Long-term prognosis of unheralded myocardial infarction vs chronic angina; role of sex and coronary atherosclerosis burden.

BACKGROUND: Angina pectoris (AP) and unheralded myocardial infarction (MI) are considered random clinical equivalents of ischemic heart disease (IHD). Aim of the study was to evaluate the long-term progression of AP as opposed to unheralded MI as alternative first clinical presentations of IHD and the effect of sex on prognosis. METHODS: The study included 2272 consecutive patients, 1419 MI and 1353 AP, hospitalized from 1995 to 2007 at CNR Clinical Physiology Institute, Pisa, Italy and followed up to December 2013, who fulfilled the following criteria: unheralded MI or AP as first manifestation of IHD; age < = 70 years; known coronary anatomy; at least 10-year follow-up. Fatal and non fatal MI, all-cause, and cardiac deaths were the end-points. RESULTS: Males were predominant in MI (86%) as compared to AP (77%). Females were predominantly affected by AP (61%, MI 39%), and older than men (61 ± 7 vs 59 ± 8 years, p < 0.001). Coronary stenoses were prevalent in MI. During 115 ± 58 months follow-up, 628 deaths (23%) were observed, including 269 cardiac (43%), and 149 cancer deaths (24%). Long-term prognosis was significantly better in AP than MI group. The lowest prevalence of future MI was recorded in female AP (p < 0.001). CONCLUSIONS: MI as first clinical manifestation of IHD implies a more adverse prognosis than AP; future MI is a rare event in AP; sex influences the first presentation of IHD and its course with possible implications for preventive strategy.

Simple six-item clinical score improves risk prediction capability of stress echocardiography.

OBJECTIVES: To assess the value of a simple score integrating non-ischaemia-related variables in expanding the wall motion abnormalities risk power during stress echocardiography (SE). METHODS: Study includes 14 279 patients who underwent SE for evaluation of coronary artery disease. All-cause death was the end point. Patients were randomly divided into the modelling and validation group of equal size. In the modelling group, multivariate analysis was conducted using clinical, rest and SE data, and a score was obtained from the number of non-ischaemia-related independent prognostic predictors. The score prognostic capability was compared in both groups. RESULTS: During a median follow-up of 31 months, 1230 patients died: 622 (9%) in the modelling and 608 (9%) in the validation group (p=0.68). Independent predictors of mortality were ischaemia at SE (HR 1.77, 95% CI 1.49 to 2.12; p<0.0001) and six other parameters: age>65 years, wall motion at rest, diabetes, left bundle branch block, anti-ischaemic therapy and male sex. Risk score resulted prognostically effective in the modelling and validation groups, both with and without inducible ischaemia subset. When risk score was included in the multivariate analysis, besides ischaemia at SE it was the only independent predictor of mortality in the modelling (HR 1.70, 95% CI 1.60 to 1.82; p<0.0001), in the validation (HR 1.77, 95% CI 1.65 to 1.90; p<0.0001) and in the overall group (HR 1.73, 95% CI 1.66 to 1.82; p<0.0001). CONCLUSIONS: Simple clinical variables may be able to optimise SE risk stratification.

Stress Echocardiography Positivity Predicts Cancer Death.

BACKGROUND: Stress echocardiography (SE) predicts cardiac death, but an increasing share of cardiac patients eventually die of cancer. The aim of the study was to assess whether SE positivity predicts cancer death. METHODS AND RESULTS: In a retrospective analysis of prospectively acquired single-center, observational data, we evaluated 4673 consecutive patients who underwent SE from 1983 to 2009. All patients were cancer-free at index SE and were followed up for a median of 131 months (interquartile range 134). We separately analyzed predetermined end points: cardiovascular, cancer, and noncardiovascular, noncancer death, with and without competing risk. SE was positive in 1757 and negative in 2916 patients; 869 cardiovascular, 418 cancer, and 625 noncardiovascular, noncancer deaths were registered. The 25-year mortality was higher in SE-positive than in SE-negative patients, considering cardiovascular (40% versus 31%; P<0.001) and cancer mortality (26% versus 17%; P<0.01). SE positivity was a strong predictor of cancer (cause-specific hazard ratio 1.19; 95% confidence interval, 1.16-1.73; P=0.05) and cardiovascular mortality (1.18; 95% confidence interval, 1.03-1.35; P=0.02). Fine-Gray analysis to account for competing risk gave similar results. Cancer risk diverged after 15 years, whereas differences were already significant at 5 years for cardiovascular risk. CONCLUSIONS: SE results predict cardiovascular and cancer mortality. SE may act as a proxy of the shared risk factor milieu for cancer or cardiovascular death.

Left ventricular contractile reserve by stress echocardiography as a predictor of response to cardiac resynchronization therapy in heart failure: a systematic review and meta-analysis.

BACKGROUND: The presence of left ventricular contractile reserve (LVCR) during stress echo (SE) may provide favorable response to cardiac resynchronization therapy (CRT) in heart failure patients. The aim of the study was to perform a meta-analysis of available SE data in this set of patients. METHODS: From a Pubmed and Advance Google Scholar database web based search scan up to December 2016, we initially identified 5906 records. From this initial set, we removed that did not include SE and duplicate studies. We assessed for eligibility 71 full-text articles assessed for eligibility, and 60 of them did not meet the inclusion criteria as follow: 1) heart failure patients with NYHA class III and IV, depressed ejection fraction (EF <35%) and QRS duration ≥120 ms at study entry; 2) SE with assessment of LVCR; 3) Follow-up data. LVCR during SE was identified as reduction in wall motion score index and/or an increase in EF. RESULTS: Eleven studies with 861 patients (mean age 67 ± 9 years, ejection fraction 25 ± 6%) were included in the meta-analysis. The type of stress was either exercise (n = 2) or dobutamine (n = 9), the latter with low-dose (10 mcg) in two, intermediate-dose (20 mcg) in five, and high-dose (40 mcg) protocol in two studies. LVCR was detected in 555 patients (63%) and CRT-response was present in 584 (66%). The overall odds ratio for LVCR to predict a favorable CRT response was 2.06 (95%, CI 1.70-2-43), Z score: 11.055, p < 0.001. CONCLUSION: The presence of LVCR during SE with either dobutamine or exercise is associated with a greater chance of response to CRT. This parameter is now ready to be tested in a prospective multicenter trial to select patients more likely to benefit from CRT.

Variability of radiation doses of cardiac diagnostic imaging tests: the RADIO-EVINCI study (RADIationdOse subproject of the EVINCI study).

BACKGROUND: Patients with coronary artery disease can accumulate significant radiation dose through repeated exposures to coronary computed tomographic angiography, myocardial perfusion imaging with single photon emission computed tomography or positron emission tomography, and to invasive coronary angiography. Aim of the study was to audit radiation doses of coronary computed tomographic angiography, single photon emission computed tomography, positron emission tomography and invasive coronary angiography in patients enrolled in the prospective, randomized, multi-centre European study-EVINCI (Evaluation of Integrated Cardiac Imaging for the Detection and Characterization of Ischemic Heart Disease). METHODS: We reviewed 1070 tests (476 coronary computed tomographic angiographies, 85 positron emission tomographies, 310 single photon emission computed tomographies, 199 invasive coronary angiographies) performed in 476 patients (mean age 60 ± 9 years, 60% males) enrolled in 12 centers of the EVINCI. The effective doses were calculated in milli-Sievert (mSv) as median, interquartile range (IQR) and coefficient of variation of the mean. RESULTS: Coronary computed tomographic angiography (476 exams in 12 centers) median effective dose was 9.6 mSv (IQR = 13.2 mSv); single photon emission computed tomography (310 exams in 9 centers) effective dose was 9.3 (IQR = 2.8); positron emission tomography (85 in 3 centers) effective dose 1.8 (IQR = 1.6) and invasive coronary angiography (199 in 9 centers) effective dose 7.4 (IQR = 7.3). Inter-institutional variability was highest for invasive coronary angiography (100%) and coronary computed tomographic angiography (54%) and lowest for single photon emission computed tomography (20%). Intra-institutional variability was highest for invasive coronary angiography (121%) and coronary computed tomographic angiography (115%) and lowest for single photon emission computed tomography (14%). CONCLUSION: Coronary computed tomographic angiography and invasive coronary angiography doses vary substantially between and within centers. The variability in nuclear medicine procedures is substantially lower. The findings highlight the need to audit doses, to track cumulative exposures and to standardize doses for imaging techniques. TRIAL REGISTRATION: The study protocol is available at https://www.clinicaltrials.gov/ (ClinicalTrials.gov Identifier: NCT00979199 ). Information provided on September 16, 2009.

The declining frequency of inducible myocardial ischemia during stress echocardiography over 27 consecutive years (1983-2009).

BACKGROUND: Previous studies have suggested a decline in positivity of stress cardiac imaging, suggesting the need for developing better strategies for test selection to achieve acceptable cost-effectiveness balance. The aim of this retrospective study was to assess the rate of positivity of stress echocardiography (SE) over 27 consecutive years. METHODS: We assessed the rate of SE positivity in 2007 patients without previous myocardial infarction or coronary revascularization who performed SE in a tertiary care referral center from 1983 to 2009. SE was performed with dipyridamole (1427), dobutamine (136) or exercise (444). RESULTS: There was a progressive decline over time in the rate of SE positivity from 42% (1983-1991) to 22% (2001-2009), with a relative increase of patients with low pre-test probability of disease (from 5% to 27%). The percentage of patients studied with SE under anti-ischemic therapy increased markedly (from 8% in the first to 61% in the last nine years). CONCLUSION: Over 27 consecutive years, we observed a steady decline in SE positivity rate (with >5-fold increase of low probability patients), with almost 8-fold increase in anti-ischemic therapy at testing. We probably need refined criteria of referral for testing and/or better ways to titrate the negative response beyond wall motion abnormalities during SE.

Survival protection by bodyweight in isolated scleroderma-related pulmonary artery hypertension.

In chronic heart failure (CHF) due to systemic cardiovascular disease, obese patients have better survival. Bodyweight versus survival was analyzed post hoc in subjects with limited scleroderma (SSc) and isolated pulmonary artery hypertension (PAH), i.e. with CHF due to pulmonary vascular disease. Rheumatologists referred scleroderma subjects for evaluation, and PAH was ascertained by right heart catheterization (RHC). Forty-nine SSc-PAH subjects were stratified by body mass index (BMI): obese 7 (14.3 %), overweight 11 (22.4 %), normal weight 21 (42.9 %), and underweight 10 (20.4 %) for 24-month follow-up and pooled together for long-term 72-month follow-up. Survival was analyzed by Kaplan-Meier method. Multivariate Cox proportional hazards modeling helped to assess variables associated to survival. At 24 months (17 events), survival increases with BMI across four groups (logrank for trend P = 0.031). By Cox multivariate mortality, best model included: BMI (P = 0.043), low lung diffusion (DLco, P = 0.007), and reduced stroke volume index (SVI, P = 0.017). At 72 month (37 events), higher BMI values were associated with better survival but not significantly (P = 0.076). By multivariate modeling BMI did not enter any model, whereas low DLco entered all (P < 0.001). Also low SVI (P = 0.02) and low mixed venous saturation (SvO2, P = 0.009) were associated with the prognosis. From PAH diagnosis to final event, BMI had small (5.4 %), but significant decline (P < 0.001). This is ascribed to CHF progression, and may explain BMI predictive power weakening. The results suggest BMI decline should be contrasted, DLco is useful for screening and with SVI and SvO2 for assessing prognosis and treatment.

Long-term outcome and medical radiation exposure in patients hospitalized for cardiovascular disease.

BACKGROUND: Low radiation doses from diagnostic and therapeutic procedures may increase cancer incidence after decades in cardiac patients. The aim of the study was to evaluate the long-term outcome and the prognostic effect of radiological exposure. METHODS: A retrospective cohort study examined 16,311 Italian cardiac patients without cancer consecutively hospitalized between 1970 and 2009 and followed-up for a median of 10 years. Cumulative estimated effective dose was calculated for the imaging procedures. Main causes of death and primary cancer onset were the end points and their relation with radiation exposure was analyzed by Cox model. RESULTS: Over the years, there was an increasing trend of cancer, a decreasing trend of cardiovascular, with stability of other-causes death. Cumulative estimated effective radiation dose was higher in patients who died for cancer (20 ± 19 mSv) compared to cardiovascular (17 ± 17, P < 0.001) and other-causes deaths (15 ± 17, p < 0.001). The cumulative estimated effective dose adjusted HR was 1.004 (95% CI 1.000-1.009, p = 0.045) for cancer death and 1.008 (95% CI 1.005-1.011, p < 0.001) for (fatal and non-fatal) cancer onset. Radiation effective dose was not predictive of cardiovascular mortality (HR = 0.991), nor it was of other types of deaths (HR = 0.995). Smoking was a predictor for cardiovascular mortality, but it was not of other types of deaths. CONCLUSIONS: Non-cardiovascular causes of death are responsible for almost half of later deaths in cardiac patients. The radiological exposure from medical imaging procedures is predictive of cancer risk and cancer death.

Improved survival in limited scleroderma-related pulmonary artery hypertension.

Reportedly, patients with scleroderma-related pulmonary hypertension (SSc-PAH) respond poorly to new vasoactive drugs (NVD). Forty-nine SSc-PAH patients underwent right heart catheterization (RHC) and, according to NVD availability, divided as follows: Group 1 (n = 23, from 1999 to 2004, poor availability), and Group 2 (n = 26, from 2005 to 2010, good availability). Before diagnostic RHC, NVD had been given to 30 % of the patients in Group 1, and 58 % of those in Group 2 (p = 0.049). At diagnosis, patients in Group 1 had greater heart dilatation (p < 0.01), higher mean pulmonary artery pressure (p < 0.05), lower pulmonary artery capacitance (p < 0.05), and lower carbon monoxide lung diffusing capacity (DLco, p < 0.05) than those in Group 2. At a median follow-up time of 15.5 months, DLco further decreased in Group 1 (p < 0.05), whereas cardiac index increased in Group 2 (p < 0.05). At 36 months of follow-up, 72.4 % of the patients in Group 2 were still alive as opposed to 30.4 % in Group 1 (p = 0.02). In multivariate analysis, DLco and mixed venous oxygen saturation (SvO2) were independent predictors of survival. A value of DLco <7.2 mL/mmHg/min was associated with a hazard ratio (HR) of 5.3 (p < 0.001); for SvO2 <63.8 %, the HR was 3.7 (p < 0.01).NVD have beneficial effects in patients with SSc-PAH. Both DLco and SvO2 are predictors of survival and may assist in planning treatment.

Interpretation of the "obesity paradox": a 30-year study in patients with cardiovascular disease.

BACKGROUND: Several epidemiological reports indicate that the body mass index (BMI) is inversely related with mortality, in spite of the notion that obesity is a recognized cardio-metabolic risk factor. The aim of the study was to evaluate the independent impact of overweight and obesity on long-term mortality in a large cohort of patients with heart disease (HD). METHODS: The study included 10,446 patients hospitalized in the last three decades for ischemic (60%) or non-ischemic HD and followed-up for 10 years. The relationship between BMI and total or cardiovascular mortality was analyzed in the whole cohort, and in age-stratified categories (≤ 65 and >65 years). Considering that survival in HD patients has improved after the introduction of revascularization, beta-blockers, ACE inhibitors, and statins, the relationship was re-examined separately in patients hospitalized before and after 1990. RESULTS: Diabetes, hyperuricemia, hypertension, glycaemia, and triglyceridemia increased across BMI groups. During follow-up (73 ± 59 months) there were 1707 all-cause deaths (47% cardiac). Any relationship between BMI and mortality was lost in the ≤ 65 age category and in patients hospitalized before 1990, but it persisted in old patients hospitalized after 1990. Most significant independent predictors of mortality in all groups were hyperuricemia, diabetes and impaired ejection fraction. CONCLUSIONS: No independent relationship was found between BMI and mortality in subjects ≤ 65 years of age. This neutral relationship seems to be partly counteracted by treatment, particularly in old patients. A different effect of obesity onset in old vs. young age cannot be ruled out.

Improved survival in patients with inoperable chronic thromboembolic pulmonary hypertension.

Patients with inoperable chronic thromboembolic pulmonary hypertension (Inop-CTEPH) treated with conventional therapy have a poor survival. We compare the 3-year survival between those treated with conventional therapy and those treated with conventional therapy and a combination of novel drugs. We also evaluate the clinical course. A total of 34 Inop-CTEPH consecutive patients were evaluated from 1991 to 2009 including right heart catheterization (RHC) and perfusion lung scan (PLS): 7 underwent surgical treatment while 27 were confirmed inoperable. Of these 27 patients, 12 evaluated from 1991 to 2003 (Group 1) were treated with conventional therapy and 15 evaluated from 2004 to 2009 (Group 2) were treated with conventional and novel therapies. At baseline, no group difference emerged at RHC. Based on clinical course, novel drugs and oxygen supplementation were given to patients of Group 2. Seven of these who had worse clinical course repeated RHC and four of them also PLS during therapy. Those without repeat RHC had baseline pulmonary artery mean pressure and brain natriuretic peptide (NT-proBNP) lower and mixed venous saturation (SvO2) and exercise test higher (p = 0.022, 0.015, 0.044 and 0.003, respectively). During therapy, those with repeat RHC had total pulmonary vascular resistance reduced (p = 0.012), base excess increased (p = 0.002) and significant redistribution of pulmonary blood flow at PLS. At the 3-year follow-up, survival was 86% in Group 2 and 31% in Group 1 (p = 0.031). In Inop-CTEPH patients, the clinical course may help to select drugs and the level of oxygen supply that can improve hemodynamics, gas exchange and long-term survival.

Trends of increasing medical radiation exposure in a population hospitalized for cardiovascular disease (1970-2009).

BACKGROUND: High radiation doses employed in cardiac imaging may increase cancer frequency in exposed patients after decades. The aim of this study was to evaluate the relative trends in medical radiation exposure in a population hospitalized for cardiovascular disease. METHODS AND RESULTS: An observational single-center study was conducted to examine 16,431 consecutive patients with heart disease admitted to the Italian National Research Council Institute of Clinical Physiology between January 1970 and December 2009. In all patients, the cumulative estimated effective dose was obtained from data mining of electronic records of hospital admissions, adopting the effective dose typical values of the American Heart Association 2009 statement and Mettler's 2008 catalog of doses. Cumulative estimated effective dose per patient in the last 5 years was 22 (12-42) mSv (median, 25(th)-75(th) percentiles), with higher values in ischemic heart disease (IHD), 37 (20-59) vs non-IHD, 13 (8-22) mSv, p<0.001. Trends in radiation exposure showed a steady increase in IHD and a flat trend in non-IHD patients, with variation from 1970-74 to 2005-2009 of +155% for IHD (p<0.001) and -1% in non-IHD (NS). The relative contribution of different imaging techniques was remodeled over time, with nuclear cardiology dominating in 1970s (23% of individual exposure) and invasive fluoroscopy in the last decade (90% of individual exposure). CONCLUSION: A progressive increase in cumulative estimated effective dose is observed in hospitalized IHD patients. The growing medical radiation exposure may encourage a more careful justification policy regarding ionizing imaging in cardiology patients applying the two main principles of radiation protection: appropriate justification for ordering and performing each procedure, and careful optimization of the radiation dose used during each procedure.

Long-term prognosis in stable angina; medical treatment or coronary revascularization in patients younger than 70 years?

BACKGROUND: Literature on the appropriateness of coronary revascularization in chronic angina is still scanty. The study aimed to compare long-term effects of revascularization with those of medical therapy in stable angina. METHODS: In an observational single center study, we assessed 10 year follow-up of 1442 consecutive patients with chronic angina, at least one coronary vessel disease, no previous myocardial infarction, screened for inducible ischemia. Patients>70 years were excluded. The event-free probabilities were estimated by Kaplan-Meier curves; all cause death, cardiac death, non-fatal myocardial infarction were the considered end points. RESULTS: Age was 56±8 yrs. Global left ventricular function was preserved in all. Myocardial ischemia was documented in 1190 patients. Coronary disease was more severe in patients with inducible ischemia as compared to those with negative stress test (p<0.001); 868 patients underwent one revascularization procedure, 511 coronary angioplasty. Median follow-up was 106 months; 13% all cause deaths, 8% cardiac deaths, 6% non-fatal myocardial infarction were registered. When provocative test was negative revascularization did not improve survival (1% per year mortality irrespective of type of treatment). Conversely survival was significantly improved by revascularization when ischemia was documented (0.7% vs 1.8% per year mortality for revascularization vs medical therapy, p<0.05). Incidence of non-fatal myocardial infarction was low and similar in both groups. CONCLUSION: In low-risk chronic angina coronary revascularization does not improve long-term prognosis unless inducible myocardial ischemia is present. This suggests considering coronary revascularization as an effective tool in treating coronary artery disease only when myocardial ischemia has been documented.

Religiosity associated with prolonged survival in liver transplant recipients.

We tested the hypothesis that religiosity (ie, seeking God's help, having faith in God, trusting in God, and trying to perceive God's will in the disease) is associated with improved survival in patients with end-stage liver disease who have undergone orthotopic liver transplantation. We studied a group of 179 candidates for liver transplantation who responded to a questionnaire on religiosity during the pretransplant psychological evaluation and underwent transplantation between 2004 and 2007. The demographic data, educational level, employment status, clinical data, and results of the questionnaire were compared with the survival of patients during follow-up, regardless of the cause of any deaths. Factorial analysis of responses to the questionnaire revealed 3 main factors: searching for God (active), waiting for God (passive), and fatalism. The consistency of the matrix was very high (consistency index = 0.92). Eighteen patients died during follow-up (median time = 21 months). In multivariate analysis, only the searching for God factor [hazard ratio (HR) = 2.95, 95% confidence interval (CI) = 1.05-8.32, χ(2) = 4.205, P = 0.040] and the posttransplant length of stay in the intensive care unit (HR = 1.05, 95% CI = 1.01-1.08, χ(2) = 8.506, P = 0.035) were independently associated with survival, even after adjustments for the waiting for God factor, fatalism, age, sex, marital status, employment, educational level, viral etiology, Child-Pugh score, serum creatinine level, time from the questionnaire to transplantation, donor age, and intraoperative bleeding. Patients who did not present the searching for God factor were younger than those who did, but they had shorter survival times (P = 0.037) and a 3-fold increased relative risk of dying (HR = 3.01, 95% CI = 1.07-8.45). In conclusion, religiosity is associated with prolonged survival in patients undergoing liver transplantation.

ABO blood group alleles: A risk factor for coronary artery disease. An angiographic study.

OBJECTIVES: To analyze the impact of ABO groups on coronary heart disease risk factors, coronary involvement and prognosis. METHODS: An observational single center study was conducted to examine 4901 consecutive patients with heart disease receiving coronary angiography and ABO group determination at National Research Council Institute of Clinical Physiology between January 1993 and December 2003, with maximum 10 years follow-up. All-cause death and cardiac death, were the considered end points. RESULTS: When compared to the official distribution of ABO groups in the Italian population (O 40%, A 36%, B 17%, AB 7%), a substantially different distribution was observed in the study population (O 43.3%, A 41.4%, B 11.2%, AB 4.1%). In addition, a significant association was found between group non-O and family history of ischemic heart disease, hypercholesterolemia and presence of coronary atherosclerosis. Higher prevalence of A and B alleles was found in patients with myocardial infarction (P<0.05). Group non-O was a powerful predictor of cardiac mortality in patients aged <65 years, particularly in women (HR 1.53, 95% CI 1.06-2.21 and HR 5.29, 95% CI 1.57-17.82, respectively). CONCLUSIONS: Group non-O is associated with increased mortality in patients with ischemic heart disease. Group non-O increases the risk for cardiac death in non-elderly patients, particularly in younger females, and groups A and B prevail in myocardial infarction. ABO group determination might aid in genetic screening for ischemic heart disease and become relevant in the management of risk factor control.

Arterial base deficit in pulmonary embolism is an index of severity and diagnostic delay.

In acute pulmonary embolism, patients free from circulatory failure usually present a blood gas pattern consistent with respiratory alkalosis. We investigated whether the appearance of arterial base deficit in these patients indicates disease severity and diagnostic delay. Twenty-four consecutive patients with pulmonary embolism were retrospectively evaluated. Twelve patients had arterial base excess > or =0 mmol/L (Group 1), and 12 patients arterial base deficit <0 mmol/L (Group 2). No patient showed signs of circulatory failure. Group 1 was characterized by a mean base excess of 2.2 +/- 1.7 mmol/L, while in Group 2, the mean base deficit was -1.9 +/- 0.7 mmol/L (p < 0.0001). At 1 week since the embolism, 11 patients of Group 1 and 6 of Group 2 received a PE diagnosis (p < 0.05). The vascular obstruction index was more severe in Group 2 than in Group 1 (48 +/- 12 vs. 36 +/- 17%, respectively, p < 0.05). In Group 2, the PaCO(2) was lower (33 +/- 3 vs. 36 +/- 5 mmHg, respectively, p < 0.05), the arterial pH was decreased (7.442 +/- 0.035 vs. 7.472 +/- 0.050, respectively, p = 0.097), the Pv(50) was lower (28.3 +/- 1.7 vs. 29.8 +/- 1.6 mmHg, respectively, p < 0.05), the aHCO(3) (-) was lower (22.5 +/- 0.7 vs. 26.1 +/- 1.6 mmol/L, respectively; p < 0.0001), while between the Groups, O(2) delivery, O(2) mixed venous saturation, and O(2) extraction ratio were equivalent. Despite no signs of circulatory failure, an arterial Base deficit develops in patients with respiratory alkalosis subsequent to more severe pulmonary vascular obstruction. Diagnostic delay favors a base deficit. Depending on the degree of hypocapnia, there may be limitation of peripheral O(2) uptake despite adequate O(2) availability. Progressive bicarbonate deficit suggests an increased risk for underlying conditions such as cardio-respiratory disorders or cancer, and requires close control and treatment.

Additive prognostic value of gamma-glutamyltransferase in coronary artery disease.

BACKGROUND: Serum gamma-glutamyltransferase activity (GGT) has been documented as an independent cardiovascular risk factor. However, to-date its value has not been compared with C-reactive protein (CRP) and other indexes in a multimarker prognostic strategy in patients with coronary artery disease. METHODS: We prospectively evaluated 474 subjects with angiographically documented CAD. GGT and traditional humoral and clinical parameters were measured at hospital admission. A multivariate model was used to predict all-cause and cardiac mortality. RESULTS: GGT showed an independent prognostic value after adjustment for possible confounders, including alcohol consumption, and beyond established risk factors, such as extent of coronary atherosclerotic disease, left ventricular ejection fraction, age, serum glucose, cholesterol subfractions, and C-reactive protein (CRP). At a 3-year follow-up, cardiac mortality was 9% in patients with serum GGT activity >25 U/L vs. 3.5% in those with serum GGT<25 U/L (p=0.028). The association of three independent biomarkers (higher GGT, CRP, fasting glucose) identified a subgroup of 45 patients with the highest risk of cardiac death at 3 years (26.6%, vs. no event or 2.7% in the subsets of 87 and 198 patients with, respectively, no/one risk factor above cut-off value, p<0.0001). CONCLUSIONS: GGT is confirmed as independent risk factor in patients with established coronary artery disease. GGT, CRP, fasting glucose show an additive prognostic value, whereas low values of these biomarkers identify a subset of patients with the lowest risk of cardiac death.

Predictive value of elevated neutrophil-lymphocyte ratio on cardiac mortality in patients with stable coronary artery disease.

BACKGROUND: An association between white blood cell count (WBC), severity of coronary artery disease (CAD) and survival has been described in patients with acute coronary syndrome. Our aim was to analyze the predictive ability for cardiac events of differential WBC, which is still not well characterized, against established risk factors in angiographically proven CAD patients. METHODS: We prospectively evaluated complete blood count, biomarkers of inflammation [(C-reactive protein (CRP) and serum iron (SI)], glucose/lipid metabolism [(fasting glucose (FG), total, high-density lipoprotein (HDL) and low-density lipoprotein cholesterol] and established risk factors in 422 consecutive ischemic patients with angiographically documented stable CAD. On a 3-year follow-up, cardiac death and non-fatal myocardial infarction (MI) were considered as end-points. RESULTS: At multivariate analysis neutrophil to lymphocyte ratio (N/L) emerged as independent predictor of cardiac death (HR 8.13; p=0.02) together with CRP, left ventricular ejection fraction (LVEF), FG, HDL and SI. CRP, LVEF, and HDL showed an independent prognostic value for cardiac death and non-fatal MI. Event-free survival according to N/L tertiles was 99% for the first tertile (1.23+/-0.26), 96.5% for the second (2.05+/-0.29), and 88.8% for the third one (5.19+/-3.81). CONCLUSIONS: N/L is an independent predictor of cardiac mortality in stable CAD patients.

Personality traits and heart rate variability predict long-term cardiac mortality after myocardial infarction.

AIMS: To investigate personality traits and sympatho-vagal modulation of heart rate variability (HRV) during acute myocardial infarction (AMI), assessing their relationships and their long-term prognostic value. METHODS AND RESULTS: Psychological traits and 24 h HRV were prospectively investigated in 246 patients at discharge of an AMI. Patients were followed-up to 8 years for the occurrence of cardiac death and non-fatal reinfarction. Low coping and anxiety traits associated with reduced HRV characterized the study population. At univariate analysis, low emotional sensitivity and insecurity, relative tachycardia, reduced high frequency (HF), and low frequency power and pNN50 were predictive of cardiac death at 8-year follow-up. At multivariable analysis, low emotional sensitivity and low HF power remained predictive, with a relative risk of 4.18 (P=0.003) and 2.76 (P=0.007), respectively; also the type of infarction (Q vs. non-Q) and hospital length of stay were independent predictive variables. CONCLUSION: Anxiety and emotional sensitivity were significant predictors of 8-year cardiac mortality after AMI. Reduced HF power, a recognized marker of vagal withdrawal, increased the risk.

Early assessment of heart rate variability is predictive of in-hospital death and major complications after acute myocardial infarction.

BACKGROUND: Depressed heart rate variability at acute myocardial infarction discharge is associated with poor long-term prognosis. However, its early (<48 h) predictive value has not been extensively investigated. Aim of this Multicenter Italian Study was to investigate, during acute myocardial infarction, in-hospital prognostic value of heart rate variability and its short-term evolution. METHODS: Twenty-four hour ECG monitoring was prospectively obtained on admission in 413 patients with new-onset acute myocardial infarction and repeated in 349 at discharge. Heart rate variability statistical and frequency domain indices, peak creatine kinase, echocardiographic wall motion score index and risk factors were obtained. The occurrence of cardiac death and resuscitated ventricular fibrillation were the primary end-points; cardiogenic shock, ventricular tachycardia, post-infarction angina and heart failure the secondary end-points. RESULTS: At admission, a marked reduction in heart rate variability indices was evident. Nine patients died during hospitalization and 13 were resuscitated from ventricular fibrillation. Secondary endpoints occurred in other 91 patients. At univariate analysis, low frequencies (LF), mean time interval between consecutive heart beats (RR), wall motion score index and family history of ischemic heart disease were predictive of combined primary and secondary end-points. At multivariate analysis, only LF and family history were predictive with a relative risk of 2.01 and 1.84, respectively (P<0.003). In survivors, heart rate variability indices significantly increased during hospitalization, still remaining below reference values. CONCLUSIONS: A depressed heart rate variability was present in the early phase of infarction and improved at discharge. LF power was an independent predictor of the combined unfavorable short-term events.