Age-related burden and characteristics of embolic stroke of undetermined source in the real world clinical practice.

Few data are available on age-related burden and characteristics of embolic stroke of undetermined source (ESUS) in the real world clinical practice. The aim of our study was to provide information about it. We retrospectively analyzed data of patients consecutively admitted to our Stroke Unit along 1 year (2017, November 1st-2018, October 31st). The etiology of ischemic stroke was defined at hospital discharge; ESUS was considered as a subset of cryptogenic stroke, and defined according to the 2014 international criteria. In the analyzed period, 306 patients, 52.3% females, mean age ± SD 77.9 ± 11.9 years, were discharged with diagnosis of ischemic stroke. Ischemic strokes of cardioembolic and lacunar origin were the most frequent subtypes: 30.1% and 29.4%, respectively. Cardioembolic strokes were particularly frequent in patients ≥ 75 years, and almost always associated with atrial fibrillation. Overall, in 80 patients (26.1%) the etiology of stroke was undetermined; in 25 (8.2%) it remained undefined because of death or severe comorbidity, making further diagnostic work-up not worthy. Cryptogenic stroke occurred in 55 patients (18%), and ESUS criteria were satisfied in 39 of them (12.7%). According to age, cryptogenic stroke was diagnosed in 21.1% (21.1% ESUS) of patients < 65 years, 24.2% (19.4% ESUS) of patients aged 65-74 years, 15.5% (9.2% ESUS) of patients ≥ 75 years. After diagnostic work-up, patent foramen ovale was most commonly associated with ESUS (17.9%), especially in patients < 65 years (62.5%); covert paroxysmal atrial fibrillation was detected in 10.5% of ESUS patients ≥ 75 years. In the real world clinical practice, the frequency of ischemic strokes of undetermined etiology, and of those satisfying ESUS criteria, is not negligible, especially in younger patients. A thorough diagnostic work-up, with an age-specific approach, is therefore necessary and of the utmost importance for the identification of stroke etiology, in order to optimize secondary stroke prevention strategies.

Case report: Germline POT1 mutation in a patient with GIST and lung adenocarcinoma.

The gene protection of telomere 1 (POT1) is involved in telomere maintenance and stability and plays a crucial role in the preservation of genomic stability. POT1 is considered a high-penetrance melanoma susceptibility gene; however, the number of cancer types associated with the pathogenic germline variants of POT1 is gradually increasing, including chronic lymphocytic leukemia (CLL), angiosarcomas, and gliomas, even though many associations are still elusive. Here, we reported a case of a 60-year-old man who showed early-onset multiple neoplasms, including multiple melanomas, gastrointestinal stromal tumor (GIST), and lung adenocarcinoma. Next-generation sequencing (NGS) analyses revealed a germline heterozygous pathogenic variant in the POT1 gene. Notably, GIST and lung adenocarcinoma were not previously reported in association with the POT1 germline variant. Lung cancer susceptibility syndrome is very rare and the actual knowledge is limited to a few genes although major genetic factors are unidentified. Recently, genome-wide association studies (GWAS) have pointed out an association between POT1 variants and lung cancer. This case report highlights the clinical relevance of POT1 alterations, particularly their potential involvement in lung cancer. It also suggests that POT1 testing may be warranted in patients with familial cancer syndrome, particularly those with a history of melanoma and other solid tumors.

Impact of High-to-Moderate Penetrance Genes on Genetic Testing: Looking over Breast Cancer.

Breast cancer (BC) is the most common cancer and the leading cause of cancer death in women worldwide. Since the discovery of the highly penetrant susceptibility genes BRCA1 and BRCA2, many other predisposition genes that confer a moderate risk of BC have been identified. Advances in multigene panel testing have allowed the simultaneous sequencing of BRCA1/2 with these genes in a cost-effective way. Germline DNA from 521 cases with BC fulfilling diagnostic criteria for hereditary BC were screened with multigene NGS testing. Pathogenic (PVs) and likely pathogenic (LPVs) variants in moderate penetrance genes were identified in 15 out of 521 patients (2.9%), including 2 missense, 7 non-sense, 1 indel, and 3 splice variants, as well as two different exon deletions, as follows: ATM (n = 4), CHEK2 (n = 5), PALB2 (n = 2), RAD51C (n = 1), and RAD51D (n = 3). Moreover, the segregation analysis of PVs and LPVs into first-degree relatives allowed the detection of CHEK2 variant carriers diagnosed with in situ melanoma and clear cell renal cell carcinoma (ccRCC), respectively. Extended testing beyond BRCA1/2 identified PVs and LPVs in a further 2.9% of BC patients. In conclusion, panel testing yields more accurate genetic information for appropriate counselling, risk management, and preventive options than assessing BRCA1/2 alone.

Predictive Factors for Hemorrhagic Transformation in Acute Ischemic Stroke in the REAL-World Clinical Practice.

BACKGROUND: Few data exists on predictive factors of hemorrhagic transformation (HT) in real-world acute ischemic stroke patients. The aims of this study were: (i) to identify predictive variables of HT (ii) to develop a score for predicting HT. METHODS: We retrospectively analyzed the clinical, radiographic, and laboratory data of patients with acute ischemic stroke consecutively admitted to our Stroke Unit along two years. Patients with HT were compared with those without HT. A multivariate logistic regression analysis was performed to identify independent predictors of HT on CT scan at 24 hours to develop a practical score. RESULTS: The study population consisted of 564 patients with mean age 77.5±11.8 years. Fifty-two patients (9.2%) showed HT on brain CT at 24 hours (4.9% symptomatic). NIHSS score ≥8 at Stroke Unit admission (3 points), cardioembolic etiology (2 points), acute revascularization by systemic thrombolysis and/or mechanical thrombectomy (1 point), history of previous TIA/stroke (1 point), and major vessel occlusion (1 point) were found independent risk factors of HT and were included in the score (Hemorrhagic Transformation Empoli score (HTE)). The predictive power of HTE score was good with an AUC of 0.785 (95% CI: 0.749-0.818). Compared with 5 HT predictive scores proposed in the literature (THRIVE, SPAN-100, MSS, GRASPS, SITS-SIC), the HTE score significantly better predicted HT. CONCLUSIONS: NIHSS score ≥8 at Stroke Unit admission, cardioembolism, urgent revascularization, previous TIA/stroke, and major vessel occlusion were independent predictors of HT. The HTE score has a good predictive power for HT. Prospective studies are warranted.

Beyond BRCA1/2: Homologous Recombination Repair Genetic Profile in a Large Cohort of Apulian Ovarian Cancers.

BACKGROUND: Pathogenic variants in homologous recombination repair (HRR) genes other than BRCA1/2 have been associated with a high risk of ovarian cancer (OC). In current clinical practice, genetic testing is generally limited to BRCA1/2. Herein, we investigated the mutational status of both BRCA1/2 and 5 HRR genes in 69 unselected OC, evaluating the advantage of multigene panel testing in everyday clinical practice. METHODS: We analyzed 69 epithelial OC samples using an NGS custom multigene panel of the 5 HRR pathways genes, beyond the genetic screening routine of BRCA1/2 testing. RESULTS: Overall, 19 pathogenic variants (27.5%) were detected. The majority (21.7%) of patients displayed a deleterious mutation in BRCA1/2, whereas 5.8% harbored a pathogenic variant in one of the HRR genes. Additionally, there were 14 (20.3%) uncertain significant variants (VUS). The assessment of germline mutational status showed that a small number of variants (five) were not detected in the corresponding blood sample. Notably, we detected one BRIP1 and four BRCA1/2 deleterious variants in the low-grade serous and endometrioid histology OC, respectively. CONCLUSION: We demonstrate that using a multigene panel beyond BRCA1/2 improves the diagnostic yield in OC testing, and it could produce clinically relevant results.

Spondylodiscitis in hemodialysis patients: a new emerging disease? Data from an Italian Center.

Hemodialysis (HD) patients are at high risk for infectious complications such as spondylodiscitis. The aim of this retrospective study was to evaluate the cases of infective spondylodiscitis occurred between May 2005 and October 2019 among HD patients at our center. In 14 years, there were 9 cases (mean age 69±12 years). The main comorbidities found were diabetes mellitus (55.6% of patients), hypertension (55.6%), bone diseases (22.2%), cancer (11.1%) and rheumatoid arthritis treated with steroids (11.1%). The clinical onset included back pain (100% of cases), fever (55.6%), neurological deficits (33.4%), leukocytosis (55.6%) and elevated CRP level (88.9%). Most cases were diagnosed by magnetic resonance imaging (66.7%) with more frequent involvement of lumbar region (77.8%). Blood cultures were positive in five patients (mostly for S. aureus); three of them used catheters as vascular access and, in two cases, their removal was necessary. The mean time interval between the onset of symptoms and the diagnosis was 34±42 days. All patients received antibiotic treatment for a mean duration of 6 weeks; most cases were initially treated with vancomycin or teicoplanin plus ciprofloxacin. Most patients (77.8%) recovered after a mean of 3.5 months; one patient had a relapse after 2 years and one patient had long-term neurologic sequelae. Infective spondylodiscitis in HD must be suspected in the presence of back pain, even in the absence of fever or traditional risk factors. An early diagnosis could improve the outcome. Close monitoring of vascular access, disinfection procedures and aseptic techniques are important to avoid this complication.

Case report: the thoracoscopic surgery in peritoneal-pleural leakage. A valid therapeutic strategy.

Pleuro-peritoneal leakage is an uncommon complication of peritoneal dialysis (PD). In this study, we report the case of a male patient (age 83), treated with PD (daytime single-exchange). In October 2019, hospitalization was necessary due to dyspnoea and a reduction of peritoneal ultrafiltration. A right pleural leakage resulted at chest x-ray. A regression of the pleural leakage was immediately observed after interrupting PD. It was then performed a pleuro-peritoneal CT scan at baseline, followed by a second scan performed 4 hours after the injection of 2 L of isotonic solution with 100ml of contrast medium, which evidenced a pleuro-peritoneal communication. It was then decided to perform a video-assisted thoracoscopic surgery (VATS), that showed no evidence of diaphragm communication. It was then executed a pleurodesis using sterile talcum. The patient was released on the 3rd day, with a conservative therapy and a low-protein diet. After 2 weeks a new pleuro-peritoneal CT scan with contrast medium was executed. This time the scan evidenced the absence of contrast medium in the thoracic cavity. The patient then resumed PD therapy, with 3 daily exchanges with isotonic solution (volume 1.5 L), showing no complications. Concerning the treatment of pleuro-peritoneal leakage, VATS allows both the patch-repairing of diaphragmatic flaws and the instillation of chemical agents. In our case, VATS allowed the chemical pleurodesis which in turn enabled, in just 2 weeks of conservative treatment, the resuming of PD. In conclusion, this methodology is a valid option in the treatment of pleuro-peritoneal leakage in PD patients.

Knowledge of cardiovascular risk factors and awareness of non-pharmacological approach for risk prevention in young survivors of acute myocardial infarction. The cardiovascular risk prevention project "Help Your Heart Stay Young".

BACKGROUND AND AIMS: Knowledge of cardiovascular disease (CVD) risk factors in young patients who experienced myocardial infarction (MI) is poorly described. METHODS AND RESULTS: Knowledge of traditional CVD risk factors, non-fatal cardiovascular events and of non-pharmacological factors able to reduce CVD risk and education level were evaluated by questionnaires in subjects who visited their family doctors. Sixty-one participants with history of MI in age <50 years (MI+) were compared with 3749 subjects with age <50 years, from the same population source, but without history of MI (MI-). MI+ were more frequently men (p<0.01), did not have significantly higher prevalences of family history of CVD, diabetes and hypertension. MI+ individuals reported previous non-fatal stroke (13% vs. 0.5%, p<0.001), overweight, diabetes, and hypercholesterolemia (all p<0.001) more frequently than controls, whereas prevalence of arterial hypertension, smoking habit and physical inactivity did not differ between the two groups; MI+ and MI- individuals did not differ in terms of the proportion of those who were unaware of being hypertensive, diabetic or hypercholesterolemic. MI+ participants reported more frequently lower education level than controls (p<0.05). Knowledge of non-pharmacological approach for CVD risk reduction was similar in MI+ and MI-. In a logistic multivariate analysis, male gender (adjusted odds ratio=5.8) and high cholesterol level (adjusted odds ratio 2.8, both p<0.01) were independent correlates of MI+. CVD risk factors distribution was similar between participants with juvenile MI+ and MI in age >or=50 years (n=167) extracted from the same population source; however, stroke was reported more frequently in juvenile MI+ than in those who had MI at age >or=50 years/old (13% vs. 4%, p<0.01). CONCLUSIONS: Juvenile non-fatal MI was associated with metabolic CVD risk factors, with higher cerebrovascular co-morbidity and lower education level.

Home peritoneal ultrafiltration in patients with severe congestive heart failure without end-stage renal disease.

Congestive heart failure (CHF), mainly because of ischemic heart disease, is becoming a common medical problem. As CHF worsens and reaches New York Heart Association (NYHA) class IV, many patients can become refractory to medical therapy, especially those who are elderly or who have pre-existing non uremic chronic renal failure. For such patients, quality of life, morbidity, and mortality are expected to be bad. Our objective in the present study was to make a preliminary assessment of the usefulness of icodextrin administered in a single nocturnal peritoneal exchange to patients nonrespondent to the maximal conventional medical therapy. We studied two patients (aged 80 and 87 years), who were affected by severe dilatative cardiomyopathy and moderate-to-severe chronic renal failure. After at least 12 months of treatment, we observed a significant improvement in quality of life and a reduction in morbidity and hospitalization in both patients. Both patients also significantly increased their creatinine clearance. One patient maintained ejection fraction stability (22%-->27%); the other experienced an increase in ejection fraction to 50%from 25%. These preliminary observations suggest that a single nocturnal exchange with icodextrin can be an effective treatment in patients affected by refractory CHF and moderate-to-severe chronic renal failure.

A randomized, double-blind, multicenter trial of nimesulide-beta-cyclodextrin versus naproxen in patients with osteoarthritis.

BACKGROUND: Nonsteroidal anti-inflammatory drugs are the most widely used agents in the symptomatic treatment of osteoarthritis (OA). No data are presently available on the medium-term management of this disease with an on-demand treatment regimen, which nevertheless reflects medical practice. OBJECTIVES: The aim of this study was to compare nimesulide-beta-cyclodextrin and naproxen in terms of short-term (2 weeks) pain control with scheduled dosing and medium-term (5.5 months) pain control with on-demand dosing in patients with OA. METHODS: In this multicenter, randomized, double-blind, controlled study, we compared 2 weeks of scheduled treatment plus 5.5 months of on-demand treatment in patients with OA of the hip and/or knee and moderate to severe pain, with no important concomitant disorders. Treatment consisted of nimesulide-beta-cyclodextrin (400 mg BID, orally = 100 mg nimesulide BID) or naproxen (500 mg BID). The primary outcome measures for scheduled dosing were pain on movement (measured by visual analog scale), morning stiffness score, Lequesne index, and adverse events. For on-demand dosing, the measures were the same as for scheduled dosing, plus duration of treatment and global assessment of efficacy and tolerability by patient and physician. RESULTS: After 2 weeks, there was equivalent reduction from baseline in pain on movement in the 2 treatment groups (nimesulide-beta-cyclodextrin, -41.5%; naproxen, -40.5%); the reduction was significant after 1 week (P < 0.001). The findings were also similar for the morning stiffness score and Lequesne index. There were no significant differences in mean duration of on-demand treatment (nimesulide-beta-cyclodextrin, 163.03 days; naproxen, 166.3 days) or in mean consumption of study drug (nimesulide-beta-cyclodextrin, 0.85 +/- 0.61 sachets/d; naproxen, 0.74 +/- 0.42 sachets/d). Withdrawal due to intolerance occurred in 8 patients given nimesulide-beta-cyclodextrin and 13 patients given naproxen, with no significant difference between groups; 3 and 12 patients, respectively, withdrew due to gastrointestinal intolerance, a finding that was significantly different between groups (P < 0.01). Global assessment of efficacy by patient and physician was similar for both drugs. Assessment of tolerability significantly favored nimesulide-beta-cyclodextrin on the physician assessments (P < 0.05) but was similar for the 2 drugs on the patient assessments (physicians, 46.9% vs 30.9%; patients, 43.5% vs 33.3%). CONCLUSIONS: The results suggest that nimesulide-beta-cyclodextrin provides similar pain relief to naproxen in the management of OA of the hip and/or knee and is associated with fewer gastrointestinal adverse reactions. On-demand dosing may be an effective and well-tolerated low-dose regimen of nonsteroidal anti-inflammatory drugs for the maintenance of pain control in OA in the medium term.

Morpho-functional study of peritoneum in peritoneal dialysis patients.

BACKGROUND: Structure and function of the peritoneal membrane (PM) are impaired on peritoneal dialysis (PD). The aim of this study was to examine the relationship between dialytic parameters and histological and functional characteristics of the peritoneum of PD patients. METHODS: A peritoneal biopsy (PB) was performed on 31 PD patients during catheter removal due to malfunction or after drop-out from treatment. PB was performed at least 5 cm from the catheter insertion. For each patient PM transport was evaluated by the last peritoneal equilibration test (PET) before PB. Each daily glucose load was calculated. Tissue was formalin-embedded and stained for histological and immunohistochemical studies. RESULTS: (1) Duration of treatment was longer in patients with mesothelial impairment. (2) Patients showing sub-mesothelial sclerosis (SS) and those with impairment of submesothelial basement membrane and subendothelial vascular membrane (SVM) were submitted to a larger daily glucose load. (3) SS exceeding 50 mm was more frequent among high transporters, who were exposed to larger daily glucose load compared to medium-high transporters. (4) Mesothelial loss correlated to SS and vascular alterations. (5) SS was related to vascular injuries but not to inflammatory infiltrate. CONCLUSIONS: SS is not constant in PD patients and is not a prominent factor in treatment drop-out. Mesothelial impairment seems to be mainly related to duration of PD treatment. Glucose load seems to mainly damage the sub-mesothelial layer.

VEGF-C and VEGF-D blockade inhibits inflammatory skin carcinogenesis.

VEGF-C and VEGF-D were identified as lymphangiogenic growth factors and later shown to promote tumor metastasis, but their effects on carcinogenesis are poorly understood. Here, we have studied the effects of VEGF-C and VEGF-D on tumor development in the murine multistep chemical carcinogenesis model of squamous cell carcinoma by using a soluble VEGF-C/VEGF-D inhibitor. After topical treatment with a tumor initiator and repeated tumor promoter applications, transgenic mice expressing a soluble VEGF-C/VEGF-D receptor (sVEGFR-3) in the skin developed significantly fewer squamous cell tumors with a delayed onset when compared with wild-type mice or mice expressing sVEGFR-3 lacking the ligand-binding site. Epidermal proliferation was reduced in the carcinogen-treated transgenic skin, whereas epidermal keratinocyte proliferation in vitro was not affected by VEGF-C or VEGF-D, indicating indirect effects of sVEGFR-3 expression. Importantly, transgenic mouse skin was less sensitive to tumor promoter-induced inflammation, with reduced angiogenesis and blood vessel leakage. Cutaneous leukocytes, especially macrophages, were reduced in transgenic skin without major changes in macrophage polarization or blood monocyte numbers. Several macrophage-associated cytokines were also reduced in transgenic papillomas, although the dermal macrophages themselves did not express VEGFR-3. These findings indicate that VEGF-C/VEGF-D are involved in shaping the inflammatory tumor microenvironment that regulates early tumor progression. Our results support the use of VEGF-C/VEGF-D-blocking agents not only to inhibit metastatic progression, but also during the early stages of tumor growth.

Right-to-left shunt, atrial septal aneurysm and thrombophilia in patients with cryptogenic stroke or TIA vs. those with venous thrombo-embolism.

Whether intracardiac right-to-left shunt (RLS) is an independent risk factor for cerebrovascular accidents is disputed. In patients with RLS, venous thrombo-embolism (VTE) may predispose to paradoxical embolic events, among which stroke and transient ischemic attack (TIA). Whether genetic or acquired thrombophilia is associated with RLS is unclear. Thus, we compared prevalences of intra- and extracardiac intrapulmonary RLS and of atrial septal aneurysm (ASA) between 29 nondiabetic patients with cryptogenic stroke (n=17) or TIA (n=12) and 19 patients with VTE but without history of stroke/TIA, or autoimmune systemic disease or migraine. Carotid atherosclerosis was excluded in all patients. RLS and ASA were also evaluated in 30 healthy volunteers. We found that intracardiac RLS (31%) and ASA (21%) were detected in stroke/TIA patients and not in our selected VTE patients (both p<0.05); however, those prevalences were comparable to those detected in our controls (20% intracardiac RLS, 7% ASA, respectively, both p=NS). Within patients, thrombophilia was not associated with intracardiac RLS, but tended to be associated with ASA (83% in those with vs. 43% in those without ASA, p=0.08). In conclusions, intracardiac RLS may have a role in selected populations in the frame the multi-factorial pathogenesis of stroke/TIA of embolic origin. ASA appears to be an independent risk factor for stroke/TIA with possible interaction with thrombophilia.

Cycle-ergometry stress testing and use of chronotropic reserve adjustment of ST depression for identification of significant coronary artery disease in clinical practice.

Diagnostic reliability of indexations of peak exercise ST segment depression (DeltaST) for heart rate reserve (HRi) or chronotropic reserve (CR) to identify significant coronary artery disease (CAD) by cycle-ergometer exercise testing has not been evaluated previously. Exercise testing by upright cycle-ergometer (25 W/3 min) were performed in consecutive patients in primary prevention with history of exercise-related chest discomfort and cardiovascular risk factors, or with overt peripheral artery disease, with or type-2 diabetes associated with two or more additional cardiovascular risk factors. Coronary angiography was performed after the test to assess significant CAD. Three different criteria for definition of inducible myocardial ischemia were tested versus significant CAD: peak DeltaST>or=100 microV, ST/HRi>1.69 microV/bpm or ST/CR>1.76 microV/%. Diagnostic accuracy vs. CAD of DeltaST>or=100 microV, of ST/HRi>1.69 microV/bpm, and of ST/CR>1.76 microV/% were 78%, 72%, and 89% respectively; sensitivity and specificity of the three criteria were 91% and 50%, 84% and 43%, 88% and 93%, respectively. Abnormal ST/CR predicted CAD independent of risk factors, pre-test probability, and more strongly than DeltaST. Combination of ST/HRi and ST/CR criteria did not improve CAD prediction. In conclusions, in clinical setting in patients in primary prevention but with moderate-to-high pre-test probability of CAD, exercise testing by cycle-ergometry and use of ST/CR>1.76 microV/% showed elevated sensitivity and specificity, and the best accuracy for diagnosis of significant CAD.

[Cycle ergometer stress testing for identification of significant coronary artery disease: improved accuracy by the use of chronotropic reserve adjustment of ST-segment depression]. / Accuratezza diagnostica del test al cicloergometro: superiorità dell'indicizzazione del sottoslivellamento del tratto ST per la riserva cronotropa nell'identificare una coronaropatia emodinamicamente significativa.

BACKGROUND: Diagnostic reliability of indexations of peak exercise ST-segment depression (deltaST) for heart rate reserve (HRi) or chronotropic reserve (CR) to identify significant coronary artery disease (CAD) by bicycle exercise testing has not been evaluated previously. METHODS: Upright bicycle exercise testing (25 W increment every 3 min) was performed in consecutive patients in primary prevention with at least one of the following criteria: history of exercise-induced chest discomfort and cardiovascular risk factors; overt peripheral arterial disease; type 2 diabetes associated with two or more additional cardiovascular risk factors. Coronary angiography was performed to define significant CAD (stenosis > or = 70% of the main coronary arteries or of their major branches, or isolated left main stenosis > or = 50%, or two or more stenoses 50-69%). Duke angina index was used to grade exercise-induced chest pain; deltaST, ST/HRi and ST/CR were calculated at peak exercise; three different criteria for the definition of inducible myocardial ischemia were tested versus significant CAD: peak deltaST > or =100 microV, ST/HRi > 1.69 microV/b/min or ST/CR > 1.76 microV/%. RESULTS: Of the study sample (n = 46), 40% had typical angina; during stress test 80% showed deltaST > or = 100 microV; 76% had ST/HRi > 1.69 microV/b/min; 62% had ST/CR >1.76 microV/%. Diagnostic accuracy of deltaST > or = 100 microV, of ST/HRi > 1.69 micro5V/b/min, and of ST/CR > 1.76 microV/% were 78%, 72%, and 89% respectively (p < 0.001 for the difference in diagnostic performance). ST/CR > 1.76 microV/% showed the highest diagnostic accuracy both in patients with submaximal exercise (96%) and in women (92%). Similarly, ST/CR >1.76 microV/% was associated with the highest diagnostic accuracy both in patients with maximal exercise (78%) and in men (88%). Analyses of the ROC curve revealed that ST/CR was associated with the greatest area under the curve, and a population-specific cut-off of 1.77 microV/% was associated with a sensitivity of 88% and a specificity of 90%. CONCLUSIONS: Our pilot study suggests that in patients undergoing bicycle stress testing for differential diagnosis or screening of significant CAD, and with moderate-to-high pre-test probability, the use of ST/CR > 1.76 microV/% may provide elevated sensitivity and specificity, and the best diagnostic accuracy, which was consistent in patients with submaximal exercise test and in women.

Troponin I and right ventricular dysfunction for risk assessment in patients with nonmassive pulmonary embolism in the Emergency Department in combination with clinically based risk score.

To determine whether troponin I (cTnI) and right ventricular (RV) dysfunction predict adverse in-hospital outcomes in patients admitted to the Emergency Department (ED) with definite nonmassive pulmonary embolism (PE) independent of and in addition to a recently validated clinical prognostic risk score. From a pool of 168 patients with suspected PE, 89 had nonmassive PE confirmed by spiral lung angio-computed tomography. By the clinical prognostic score, in our study sample, 14% had very low risk; 17% had low risk, 20% had intermediate risk, whereas high risk and very high risk were identified in 29 and 20%, respectively. Prevalence of elevated cTnI (>0.1 microg/L, 57%) at admission was comparable among patients grouped by clinical prognostic score (P = NS); echocardiographic RV dysfunction (54%) was more prevalent with intermediate or high clinical risk score (P < 0.02). Increased cTnI predicted primary end-point (development of hemodynamic instability, overall 33 cases, 37%) independent of and in addition to the clinical risk class and RV dysfunction (P < 0.01 for interaction). Fatal events (12 cases, 14%, 5 definite, 7 possible PE-related) were predicted by higher clinical risk score (P < 0.05). In patients with nonmassive central PE admitted to the ED, increased cTnI contributed to identifying those with increased risk of development of hemodynamic instability independent of and in addition to a validated clinically based risk score.

Isolated left ventricular diastolic dysfunction: implications for exercise left ventricular performance in patients without congestive heart failure.

OBJECTIVE: Clinical relevance of left ventricular (LV) diastolic dysfunction in the absence of congestive heart failure (CHF) and LV systolic dysfunction is not fully established. METHODS: Asymptomatic outpatients, sedentary, with cardiovascular risk factors but no history of cardiovascular events, underwent echocardiographic evaluation of LV structure and function by standard Doppler, color M-mode, and Doppler tissue methods, and exercise testing with simultaneous noninvasive assessment of LV stroke index and cardiac index. LV ejection fraction less than 50% and significant valvular disease or stress test suggestive of coronary disease were additional exclusion criteria. RESULTS: In 70 patients selected (40 +/- 10 years old, 63% men, 34% hypertensive, 34% diabetic, 4% diabetic and hypertensive, 11% with LV hypertrophy), LV diastolic dysfunction was detected in 26%, which was associated with hypertension, higher LV mass index, lower systolic function, lower peak exercise heart rate, and chronotropic reserve (all P < .05), and with lower peak exercise stroke index and cardiac index (both covariates adjusted P < .05), but not with lower peak exercise metabolic equivalents (P > .5). Abnormal LV relaxation was independently correlated with lower peak exercise cardiac index and stroke index (both P < .05). Peak exercise systolic and cardiac indices were comparable between patients with CHF risk factors (74%) versus those without. CONCLUSIONS: Isolated LV diastolic dysfunction was independently associated with lower peak exercise LV systolic performance in patients without CHF. Its diagnosis may provide a target for aggressive CHF risk management.