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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.

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,p1190/24h 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.

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.

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 50% reduction of attacks was reported by 87% and 21%, respectively (p 50% reduction occurred in 89% and 17%, respectively (p 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.

Rheumatoid arthritis (RA) is associated with an increased risk of myocardial infarction and congestive heart failure. In RA patients, elevated NT-proBNP levels have been reported to be a prognostic marker of left ventricular dysfunction. In this study, we evaluated cardiorespiratory functional capacity and NT-proBNP levels before and during cardiopulmonary exercise test in early RA (ERA) patients. Twenty ERA patients and 10 healthy controls were studied by color Doppler echocardiography to evaluate ventricular systolic and diastolic function. Arterial stiffness and wave reflections were quantified non-invasively using applanation tonometry of the radial artery. Cardiopulmonary treadmill test was performed to measure peak VO2 and VE/VCO2 parameters. NT-proBNP plasma levels were measured before and at the exercise peak during cardiopulmonary exercise. The peak oxygen uptake [VO2 (ml/min/kg)], the ventilatory equivalents for carbon dioxide (EqCO2), respiratory exchange ratio and arterial stiffness were similar between patients and controls during cardiopulmonary exercise test. Basal and peak cardiopulmonary exercise NT-proBNP plasma levels were comparable in ERA patients with respect to healthy controls. When we analyzed patients according to disease characteristics and cardiovascular risk factors, ERA patients with high disease activity, BMI > 25 kg/m2 and ACPA positivity presented significantly higher baseline and exercise peak NT-proBNP levels. Cardiorespiratory function is preserved in patients with recent onset of rheumatoid arthritis. The increased basal and exercise peak NT-proBNP plasma levels in patients with negative disease prognostic factors represent a possible marker to stratify the cardiovascular risk in patients with early rheumatoid arthritis.

Preeclampsia is characterized by hypertension, proteinuria, and edema occurring in the second half of pregnancy. The main ocular manifestations are related to dysfunction of both retinal and choroidal circulation [1, 2]. Similarly to hypertensive retinopathy, cotton wool spots, hemorrhages, edema, papilloedema, serous retinal detachment and lesions of the retinal pigment epithelium (RPE) may develop in preeclampsia. Fluorescein angiography shows areas of choroidal hypoand nonperfusion (Elschnig spots) in preeclamptic women with serous retinal detachment [3, 4]. It has been proposed that intense spasm of the choroidal arterioles may be responsible for choroidal ischemia, resulting in increased vascular permeability, and subsequently, accumulation of serous fluid in the subretinal space [4]. We investigate the changes in the outer retina and choroid by means of enhanced depth imaging (EDI) [5] spectral-domain optical coherence tomography (SD-OCT) in a preeclamptic women with serous retinal detachment. A 38-year-old woman developed hypertension (190/ 110 mmHg), proteinuria, and generalized edema in the 35th week of pregnancy. Two days after undergoing a cesarean section, the patient was referred to our department for impairment of vision in both eyes. Best-corrected visual acuity was 20/25 in the right eye (RE) and 20/80 in the left eye (LE). Fundus biomicroscopy showed a peripapillary serous retinal detachment bilaterally, with involvement of the LE macula. Blue fundus autofluorescence (b-FAF) showed inhomogeneous increased autofluorescence in the peripapillary area, while near-infrared fundus autofluorescence (nirFAF) revealed peripapillary areas of hypoautofluorescence together with focal points of intensely decreased nir-FAF (Fig. 1). EDI SD-OCT scans through the areas of abnormal autofluorescence and the macula showed peripapillary serous retinal detachment bilaterally with focal RPE elevations, and serous macular detachment in the LE (Fig. 2). Choroidal thickness in the scan passing through the macula was 475 lm RE, 361 lm LE subfoveally, and 263 lm RE, 367 lm LE in the peripapillary area (Fig. 2) (increased compared with reference values) [5]. Two weeks later, BCVA improved to 20/20 in both eyes, and fundus biomicroscopy revealed disappearance of serous retinal detachment. b-FAF still showed increased autofluorescence in the peripapillary area, while nir-FAF revealed almost complete disappearance of both peripapillary areas of hypoautofluorescence and focal points of decreased nir-FAF (Fig. 1). EDI SD-OCT scans confirmed the disappearance of serous retinal detachment in both eyes, and showed persistence of focal RPE elevations (Fig. 2). Choroidal thickness in the scan passing through the macula was unchanged subfoveally, while decreased to 186 lm RE, 284 lm LE in the peripapillary area (Fig. 2). Previous reports have documented, by time domain OCT, the presence of serous retinal detachment in preeclamptic women [6]. To the best of our knowledge this is the first case study to describe the SD-OCT features of serous retinal detachment in preeclampsia. SD-OCT revealed focal RPE elevations in the peripapillary areas of abnormal FAF (both b-FAF and nir-FAF) suggesting compromised fluid transport (choroid-RPE-retina) in the acute phase of the disease, which persisted also after the resolution of both serous retinal detachment and focal L. Querques G. Querques (&) F. Loperfido R. Lattanzio F. Bandello Department of Ophthalmology, University Vita Salute San Raffaele, Via Olgettina 60, 20132 Milan, Italy e-mail: giuseppe.querques@hotmail.it

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.

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.

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

Objective. We evaluated dobutamine stress electrocardiography for detecting potentially reversible contractile dysfunction or residual ischemia in the infarct-related area. Background. ST-T segment changes in pathologic Q wave leads during stress testing may reflect contractile reserve, inducible ischemia or passive mechanical stretching. Dobutamine echocardiography allows detection of contractile reserve at low doses and inducible ischemia at high doses. Methods. We used low (5 to 10 μg/kg body weight per min) and high doses (20 to 40 μg/kg per min) of dobutamine in 49 patients with a previous Q wave myocardial infarction and analyzed the relation between ST-T segment changes in pathologic Q wave leads and regional contraction. Results. At low dose dobutamine, regional contraction improved in the infarct-related area in 23 patients. New or further ST segment elevation and pseudonormalization of negative T waves developed at low doses more frequently in patients with than without contractile reserve (both p < 0.001), giving a sensitivity of 43.5% and 60.9% and a specificity of 100% and 96.2%, respectively. At high dose dobutamine (43 patients), new or further ST segment elevation and pseudonormalization of negative T waves, occurring beyond those observed at low doses, lead a low predictive accuracy for contractile reserve (sensitivity of 9.5% and 14.3% and specificity of 68.2% and 81.8%, respectively). Pseudonormalization of negative T waves at high dose dobutamine was 100% specific (but only 25% sensitive) for homozonal ischemia. Conclusions. ST segment elevation or pseudonormalization of negative T waves, or both, is indicative of contractile reserve in the infarct-related area when either develops at low dose dobutamine, but may be associated with worsening or no change in contractile function at high doses.

The purpose of this study was to assess endothelium-mediated vasodilation in the peripheral circulation of patients with coronary artery disease who are free from hypertension, hypercholesterolemia, diabetes mellitus, and congestive heart failure. The vascular response of the superficial femoral artery to an endothelium-dependent (i.e., acetylcholine 10-7, 10-6, and 10-5 mol/L) and to an endothelium-independent (i.e., nitroglycerin 10-8 and 10-6 mol/L) dilator was compared in 13 patients with angiographically documented coronary artery disease and in 7 patients with normal coronary angiograms. Vascular response was assessed by Doppler ultrasonography. Whereas the vascular responses to nitroglycerin in patients with abnormal and normal findings on coronary angiograms were similar, the responses to acetylcholine were clearly different. The ratio of mean blood flow velocity (+/-SD) measured during administration of acetylcholine 10-6 mol/L and mannitol was significantly lower in patients with abnormal versus normal results of coronary angiography (1.15 +/- 0.35 vs 2.20 +/- 1.06; p0.05). The vascular response to acetylcholine 10-5 mol/L in patients with an abnormal finding on their coronary angiogram was highly variable when compared with that in patients with normal results. Thus, in patients with angiographically proven coronary artery disease, the response of the peripheral circulation to acetylcholine is characterized by a great variability and a reduced sensitivity, when compared with that in patients with normal findings on coronary angiography.

To validate color Doppler ultrasonography of renal arteries for the assessment of renal blood flow (RBF), we compared left and right RBF estimates and their sum (total RBF) by echo-Doppler with data obtained by iodine 123-123I-p-aminohippuric acid (PAH) scintigraphy in 19 patients with heart failure and 7 normal control subjects. Single-side and total RBF estimates by echo-Doppler ranged, respectively, between 179 and 428 mL/min/m2 and from 378 to 835 mL/min/m2 in patients with heart failure and between 265 and 601 mL/min/m2 and from 564 to 1,182 mL/min/m2 in normal control subjects. Single-side and total RBF estimates by echo-Doppler correlated well with measurements obtained by scintigraphy (r = 0.74 and 0.76, respectively, in patients with heart failure; both: p0.001). At Bland and Altman's analysis of correspondence between the 2 techniques, there were 17 disagreements (33.7%) for single-side RBF and 8 disagreements (31.8%) for total RBF. However, the two techniques disagreed markedly in only two single-side and one total RBF estimates. Thus, in patients with heart failure, RBF assessed noninvasively by color Doppler ultrasonography has a good correlation with 123I-PAH renal scintigraphy data over a wide range of blood flow.

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.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.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; P0.001 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, P0.001), except in patients with ASA (36%, κ = 0.02, P = NS).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.

Myocardial hypertrophy and interstitial fibrosis are common in acromegalic hearts and may induce left ventricular (LV) dysfunction. The transmitral flow pattern was examined by pulsed-wave Doppler in 20 patients with active acromegaly and nine with acromegaly cured by pituitary microsurgery. Control groups consisted of 25 normal subjects and 13 patients with systemic hypertension. We related Doppler indices of LV filling (E and A peak velocities and E/A ratio) to the duration of acromegalic disease, the GH plasma levels and LV mass. The LV mass/BSA was significantly greater in active acromegaly (187 ±53 g/sq m) and systemic hypertension groups (161 ±48 g/sq m) than in cured acromegaly (125 ±35 g/sq m) and the normal control group (109 ±36 g/sq m) (p .

A catecholamine-induced dilated cardiomyopathy is reported in a patient with multiple endocrine neoplasia, type 3. A histologic and ultrastructural study has been undertaken in cardiac biopsy samples, together with determination of myocardial Ca++ and cellular membrane fatty acids. Contraction band necrosis of cardiocytes with supercontraction of sarcomeres progressing to myofibrolysis and increased levels of myocardial Ca++ have been found as morphologic and biochemical abnormalities, respectively. No lipoperoxidation of cellular membranes or an α-adrenergic mediated reduction of coronary supply could be recognized in the study. We indicate a receptor-mediated intracellular Ca++ overload as the main abnormality responsible for myocardial impairment.

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).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.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.The number of total attacks decreased more in the closure group (32 +/- 9 to 7 +/- 7, p0.001) than in the control group (36 +/- 13 to 30 +/- 21, p = NS) (p0.001). A significant reduction in disabling attacks was observed only in the closure group (20 +/- 12 to 2 +/- 2, p0.001; 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 (p0.001). Disabling attacks disappeared in 53% of closure group patients and 7% of controls (p0.001);50% reduction occurred in 89% and 17%, respectively (p0.001).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.

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.

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.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 of50% SB stenosis. Provisional SB-stenting (using another DES) was reserved to cases with persisting50% 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 scheduled6 and 9 months after PCI, respectively.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%]).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.

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.

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.

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. 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. At MCE 153 (68%) of segments were suitable for analysis compared to 220 (98%) segments at MRI (p

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.

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.

In a patient with obstructive left atrial myxoma, we analyzed by pulsed Doppler echocardiography the flow pattern through the mitral valve and in the pulmonary veins. Two mitral flow patterns were observed: the first was present near the medial commissure and along the anterior leaflet and was characterized by the absence of mid-to-late diastolic filling flow; the second was found near the lateral commissure and was characterized by the obstruction of mid-to-late diastolic filling flow, mimicking mitral stenosis. The pulmonary vein flow showed brief and rapidly decelerating anterograde diastolic flow wave and an early systolic retrograde flow wave. These waves were respectively related to the diastolic forward and the systolic backward movement of the tumor. This case report shows that pulmonary vein flow analysis may give new insights into left atrial filling and emptying dynamics in left atrial myxoma.

To evaluate dipyridamole stress echocardiography (DSE) for predicting coronary artery diseases (CADs) in patients with complete left bundle-branch block (LBBB).Comparison of DSE and dipyridamole sestamibi myocardial perfusion scintigraphy (sestamibi).Tertiary-care cardiac referral center.Fifty-four consecutive patients (26 men; mean [+/- SD] age, 59 +/- 7 years) with complete LBBB (14 patients with left ventricular [LV] dilatation) and intermediate probability of CAD.Simultaneous single photon emission CT scan (20 mCi technetium Tc 99m stress/rest sestamibi) and echocardiography (second harmonic imaging) during a two-step (0.56 to 0.84 mg/kg) dipyridamole infusion protocol. Two sestamibi readings were performed. The first reading considered only those studies with reversible defects (sestamibi-1) to be positive. The second reading considered those studies with any defect (sestamibi-2) to be positive. CAD was defined as aor= 50% reduction in diameter in at least one major vessel seen on coronary angiography.CAD was present in 17 patients (31.5%). The global predictive accuracy for CAD was significantly higher for DSE (87.0%) and sestamibi-1 (79.6%) than for sestamibi-2 (57.4%) [p0.01 vs DSE; p0.05 vs sestamibi-1]. No significant differences in sensitivity were present, but specificity was significantly higher for DSE (94.6%) and sestamibi-1 (81.1%) than for sestamibi-2 (43.2%; p0.01 vs both the other two tests). Of 14 patients with LV dilatation, 26.8% were falsely positive for CAD (in some cases for posterior defects) as determined by sestamibi-1 and 64.3% were falsely positive for CAD by sestamibi-2 vs none by DSE.DSE is at least as accurate as dipyridamole sestamibi scintigraphy for predicting CAD in patients with complete LBBB and tends to be more specific in those patients with underlying LV dilatation.

Detection of contractile reserve is important in heart failure patients. To determine if detection of contractile reserve is influenced by neuroadrenergic activation, we examined the relation between dobutamine stress echocardiography (DSE) findings and plasma norepinephrine levels (NE) at rest in 35 patients with nonischemic left ventricular (LV) dysfunction (New York Heart Association classIII in all; LV ejection fraction 0.27 +/- 0.5). Changes in global wall motion score (WMS), and separately in WMS of hypokinetic segments and akinetic segments, were analyzed. A patient was considered to be responsive to dobutamine if the change in global WMS was/=4. Twenty-three patients were responsive and 12 were not responsive to dobutamine. Plasma NE and baseline heart rate were significantly higher in nonresponsive patients (p0.001). Changes in global WMS and in hypokinetic segment WMS were inversely related to either plasma NE (r -0.68 and -0.67, respectively) or baseline heart rate (r -0.60 and -0.66, respectively). The change in akinetic segment WMS was related to plasma NE only (r -0.50). Changes in WMS were not related to age, diastolic and systolic LV volume, baseline global WMS, or number of akinetic segments at baseline. Plasma NE602 pg/ml predicted a blunted or absent contractile reserve at DSE (sensitivity 92%; specificity 87%). Neuroadrenergic activation may influence contractile reserve found at DSE in patients with heart failure due to nonischemic LV dysfunction.

sclerosis patients. Alternative Therap Health Med 1996;2:75–79. 8. Wallace RK, Benson H, Wilson AF. A wakeful hypometabolic state. Am J Phys 1971;3:795–799. 9. Benson H, Malhoutra M, Goldman R, Jacobs G, Hopkins P. Three case reports of the metabolic and electroencephalographic changes during advance Buddhist meditation techniques. Behav Med 1990;16:90–95. 10. Ornish D, Scherwitz LW, Doody RS, et al. Effect of stress management training and dietary changes in treating ischemic heart disease. JAMA 1983;249: 54–59. 11. Rector TS, Kubo SH, Cohn JN. Patients’ self-assessment of their congestive heart failure. Part 2: Content reliability and validity of a new measure, the Minnesota Living with Heart Failure questionnaire. Heart Failure 1987;198– 209. 12. Guyatt GH. Thompson PJ. Berman LB, Sullivan M, Townsend M, Jones N, Pugseey S. How should we measure function in patients with chronic heart and lung disease? J Chronic Dis 1985;38:517–524. 13. McGavin CR, Artvinli M, Naol H. Dyspnea, disability and distance walked: comparison of extimates of exercise performance in respiratory disease. BMJ 1978;2:241–243. 14. Mahler DA, Weinberg DH, Wells CK, Feinstein AR. The measurement of dyspnea: contents, interobserver agreement and physiologic correlates of two new clinical indexes. Chest 1984;85:751–58. 15. Borg GAV. Psychophysical bases of perceived exertion. Med Sci Sports Exerc 1982;14:377–381. 16. Epstein G, Barrett EAM, Halper JP, Seriff NS, et al. Alleviating asthma with mental imagery: a phenomenological approach. Alternative Complement Therap1997. 17. Cohn J, Goldstein S, Greenberg B, Lorell B, Bourge R, Jaski B, Gottlieb S, McGrew F, DeMets D, White B. A dose-dependent increase in mortality with vesnarinone among patients with severe heart failure. N Eng J Med 1998;339: 1810–1816. 18. Kubo S, Gollub S, Bourge R, Rahko P, Cobb F, Jessup M, Brozena S, Brodsky M, Kirlin D, Shanes J. Beneficial effects of pimobendan on exercise tolerance and quality of life in patients with heart failure. Results of a multicenter trial. Circulation 1992;85:942–999. 19. Konstam V, Salem D, Pouleur H, Kostis J, Gorkin L, Shumaker S, Mottard I, Woods P, Konstam M, Yusuf S. Baseline quality of life as a predictor of mortality and hospitalization in 5,025 patients with congestive heart failure. Am J Cardiol 196;78:890–895. 20. Epstein G. Healing Visualizations: Creating Health Through Imagery. New York: Bantam, 1989.

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.

Patients with advanced peripheral vascular disease have an increased cardiac morbidity and mortality. The aim of this study was to assess the predictive value of rest and stress echocardiography for perioperative and late cardiac events in 110 patients undergoing limb revascularization. All patients underwent preoperative clinical and echocardiographic evaluation at rest and by dipyridamole stress testing to assess cardiac risk. Patients with > or =3 clinical Eagle markers, low left ventricular ejection fraction at rest, or positive dipyridamole stress test results were considered at high cardiac risk. To record adverse cardiac events, all patients were monitored during and after surgery, and followed for at least 1 year after hospital discharge. Cardiac complications occurred in 10 patients (9.7%) perioperatively (2 fatal myocardial infarctions), and in 13 (13%) at 1-year follow-up (7 fatal myocardial infarctions). Echocardiographic evaluation was the best predictor of early (p

Pulsed-wave Doppler ultrasonography is widely used to noninvasively diagnose renal artery stenosis. The use of steerable continuous-wave Doppler has never been tested. We compared pulsed and steerable continuous-wave Doppler ultrasonography, demonstrating that although both methods are highly sensitive for severe stenoses, continuous-wave Doppler shows a better sensitivity for mild to moderate stenoses.

We sought to investigate the effects of revascularization on the contractile reserve of dysfunctional myocardium.The improvement in dysfunctional but viable myocardium after revascularization is frequently less than expected from the amount of contractile reserve detected on dobutamine stress echocardiography. The fate of the contractile reserve, when it does not result in an adequate contractile recovery, is unknown.Basal contraction and contractile reserve of infarct zones were assessed by dobutamine stress echocardiography in 21 postinfarction male patients before and3 months after revascularization (30 infarct zones; mean +/- SD left ventricular ejection fraction 35 +/- 8%). An infarct zone wall motion score index (WMSI) was calculated.Before revascularization, contractile reserve was present in 14 infarct zones (12 patients) and absent in 16 (9 patients). After revascularization, ejection fraction increased by 5 +/- 4% (p0.01) in patients classified as positive for contractile reserve and remained unchanged in those classified as negative. New York Heart Association classification improved in 58.3% and 22.2% of patients, respectively. Basal contraction improved in eight zones with previous contractile reserve (57.1%) and in one zone without (6.3%) (p0.01). Contractile reserve was still evident in 13 zones with previous contractile reserve (93%; 8 with contractile recovery), and it developed in 6 zones without (38%; none with contractile recovery). WMSI values after revascularization were decreased from values before revascularization during low dose dobutamine in zones with and without previous contractile reserve (p0.01 and0.05, respectively).After revascularization, contractile reserve is maintained or even increases in viable infarct zones that do not recover as expected. It may also develop in some infarct zones judged not to be viable before revascularization. This increased contractile reserve may play a role in the functional improvement of patients after revascularization.

To distinguish between ischemic and nonischemic dilated cardiomyopathy (DCM), we studied 43 patients with left ventricular dysfunction (15 ischemic and 28 nonischemic detected by coronary angiography) by dobutamine stress echocardiography. At rest, there were more normal segments (p

Mitral regurgitation (MR) was evaluated by color Doppler echocardiography during percutaneous transluminal coronary angioplasty (PTCA) in 28 patients with one-vessel artery disease (left anterior descending artery in 11, right coronary artery in 8, and circumflex artery in 9) and normal left ventricular function. In all three groups, left ventricular ejection fraction (LVEF) and wall motion score index (WMSI) decreased significantly during artery occlusion in comparison with baseline values (no differences among various groups). Anterior and inferior akinesia/dyskinesia was observed in all patients during left anterior descending and right coronary artery occlusion, respectively. Lateral akinesia/dyskinesia was induced by occlusion of the circumflex artery in six patients (all with proximal lesions [p0.05 vs the other two groups]) and the right coronary artery in one. Only the six patients with circumflex artery occlusion showed PTCA-related MR (2+ in two). LVEF and WMSI were similar during artery occlusion in patients with and without MR. Neither mitral leaflet prolapse nor anulus dilation occurred during PTCA in any of the patients. Our data show that during brief occlusion of the proximal circumflex artery, functional MR (usually mild) frequently occurs in relation to specific lateral akinesia/dyskinesia.

Systemic emboli occur in dilated cardiomyopathy (DC) at an annual rate of about 4%. 1 Left ventricular thrombus is often considered the source for embolic events in DC. 2 A relation between left ventricular thrombi and rate of embolic events, however, has not been found in a recent study. 3 Left atrial thrombi may constitute an alternative source for systemic embolism in DC. 4

We examined the relation between left ventricular (LV) flow dynamics measured by color Doppler, and either global or regional LV function in 19 normal subjects (group 1), in 55 patients with old myocardial infarction (MI) (29 without [group 2] and 26 with LV aneurysm [group 3]), and in 16 with idiopathic dilated cardiomyopathy (group 4). We calculated by M-mode color Doppler a flow persistence index (FPI) (duration of flow directed in systole toward the apex/LV ejection time). Contrast echocardiography was performed as a control method in 14 patients of the four groups. In normal subjects, rapid systolic inversion of flow toward the aorta was evident (FPI: 0.11 +/- 0.16). In all but one patient in group 2, a similar LV flow pattern was observed, but FPI was greater (0.32 +/- 0.26). In groups 3 and 4, a paradoxical antegrade LV flow pattern was evident during the entire period of systole (FPI: 1.13 +/- 0.42 and 1.28 +/- 0.36, respectively). LV flow patterns were reproduced in echo-contrast studies. FPI was related to LV end-diastolic volume (r = 0.77), end-systolic volume (r = 0.82), and ejection fraction (r = -0.84). However, when data were analyzed separately in the different groups, these correlations were significant only in groups 2 and 3. Paradoxical flow pattern is not peculiar to regional LV dysfunction; it also occurs in global LV dysfunction. This LV flow abnormality may develop after MI even in the absence of severe LV dyssynergy or dilation, and is quantitatively related to the degree of LV dysfunction.

The electrocardiographic and echocardiographic (M-mode) data were analyzed in 29 patients affected by mitral or combined mitral and aortic valve disease and with hemodynamically documented biventricular overload. No electrocardiographic parameter significantly correlated with the left ventricular internal dimension at end diastole (LVIDd), the left posterior wall (LVPW) thickness and the left ventricular mass (LV mass). A significant correlation was observed between the R/S ratio in V1 and V2, the rV1 and either the end-diastolic right ventricular internal dimension (RVIDs) or the pulmonary artery systolic pressure (PASP). The R/S ratio greater than or equal to 1 in V1 was the most sensitive among the conventional electrocardiographic criteria of right ventricular enlargement. Three groups of patients were selected on the basis of RVIDd and LV mass: Group A included nine patients with right ventricular dilatation and normal LV mass; Group B included ten patients without right ventricular dilatation and with increased LV mass; Group C included ten patients without right ventricular dilatation and with normal LV mass. The R/S ratio in V1 was significantly greater in patients in group A than in those in groups B or C. No electrocardiographic parameter was found to be significantly different between groups B and C. When only LV mass was considered (independently from RVId and PASP), no electrocardiographic parameter differentiated patients with LV mass greater than 203 g from those with LV mass less than 203 g. We conclude that in patients with biventricular overload secondary to acquired valvular disease: 1) the electrocardiographic diagnosis of left ventricular enlargement is unreliable; and 2) the R/S ratio in V1 is the most sensitive parameter to predict right ventricular enlargement or severe pulmonary hypertension.

Pulsed Doppler echocardiography was tested to assess the degree of tricuspid regurgitation (TR), classified by right ventriculography, in 47 patients. Forty-eight subjects without TR served as controls (39 with sinus rhythm and 9 with atrial fibrillation). Two Doppler methods were used: the distance of systolic turbulence within right atrium from the tricuspid plane and the quantitative analysis of the flow-velocity traces from the hepatic veins (HVs). Right atrial systolic turbulence was found in 41 of 47 patients with TR and in none of the control subjects, and moderately correlated with the angiographic grading (r = 0.57). In control subjects, TR flow-velocity traces from the HVs showed 2 anterograde flow waves, systolic and diastolic. The ratio of anterograde systolic/anterograde diastolic velocity was more than 0.6 in 38 subjects with sinus rhythm and in 8 with atrial fibrillation. Twenty-two control subjects had a positive wave (designated as "v") coincident with the end of T wave. In 30 patients with TR, a retrograde holosystolic wave was present. Of the remaining patients, 12 had a ratio of anterograde systolic/anterograde diastolic velocity less than 0.6. Fifteen had an end-systolic "v-like" wave, which occurred earlier than the v wave in control subjects (p less than 0.001). In patients with TR, maximal velocities of the anterograde diastolic and retrograde systolic flow correlated with angiographic grading (r = 0.74 and 0.73, respectively). An anterograde diastolic flow velocity more than 26 cm/s and a retrograde systolic flow velocity more than 16 cm/s excluded mild TR. Analysis of Doppler recordings of the HVs is valuable to semiquantitatively assess TR, complementing the right atrial Doppler findings.