The risk of coronary artery disease and cerebrovascular disease in patients with hepatitis C: A systematic review and meta-analysis.

BACKGROUND/OBJECTIVES: Some studies suggest that patients with hepatitis C virus (HCV) infection have an increased risk of coronary artery disease (CAD) and cerebrovascular disease. Unfortunately, available data on this association are widely variable. We have performed a systematic review and meta-analysis of literature to evaluate the risk of cardio-cerebrovascular disease (CCD) associated with HCV. METHODS: Studies reporting on CCD risk associated with HCV were systematically searched in the PubMed, Web of Science, Scopus and EMBASE databases. RESULTS: Twenty-seven studies (34 data-sets) showed a significantly increased CCD risk in 297,613 HCV patients as compared with 557,814 uninfected controls (OR: 1.428; 95% CI: 1.214, 1.681). These results were confirmed when separately considering the risk of CAD (20 studies, OR: 1.382; 95% CI: 1.103, 1.732) and of cerebrovascular disease (13 studies, OR: 1.485; 95% CI: 1.079, 2.044). Similar results were confirmed when analyzing 21 studies reporting adjusted risk estimates (OR: 1.448; 95% CI: 1.218, 1.722) and when, after excluding studies defining CAD as positive angiographic or electrocardiographic evidence, we specifically included the 17 studies reporting on acute CCD-related events (OR: 1.357; 95% CI: 1.103, 1.670). Moreover, 4 studies evaluating CCD-related deaths showed a higher risk in HCV patients than controls (OR: 1.772; 95% CI: 1.448, 2.168; P<0.0001). Meta-regression models suggested a direct association between prevalence of cirrhosis and difference in CCD risk between HCV patients and controls. CONCLUSIONS: Results of our large meta-analysis suggest that HCV-infected subjects experience an increased risk of CCD. This should be considered to plan specific cardiovascular prevention strategies in this clinical setting.

The risk of venous thromboembolism in patients with hepatitis C. A systematic review and meta-analysis.

Some studies suggest that patients with hepatitis C virus (HCV) infection have an increased risk of deep venous thrombosis (DVT) and pulmonary embolism (PE). Unfortunately, available data on this association are contrasting. A systematic review and meta-analysis of literature studies was performed to evaluate the risk of venous thromboembolism (VTE) associated with HCV. Studies reporting on VTE risk associated with HCV were systematically searched in the PubMed, Web of Science, Scopus and EMBASE databases. Six studies (10 data-sets) showed a significantly increased VTE risk in 100,364 HCV patients as compared with 8,471,176 uninfected controls (odds ratio [OR]: 1.900; 95 % confidence interval [CI]: 1.406, 2.570; p<0.0001). These results were confirmed when specifically considering the risk of DVT (6 studies, OR: 1.918; 95 %CI: 1.351, 2.723; p<0.0001), whereas a trend towards an increased risk of PE was documented in HCV patients (4 studies, OR: 1.811; 95 %CI: 0.895, 3.663; p=0.099). The increased VTE risk associated with HCV infection was consistently confirmed when analysing four studies reporting adjusted risk estimates (OR: 1.876; 95 %CI: 1.326, 2.654; P<0.0001), and after excluding studies specifically enrolling populations exposed to transient risk factors for VTE (4 studies, OR: 1.493; 95 %CI: 1.167, 1.910; p=0.001). Meta-regression models suggested that age and male gender may significantly impact on the risk of VTE associated with HCV-positivity. Results of our meta-analysis suggest that HCV-infected subjects may exhibit an increased risk of VTE. However, further high quality studies are needed to extend and confirm our findings.

Lytic failure in the current pharmacointensive ST-elevated acute myocardial infarction care: insights from a pilot real-world study.

BACKGROUND: Thrombolysis remains a very acceptable reperfusion option for ST-elevated acute myocardial infarction (STEMI); however, it fails relatively frequently and unpredictably. AIM AND METHODS: To investigate correlates of lytic failure (according to the standard ST resolution criterion) in current pharmacointensive STEMI care (dual antiplatelets with antithrombin), we analyzed retrospectively clinical data and echocardiographic left ventricular systolic function before initiation of reperfusion treatment in Killip I-III STEMI patients admitted to our 'spoke' intensive cardiac care unit between 1 January and 31 December 2010. RESULTS: Of the 53 STEMI patients enrolled, 28% failed thrombolysis. Patients who did not reperfuse were less frequently active smokers (P < 0.05, odds ratio 4.33) and had a higher prevalence of hemodynamic instability [heart rate/SBP (i.e. shock index) >0.75; P < 0.05, odds ratio 13.45) and left ventricular systolic dysfunction (ejection fraction <45%; P < 0.005, odds ratio 11.14). In an exploratory multivariable logistic regression analysis, those variables were the only discriminators independently associated with lytic failure (adjusted odds ratio 8.74, 230.10, and 18.22, respectively, all P < 0.05). Moreover, the combined variables had a high accuracy for prediction of failed thrombolysis (all discriminators positive, 99% specificity and 83% positive predictive value). CONCLUSION: Our pilot study indicates that thrombolysis still fails in about one-third of STEMI patients despite the current pharmacointensive approach and suggests that failed ST resolution might be independently associated with nonsmoking habit and pretreatment hemodynamic instability and left ventricular systolic dysfunction. Larger trials are needed to verify the potential clinical implications of our preliminary observation.

[Cardiac resynchronization therapy: mortality, rehospitalization, and procedure-related complications. A three-year single-center observational study within the Italian Health System]. / Resincronizzazione cardiaca: morte, riospedalizzazione e complicanze correlate all'impianto. Studio osservazionale triennale in un singolo centro del Sistema Sanitario Nazionale.

BACKGROUND: The aim of this study was to evaluate whether the benefit of cardiac resynchronization therapy with an implantable defibrillator (CRT-D) may differ among classes of indications to device therapy. METHODS: All-cause mortality, first hospitalization for non-fatal heart failure, stable improvement of NYHA functional class (responders), and implant-related complications were evaluated retrospectively in 103 patients selected among those (n = 133) who received consecutively CRT-D between 2006 and 2009. Patients were divided into three groups: group IA (n = 65) included patients receiving CRT-D for a class IA indication; group IIa (n = 26) included patients with atrial fibrillation and QRS ≥ 130 ms receiving CRT-D for a class IA indication; nonconventional group (NC) (n = 12) included patients with an indication to defibrillator implantation extended to CRT-D because of NYHA class III-IV and echocardiographic evidence of electromechanical dyssynchrony. Echocardiographic examination was performed in all patients to identify wall target for left-side lead placement. RESULTS: Group IIa patients were slightly older than group IA patients (p<0.05); gender distribution, left ventricular ejection fraction at implantation, ischemic etiology, and heart failure treatment were comparable among groups (all p>0.5), except for a higher digitalis use in group IIa patients (p<0.05). In a mean observation period of 3 years (up to December 2010), the rates of fatal events (IA: 22%, IIa: 23%, NC: 20%), rehospitalization for worsening heart failure (IA: 30%, IIa: 33%, NC: 22%), clinical responders (IA: 78%, IIa: 78%, NC: 78%), implant-related complications requiring reintervention (IA: 15%, IIa: 19%, NC: 25%), including pocket or catheter infections (IA: 5%, IIa: 11%, NC: 8%) were comparable among groups (all p>0.5). CONCLUSIONS: In the "real world", the benefit of CRT-D in advanced heart failure patients might be comparable among class IA, IIa or NC indication.

[Home-based telemonitoring of simple vital signs to reduce hospitalization in heart failure patients: real-world data from a community-based hospital]. / Telemetria per il controllo domiciliare della pressione arteriosa, della frequenza cardiaca e della saturimetria di ossigeno nello scompenso cardiaco: impatto sulle ospedalizzazioni in un contesto non sperimentale.

BACKGROUND: Whether home telemonitoring after acute episodes of heart failure (HF) may reduce de-novo cardiac decompensation is disputed. We tested home telemonitoring of blood pressure (BP), heart rate (HR), and blood oxygen saturation (SO2) to reduce rehospitalization in patients with recent admission for acute HF. METHODS; We screened patients hospitalized in Cardiology due to prominent cardiac cause of acute dyspnea, and pulmonary/peripheral congestion, and with one admission or more for similar symptoms/signs in the previous year. Patients with acute coronary syndrome, poor prognosis due to extracardiac causes, and reduced self-sufficiency and cognitive ability were excluded. Of the selected patients, 63% accepted and received a device for BP, HR and SO2 measurement connected to an analogical modem for data transmission to a hospital server. Patients were educated to measure vital signs 3 times/week. A dedicated doctor-nurse unit monitored the patients' data twice weekly to manage therapeutic adjustments of diuretic dosage or in-hospital visits if necessary. HF treatment was standardized based on current guidelines. Unplanned hospitalizations for HF or all-cause death were primary endpoints; unplanned hospitalizations (total) for any cause, and all-cause death were the composite endpoints. RESULTS: Twenty-three patients (mean age 70 years, range 44-80 years) were recruited: 26% were women, 61% had coronary heart disease, 52% chronic lung disease, 57% renal insufficiency, 30% anemia; 17% had moderate or severe mitral regurgitation. At a mean follow-up of 302 days (range 55-622 days), 12 patients experienced the composite endpoints (52%, p=0.1), with the primary endpoint occurring in 8 patients (35%, 1 sudden death, p=0.058), the secondary endpoints occurring in 2 patients, and hospitalization not for HF occurring in 2 patients. The total number of hospitalizations/patient/year decreased from 2.2 ± 1.3 in the previous year to 0.9 ± 1.2 during the study period (p<0.01). On average, systolic BP tended to decrease, but BP, HR and SO 2 values prior to the index event (1-7 days) did not significantly differ from those recorded at the beginning of telemonitoring. CONCLUSIONS: In HF, home telemonitoring of simple variables had no significant impact on all-cause hospitalization/mortality, but was associated with a higher patient compliance and achievement of therapeutic targets, which may translate into a reduction in hospitalization rates for HF.

Relation of flow-mediated dilation to global arterial load: impact of hypertension and additional cardiovascular risk factors.

BACKGROUND: Endothelial dysfunction may be related to increased left ventricular (LV) mass due to an association between endothelial dysfunction with increased arterial load. Therefore, we evaluated whether brachial artery flow-mediated dilation (FMD) is related to global arterial load. METHODS: Pulse pressure/stroke index (PP/SVi, global arterial stiffness, prognostically validated), stroke volume/PP (SV/PP, global arterial compliance), and % of the predicted SV/PP by heart rate, age and body weight (confounder-adjusted global compliance, prognostically validated) were used as LV geometry-related indices of global arterial load. RESULTS: Compared to normotensive participants (NT, n = 50), those with hypertension (HTN, n = 51) had lower FMD (8.3% ± 5.4 vs. 12.8% ± 6.5), higher PP/SVi (1.24 ± 0.34 vs. 1.04 ± 0.28 mmHg m(2)/ml), higher LV mass and higher relative wall thickness (all p < 0.01); in contrast, SV/PP and % of predicted SV/PP did not differ between NT and HTN (all p>0.1). Impaired FMD was 3-4-fold more prevalent than LV hypertrophy or increased arterial load both in NT and in HTN. Within NT and HTN separately, PP/SVi, SV/PP and % of predicted SV/PP were comparable among tertiles of FMD. Only in NT, lower FMD was associated with higher peak exercise systolic BP (p < 0.05). In multivariable regression models, FMD was not associated with indices of arterial load independently (all p > 0.1). CONCLUSIONS: In young-to-middle-age subjects with cardiovascular risk factors, impaired FMD is more prevalent than traditional preclinical manifestation of cardiovascular disease, and may exist independent to increased arterial load. Thus, endothelial dysfunction assessment may refine cardiovascular risk profile and risk-reduction strategies based on detection of traditional target organ damage.

Test-re-test reproducibility of Doppler echocardiography for assessment of electromechanical dyssynchrony: implications for heart failure clinic.

BACKGROUND: Reproducibility of Doppler echocardiography for assessment of inter-ventricular and intra-left ventricular (LV) dyssynchrony, and its clinical implications, have not been established. METHODS: Twenty-eight subjects (heart failure stages A-C, 61% with QRS ≥ 120 ms, ejection fraction (EF) ≤ 35%) underwent two consecutive echo-studies within 24h to evaluate test-re-test reproducibility of inter-ventricular electromechanical delay (VV delay, by traditional pulsed-Doppler), and intra-LV electromechanical delay between opposite LV walls by color-coded Doppler tissue-velocity (COLOR-DTI), and by pulsed-Doppler tissue spectrum (PW-DTI). Reproducibility of LV internal diastolic diameter (LVIDD) and of EF (by Simpson's method) assessments was evaluated contextually for reference. RESULTS: Intra-study and inter-study reproducibility of inter-ventricular and intra-LV electromechanical dyssynchrony was in general good, and comparable to the reproducibility of LVIDD and EF assessments. Between-study reproducibility of PW-TDI method was fair, but showed poor agreement with COLOR-TDI method. In repeated studies, agreement of significant electromechanical delay by COLOR-TDI was comparable to the agreement of EF ≤ 35%. In the 5 patients who had simultaneously large QRS, EF ≤ 35%, and significant inter- and intra-ventricular dyssynchrony at study #1, 3 had EF 36-40% and 1 showed no significant dyssynchrony by study #2. CONCLUSION: In serial echocardiographic studies, Doppler echocardiography showed a good test-re-test reproducibility for the identification of significant electromechanical delay. Planimetry for EF assessment was a source of variability as relevant as Doppler echocardiography, but COLOR-DTI may add meaningful and reproducible information to QRS duration for cardiac-resynchronization therapy.

Novel wall motion score-based method for estimating global left ventricular ejection fraction: validation by real-time 3D echocardiography and global longitudinal strain.

AIMS: To evaluate the reliability of a regional wall motion score index (WMSI)-based method for assessment of left ventricular (LV) ejection fraction (EF). METHODS AND RESULTS: Two-dimensional (2D) echocardiography was used to assess a LV 16-segment-based regional wall motion. Each segment received a score based on contractility status: 4, normal kinesis; 3, mild; 2.5, moderate; and 1.5, severe hypo-kinesis; 0, akinesis; -1, dyskinesis; 3.5 and 4.5 were used for low-normal and high-normal kinesis; 5 for hyper-kinesis. Hence, WMSI-based EF was derived by summing the score assigned to each segment. Contextually, EF was evaluated by real-time three-dimensional (3D) echocardiography and by traditional Simpson's method (2D). Global longitudinal strain (GLS) by speckle-tracking method was derived as a volume-independent indicator of LV chamber contractility sensitive to regional wall motion abnormalities. In 40 subjects with 3D-EF ranging from 14 to 80%, including clinically healthy hypertensive and patients with Stage B-D congestive heart failure with global or segmental wall motion abnormalities, on average, WMSI-EF did not differ from EF measured by 3D or 2D (all P > 0.5). By intraclass correlation coefficients, reliability of WMSI-EF vs. 3D method was as good as the reliability of 2D method vs. 3D method. GLS correlated with WMSI-EF as strongly as with 3D-EF (both r(2) = 0.90). Moderate-severe mitral regurgitation was associated with increased difference between WMSI-EF and 3D-EF, independent to potential confounders. Intra-observer and inter-observer reproducibility of WMSI-EF was comparable to the reproducibility of EF estimated by 3D echocardiography. Feasibility (WMSI, 3D, 2D, and GLS all available) was 78%; however, feasibility of WMSI per se was approximately 92% in clinical series. CONCLUSION: Trained readers may rapidly estimate EF by a novel WMSI system, which was found to be accurate compared with 3D method and GLS.

Changes in components of left ventricular mechanics under selective beta-1 blockade: insight from traditional and new technologies in echocardiography.

AIMS: Myocardial inotropism is considered to be reduced under beta-1 adrenoreceptor blockage (beta1-block). However, relationships between components of left ventricular (LV) systolic mechanics under beta1-block accounting for physiological correlates are only partially explored. METHODS AND RESULTS: Hypertensive outpatient without previous cardiovascular events and with normal LV ejection fraction (EF) at rest underwent echocardiographic evaluations of LV size and systolic function by standard, tissue-Doppler, and speckle-tracking methods before and after 2 weeks of treatment with bisoprolol to obtain change in LV systolic mechanics at a stable heart rate reduction (-20 +/- 10% from baseline) without significant change in LV mass. In the study sample (n = 26, 62% women, mean age 52 +/- 10 years), under bisoprolol, afterload [i.e. circumferential (CESS) and meridional (MESS) end-systolic stress], LV mass, left atrial volume, and EF did not change significantly; LV chamber contractility [i.e. CESS/LV end-systolic volume index (CESS/ESVi) as well as MESS/ESVi] and relative wall thickness (RWT) decreased; stroke volume increased (all P < 0.05). Circumferential LV contractility (i.e. stress-corrected midwall shortening) increased, whereas regional longitudinal strain and strain rate, and global longitudinal strain decreased (all P < 0.05). Peak velocities of the systolic displacement of the lateral and medial mitral anulus did not change under bisoprolol. Parameters of longitudinal LV systolic function did not correlate with preload, afterload, RWT, or with stoke volume. CONCLUSION: In hypertensive subjects with preserved LV EF, parameters of longitudinal LV systolic mechanics may not reflect the LV myocardial contractility status in steady-state conditions under short-term treatment with beta1-block.

[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.

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.

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.

Uncomplicated type 1 diabetes and preclinical left ventricular myocardial dysfunction: insights from echocardiography and exercise cardiac performance evaluation.

OBJECTIVES: Left ventricular (LV) diastolic dysfunction is considered the earliest manifestation of diabetic cardiomyopathy. Whether LV abnormalities identified at rest by echocardiography predict peak exercise LV performance in uncomplicated type 1 diabetes mellitus (DM1) is largely unknown. RESEARCH DESIGN AND METHODS: We evaluated LV size, mass, and functions and peak exercise LV performance in 25 subjects with uncomplicated DM1 (median disease duration 13.5 years, 1-30 years) and in 56 non-DM subjects (24 hypertensive (HT) and 32 normotensive (NT)). Overt coronary heart disease, significant microangiopathy and central autonomic neuropathy were minimized by exclusion criteria. Peak exercise LV stroke index (SVi), cardiac index (COi), LV ejection fraction (EF), LV end-diastolic and end-systolic volumes were assessed noninvasively. No subject was on cardiovascular medications at the time of evaluation. RESULTS: In our study, DM1 did not show LV hypertrophy or impaired LV systolic function at rest. Prevalence of diastolic dysfunction was 8% among DM1, 18% among NT and 50% among HT. Pre-exercise heart rate, SVi, COi, and peak exercise blood pressure (BP) and heart rate were comparable among the three groups, but peak exercise LV EF, SVi and COi were lower in DM1 than in HT and NT independent to covariates (p<0.05). In separate analyses, DM1 predicted lower peak exercise SVi (B=-6.2) and COi (B=-1.6, both p<0.05) independently. Within DM1, glycated haemoglobin (HbA1c) and disease duration did not predict peak exercise LV systolic function. CONCLUSIONS: Our study suggests that uncomplicated DM1 may be associated with subnormal LV contractility reserve, which might not be predicted by LV dysfunction evaluated at rest.

Increased troponin I predicts in-hospital occurrence of hemodynamic instability in patients with sub-massive or non-massive pulmonary embolism independent to clinical, echocardiographic and laboratory information.

INTRODUCTION: Whether in patients with acute central sub-massive or non-massive pulmonary embolism, mild troponin I increase (>0.03 mug/L) predicts in-hospital occurrence of hemodynamic instability and death independent to prognostically relevant clinical, laboratory and echocardiographic information is not fully established. METHODS AND RESULTS: We evaluated consecutively patients admitted to the Emergency Room for pulmonary embolism; those in stable hemodynamics in whom central pulmonary embolism was confirmed by spiral-computed tomography were recruited. All participants underwent standardized study protocol, including clinical and diagnostic evaluation for assessment of severity of pulmonary embolism; therapy was established accordingly; troponin I was measured, but treatment protocol was not affected by knowledge of troponin I levels. Of 90 patients enrolled in the study, 33 (37%) developed hemodynamic instability during hospitalization (on average, 90 h +/-20 from admission). Troponin I was >0.03 microg/L in 56% of the study population at admission, and predicted occurrence of hemodynamic instability during hospitalization (adjusted hazard ratio 9.8, 95% confidence interval 1.2-79.2), independent to age, gender, co-morbidity, systolic blood pressure, CK-MB, echocardiographic right ventricular dysfunction and other covariates. Twelve patients died during hospitalization (mean time to event 107 h +/-24 from admission); troponin I >0.03 microg/L predicted mortality in univariate analysis, but not after accounting for age, sex and clinical variables. Nevertheless, higher troponin as continuous variable correlated with higher likelihood of in-hospital death (adjusted likelihood ratio 2.2/microg/L, 95% confidence interval 1.1-4.3) in multivariate analysis. In a further multivariate model, CK-MB predicted mortality independent of covariates and troponin I. CONCLUSIONS: In patients with acute central sub-massive or non-massive pulmonary embolism, even mild increase in troponin I >0.03 microg/L may provide relevant short-term prognostic information independent to clinical, laboratory and echocardiographic data.

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.

Left ventricular chamber and myocardial systolic function reserve in patients with type 1 diabetes mellitus: insight from traditional and Doppler tissue imaging echocardiography.

OBJECTIVE: We sought to evaluate in patients with type 1 diabetes mellitus (DM1): (1) whether myocardial afterload correlates with left ventricular (LV) circumferential and longitudinal systolic function at rest and during low-dose dobutamine (LDD) infusion, and whether longitudinal and circumferential LV systolic function reserves are correlated; and (2) to explore relations between LV systolic mechanics and LV chamber output reserves. METHODS: A total of 20 patients with DM1 underwent echocardiography to assess LV systolic function at rest and at peak LDD (7.5 microg/kg/min). At rest, echocardiographic data of patients with DM1 were compared with those from 24 healthy control subjects. LV afterload was estimated by computing circumferential end-systolic stress (ESS). LV chamber systolic function was assessed by computing ejection fraction and ESS/end-systolic volume index; LV circumferential myocardial contractility was explored by computing midwall fractional shortening (MWS) and ESS-corrected MWS. Longitudinal LV systolic function was assessed using color Doppler tissue (DTI) to assess peak systolic velocities and maximal displacement of the lateral and medial mitral annulus in apical 4-chamber view; regional deformation analyses were computed at the midportion of the posterior interventricular septum (peak strain and peak strain rate); strain/ESS was assessed as an alternative indicator of longitudinal myocardial contractility. LV chamber output was assessed by computing stroke index. RESULTS: DM1 and control groups did not differ in terms of sex distribution, mean age, blood pressure, LV mass index and geometry, and at-rest parameters of LV systolic function (all P > .1), whereas body mass index was higher and systolic lateral mitral annulus velocity was lower in the DM1 than control group (both P < .01). At rest, in both groups, higher ESS correlated with lower ejection fraction and lower MWS; ESS did not show significant correlation with longitudinal systolic function parameters. At peak LDD in DM1, heart rate changed minimally; ESS decreased significantly (P < .01); circumferential and longitudinal LV systolic functions increased significantly but did not show intercorrelation; higher ESS correlated with lower ejection fraction; longitudinal LV systolic function parameters did not show correlation with ESS. In a multivariate analysis, percent increase in stroke index correlated with percent change of MWS (beta = 0.74, P < .01), and to a lesser extent with the percent increase of systolic lateral mitral annulus velocity (beta = 0.47, P = .04), independent to age, sex, percent change of ESS, and heart rate. CONCLUSIONS: LV longitudinal systolic function (DTI) parameters did not fall into the paradigm of the stress-shortening relationship used to describe LV contractility. However, both LV circumferential contractility and longitudinal systolic function reserves correlated with stroke index reserve during LDD.

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.