Ophthalmology and SARS-CoV-2: Blind toward those who fight blindness?

SARS-CoV-2 infection recently reached pandemic proportions, with high risk of death for the worldwide population. In this dramatic scenario, all the resources are addressed to the intensive care units for the assessment of the emergency. However, more attention should be paid with respect to the risk of viral diffusion among asymptomatic people. Italy is the second most involved country in the world, and we needed to gain a lot of experience in a very limited time. At least 1 m of distance among people is recommended; however, some clinical practices cannot allow this distance. In this context, we believe that the careful safety assessment of clinical settings, like ophthalmologic ones, may have a remarkable impact on the fight against SARS-CoV-2 spread.

Prognostic Role of Ventricular Ectopic Beats in Systemic Sclerosis: A Prospective Cohort Study Shows ECG Indexes Predicting the Worse Outcome.

BACKGROUND: Arrhythmias are frequent in Systemic Sclerosis (SSc) and portend a bad prognosis, accounting alone for 6% of total deaths. Many of these patients die suddenly, thus prevention and intensified risk-stratification represent unmet medical needs. The major goal of this study was the definition of ECG indexes of poor prognosis. METHODS: We performed a prospective cohort study to define the role of 24h-ECG-Holter as an additional risk-stratification technique in the identification of SSc-patients at high risk of life-threatening arrhythmias and sudden cardiac death (SCD). One-hundred SSc-patients with symptoms and/or signs suggestive of cardiac involvement underwent 24h-ECG-Holter. The primary end-point was a composite of SCD or need for implantable cardioverter defibrillator (ICD). RESULTS: Fifty-six patients (56%) had 24h-ECG-Holter abnormalities and 24(24%) presented frequent ventricular ectopic beats (VEBs). The number of VEBs correlated with high-sensitive cardiac troponin T (hs-cTnT) levels and inversely correlated with left-ventricular ejection fraction (LV-EF) on echocardiography. During a mean follow-up of 23.1±16.0 months, 5 patients died suddenly and two required ICD-implantation. The 7 patients who met the composite end-point had a higher number of VEBs, higher levels of hs-cTnT and NT-proBNP and lower LV-EF (p = 0.001 for all correlations). All these 7 patients had frequent VEBs, while LV-EF was not reduced in all and its range was wide. At ROC curve, VEBs>1190/24h showed 100% of sensitivity and 83% of specificity to predict the primary end-point (AUROC = 0.92,p<0.0001). Patients with VEBS>1190/24h had lower LV-EF and higher hs-cTnT levels and, at multivariate analysis, the presence of increased hs-cTnT and of right bundle branch block on ECG emerged as independent predictors of VEBs>1190/24h. None of demographic or disease-related characteristics emerged as predictors of poor outcome. CONCLUSIONS: VEBS>1190/24h identify patients at high risk of life-threatening arrhythmic complications. Thus, 24h-ECG-Holter should be considered a useful additional risk-stratification test to select SSc-patients at high-risk of SCD, in whom an ICD-implantation could represent a potential life-saving intervention.

Residual shunt after percutaneous closure of patent foramen ovale with AMPLATZER occluder devices - influence of anatomic features: a transcranial Doppler and intracardiac echocardiography study.

AIMS: To evaluate the relationship between the anatomic features of the fossa ovalis (FO) and residual right-to-left shunt (RLS) after percutaneous patent foramen ovale (PFO) closure with AMPLATZER PFO occluder devices. METHODS AND RESULTS: FO anatomic features were assessed by intracardiac echocardiography in 127 patients with large RLS at contrast-enhanced transcranial colour Doppler (TCCD) undergoing percutaneous PFO closure with an AMPLATZER device. Residual RLS was evaluated by TCCD three and 12 months after the procedure. PFO closure was successful in all but two patients. At TCCD, a significant residual RLS (grade ≥2) was observed in 27 (21.6%) and 17 (13.6%) patients at three and 12 months, respectively. Larger baseline RLS, presence of atrial septal aneurysm, greater longitudinal and transverse FO dimensions, and use of larger devices were associated with significant residual RLS. At multivariate analysis, the presence of atrial septal aneurysm (OR 7.6; 95% CI: 1.38-42.35; p=0.02) and longitudinal FO dimension >20.8 mm (OR 8.5; 95% CI: 1.55-46.95; p=0.014) were identified as independent predictors of significant residual RLS at 12 months. CONCLUSIONS: Our study suggests that a large FO and the presence of atrial septal aneurysm are independent predictors of persistent residual RLS after PFO closure with AMPLATZER devices.

Temporal changes in standard and tissue Doppler imaging echocardiographic parameters after anthracycline chemotherapy in women with breast cancer.

Anthracyclines are established cardiotoxic agents; however, the exact extent and time course of such cardiotoxicity has not been appraised in detail. We aimed to exploit serial measurements of standard and tissue Doppler imaging (TDI) echocardiographic parameters collected in a prospective clinical trial to clarify the outlook of cardiac function during and long after anthracycline chemotherapy. Women enrolled in a randomized trial focusing on liposomal doxorubicin-based chemotherapy for breast cancer and providing ≥4 separate echocardiographic assessments were included. Repeat-measure nonparametric analyses were used to appraise changes over time in the standard and tissue Doppler imaging echocardiographic parameters. A total of 39 patients with serial imaging evaluations were enrolled. Significant temporal changes were found for the left ventricular ejection fraction and diastolic parameters, despite different temporal trends. Specifically, the left ventricular ejection fraction exhibited a V-shaped trend, decreasing initially from 63% to 61% but then recovering to 64% (p <0.001), with a similar trend in the TDI E/Em ratio (p = 0.011). In contrast, persistent impairments typical of an L-shaped trend were found for the E wave (p = 0.006), TDI lateral Em wave (p = 0.001), and TDI septal Em wave (p = 0.001). In conclusion, subclinical temporal changes in the standard and TDI echocardiographic parameters after anthracycline chemotherapy showed a distinctive pattern of transient impairment followed by full recovery of the left ventricular ejection fraction versus a persistent impairment of the diastolic parameters, which must be taken into account in the everyday treatment of such patients.

Comparative cardiac toxicity of anthracyclines in vitro and in vivo in the mouse.

PURPOSE: The antineoplastic efficacy of anthracyclines is limited by their cardiac toxicity. In this study, we evaluated the toxicity of doxorubicin, non-pegylated liposomal-delivered doxorubicin, and epirubicin in HL-1 adult cardiomyocytes in culture as well as in the mouse in vivo. METHODS: The cardiomyocytes were incubated with the three anthracyclines (1 µM) to assess reactive oxygen generation, DNA damage and apoptotic cell death. CF-1 mice (10/group) received doxorubicin, epirubicin or non-pegylated liposomal-doxorubicin (10 mg/kg) and cardiac function was monitored by Doppler echocardiography to measure left ventricular ejection fraction (LVEF), heart rate (HR) and cardiac output (CO) both prior to and 10 days after drug treatment. RESULTS: In HL-1 cells, non-pegylated liposomal-doxorubicin generated significantly less reactive oxygen species (ROS), as well as less DNA damage and apoptosis activation when compared with doxorubicin and epirubicin. Cultured breast tumor cells showed similar sensitivity to the three anthracyclines. In the healthy mouse, non-pegylated liposomal doxorubicin showed a minimal and non-significant decrease in LVEF with no change in HR or CO, compared to doxorubicin and epirubicin. CONCLUSION: This study provides evidence for reduced cardiac toxicity of non-pegylated-liposomal doxorubicin characterized by attenuation of ROS generation, DNA damage and apoptosis in comparison to epirubicin and doxorubicin.

Echocardiographic guidance of percutaneous patent foramen ovale closure: head-to-head comparison of transesophageal versus rotational intracardiac echocardiography.

BACKGROUND: Transesophageal (TEE) and intracardiac (ICE) echocardiography are commonly used to guide percutaneous patent foramen ovale (PFO) closure. The study aim was to perform a head-to-head comparison between TEE and rotational ICE echocardiography in the measurement of the fossa ovalis and device selection. METHODS: In 45 patients with cryptogenic stroke or peripheral embolism and PFO with large right-to-left shunt, fossa ovalis dimensions were assessed preoperatively by TEE and intraoperatively by rotational ICE. The Amplatzer devices, deployed on the basis of ICE, were compared with those that would have been selected by TEE. RESULTS: A good correlation between TEE and rotational ICE was observed for both longitudinal and transverse fossa ovalis dimensions (TEE four-chamber vs. ICE four-chamber: r = 0.75; TEE bicaval vs. ICE four-chamber: r = 0.77; TEE aorta vs. ICE aorta: r = 0.59; P < 0.001 for all). However, no such correlation was found in 13 patients with atrial septal aneurysm (ASA) (TEE four-chamber vs. ICE four-chamber: r = 0.33; TEE bicaval vs. ICE four-chamber: r = 0.49; TEE aorta vs. ICE aorta: r = 0.05; P = NS for all). At Bland-Altman analysis, slight systematic differences with wide limits of agreement for each comparison were observed, particularly in patients with ASA, suggesting that the two imaging modalities cannot be used interchangeably. As regards device selection, a moderate agreement was found between TEE- and ICE-guided device size (72%, κ = 0.53, P < 0.001), except in patients with ASA (36%, κ = 0.02, P = NS). CONCLUSIONS: Our study suggests a significant disagreement between TEE and rotational ICE in measuring fossa ovalis and selecting the device for PFO closure, particularly in patients with ASA.

Improvement of migraine after patent foramen ovale percutaneous closure in patients with subclinical brain lesions: a case-control study.

OBJECTIVES: We sought to evaluate the benefits on frequency and severity of migraine recurrence after patent foramen ovale (PFO) closure in patients with subclinical brain lesions at magnetic resonance imaging (MRI). BACKGROUND: Migraine improvement has been reported after PFO closure in patients with cerebrovascular symptomatic events. Subclinical brain MRI lesions are detectable in patients with PFO and in migraineurs. METHODS: A total of 82 patients with moderate/severe migraine, PFO, large right-to-left shunt, and subclinical brain MRI lesions were prospectively examined for a 6-month period. Patients were subdivided into closure (n = 53) and control (n = 29) group according to their consent to undergo percutaneous PFO closure. In controls, therapy for migraine was optimized. Six-month frequency and severity of migraine recurrence were compared with baseline. RESULTS: The number of total attacks decreased more in the closure group (32 +/- 9 to 7 +/- 7, p < 0.001) than in the control group (36 +/- 13 to 30 +/- 21, p = NS) (p < 0.001). A significant reduction in disabling attacks was observed only in the closure group (20 +/- 12 to 2 +/- 2, p < 0.001; controls: 15 +/- 12 to 12 +/- 12, p = NS). Migraine disappeared in 34% of the closure group patients and 7% of controls (p = 0.007); >50% reduction of attacks was reported by 87% and 21%, respectively (p < 0.001). Disabling attacks disappeared in 53% of closure group patients and 7% of controls (p < 0.001); >50% reduction occurred in 89% and 17%, respectively (p < 0.001). CONCLUSIONS: In migraineurs with a large PFO and subclinical brain MRI lesions, a significant reduction in frequency and severity of migraine recurrence can be obtained by PFO closure when compared with frequency and severity in controls.

Pulmonary embolism: a late complication of a correctly positioned occluder device for patent foramen ovale.

We describe a patient with pulmonary embolism originating from right atrial thrombosis that developed at least 18 months after patent foramen ovale (PFO) device implantation. On surgical inspection, the PFO device was found to be correctly positioned, stable and well endothelialized. We then hypothesize that current smoker status, double antiplatelet regimen discontinuation and mild hyperhomocysteinaemia may have had a role in determining this severe, unexpected and late complication in this patient.

Clinical and brain magnetic resonance imaging follow-up after percutaneous closure of patent foramen ovale in patients with cryptogenic stroke.

Patent foramen ovale (PFO) closure is reported to result in fewer episodes of clinically manifest recurrent cerebral ischemia than medical treatment. We evaluated by means of magnetic resonance imaging (MRI) whether silent cerebral ischemic episodes are also decreased by PFO closure. Seventy-one patients with PFO were selected for percutaneous closure of PFO at our center. All had PFO with large right-to-left shunt documented by transcranial Doppler ultrasound and transesophageal echocardiography, > or =1 previous stroke or transient ischemic attack with MRI documentation at the index event, and no alternative cause for cerebral ischemia. MRI studies were performed in all patients 24 hours before the procedure and at 1-year follow-up (or before in the case of a suspected new neurologic event). Eight patients (11%) had >1 clinical event before the procedure. Comparing the 2 MRI studies before the procedure, silent ischemic lesions were observed in 14 other patients (20%). Thus, considering clinical and silent events together, >1 event was present at baseline in 22 patients (31%). After PFO closure (follow-up 16 +/- 7 months), 1 recurrent neurologic event occurred (1%, p = 0.02 vs preprocedural clinical events); however, urgent brain MRI results were negative. Moreover, only 1 patient showed 1 new silent lesion at brain MRI at follow-up (1%, p <0.001 vs preprocedural silent brain lesions). Considering clinical and silent events, relapses occurred in 2 patients only (p <0.001 vs before procedure). Recurrent events were limited to those with incomplete PFO closure at postprocedural transcranial Doppler ultrasound (p = 0.02). In conclusion, percutaneous PFO closure results in few clinical or silent events after 1-year follow-up, especially when complete PFO closure is successfully accomplished.

Provisional T-drug-eluting stenting technique for the treatment of bifurcation lesions: clinical, myocardial scintigraphy and (late) coronary angiographic results.

BACKGROUND: Treatment of bifurcation stenoses (BS) by percutaneous coronary intervention (PCI) remains challenging, even with drug-eluting stents (DES). We aimed to appraise clinical, myocardial scintigraphy and late (>9 months) exploratory angiographic outcomes of provisional T-stenting in the management of BS. METHODS: We enrolled 53 consecutive patients with BS in the proximity of a greater than or equal to 2 mm side branch (SB). The provisional T-technique was performed in all cases, with implantation of DES in the main branch (MB), SB balloon-only dilatation, and final kissing in the event of >50% SB stenosis. Provisional SB-stenting (using another DES) was reserved to cases with persisting >50% stenosis/dissection and reduced TIMI flow. Further kissing inflation was recommended in such patients. Stress/rest single-photon emission computed tomography (MIBI) and coronary angiography follow up were scheduled >6 and 9 months after PCI, respectively. RESULTS: Major adverse cardiac events at 14 +/- 3 months occurred in 5 patients (9.4% [95% confidence interval 0.1-17.4%]: 1 (1.9% [0.1-5.8%]) non-Q-wave myocardial infarction for subacute stent thrombosis, 2 (3.8% [0.1-9.0%]) target lesion revascularizations and 2 (3.8% [0.1-9.0%]) target vessel revascularizations. Six-month MIBI was performed in 51 patients (96.3%): 4 patients had positive results (7.8% [0.2-15.4%]). Angiography was performed in 4 of these patients and in another 27 patients, with clinical restenosis occurring overall in only 5 (16.1% [8.9-23.3%]), 1 case of clinical restenosis in the MB (3.2% [0.6-9.4%]), and 4 in the SB (12.9% [5.1-24.9%]). CONCLUSIONS: This study suggests the safety and efficacy of provisional T-drug-eluting stent implantation in bifurcation coronary lesions, and supports the use of follow-up myocardial scintigraphy, with angiography reserved for selected patients and lesions.

Apical ballooning syndrome without myocardial necrosis: proof of concept from a case report.

The "apical ballooning" is a cardiac syndrome characterized by acute extensive but reversible akinesia of the apex and mid part of the left ventricle (LV), without obstructive coronary artery disease (CAD), triggered by emotional or physical stress, accompanied by chest pain and/or dyspnoea, electrocardiographic changes mimicking acute coronary syndromes (ACS), and minimal but, to date, obligatory release of cardiac enzymes. Today the precise aetiology remains unknown, but prognosis is generally excellent. We hereby report a unique case of a 60-year-old woman presenting with transient wide anterolateral akinesia and severe LV dysfunction with persistently normal myocardial markers, despite the extent of wall motion abnormalities. This clinical vignette is the first proof of the concept that timely recognition and management may be able to prevent myocardial necrosis in patients with apical ballooning syndrome.

Lupus anticoagulant and ischemic myocardial microangiopathy in rheumatoid arthritis.

BACKGROUND: A 49-year-old man presented at a hospital with an arthritic flare-up and stress dyspnea with a cough. He had a 5-year history of symmetrical polyarthritis, for which he was prescribed 5-15 mg prednisolone daily. He was subsequently diagnosed with rheumatoid arthritis and prescribed 20 mg methotrexate weekly, 3 mg/kg ciclosporin daily and 5 mg prednisolone daily. Infliximab therapy was initiated after 3 months because of persistent joint pain and inflammation. Six months later, however, the patient was readmitted to hospital with a new arthritic flare-up, acute retrosternal chest pain and stress dyspnea. INVESTIGATIONS: Laboratory analyses, electrocardiography, chest radiography, high-resolution CT, echocardiography, technetium-99m-labeled (99mTc)-methoxyisobutyl-isonitrile stress myocardial scintigraphy and coronary angiography. DIAGNOSIS: Lupus anticoagulant and ischemic myocardial microangiopathy. MANAGEMENT: Drug therapy with prednisolone, methotrexate, anakinra, aspirin and clopidogrel.

Assessment of resting perfusion defects in patients with acute myocardial infarction: comparison of myocardial contrast echocardiography, combined first-pass/delayed contrast-enhanced magnetic resonance imaging and 99mTC-sestamibi SPECT.

BACKGROUND: Information on the accuracy of both magnetic resonance imaging (MRI) and myocardial contrast echocardiography (MCE) for the identification of perfusion defects in patients with acute myocardial infarction is limited. We evaluated the accuracy of MRI and MCE, using Single Photon Emission Computed Tomography (SPECT) imaging as reference technique. METHODS: Fourteen consecutive patients underwent MCE, MRI and 99mTc-MIBI SPECT after acute myocardial infarction to assess myocardial perfusion. MCE was performed by Harmonic Power Angio Mode, with end-systolic triggering 1:4, using i.v. injection of Levovist. First-pass and delayed enhancement MRI was obtained after i.v administration of Gadolinium-DTPA. At MCE, homogeneous perfusion was considered as normal and absent or "patchy" perfusion as abnormal. At MRI, homogenous contrast enhancement was defined as normal whereas hypoenhancement at first-pass followed by hyperenhancement or persisting hypoenhancement in delayed images was defined as abnormal. RESULTS: At MCE 153 (68%) of segments were suitable for analysis compared to 220 (98%) segments at MRI (p<0.001). Sensitivity, specificity and accuracy of MCE for segmental perfusion defects in these 153 segments were 83, 73 and 77%, respectively. Sensitivity, specificity and accuracy of MRI were 63, 82, and 77%, respectively. MCE and MRI showed a moderate agreement with SPECT (k: 0.52 and 0.46, respectively). The agreement between MCE and MRI was better (k: 0.67) that the one of each technique with SPECT. CONCLUSION: MCE and MRI may be clinically useful in the assessment of perfusion defects in patients with acute myocardial infarction, even thought MCE imaging may be difficult to obtain in a considerable proportion of segments when the Intermittent Harmonic Angio Mode is used.

Inaccuracy of dipyridamole echocardiography or scintigraphy for the diagnosis of coronary artery disease in patients with both left bundle branch block and left ventricular dysfunction.

Non-invasive diagnosis of coronary artery disease (CAD) in patients with left ventricular (LV) dysfunction and left bundle branch block (LBBB) remains challenging, and there is no consensus on the role of myocardial sesta-MIBI perfusion scintigraphy with pharmacological stress (dip-MIBI) or dipiridamole echocardiography (dip-ECHO). We thus performed a prospective study to test the diagnostic accuracy of such non-invasive tests. 27 consecutive patients with both LV dysfunction and LBBB undergoing diagnostic work-up for CAD were studied simultaneously with dip-ECHO and dip-MIBI. The sensitivity for CAD for dip-ECHO and dip-MIBI was respectively 42% and 67%, with specificity 93% and 53%, and likelihood ratio (LR)-positive 6.3 and LR-negative 0.6 for both. Given the low accuracy of both dip-ECHO and dip-MIBI in detecting CAD in patients with concomitant LV dysfunction and LBBB, coronary angiography should be performed as the default diagnostic strategy in such patients.

Ischemic cardiomyopathy, left coronary trunk hypoplasia and subsidiary coronary supply from the descending thoracic aorta.

Clinical symptoms of acute or chronic myocardial ischemia due to congenital coronary anomalies occasionally develop during adult life. While several types of coronary anomalies have been already reported, origin of the coronary arteries outside of the ascending aorta and pulmonary trunk is exceedingly rare, and has indeed been described to date only in a 6-day-old newborn. We hereby report to the best of our knowledge the first and unique case of an adult patient with ischemic cardiomyopathy, in whom coronary angiography and aortography disclosed both left main trunk hypoplasia and subsidiary left coronary supply provided by an ectopic artery arising from the descending thoracic aorta.

Coronary vasospasm secondary to hypercholinergic crisis: an iatrogenic cause of acute myocardial infarction in myasthenia gravis.

Patients with myasthenia gravis undergo lifelong treatment with anticholinesterase agents. While the heart is usually unaffected by this disease, clinicians should bear in mind the potential adverse interaction between cardiac function and the underlying myasthenic disease or its specific medications. In the present article we report, to the best of our knowledge for the first time in the literature, a case of vasospastic acute myocardial infarction due to iatrogenic hypercholinergic crisis secondary to anticholinesterase therapy in an elderly female with myasthenia gravis. This clinical vignette emphasizes the importance of taking into account the potential vasospastic effect of anticholinesterase drugs. Indeed, prompt recognition of the pathophysiology of myocardial ischemia due to iatrogenic hypercholinergic crisis is pivotal to the timely and appropriate management of this medical emergency, as well as prevention of future recurrences.