A Novel Data Augmentation Method for Radiomics Analysis Using Image Perturbations.

Radiomics extracts hundreds of features from medical images to quantitively characterize a region of interest (ROI). When applying radiomics, imbalanced or small dataset issues are commonly addressed using under or over-sampling, the latter being applied directly to the extracted features. Aim of this study is to propose a novel balancing and data augmentation technique by applying perturbations (erosion, dilation, contour randomization) to the ROI in cardiac computed tomography images. From the perturbed ROIs, radiomic features are extracted, thus creating additional samples. This approach was tested addressing the clinical problem of distinguishing cardiac amyloidosis (CA) from aortic stenosis (AS) and hypertrophic cardiomyopathy (HCM). Twenty-one CA, thirty-two AS and twenty-one HCM patients were included in the study. From each original and perturbed ROI, 107 radiomic features were extracted. The CA-AS dataset was balanced using the perturbation-based method along with random over-sampling, adaptive synthetic (ADASYN) and the synthetic minority oversampling technique (SMOTE). The same methods were tested to perform data augmentation dealing with CA and HCM. Features were submitted to robustness, redundancy, and relevance analysis testing five feature selection methods (p-value, least absolute shrinkage and selection operator (LASSO), semi-supervised LASSO, principal component analysis (PCA), semi-supervised PCA). Support vector machine performed the classification tasks, and its performance were evaluated by means of a 10-fold cross-validation. The perturbation-based approach provided the best performances in terms of f1 score and balanced accuracy in both CA-AS (f1 score: 80%, AUC: 0.91) and CA-HCM (f1 score: 86%, AUC: 0.92) classifications. These results suggest that ROI perturbations represent a powerful approach to address both data balancing and augmentation issues.

Collateral presence and extent do not predict myocardial viability and ischemia in chronic total occlusions: A stress-CMR study.

BACKGROUND: Well-developed collaterals are assumed as a marker of viability and ischemia in chronic total occlusions (CTO). We aim to correlate viability and ischemia with collateral presence and extent in CTO patients by cardiac magnetic resonance (CMR). METHODS: Multicentre study of 150 CTO patients undergoing stress-CMR, including adenosine if normal systolic function, high-dose-dobutamine for patients with akinetic/>2 hypokinetic segments and EF ≥35%, otherwise low-dose-dobutamine (LDD); all patients underwent late gadolinium enhancement (LGE) imaging. Viability was defined as mean LGE transmurality ≤50% for adenosine, as functional improvement for dobutamine-stress-test, ischemia as ≥1.5 segments with perfusion defects outside the scar zone. RESULTS: Rentrop 3/CC 2 defined well-developed (WD, n = 74) vs poorly-developed collaterals (PD, n = 76). Viability was equally prevalent in WD vs PD: normo-functional myocardium with ≤50% LGE in 52% vs 58% segments, p = 0.76, functional improvement by LDD in 48% vs 52%, p = 0.12. Segments with none, 1-25%,26-50%,51-75% LGE showed viability by LDD in 90%,84%,81%,61% of cases, whilst in 12% if 76-100% LGE (p < 0.01). There was no difference in WD vs PD for ischemia presence (74% vs 75%, p = 0.99) and extent (2.7 vs 2.8 segments, p = 0.77). CONCLUSIONS: In a large cohort of CTO patients, presence and extent of collaterals did not predict viability and ischemia by stress-CMR. Scar extent up to 75% LGE was still associated with viability, whereas ischemia was undetectable in 25% of patients, suggesting that the assessment of CTO patients with CMR would lead to a more comprehensive evaluation of viability and ischemia to guide revascularization.

Cardiac magnetic resonance for ischaemia and viability detection. Guiding patient selection to revascularization in coronary chronic total occlusions: The CARISMA_CTO study design.

BACKGROUND: It is debated whether percutaneous revascularization (PCI) of total coronary chronic occlusion (CTO) is superior to optimal medical therapy (OMT) in improving symptoms, left ventricular (LV) function and major adverse cardiac/cerebrovascular events (MACCE). Furthermore, CTO-PCI is a challenging technique, with lower success rate than in other settings. A systematic analysis of baseline LV function, infarction extent and ischaemic burden to predict response to revascularization has never been performed. PURPOSES: To establish a CMR protocol to identify patients (pts) who can benefit most from CTO-PCI. Myocardial viability/ischaemia retains high biological plausibility as predictors of response to revascularization. Therefore, baseline viability (necrotic tissue extent, response to inotropic stimulation) and ischaemia (perfusion defect, wall motion abnormality during stress) will be studied as potential predictors of mechanical LV segmental improvement and ischaemic burden reduction in CTO territory (primary endpoint), LV remodelling and global function, Seattle Angina Questionnaire, and MACCE improvement (secondary endpoints) in the follow-up. METHODS: Pts with CTO suitable for PCI undergo stress-CMR for viability/ischaemia assessment. Pts with normal LV function undergo adenosine, those with moderately-reduced ejection fraction (EF) and wall motion abnormalities high-dose dobutamine, pts with EF <35% low-dose dobutamine. All pts undergo late gadolinium enhancement and repeat the same scan at 12 ±â€¯3 months, regardless of PCI success or decision for OMT. CONCLUSIONS: A multi-parameter CMR protocol tailored on pts characteristics to study viability/ischaemia could help in identifying responders in terms of LV function, ischaemic burden and clinical outcome among pts suitable for CTO-PCI, improving selection of best candidates to percutaneous revascularization.

A statistical shape model of the left ventricle from real-time 3D echocardiography and its application to myocardial segmentation of cardiac magnetic resonance images.

OBJECT: We present in this paper the application of a statistical shape model of the left ventricle (LV) built from transthoracic real time 3D echocardiography (3DE) to segment the LV endocardium and epicardium in cardiac magnetic resonance (CMR) images. MATERIAL AND METHODS: The LV model was built from a training database constituted by over 9000 surfaces obtained from retrospectively selected 3DE examination of 435 patients with various pathologies. Three-dimensional segmentation of the endocardium and the epicardium was obtained by processing CMR images acquired in 30 patients with a dedicated active shape modelling (ASM) algorithm using the proposed LV model. RESULTS: The segmentation results obtained with the proposed method were compared with those obtained by the manual reference technique; similarity was proven by computing: i) point to surface distance (<2 mm), ii) Dice similarity coefficient (>89%), iii) Hausdorff distance (∼5 mm). This was furthermore confirmed by equivalence testing, linear regression and Bland Altman analysis applied on derived clinical parameters, such as LV volumes and mass. CONCLUSIONS: This study showed the potential usefulness of the proposed inter-modal ASM approach featuring a 3DE-based LV model for the 3D segmentation of the LV myocardium in CMR images.

Clinical Markers of Anxiety Subtypes in Parkinson Disease.

OBJECTIVE: The aim of this work was to investigate marker profiles for proposed anxiety subtypes in Parkinson disease (PD). METHODS: We used the persistent anxiety, episodic anxiety, and avoidance behavior subscales of the Parkinson Anxiety Scale as dependent variables in multivariable linear regression analyses using a cross-sectional data set of 311 patients with PD. Independent variables consisted of a range of demographic, psychiatric, and disease-specific markers. RESULTS: In the most parsimonious model of persistent anxiety, higher Hamilton Depression Rating Scale scores, a history of anxiety, fewer years of education, lower Mini-Mental State Examination scores, lower Lawton Instrumental Activities of Daily Living scores, female sex, and complications of therapy (higher Unified Parkinson Disease Rating Scale part IV scores) were all associated with more severe persistent anxiety. Markers associated with more severe episodic anxiety included PD-specific disturbances of activities of daily living, complications of therapy, higher Hamilton Depression Rating Scale scores, female sex, and a history of anxiety. Finally, higher Hamilton Depression Rating Scale scores, a history of anxiety, complications of therapy, and longer disease duration were associated with avoidance behavior. After excluding clinically depressed patients with PD, disease severity and longer disease duration were significantly associated with episodic anxiety, but not with persistent anxiety. CONCLUSION: Persistent anxiety is mainly influenced by nonspecific markers, while episodic anxiety seems to be more PD-specific compared to persistent anxiety and may be more situational or contextual. These results provide support for possible distinct underlying constructs for anxiety subtypes in PD.

Cardiac mesenchymal stromal cells are a source of adipocytes in arrhythmogenic cardiomyopathy.

AIM: Arrhythmogenic cardiomyopathy (ACM) is a genetic disorder mainly due to mutations in desmosomal genes, characterized by progressive fibro-adipose replacement of the myocardium, arrhythmias, and sudden death. It is still unclear which cell type is responsible for fibro-adipose substitution and which molecular mechanisms lead to this structural change. Cardiac mesenchymal stromal cells (C-MSC) are the most abundant cells in the heart, with propensity to differentiate into several cell types, including adipocytes, and their role in ACM is unknown. The aim of the present study was to investigate whether C-MSC contributed to excess adipocytes in patients with ACM. METHODS AND RESULTS: We found that, in ACM patients' explanted heart sections, cells actively differentiating into adipocytes are of mesenchymal origin. Therefore, we isolated C-MSC from endomyocardial biopsies of ACM and from not affected by arrhythmogenic cardiomyopathy (NON-ACM) (control) patients. We found that both ACM and control C-MSC express desmosomal genes, with ACM C-MSC showing lower expression of plakophilin (PKP2) protein vs. CONTROLS: Arrhythmogenic cardiomyopathy C-MSC cultured in adipogenic medium accumulated more lipid droplets than controls. Accordingly, the expression of adipogenic genes was higher in ACM vs. NON-ACM C-MSC, while expression of cell cycle and anti-adipogenic genes was lower. Both lipid accumulation and transcription reprogramming were dependent on PKP2 deficiency. CONCLUSIONS: Cardiac mesenchymal stromal cells contribute to the adipogenic substitution observed in ACM patients' hearts. Moreover, C-MSC from ACM patients recapitulate the features of ACM adipogenesis, representing a novel, scalable, patient-specific in vitro tool for future mechanistic studies.

Ultra-low-dose CT for left atrium and pulmonary veins imaging using new model-based iterative reconstruction algorithm.

AIMS: To evaluate the feasibility of ultra-low-dose CT for left atrium and pulmonary veins using new model-based iterative reconstruction (MBIR) algorithm. METHODS AND RESULTS: Two hundred patients scheduled for catheter ablation were randomized into two groups: Group 1 (100 patients, Multidetector row CT (MDCT) with MBIR, no ECG triggering, tube voltage and tube current of 100 kV and 60 mA, respectively) and Group 2 [100 patients, MDCT with adaptive statistical iterative reconstruction algorithm (ASIR), no ECG triggering, and kV and mA tailored on patient BMI]. Image quality, CT attenuation, image noise, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR) of left atrium (LA) and pulmonary veins, and effective dose (ED) were evaluated for each exam and compared between two groups.No significant differences between groups in terms of population characteristics, cardiovascular risk factors, anatomical features, prevalence of persistent atrial fibrillation and image quality score. Statistically significant differences were found between Group 1 and Group 2 in mean attenuation, SNR, and CNR of LA. Significantly, lower values of noise were found in Group 1 versus Group 2. Group 1 showed a significantly lower mean ED in comparison with Group 2 (0.41 ± 0.04 versus 4.17 ± 2.7 mSv). CONCLUSION: The CT for LA and pulmonary veins imaging using MBIR is feasible and allows examinations with very low-radiation exposure without loss of image quality.

Designing a new scale to measure anxiety symptoms in Parkinson's disease: item selection based on canonical correlation analysis.

BACKGROUND AND PURPOSE: The lack of appropriate measures has hindered the research on anxiety syndromes in Parkinson's disease (PD). The objective of the present cross-sectional, international study was to identify shared elements and grouping of components from anxiety scales as a basis for designing a new scale for use in PD. METHODS: For this purpose, 342 consecutive PD patients were assessed by means of the Mini International Neuropsychiatric Inventory (depression and anxiety sections), the Clinical Global Impression of severity of the anxiety symptoms, the Hamilton Anxiety Rating Scale (HARS), the Neuropsychiatric Inventory (section E), the Beck Anxiety Inventory (BAI) and the Anxiety subscale of the Hospital Anxiety and Depression Scale (HADS-A). RESULTS: As the HADS-A showed a weak correlation with the HARS and BAI, it was not considered for more analyses. HARS and BAI exploratory factor analysis identified nine factors (62% of the variance), with only two of them combining items from both scales. Therefore, a canonical correlation model (a method to identify relations between components of two groups of variables) was built and it showed four factors grouping items from both scales: the first factor corresponded to 'generalized anxiety'; the second factor included muscular, sensory and autonomic 'non-specific somatic symptoms'; the third factor was dominated by 'respiratory symptoms'; and the fourth factor included 'cardiovascular symptoms'. CONCLUSIONS: BAI is heavily focused on panic symptoms, whilst HARS is more focused towards generalized anxiety symptoms. The new scale should include additional components in order to assess both episodic and persistent anxiety as well as items for evaluation of avoidance behaviour.

A comparison of nine scales to detect depression in Parkinson disease: which scale to use?

OBJECTIVE: The Methods of Optimal Depression Detection in Parkinson's Disease (MOOD-PD) study compared the psychometric properties of 9 depression scales to provide guidance on scale selection in Parkinson disease (PD). METHODS: Patients with PD (n = 229) from community-based neurology practices completed 6 self-report scales (Beck Depression Inventory [BDI]-II, Center for Epidemiologic Studies Depression Rating Scale-Revised [CESD-R], 30-item Geriatric Depression Scale [GDS-30], Inventory of Depressive Symptoms-Patient [IDS-SR], Patient Health Questionnaire-9 [PHQ-9], and Unified Parkinson's Disease Rating Scale [UPDRS]-Part I) and were administered 3 clinician-rated scales (17-item Hamilton Depression Rating Scale [HAM-D-17], Inventory of Depressive Symptoms-Clinician [IDS-C], and Montgomery-Åsberg Depression Rating Scale [MADRS] and a psychiatric interview. DSM-IV-TR diagnoses were established by an expert panel blinded to the self-reported rating scale data. Receiver operating characteristic curves were used to estimate the area under the curve (AUC) of each scale. RESULTS: All scales performed better than chance (AUC 0.75-0.85). Sensitivity ranged from 0.66 to 0.85 and specificity ranged from 0.60 to 0.88. The UPDRS Depression item had a smaller AUC than the BDI-II, HAM-D-17, IDS-C, and MADRS. The CESD-R also had a smaller AUC than the MADRS. The remaining AUCs were statistically similar. CONCLUSIONS: The GDS-30 may be the most efficient depression screening scale to use in PD because of its brevity, favorable psychometric properties, and lack of copyright protection. However, all scales studied, except for the UPDRS Depression, are valid screening tools when PD-specific cutoff scores are used.

Feasibility and diagnostic accuracy of a low radiation exposure protocol for prospective ECG-triggering coronary MDCT angiography.

AIM: To compare the feasibility, accuracy, and effective radiation dose (ED) of multidetector computed tomography (MDCT) in the detection of coronary artery disease using a combined ED-saving strategy including prospective electrocardiogram (ECG) triggering with a short x-ray window and a body mass index (BMI)-adapted imaging protocol using adaptive statistical iterative reconstruction (ASIR; group 1), in comparison with a prospective ECG triggering strategy alone (group 2). MATERIALS AND METHODS: One hundred and seventy patients scheduled for invasive coronary angiography (ICA) were evaluated. Fourteen patients were not eligible for MDCT. The remaining 156 patients were randomized to group 1 (78 patients) and group 2 (78 patients). Eight and 11 patients in groups 1 and 2, respectively, were excluded after randomization because the patients' heart rates were >65 beats/min. MDCT images were assessed for feasibility, signal-to-noise ration (SNR), and contrast-to-noise ratio (CNR), accuracy in detection of coronary stenoses >50% versus ICA and for ED. RESULTS: The feasibility, SNR, CNR, accuracy in a segment-based and patient-based model were similar in both groups (97 versus 95%, 14.5 ± 3.9 versus 14.2 ± 4.1, 16 ± 4.6 versus 16.5 ± 4.4, 95 versus 94% and 97 versus 99%, respectively). The ED in group 1 was 72% lower than in group 2 (2.1 ± 1.2 versus 7.5 ± 1.8 mSv, respectively; p<0.01). CONCLUSIONS: The use of a multi-parametric ED saving protocol results in a significant reduction in ED without a negative impact on accuracy.

Accuracy of multidetector spiral computed tomography in detecting significant coronary stenosis in patient populations with differing pre-test probabilities of disease.

AIM: To investigate the clinical impact of multidetector computed tomography (MDCT) in patients with a low versus a high pre-test likelihood of coronary artery disease (CAD). MATERIALS AND METHODS: A cohort of 120 patients with suspected CAD, scheduled for conventional coronary angiography, underwent MDCT. Using the American Heart Association (AHA)/American College of Cardiology (ACC) guidelines, the population was divided into two groups: patients with a low (group 1) and a high (group 2) likelihood of CAD. RESULTS: Analysis of all segments showed a high feasibility (92%), and a patient based-model showed excellent sensitivity and negative predictive values (NPV; both 100%) and acceptable specificity and positive predictive values (PPV; 86 and 90%, respectively), with an accuracy of 94%. Using MDCT in patients with lower pre-test likelihoods of CAD, according to the ACC/AHA guidelines, the accuracy remained high (93%); conversely, in patient groups with a high prevalence of CAD, a non-significant reduction in accuracy (85%) occurred using MDCT. Particularly, MDCT can be used effectively to exclude a diagnosis of CAD because of its high sensitivity and NPV (100%), but shows a significant reduction in specificity (58%). This reduction was due to an increase in the false-positive:true-negative ratio because of the higher percentage of calcified plaque (a relative but non-significant increase in false positives), and the high prevalence of CAD (significant reduction in true negatives). No differences were found between MDCT and quantitative coronary angiography (QCA) concerning the number of vessels narrowed. CONCLUSION: Because of its excellent sensitivity and specificity in patients with a low pre-test likelihood of CAD, MDCT could be helpful in clinical decision-making in this population.

Alveolar--capillary membrane gas conductance: a novel prognostic indicator in chronic heart failure.

AIMS: Lung dysfunction occurring in chronic heart failure worsens clinical status and exercise performance. The prognostic value of airway and alveolar function measurements in chronic heart failure has not been explored. We aimed to evaluate the prognostic value of lung function tests in a population of patients with stable chronic heart failure. METHODS AND RESULTS: One hundred and six stable chronic heart failure patients (whose left ventricular ejection fraction averaged 33 +/- 1%) underwent echocardiography, metabolic stress testing, assessment of pulmonary function at rest (by spirometry), of alveolar diffusing capacity (DLco) (with carbon monoxide technique) and of its membrane (DM) and capillary blood volume (Vc) components. Prognostic relevance of pulmonary variables was assessed by the Kaplan-Meier approach with log-rank testing and by Cox regression analysis. Cut-off values of lung parameters were based on the 33rd and 66th centiles. Seventeen patients died for cardiac reasons. Non-survivors compared to survivors showed lower forced expiratory volume in 1 s (2 X 1 +/- 0 X 1 vs 2 X 4 +/- 0 X 1 l; P<0 X 01), forced vital capacity (2 X 6 +/- 0 X 1 vs 2 X 9 +/- 0 X 1 l; P<0 X 01), maximal voluntary ventilation (80 X 7 +/- 2 X 5 vs 95 X 4 +/- 2 X 7 l; P<0 X 01), DLco (16 X 5 +/- 1 X 1 vs 19 X 3 +/- 0 X 6 ml . min(-1) . mmHg(-1); P<0 X 01) and DM (25 X 1 +/- 1 X 8 vs 31 X 9 +/- 1 X 5 ml . min(-1) . mmHg(-1); P<0 X 01). They also exhibited a smaller peak VO2 (14 X 6 +/- 0 X 7 vs 15 X 9 +/- 0 X 6 ml . min(-1) . kg(-1); P<0 X 05) and a steeper VE/VCO2 slope (45 X 0 +/- 1 X 7 vs 41 X 9 +/- 1 X 5; P<0 X 01). Multivariate analysis revealed that DM was the only independent predictor of cardiac death. Cases at high risk for adverse outcome were identified by a DM<24 X 7 ml . min(-1) . mmHg(-1). Patients receiving ACE-inhibitors presented with a higher DM (32 X 1 +/- 1 X 7 vs 27 X 9 +/- 1 X 7 ml . min(-1) . mmHg(-1), P<0 X 05) as well as a better Cox estimated survival rate. CONCLUSIONS: Impaired DM is a powerful independent predictor of worse prognosis in stable chronic heart failure and may be considered an additional index of disease severity, as well as a specific therapeutic target.

A prospective comparison between two seizure classifications.

The International Classification of Epileptic Seizures is the most widely used, but an alternative system based purely on ictal symptoms and signs has been proposed: the semiological classification. Our objective was to compare the two in a sample of patients evaluated at epilepsy centers. We collected 78 consecutive patients evaluated in outpatient epilepsy clinics who subsequently underwent noninvasive video-EEG monitoring at three centers. Patients with pseudoseizures were excluded. Seizures were first classified based on information obtained during clinic visits, and again after video-EEG monitoring. Each time, seizures were classified using both the International Classification and the semiological classification. Eventual epilepsy syndrome diagnosis was based on all the clinical data, video-EEG monitoring, and other independent tests including imaging studies. Sixty-six (87%) patients were classified as having 'complex partial seizures' in the International Classification. Using the semiological classification, these same 66 patients were classified as follows: automotor (34), dialeptic (17), hypermotor (13), hypomotor (2). Seizure classification changed between initial 'clinic-based' data and the 'monitoring-based' classification in 27 cases using the ILAE, vs. six using the semiological classification. Seizure classification tended to change significantly between pre- and post-monitoring using the ILAE but not the semiological classification. The term complex partial seizure included multiple categories of the semiological classification, and was very nonspecific. The semiological classification may be better suited for everyday clinic use, since it is based solely on clinical characteristics.

Synergistic efficacy of enalapril and losartan on exercise performance and oxygen consumption at peak exercise in congestive heart failure.

Oxygen consumption at peak exercise (peak VO2) is a strong independent predictor of the outcome in congestive heart failure (CHF). Renin-angiotensin system inhibition with either ACE or AT1 receptor blockers is effective on peak VO2. We evaluated whether mechanisms are similar for the 2 categories of drugs and whether their combination is able to produce a synergistic effect. Twenty CHF patients were randomized to receive, in a double-blind fashion, placebo + placebo (P+P), enalapril (20 mg/day) + placebo (E+P), losartan (50 mg/day) + placebo (L+P), and enalapril + losartan (E+L) or the same preparations in a reverse order, each for 8 weeks. Two patients did not complete the trial. Pulmonary function, cardiopulmonary exercise test, plasma neurohormones, and quality of life were assessed at the end of each treatment. Compared with P+P, E+P, and L+P similarly (16% and 15%, respectively) and significantly (p <0.01) augmented peak VO2. Enalapril improved lung function (reduced slope of ventilation vs carbon dioxide production and dead space to tidal volume ratio, and increased alveolar membrane conductance and tidal volume). Losartan likely activated the exercising muscle perfusion (raised delta VO2/delta work rate, which is a measure of aerobic work efficiency). In combination, they further increased peak VO2, 10% from E+P (p <0.05) and 11% from L+P (p <0.05). Compared with run-in, E+P and L+P significantly reduced plasma norepinephrine by 70 +/- 14 pg/ml and 100 +/- 16 pg/ml and aldosterone by 1.6 +/- 0.7 ng/dl and 1.6 +/- 0.8 ng/dl. These changes were significantly greater when the drugs were combined (140 +/- 20 pg/ml for norepinephrine, and 5.6 +/- 0.9 ng/dl for aldosterone). Quality-of-life score did not improve significantly at each treatment step. Thus, lorsartan and enalapril similarly increased peak VO2 in CHF patients, but mediators of this effect were, at least in part, different therapeutic targets that may be synergistic when the 2 drugs are combined.

Pulmonary function, cardiac function, and exercise capacity in a follow-up of patients with congestive heart failure treated with carvedilol.

BACKGROUND: Chronic heart failure causes disturbances in ventilation and pulmonary gas transfer that participate in limiting peak exercise oxygen uptake (VO(2p )). The beta-adrenergic receptor blocker carvedilol improves left ventricular (LV) function and not VO(2p). This study was aimed at investigating the pulmonary response to changes in LV performance produced by carvedilol in patients with chronic heart failure. METHODS: Twenty-one patients with New York Heart Association class II to III heart failure were randomly assigned (2 to 1) to carvedilol (25 mg twice daily, n = 14) or placebo (n = 7) for 6 months. Rest forced expiratory volume (FEV(1)), vital capacity, total lung capacity, carbon monoxide diffusing capacity, its alveolar-capillary membrane component, pulmonary venous and transmitral flows (for monitoring changes in LV end-diastolic pressure), LV diastolic and systolic dimensions, stroke volume, ejection fraction, and fiber shortening velocity were measured at baseline and at 3 and 6 months. VO(2p), peak ratio of dead space to tidal volume (VD/VT(p)), ventilatory equivalent for carbon dioxide production (VE/VCO(2)), and VO(2) at anaerobic threshold (VO(2at)) were also determined. RESULTS: FEV(1), vital capacity, total lung capacity, carbon monoxide diffusing capacity, and the alveolar-capillary membrane component were impaired in chronic heart failure compared with 14 volunteers and did not vary with treatment. Carvedilol reduced end-diastolic pressure, end-diastolic diameter, and end-systolic diameter and increased ejection fraction, stroke volume, and fiber shortening velocity without affecting VO(2p), VO(2at), VD/VT(p), or VE/VCO(2) at 3 and 6 months. Placebo did not produce significant changes. CONCLUSIONS: In chronic heart failure carvedilol ameliorates LV function at rest and does not significantly affect ventilation and pulmonary gas transfer or functional capacity. These results suggest that improvement in cardiac hemodynamics with carvedilol does not reverse pulmonary dysfunction. Persistent lung impairment might have some role in the failure of carvedilol to improve exercise performance.

Aspirin worsens exercise performance and pulmonary gas exchange in patients with heart failure who are taking angiotensin-converting enzyme inhibitors.

BACKGROUND: Pulmonary function abnormalities participate in causing exercise disability in patients with congestive heart failure (CHF). Impaired pulmonary gas transfer is one of these abnormalities. Angiotensin-converting enzyme (ACE) inhibitors improve diffusion for carbon monoxide and exercise capacity, an effect that is seemingly mediated through prostaglandin activation because it is inhibited by cyclooxygenase blockade with aspirin. This suggests the possibility that aspirin may disturb the pulmonary function and exercise ability in CHF, at least in those patients who are taking ACE inhibitors. This study was aimed at probing this hypothesis. METHODS: A dose of 325 mg aspirin was given daily for 8 weeks to 26 consecutive patients with primary dilated cardiomyopathy (New York Heart Association class II or III) whose current outpatient antifailure therapy included (group 1, 18 cases) or did not include (group 2, 8 cases) an ACE inhibitor in addition to digoxin and furosemide. During the study ACE inhibition was continued in group 1 by giving enalapril 20 mg daily. RESULTS: Tests repeated at 8 weeks proved that aspirin was deleterious in group 1. Compared with run-in, rest carbon dioxide, peak exercise oxygen uptake (peak VO(2 )), and tidal volume levels were diminished in this group; the ratio of exercise minute ventilation to carbon dioxide production (VE/VCO(2)) was augmented and its variations were inversely related to those of peak VO(2). Similar results were not observed in group 2; however, once this part of the study was completed and enalapril was included in the current therapeutic regimen, an inhibitory effect of aspirin on carbon dioxide, peak VO(2), peak tidal volume, and VE/VCO(2) at 1 L levels became evident and was similar to that observed in group 1. CONCLUSIONS: Aspirin does not affect ventilation efficiency and peak VO(2 ) in patients with CHF not taking ACE inhibitors, but it worsens the pulmonary diffusion for carbon monoxide, VO(2 ), and the ventilatory response to exercise in the presence of ACE inhibition. This may be relevant in patients with CHF from ischemic heart disease. Whether the same may be true of smaller aspirin doses was not investigated in this study.

Oxygen consumption.

It gets more and more frequent to use oxygen consumption (VO2) to evaluate exercise capacity and response to treatment in heart failure patients. The amount of VO2 is due to ventilation, oxygen transport and muscle activity. No one of these single steps can define by itself VO2, but all these physiological functions are integrated each other. In this paper we examine the modifications of cardiac output, arteriovenous oxygen content difference, and the temporal behavior of their variations during exercise in heart failure. We specifically describe changes in VO2 during simulated altitude; we also contemplate mechanisms governing oxygen diffusion from capillary bed to mitochondria and critical capillary PO2 concept.

[Effectiveness of long-term ACE-inhibition on pulmonary diffusion and ventilation-perfusion ratio in chronic heart failure: correlation with physical performance]. / Efficacia a lungo termine dell'ACE-inibizione su diffusione polmonare e accoppiamento ventilazione-perfusione nell'insufficienza cardiaca cronica: relazione con la performance fisica.

Pulmonary dysfunction contributes to exercise intolerance in patients with chronic heart failure, and ACE-inhibition improves the functional capacity of these subjects. In this study, we investigated whether and how ACE-inhibitors affect pulmonary function and ventilatory response during exercise in chronic heart failure. Twenty patients with idiopathic dilated cardiomyopathy and left ventricular ejection fraction < 35% underwent pulmonary function tests and exercise evaluation with analysis of expired gases before and after 1 year of treatment with enalapril (10 mg bid). To explore whether or not the respiratory influence of ACE-inhibitors is peculiar to the syndrome of cardiac failure, we also studied 19 subjects with mild, untreated primary hypertension who followed the same protocol. In this group, enalapril exerted a neutral effect on pulmonary function. In chronic heart failure patients, lung volumes were abnormal and did not improve after enalapril treatment; on the contrary, alveolar diffusing capacity for carbon monoxide increased towards normal values. Exercise tolerance time, peak exercise oxygen consumption, ventilation, and tidal volume also improved and the dead space to tidal volume ratio was reduced at the peak exercise and intermediate exercise phases (20, 60 W). Changes in carbon monoxide diffusion were positively correlated to those occurring during peak exercise oxygen consumption. A negative correlation was found between the variations in oxygen consumption and those in dead space to tidal volume ratio at peak exercise. We conclude that in patients with chronic heart failure, ACE-inhibition restores diffusing lung properties and improves ventilation-perfusion matching during exercise. In this syndrome, sustained reduction in gas exchange resistance is a fundamental therapeutic property of this class of drugs.