. Indeed, preliminary observational findings seem to emphasize the importance of close monitoring of COVID-19 patients with myocardial injury after discharge. Residual subclinical disease may be effectively investigated by using second-level imaging modalities such as cardiac magnetic resonance, which allows better characterization of the type and extension of myocardial damage, as well as of the ongoing inflammation after the acute phase. In patients with venous thromboembolism, a very common complication of COVID-19, the type and the duration of anticoagulation therapy after the acute phase should be tailored to the patient and based on the estimation of the individual thromboembolic and hemorrhagic risk. Large randomized clinical trials are ongoing to address this clinical question. Whether the severity of cardiovascular involvement, the type of treatments adopted during the acute phase, and the hemodynamic response, may influence the long-term outcome of patients recovered from COVID-19 is unknown. An etiological diagnosis of myocardial injury during the hospitalization is the first step for an appropriate follow-up in these patients. After discharge, the screening for residual left and right ventricular dysfunction, arrhythmias, residual thrombosis, and myocardial scar should be considered on a case-by-case basis, whereas an active clinical surveillance is mandatory in any patient.

Role of multimodality imaging in evaluation of cardiovascular involvement in COVID-19.

The management of patients infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may be difficult due to the need for dedicated in-hospital pathways, protective measures for healthcare professionals and isolated beds of intensive care, particularly in areas overwhelmed by wide viral spread. Although pneumonia is the most common clinical manifestation in coronavirus disease 2019 (COVID-19), a variety of cardiovascular complications have been reported. An integrated diagnostic algorithm in SARS-CoV-2-infected patients with suspected cardiac involvement (laboratory findings of myocardial injury and electrocardiographic changes) may help to avoid unnecessary examinations and minimize the risk of operator infection. Due to its mobility and bedside feasibility, echocardiography is the first-line imaging technique in this clinical setting. It quickly provides information on ventricular functions, pulmonary hypertension, valve disease and pericardial effusion. In case of ST-segment elevation (STE), urgent coronary angiography should be performed. Cardiac ultrasound helps distinguish between ischemic and non-ischemic myocardial disease and may detect pericardial disease. Transmural ischemic electrocardiographic changes, with or without early elevated troponin levels or echocardiographic wall motion abnormalities, will determine the need for early invasive coronary angiography. Computed tomography (CT) through its multiple applications (chest CT; CT pulmonary angiography and coronary CT angiography; late iodine enhancement CT) and cardiac magnetic resonance might be helpful in reinforcing or redirecting diagnostic hypothesis emerged by other clinical, electrocardiographic and echocardiographic findings. The current pandemic makes it challenging to perform serial invasive and non-invasive diagnostic testing in COVID-19 patients and high serum troponin level. Nevertheless, thoughtful and systematic use of an appropriate multimodality imaging strategy is clinically relevant to detect cardiac injury and distinguish myocardial infarction from, myocarditis, takotsubo syndrome and pulmonary embolism.

A Rare Complication of Transcatheter Aortic Valve Replacement: Aortic Root-Left Atrium Fistulization.

The authors report the case of an 87-year-old man undergoing transcatheter aortic valve replacement via transfemoral approach who developed a life-threatening complication, i.e., fistulization between the aortic root and the left atrium, which was successfully treated by surgery. At 6-month follow-up, the clinical course was uneventful. (Level of Difficulty: Beginner.).