Chronic Thromboembolic Pulmonary Hypertension after Pulmonary Embolism in SARS-CoV-2.

INTRODUCTION: Chronic thromboembolic pulmonary disease (CTEPD) consists of persistent pulmonary vascular obstruction on imaging and involves long-term functional limitations, with or without chronic thromboembolic pulmonary hypertension (CTEPH). The aim of this study was to evaluate the incidence and risk factors of both persistent pulmonary vascular defects and CTEPH after hospitalization in patients with COVID-19 and PE during a 2-year follow-up. METHODS: A prospective observational study was carried out in a tertiary hospital center. Patients were hospitalized between March 2020 and December 2021 with a diagnosis of PE during SARS-CoV-2 infection. Patients received anticoagulant treatment for at least 3 months and were followed up for 2 years. Between the third and fourth months after discharge, all patients were evaluated for the presence of residual thrombotic defects by CTPA and/or perfusion pulmonary scintigraphy. Clinical findings, lung function tests with DLCO, exercise capacity, and echocardiograms were also assessed. RESULTS: Of the 133 patients included, 18% had persistent thrombotic defects on lung imaging at follow-up. The incidence of CTEPD was 0.75% at 2 years of follow-up. Patients with persistent defects were significantly older, had a higher prevalence of systemic arterial hypertension, higher D-dimer and NT-proBNP levels, and more severe PE at diagnosis. Furthermore, there was a higher prevalence of right ventricular dysfunction on echocardiogram at diagnosis of PE (25.0% vs. 2.7%, p = 0.006). This was the only variable independently related to persistent defects in multivariate analyses (OR: 8.13 [95% CI: 1.82-36.32], p = 0.006). CONCLUSION: The persistence of thrombotic defects after PE is a common finding after SARS-CoV-2 infection, affecting 18% of the population. However, the incidence of CTEPH appears to be lower (0.75%) in COVID-19-related PE compared to that previously observed in PE unrelated to COVID-19.

Anthracycline-induced cardiotoxicity in diffuse large B-cell lymphoma: NT-proBNP and cardiovascular score for risk stratification.

OBJECTIVE: To evaluate the role of N-terminal pro-brain-type natriuretic peptide (NT-proBNP) and a cardiovascular (CV) risk score named FRESCO for predicting anthracycline-induced cardiotoxicity (AIC) in diffuse large B-cell lymphoma (DLBCL). METHODS: A total of 130 consecutive DLBCL patients treated in first-line with anthracycline-containing immunochemotherapy. Competitive risk between NT-proBNP, FRESCO, and time to AIC was considered. RESULTS: Cumulative incidence of AIC was 12.2% and 17.5% at 1 and 5 years, respectively. Median time to development cardiotoxicity was 6.4 months, with half of the cases showing heart failure and the other half silent AIC. Both NT-proBNP levels and FRESCO score were independently associated with higher risk of AIC (P = 0.001 and P = 0.03, respectively). Patients with NT-proBNP ≥600 pg/mL or those with FRESCO ≥4.5% had 3.97 or 2.54 times higher risk of AIC than those with lower values (P = 0.001 and P = 0.048, respectively). According to the previous cutoffs, three groups of patients with a significantly different risk of AIC could be identified (P < 0.0001). CONCLUSIONS: Doxorubicin-containing chemotherapy is associated with increased risk of silent and overt AIC. Baseline NT-proBNP levels and FRESCO CV risk score are accurate predictors of AIC and can identify groups of patients at different risk, in which personalized cardiologic evaluation should be offered.

Right Ventricular Response During Exercise in Patients with Chronic Obstructive Pulmonary Disease.

AIM: Right ventricular (RV) pump function is of essential clinical and prognostic importance in a variety of heart and lung diseases. While the evaluation of RV performance at rest has been implemented in the clinical setting, it is unknown whether this assessment during exercise may provide additional benefit. With this aim, we evaluated the exercise-induced pulmonary arterial systolic pressure (PASP) increase during exercise in patients with severe chronic obstructive pulmonary disease (COPD) as an expression of RV contractile reserve. METHOD: Cardiopulmonary exercise testing (CPET) with synchronic echocardiography was performed in 81 patients. Patients were classified into two groups according to an exercise-induced PASP increase above 30mmHg (High PSAP) or below 30mmHg (Low PSAP) during maximal exercise. Patients were then followed for three years. RESULTS: Sixteen patients (20%) had low PSAP and 65 (80%) showed high PSAP. These were not significant clinical and functional differences. Low PSAP was associated with a significantly lower peak VO2 (mean (SD), 35 (2) % predicted) compared to high PSAP response (peak VO2 45 (3) % predicted), p=0.045. Factors associated with mortality were age and exercise-induced PASP. Seventeen patients died during the three years of follow-up (7 (39%) in the low PSAP group and only 10 (1%) in the high PSAP group, p=0.041). CONCLUSION: Cardiopulmonary exercise testing with a synchronic echocardiography may be a useful tool for the assessment of RV contractile reserve in severe COPD patients. Exercise-induced PSAP emerges as a possible prognostic factor in these patients.

Clinical value of ankle-brachial index in asymptomatic aortic stenosis patients.

BACKGROUND AND AIM OF THE STUDY: The study aim was to assess the prevalence and clinical value of the pathological ankle-brachial index (ABI) in asymptomatic aortic stenosis (AS) patients. METHODS: This prospective study included 203 asymptomatic AS patients, with a mean follow up of 18 ± 10.6 months. Six-minute walk tests (6MWT) and ABI measurements were performed when patients were included in the study. Study events were defined as death, hospital admission due to related symptoms, or a need for surgery. RESULTS: A total of 198 patients (95 females, 103 males; mean age 74.6 ± 9.5 years) completed the study. An abnormal ABI was found in 35.8%. Mean (± SD) values were: peak velocity Vmax 4.1 ± 0.8 m/s; maximum/mean gradient 70.5 ± 25.1/43.3 ± 16.3 mmHg; aortic valve area 0.8 ± 0.7 cm2; indexed aortic valve area 0.4 ± 0.1 cm2/m2. A pathological ABI was associated with diabetes (p = 0.01), previous peripheral vascular disease (p = 0.04) and previous stroke (p = 0.04). In multivariate analyses, diabetes was an independent factor related to pathological ABI (relative risk 1.71, 95% CI 1.22-2.19). Patients with a pathological ABI walked less in the 6MWT (263.9 m versus 328.3; p = 0.002), but did not present a worse prognosis at follow up (p = NS). CONCLUSION: Among asymptomatic AS patients, 35.8% had an abnormal ABI and this was related to previous diabetes. These patients walked less in the 6MWT but did not have a worse prognosis at follow up.

Effects of Exercise Training on Circulating Biomarkers of Endothelial Function in Pulmonary Arterial Hypertension.

INTRODUCTION: In stable patients with pulmonary arterial hypertension (PAH), pulmonary rehabilitation (PR) is an effective, safe and cost-effective non-pharmacological treatment. However, the effects of PR on vascular function have been poorly explored. This study aimed to compare the amounts of circulating progenitor cells (PCs) and endothelial microvesicles (EMVs) in patients with PAH before and after 8 weeks of endurance exercise training as markers of vascular competence. METHODS: A prospective study of 10 consecutive patients with PAH that successfully finished a PR program (8 weeks) was carried out before and after this intervention. Levels of circulating PCs defined as CD34+CD45low progenitor cells and levels of EMVs (CD31+ CD42b-) were measured by flow cytometry. The ratio of PCs to EMVs was taken as a measure of the balance between endothelial damage and repair capacity. RESULTS: All patients showed training-induced increases in endurance time (mean change 287 s). After PR, the number of PCs (CD34+CD45low/total lymphocytes) was increased (p < 0.05). In contrast, after training, the level of EMVs (CD31+ CD42b-/total EMVs) was reduced. The ratio of PCs to EMVs was significantly higher after training (p < 0.05). CONCLUSION: Our study shows, for the first time, that endurance exercise training in patients with stable PAH has a positive effect, promoting potential mechanisms of damage/repair in favor of repair. This effect could contribute to a positive hemodynamic and clinical response.

Phenotype and genotype characterization and twin association in patients with Anderson-Fabry cardiomyopathy.

Anderson-Fabry disease (FD), an X-linked recessive lysosomal storage disorder caused by a deficiency of α-galactosidase A (α-Gal A) activity, is associated with cardiac manifestations including arrhythmias, valvular abnormalities, and cardiomyopathy. Early initiation of enzyme replacement therapy (ERT) may have the potential to delay the underlying clinical outcomes in patients with FD. Clinical electrocardiogram (ECG) and echocardiography were used to characterize the cardiomyopathy. Diagnosis of FD was performed by measuring the α-Gal A activity in plasma and mutation analysis by direct sequencing using capillary electrophoresis. We identified four adult hemizygous male patients with cardiomyopathy and other symptoms related to FD; two of them were monozygotic twins. In all cases, ECG and echocardiography showed severe left ventricular (LV) hypertrophy. Some years later, all patients showed typical symptoms of FD, including angiokeratomas and neurological, renal, gastrointestinal, and ocular involvement. A deficiency of α-Gal A activity and point mutations in exon 5 of the GLA gene were detected in all patients. ERT (agalsidase-alfa) was administered every other week as a 0.2 mg/kg intravenous infusion over 40 min. In conclusion, these findings highlight the importance of screening middle-aged patients with LV hypertrophy for the early detection of FD, particularly in direct-line relatives such as twins.

Plasmatic PCSK9 Levels Are Associated with Very Fast Progression of Asymptomatic Degenerative Aortic Stenosis.

The aim of this work was to study the association of potential biomarkers with fast aortic stenosis (AS) progression. Patients with moderate-to-severe AS were classified as very fast progressors (VFP) if exhibited an annualized change in peak velocity (aΔVmax) ≥0.45m/s/year and/or in aortic valve area (aΔAVA) ≥-0.2cm2/year. Respective cut-off values of ≥0.3m/s/year and ≥-0.1cm2/year defined fast progressors (FP), whereas the remaining patients were non-fast progressors (non-FP). Baseline markers of lipid metabolism, inflammation, and cardiac overload were determined. Two hundred and nine patients (97 non-FP, 38 FP, and 74 VFP) were included. PCSK9 levels were significantly associated with VFP (OR 1.014 [95%CI 1.005-1.024], for every 10 ng/mL), as were active smoking (OR 3.48) and body mass index (BMI, OR 1.09), with an AUC of 0.704 for the model. PCSK9 levels, active smoking, and BMI were associated with very fast AS progression in our series, suggesting that inflammation and calcification participate in disease progression.

Effect of bariatric surgery on cardiac structure and function in obese patients: Role of the renin-angiotensin system.

Echocardiographic alterations have been described in obesity, but their modifications after bariatric surgery (BS) and mechanisms are little known, mostly in normotensive patients. We aimed to analyze cardiac changes 1 year post-BS and to explore possible mechanisms. A cohort of patients with severe obesity (58% normotensives) were prospectively recruited and examined before surgery and after 12 months. Clinical and echocardiographic data, 24 h BP, renin-angiotensin-aldosterone system (RAAS) components, cytokines, and inflammatory markers were analyzed at these two time points. Overall reduction in body weight was mean (IQR) = 30.0% (25.9-33.8). There were statistically significant decreases in left ventricle mass index2.7 (LVMI)2.7 , septum thickness (ST), posterior wall thickness (PWT), relative wall thickness (RWT), and E/e', both in the whole cohort and in patients without RAAS blockers (p ≤ .04 for all). Plasma renin activity (PRA) decreased from (median, IQR) = 0.8 (0.3;1.35) to 0.4 (0.2;0.93) ng/ml/h, plasma aldosterone from 92 (58.6;126) to 68.1 (56.2;83.4) ng/dl, and angiotensin-converting enzyme (ACE)-2 activity from 7.7 (5.7;11.8) to 6.8 (5.3;11.2) RFU/µl/h, p < .05. The body weight loss correlated with a decrease in both 24 h SBP and 24 h DBP (Pearson's coefficient 0.353, p = .022 and 0.384, p = .012, respectively). Variation (Δ) of body weight correlated with ΔE/e' (Pearson's coeff. 0.414, p = .008) and with Δ lateral e' (Pearson's coeff. = -0.363, p = .018). Generalized linear models showed that ΔPRA was an independent variable for the final (12-months post-BS) LVMI2.7 (p = .028). No other changes in cardiac parameters correlated with ΔBP. In addition to the respective baseline value, final values of PWT and RWT were dependent on 12-month Δ of PRA, ACE, and ACE/ACE2 (p < .03 for all). We conclude that there are cardiac changes post-BS in patients with severe obesity, normotensives included. Structural changes appear to be related to modifications in the renin-angiotensin axis.

Left Atrium Assessment by Speckle Tracking Echocardiography in Cryptogenic Stroke: Seeking Silent Atrial Fibrillation.

Silent atrial fibrillation (AF) may be the cause of some cryptogenic strokes (CrS). The aim of the study was to analyse atrial size and function by speckle tracking echocardiography in CrS patients to detect atrial disease. Patients admitted to the hospital due to CrS were included prospectively. Echocardiogram analysis included left atrial ejection fraction (LAEF) and atrial strain. Insertable cardiac monitor was implanted, and AF was defined as an episode of ≥1 min in the first year after stroke. Left atrial enlargement was defined as indexed volume > 34 mL/m2. Seventy-five consecutive patients were included, aged 76 ± 9 years (arterial hypertension 75%). AF was diagnosed in 49% of cases. The AF group had higher atrial volume and worse atrial function: peak atrial longitudinal strain (PALs) 19.6 ± 5.7% vs. 29.5 ± 7.2%, peak atrial contraction strain (PACs) 8.9 ± 3.9% vs. 16.5 ± 6%, LAEF 46.8 ± 11.5% vs. 60.6 ± 5.2%; p < 0.001. AF was diagnosed in 20 of 53 patients with non-enlarged atrium, and in 18 of them, atrial dysfunction was present. The multivariate logistic regression analysis demonstrated an independent association between detection of AF and atrial volume, LAEF, and strain. Cut-off values were obtained: LAEF < 55%, PALs < 21.4%, and PACs < 12.9%. In conclusion, speckle tracking echocardiography in CrS patients improves silent atrial disease diagnosis, with or without atrial enlargement.

Is iron deficiency modulating physical activity in COPD?

There is evidence that iron plays a key role in the adequate functioning of skeletal muscle. While it has been demonstrated that nonanemic iron deficiency (NAID) affects exercise tolerance and response to exercise training in patients with COPD, the impact on daily physical activities (DPAs) remains unknown. Eighteen COPD patients with NAID (ferritin <100 ng/mL or ferritin 100-299 ng/mL with a transferrin saturation <20%) and 18 COPD patients without this abnormality, matched for age, gender, and the degree of airflow limitation (control group), were enrolled to the study. The primary outcome was the level of DPA assessed by accelerometers. Patients were (mean [SD]) 66 (7) years and were mostly male (70%) and former smokers (52%). Their forced expiratory volume at 1 second was 41 (16)% predicted, carbon monoxide diffusing capacity was 47 (14)% predicted and oxygen arterial pressure reached 70 (11) mmHg. DPA and the number of steps per day were lower in NAID COPD patients compared with controls (physical activity level 1.39 vs 1.59, P<0.05; and 4,402 vs 6,975 steps/day, P<0.05, respectively). The percentage of patients with increased time spent sitting per day (>6 hours) was higher in patients with NAID compared with controls (73% vs 37%, P<0.05). In addition, the percentage of patients doing moderate to vigorous physical activity per day (>3 metabolic equivalents of task, at least 30 minutes) was lower in this group (66% vs 100%, P<0.05). The presence of iron deficiency was associated with reduced DPA in COPD patients. Further studies are needed to evaluate iron reposition and their impact on the level of physical activity in these patients.

Heart failure in acute ischemic stroke.

BACKGROUND: To determine the impact of heart failure (HF), with preserved or decreased left ventricular function (LVF), on outcome in patients with acute ischemic stroke (AIS). METHODS: We studied 503 unselected ischemic stroke patients. Poor outcome was defined as moderate-severe disability or death at 90 days. We analyzed the association between poor outcome and HF with preserved LVF or decreased LVF (systolic HF: ejection fraction lower than 50%). We tested this association adjusted by possible confounders in a logistic regression model. RESULTS: 89 patients (17.7 %) had HF; 49 patients (9.7%) with systolic HF, and 40 (8%) patients with HF and preserved LVF. HF with preserved LVF patients were older [79.4 (7.9) vs. 74.3 (10.4), p = 0.013],more likely to be women [p < 0.001,OR = 8.61, 95% CI (3.3-22.6)], and with lower current smoking habits [p = 0.018, OR = 8.77 (1.1-72.6)] than patients with systolic HF. 151 patients (30 %) had poor outcome. We found an independent association with initial stroke severity, systolic HF (adjusted OR = 3.01), HF with preserved LVF (adjusted OR = 2.52), thrombolytic treatment, statin pre-treatment (as protectors) and poor outcome. CONCLUSION: Both forms of HF (with or without decreased systolic function) are associated with poor outcome in AIS.

Long-term endurance sport practice increases the incidence of lone atrial fibrillation in men: a follow-up study.

AIMS: The aim of this study is to determine the incidence of lone atrial fibrillation (LAF) in males according to sport practice and to identify possible clinical markers related to LAF among marathon runners. METHODS AND RESULTS: A retrospective cohort study was designed. A group of marathon runners (n = 252) and a population-based sample of sedentary men (n = 305) recruited in 1990-92 and 1994-96, respectively, were contacted in 2002-03 and invited to attend an outpatient clinic to identify suggestive symptoms of having experienced an arrhythmia requiring medical attention. In those with suggestive symptoms of atrial fibrillation, medical records were reviewed. Finally, LAF was diagnosed on the basis of the presence of atrial fibrillation in an electrocardiographic recording. In the group of marathon runners, an echocardiogram was performed at inclusion and at the end of the study. The annual incidence rate of LAF among marathon runners and sedentary men was 0.43/100 and 0.11/100, respectively. Endurance sport practice was associated with a higher risk of incident LAF in the multivariate age- and blood pressure-adjusted Cox regression models (hazard ratio = 8.80; 95% confidence interval: 1.26-61.29). In the group of marathon runners, left atrial inferosuperior diameter and left atrial volume were both associated with a higher risk of incident LAF. CONCLUSION: Long-term endurance sport practice is associated with a higher risk of symptomatic LAF in men. This risk is associated with a larger left atrial inferosuperior diameter and volume in physically active subjects.

Level of daily physical activity in chronic obstructive pulmonary disease (COPD) patients according to GOLD classification. / Grado de actividad física diaria de los pacientes con enfermedad pulmonar obstructiva crónica (EPOC) y su relación con la clasificación Global Initiative for Chronic Obstructive Lung Disease (GOLD).

INTRODUCTION AND OBJECTIVE: The Global Initiative for Chronic Obstructive Lung Disease (GOLD guideline) for patients with chronic obstructive pulmonary disease does not adequately reflect the impact of the disease because does not take into account daily physical activity (DPA). PATIENTS AND METHODS: Forty eight patients (12 in each GOLD group) were prospectively recruited. DPA was evaluated by accelerometer. Patients were classified into 3 levels of activity (very inactive, sedentary, active). RESULTS: No significant differences in levels of physical activity among GOLD groups (P=.361) were observed. The percentages of very inactive patients were 33% in group A, 42% in group B, 42% in group C and 59% in group D. In addition, high percentage of sedentary patients were observed through 4 groups, in group A (50%), B and C (42%, each), and group D (41%). DISCUSSION: COPD patients has very low levels of physical activity at all stages of GOLD classification even those defined as low impact (such as GOLD A). Is necessary to detect patients at risk who might benefit from specific interventions.

Combined use of tissue Doppler imaging and natriuretic peptides as prognostic marker in asymptomatic aortic stenosis.

INTRODUCTION: Tissue Doppler imaging (TDI) and N-terminal-pro-Brain Natriuretic Peptide (NT-proBNP) provides useful non-invasive information about left ventricle filling pressures and both have demonstrated to be a prognostic marker in some valve disease as aortic stenosis (AS). OBJECTIVES: To assess the clinical value of combined TDI and NT-proBNP information in asymptomatic AS patients. MATERIAL AND METHODS: Prospective study of 350 initially asymptomatic moderate to severe AS patients with: Mean aortic valve area 0.8 (0.3) cm2, mean gradient 45(13) mmHg, ejection fraction 61 (9) %. Mean age: 74.6 (4.3) years. In all patients were determined NT-proBNP in the serum and TDI parameters the lateral mitral annulus. We considered clinical event the admission in the hospital due to symptoms related to AS (angina, heart failure or syncope) as well as surgical treatment or mortality. RESULTS: After a mean follow-up of 29 (10) months, 165 (47%) patients suffered some clinical event. In order to predict clinical events, Bootstrap analysis determined the best cut-point value: E/E' ratio higher than 13 and NT-proBNP higher than 515pg/mL. E/E' ratio provides more specificity (78.9% vs 55.9%) and NT-proBNP provides more sensitivity (76.6% vs 43.7%). Combined use of both parameters provides the best prognostic information (sensitivity 75.6%, specificity 67.2%, negative predictive value 82.1%, positive predictive value 57.5%, accuracy 71.4%). CONCLUSION: Combined use of TDI and natriuretic peptides information provides incremental prognostic value and is a useful tool to predict the prognosis in asymptomatic AS patients.

Sport practice and the risk of lone atrial fibrillation: a case-control study.

BACKGROUND: Lone atrial fibrillation (LAF) is characterized by the presence of atrial fibrillation in the absence of structural heart disease or other identifiable cause of arrhythmia. In a recent study, we reported sport practice to be more frequent in LAF patients than in the general population. The aim of the study was to determine the association between sport practice and the prevalence of LAF in men. METHODS: An age-matched case-control study was designed. Cases were identified from consecutive patients who attended an outpatient clinic; 51 men with LAF were included, 20 of them with vagal characteristics. Controls were selected from the general population (n=109). A questionnaire to assess former and current sport practice and the number of lifetime hours of sport practice was administered. Conditional logistic regression was used for statistical analysis. RESULTS: The proportion of patients with LAF who reported current sport practice (31%) was higher than that observed in controls (14%). In the logistic regression, current practice of sport was associated with a higher prevalence of LAF (OR=3.13; 95% CI: 1.39-7.05). The practice of more than 1500 lifetime hours of sport appears to be the threshold for the observed association. Current practice of sport with a lifetime practice greater than 1500 h was associated with LAF (OR=2.87; 95% CI: 1.20-6.91). CONCLUSION: In men, the combination of current and prolonged lifetime sport practice is associated with higher risk of LAF.

Renal volume and cardiovascular risk assessment in normotensive autosomal dominant polycystic kidney disease patients.

Cardiovascular disease, closely related to an early appearance of hypertension, is the most common mortality cause among autosomal dominant polycystic kidney disease patients (ADPKD). The development of hypertension is related to an increase in renal volume. Whether the increasing in the renal volume before the onset of hypertension leads to a major cardiovascular risk in ADPKD patients remains unknown.Observational and cross-sectional study of 62 normotensive ADPKD patients with normal renal function and a group of 28 healthy controls. Renal volume, blood pressure, and renal (urinary albumin excretion), blood vessels (carotid intima media thickness and carotid-femoral pulse wave velocity), and cardiac (left ventricular mass index and diastolic dysfunction parameters) asymptomatic organ damage were determined and were considered as continuous variables. Correlations between renal volume and the other parameters were studied in the ADPKD population, and results were compared with the control group. Blood pressure values and asymptomatic organ damage were used to assess the cardiovascular risk according to renal volume tertiles.Even though in the normotensive range, ADPKD patients show higher blood pressure and major asymptomatic organ damage than healthy controls. Asymptomatic organ damage is not only related to blood pressure level but also to renal volume. Multivariate regression analysis shows that microalbuminuria is only associated with height adjusted renal volume (htTKV). An htTKV above 480 mL/m represents a 10 times higher prevalence of microalbuminuria (4.8% vs 50%, P < 0.001). Normotensive ADPKD patients from the 2nd tertile renal volume group (htTKV > 336 mL/m) show higher urinary albumin excretion, but the 3rd tertile htTKV (htTKV > 469 mL/m) group shows the worst cardiovascular risk profile.Normotensive ADPKD patients show in the early stages of the disease with slight increase in renal volume, higher cardiovascular risk than healthy controls. An htTKV above 468 mL/m is associated with the greatest increase in cardiovascular risk of normotensive ADPKD patients with normal renal function. Early strategies to slow the progression of the cardiovascular risk of these patients might be beneficial in their long-term cardiovascular survival.