Clinical conditions and echocardiographic parameters associated with mortality in COVID-19.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a recently recognized viral infective disease which can be complicated by acute respiratory stress syndrome (ARDS) and cardiovascular complications including severe arrhythmias, acute coronary syndromes, myocarditis and pulmonary embolism. The aim of the present study was to identify the clinical conditions and echocardiographic parameters associated with in-hospital mortality in COVID-19. METHODS: This is a multicentre retrospective observational study including seven Italian centres. Patients hospitalized with COVID-19 from 1 March to 22 April 2020 were included into study population. The association between baseline variables and risk of in-hospital mortality was assessed through multivariable logistic regression and competing risk analyses. RESULTS: Out of 1401 patients admitted at the participating centres with confirmed diagnosis of COVID-19, 226 (16.1%) underwent transthoracic echocardiography (TTE) and were included in the present analysis. In-hospital death occurred in 68 patients (30.1%). At multivariable analysis, left ventricular ejection fraction (LVEF, P < .001), tricuspid annular plane systolic excursion (TAPSE, P < .001) and ARDS (P < .001) were independently associated with in-hospital mortality. At competing risk analysis, we found a significantly higher risk of mortality in patients with ARDS vs those without ARDS (HR: 7.66; CI: 3.95-14.8), in patients with TAPSE ≤17 mm vs those with TAPSE >17 mm (HR: 5.08; CI: 3.15-8.19) and in patients with LVEF ≤50% vs those with LVEF >50% (HR: 4.06; CI: 2.50-6.59). CONCLUSIONS: TTE might be a useful tool in risk stratification of patients with COVID-19. In particular, reduced LVEF and reduced TAPSE may help to identify patients at higher risk of death during hospitalization.

Pulmonary embolism in COVID-19 patients: prevalence, predictors and clinical outcome.

INTRODUCTION: The incidence, characteristics, and prognosis of pulmonary embolism (PE) in Coronavirus disease 2019 (COVID-19) have been poorly investigated. We aimed to investigate the prevalence and the correlates with the occurrence of PE as well as the association between PE and the risk of mortality in COVID-19. METHODS: Retrospective multicenter study on consecutive COVID-19 patients hospitalized at 7 Italian Hospitals. At admission, all patients underwent medical history, laboratory and echocardiographic evaluation. RESULTS: The study population consisted of 224 patients (mean age 69 ± 14, male sex 62%); PE was diagnosed in 32 cases (14%). Patients with PE were hospitalized after a longer time since symptoms onset (7 IQR 3-11 days, 3 IQR 1-6 days; p = 0.001) and showed higher D-dimers level (1819 IQR 568-5017 ng/ml vs 555 IQR 13-1530 ng/ml; p < 0.001) and higher prevalence of myocardial injury (47% vs 28%, p = 0.033). At multivariable analysis, tricuspid annular plane systolic excursion (TAPSE; HR = 0.84; 95% CI 0.66-0.98; p = 0.046) and systolic pulmonary arterial pressure (sPAP; HR = 1.12; 95% CI 1.03-1.23; p = 0.008) resulted the only parameters independently associated with PE occurrence. Mortality rates (50% vs 27%; p = 0.010) and cardiogenic shock (37% vs 14%; p = 0.001) were significantly higher in PE as compared with non-PE patients. At multivariate analysis PE was significant associated with mortality. CONCLUSION: PE is relatively common complication in COVID-19 and is associated with increased mortality risk. TAPSE and sPAP resulted the only parameters independently associated with PE occurrence in COVID-19 patients.

Abnormal Papillary Muscle Signal on Cine MRI As a Typical Feature of Mitral Valve Prolapse.

BACKGROUND: Mitral valve prolapse (MVP) is characterized by an abnormal movement of the valvular apparatus which may affect the papillary muscles (PMs) function and structure. Aim of the study was to investigate abnormal PM signal in MVP by using cardiac magnetic resonance imaging (MRI). METHODS AND RESULTS: We enrolled 47 consecutive patients with MVP evaluated by cardiac MRI. Additional groups included healthy volunteers, patients with moderate-to-severe mitral regurgitation (not caused by MVP) and patients with hypertrophic cardiomyopathy. Visual assessment of the PM signals was carried out and the signal intensity (SI) of both the antero-lateral and postero-medial PMs was normalized by that of the left ventricular (LV) parietal myocardium. Our results show that in the MVP group only, the PM signal intensity was significantly lower compared to the one of the LV parietal myocardium. This sign did not correlate with either LV late gadolinium enhancement or positive anamnesis for significant arrhythmias. CONCLUSIONS: In MVP patients only, PM signal is significantly reduced compared to LV parietal myocardium ("darker appearance"). The described findings are not clearly related to evidence of myocardial fibrosis, as assessed by MRI, and to previous occurrence of complex ventricular arrhythmias.

Accuracy and feasibility of simplified Doppler-based left ventricular ejection fraction.

Calculation of left ventricular (LV) ejection fraction (EF) by Doppler stroke volume and end-diastolic volume (EDV) derived from LV diastolic diameter (LVIDD) could be reliable and feasible in clinical practice. In subjects with a wide range of LV volumes and EFs, magnetic resonance imaging (MRI) was used to evaluate the accuracy of common formulas (Teichholz and Z method) to estimate EDV from LVIDD (EDVTeich; EDVZ) versus volumetric EDV. The accuracy of simplified Doppler-EF was tested in a separate study sample versus real-time 3-dimensional (RT3D) echocardiography and versus bidimensional Simpson's method. A new equation to calculate EDV from LVIDD was derived using MRI and tested in the RT3D echo samples. Feasibility of Doppler-EF was tested in a third sample of consecutive inpatients and outpatients. In the MRI sample, EDVTeich was greater whereas EDVZ was smaller than volumetric EDV (both p <0.01); however, a quadratic equation estimated EDV from LVIDD with accuracy (R² = 0.97). In the echocardiographic sample, independent of severe segmental wall motion abnormalities, EDVTeich was greater whereas EDV using Simpson's method was smaller than RT3D EDV (all p <0.05); Doppler-EF using EDVTeich was lower compared with EF by Simpson's rule or by RT3D-EF (all p <0.01). However, RT3D-EF showed no differences compared with Doppler-EF when EDV was calculated by the novel MRI-derived equation. Feasibility was 95% for Doppler-EF and 72% using Simpson's method. In conclusion, equations estimating EDV from LVIDD affect the accuracy of simplified Doppler-EF. However, Doppler-based EF may be accurate and feasible even in the presence of LV contractile asynergy.

[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.

Genotype-independent in vivo oxidative stress following a methionine loading test: maximal platelet activation in subjects with early-onset thrombosis.

BACKGROUND: Methionine ingestion (100mg/kg) identifies subjects in whom fasting total homocysteine (tHcy) may be normal but the post-methionine load (PML) tHcy is abnormally high. METHODS: In 96 subjects [54 M/42 F, 40.4 ± 12.3 yrs old; 28 with the 68 bp844 ins of the cystathionine-ß-synthase gene (CBSins+); 20 homozygotes for the C677T mutation of the methylene-tetrahydrofolate reductase gene (MTHFR++); 13 with the combination of the two, and 35 without any of them], we have evaluated in vivo oxidative stress and platelet activation, as reflected by urinary excretions of 8-iso-PGF(2α) and of 11-dehydro-TXB(2) respectively, before and after a methionine load test (PML). A history of early-onset thrombosis (18 arterial, 32 venous, 2 both) was present in 52/96 of them. RESULTS: Baseline; tHcy was highest in MTHFR++ carriers (p < 0,05); 8-iso-PGF(2α) and 11-dehydro-TXB(2) levels were independent of sex, MTHFR++ and/or CBSins + (p > 0.05). PML; The ~3-fold increase (p < 0.01 vs baseline) in tHcy reached a plateau within 6-8 hrs. Mean PML tHcy was maximal in MTHFR++ carriers (p = 0.000). 8-iso-PGF(2α) and 11-dehydro-TXB(2) increase reached a maximum within 4 hrs. 11-dehydro-TXB(2) increase was highest (p = 0.023 vs baseline) in subjects with a history of thrombosis. Baseline 11-dehydro-TXB(2) and a history of thrombosis independently predicted PML 11-dehydro-TXB(2) (ß = 0.287, p = 0.000 and ß = 0.308, p = 0.026, respectively).The PML increase in 8-iso-PGF(2α) or in 11-dehydro-TXB(2) were comparable in the different genotypes (p > 0.05). CONCLUSION: Regardless genotypes associated with moderate hyperhomocysteinemia, following a methionine loading test, in vivo oxidative stress and platelet activation occur, being the latter maximal in subjects with a history of early-onset thrombosis.

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.

Protein C and protein S changes in GH-deficient adults on r-HGH replacement therapy: correlations with PAI-1 and t-PA plasma levels.

BACKGROUND: In the rat liver, growth hormone (GH) affects the synthesis of vitamin-K-dependent factors, including Protein C (prot.C) and protein S (prot.S), two natural anticoagulants that prevent hypercoagulable states. Adults with GH deficiency (GHD) are at risk of thrombotic events. High circulating levels of PAI-1 and t-PA, that reflect hypercoagulable states, may contribute to such risk. In GHD adults on replacement therapy with recombinant human GH (r-HGH), %Δ PAI-1 and %Δ t-PA are related to %Δ insulin changes. OBJECTIVES: To evaluate changes in vitamin-K-dependent factors in GHD on r-HGH replacement. METHODS: In 60 GHD adults, to relate plasma levels of vitamin-K-dependent factors with those of PAI-1, t-PA and insulin before and after 6-month (6-mo) replacement therapy with r-HGH. RESULTS: After 6-mo r-HGH replacement, %Δ insulin enhancements occurred in 36/60 subjects. PAI-1, t-PA, Prot.C, Prot.S and FVIIact did not change in them. In the 24/40 subjects that experienced %Δ insulin reductions, Prot.C (p=0.025), Prot.S (p=0.031) and FVIIact (p=0.049) decreased significantly. PAI-1 (p=0.019) and t-PA antigen (p=0.009) behaved similarly. In a multivariate analysis, %∆ PAI-1 (ß=0.436, p<0.01) was the strongest predictor of %∆ prot.S, wheras %∆ t-PA (ß=0.385, p<0.008) and %∆ insulin (ß=0.429, p<0.004) were the strongest predictors of %∆ prot.C. In all cases, regardless of %Δ insulin changes, FII, FVII Ag and FIX levels did not change from baseline. CONCLUSIONS: In GHD adults on r-HGH replacement, changes in vitamin-K-dependent factors reflect a subtle adaptation of the natural anticoagulant system to PAI-1 and t-PA changes, via the response of insulin to r-HGH.

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.

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.

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.

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.

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.

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.

Relations of longitudinal left ventricular systolic function to left ventricular mass, load, and Doppler stroke volume.

AIMS: To evaluate whether the peak systolic velocities of the displacement of the lateral mitral anulus (Sa) and of the mid-portion of the interventricular septal wall (Sm) correlate with measures of left ventricular load, left ventricular mass, and Doppler stroke volume in normotensive and hypertensive subjects without clinically overt cardiovascular disease. METHODS AND RESULTS: Tissue Doppler imaging was used to evaluate Sa and Sm in apical 4-chamber view; standard echocardiographic procedures were used to assess left ventricular structure and traditional parameters of systolic function (ejection fraction, stress-corrected midwall shortening, meridional and circumferential end-systolic stress); pulsed Doppler was employed to evaluate stroke volume. In 87 subjects meeting inclusion criteria, Sa and Sm were not significantly correlated either with left ventricular end-diastolic volume and end-systolic stress, or with stroke volume; in contrast, endocardial and midwall fractional shortening were lower with higher afterload, as expected. Fractional shortening at endocardium and midwall, and Sm were lower with higher left ventricular mass. Mean Sa and Sm values were lower in subjects with low vs. those with normal stress-corrected midwall shortening, but low Sa was not associated with lower stress-corrected midwall shortening in our study sample. CONCLUSIONS: While Sa and Sm might be indices of longitudinal left ventricular systolic mechanics, they should not be considered as measures of left ventricular contractility alternative to well-established parameters of systolic function, such as stress-corrected midwall shortening, in subjects at rest without overt heart disease.

Individuals' cardiovascular risk profile projected by family doctors and individuals' knowledge of cardiovascular risk factors: a challenge for primary prevention. The cardiovascular risk prevention project "Help Your Heart Stay Young".

BACKGROUND: Whether the practice of family doctors of assessing individuals' cardiovascular risk profile improves individuals' knowledge of risk factors in primary prevention has not been established. Accordingly, we evaluated patients' knowledge of cardiovascular risk factors and lifestyle in healthy subjects whose family doctors provided individual cardiovascular risk score. METHODS: Subjects who visited their family doctor in a time frame of 3 months, who accepted to fill-in a simple questionnaire measuring their knowledge of cardiovascular risk factors and of non-pharmacological interventions able to reduce cardiovascular risk were evaluated. RESULTS: Fifty-one family doctors were involved. The study sample comprised 4239 subjects (mean age 56 +/- 9 years, 62% women) in primary prevention. They were classified by their family doctors, based on the Framingham algorithm, as being at low (< 10%; 45.7% of subjects), medium (10-20%; 38.7% of subjects) or moderate-to-high (> 20%; 15.6% of subjects) cardiovascular risk. The prevalence of obese subjects (40, 48, and 49%, respectively) and of heavy smokers (> or = 20 cigarettes/day; 26, 30, and 34%) increased from the low to the moderate-to-high risk group (both p < 0.05). The proportion of subjects unaware of personal history of arterial hypertension (5, 6, and 9%) and that of subjects who were unaware of history of elevated cholesterol levels (10, 11, and 12%, both p < 0.01) increased with higher cardiovascular risk score. The proportion of subjects self-reporting blood pressure > 135/85 mmHg, but self-reporting being normotensive (30, 50, and 52%), and the proportion of subjects who referred cholesterol levels > 200 mg/dl among those who self-referred not to have elevated cholesterol levels (13, 25, and 31%) increased both with cardiovascular risk category (p < 0.001). The proportion of subjects who were unaware of their personal history of diabetes was similar in the cardiovascular risk groups. The prevalence of low educational level was higher (56, 58, and 62%, p < 0.01) and the level of knowledge of non-pharmacological remedies to cardiovascular risk factors (63, 61, and 59%, p < 0.01) was lower in higher cardiovascular risk score group. Subjects aged < 55 years showed similar lack of knowledge about cardiovascular risk factors and the proportion of heavy smoking was as high as in the group of older participants. CONCLUSIONS: In cardiovascular primary prevention, the projection of higher individuals' risk profile by family doctors was not paralleled by an increase in individual's knowledge of major cardiovascular risk factors and of lifestyle interventions able to reduce the cardiovascular risk.