Symptomatic post COVID patients have impaired alveolar capillary membrane function and high VE/VCO2.

BACKGROUND: Post COVID-19 syndrome is characterized by several cardiorespiratory symptoms but the origin of patients' reported symptomatology is still unclear. METHODS: Consecutive post COVID-19 patients were included. Patients underwent full clinical evaluation, symptoms dedicated questionnaires, blood tests, echocardiography, thoracic computer tomography (CT), spirometry including alveolar capillary membrane diffusion (DM) and capillary volume (Vcap) assessment by combined carbon dioxide and nitric oxide lung diffusion (DLCO/DLNO) and cardiopulmonary exercise test. We measured surfactant derive protein B (immature form) as blood marker of alveolar cell function. RESULTS: We evaluated 204 consecutive post COVID-19 patients (56.5 ± 14.5 years, 89 females) 171 ± 85 days after the end of acute COVID-19 infection. We measured: forced expiratory volume (FEV1) 99 ± 17%pred, FVC 99 ± 17%pred, DLCO 82 ± 19%, DM 47.6 ± 14.8 mL/min/mmHg, Vcap 59 ± 17 mL, residual parenchymal damage at CT 7.2 ± 3.2% of lung tissue, peakVO2 84 ± 18%pred, VE/VCO2 slope 112 [102-123]%pred. Major reported symptoms were: dyspnea 45% of cases, tiredness 60% and fatigability 77%. Low FEV1, Vcap and high VE/VCO2 slope were associated with persistence of dyspnea. Tiredness was associated with high VE/VCO2 slope and low PeakVO2 and FEV1 while fatigability with high VE/VCO2 slope. SPB was fivefold higher in post COVID-19 than in normal subjects, but not associated to any of the referred symptoms. SPB was negatively associated to Vcap. CONCLUSIONS: In patients with post COVID-19, cardiorespiratory symptoms are linked to VE/VCO2 slope. In these patients the alveolar cells are dysregulated as shown by the very high SPB. The Vcap is low likely due to post COVID-19 pulmonary endothelial/vasculature damage but DLCO is only minimally impaired being DM preserved.

Chronic Heart Failure Management: Monitoring Patients and Intercepting Exacerbations.

Despite significant progress in the field of therapy and management, chronic heart failure (CHF) still remains one of the most common causes of morbidity and mortality, especially among the elderly in Western countries. In particular, frequent episodes of decompensation and, consequently, repeated hospitalizations represent an unsustainable burden for national health systems and the cause of worsening quality of life. CHF is more prevalent in elderly women, who often have "peculiar" clinical characteristics and a more preserved ejection fraction caused by endothelial dysfunction and micro-vessel damage. At the moment, noninvasive technologies that are able to remotely monitor these patients are not widely available yet, and clinical trials are underway to evaluate invasive remote sensors. Unfortunately, implantable devices for identifying decompensation are not the most practical solution in the majority of of patients with chronic heart failure. In particular, they are hypothesized to have the possibility of monitoring patients by pro-B-type natriuretic peptide, ventricular repolarization variability, and bioimpedance cardiography at the first point of care, but new technology and clinical trials must be planned to address the development and spread of these emergent possibilities.

Gender Differences and Cardiometabolic Risk: The Importance of the Risk Factors.

Metabolic syndrome (Mets) is a clinical condition characterized by a cluster of major risk factors for cardiovascular disease (CVD) and type 2 diabetes: proatherogenic dyslipidemia, elevated blood pressure, dysglycemia, and abdominal obesity. Each risk factor has an independent effect, but, when aggregated, they become synergistic, doubling the risk of developing cardiovascular diseases and causing a 1.5-fold increase in all-cause mortality. We will highlight gender differences in the epidemiology, etiology, pathophysiology, and clinical expression of the aforementioned Mets components. Moreover, we will discuss gender differences in new biochemical markers of metabolic syndrome and cardiovascular risk.

Short-period temporal repolarization dispersion in subjects with atrial fibrillation and decompensated heart failure.

BACKGROUND/OBJECTIVES: The association between chronic heart failure (CHF) and permanent atrial fibrillation is very frequent. The repolarization duration was already found predictive for atrial fibrillation. Aim of this study was to evaluate the influence of atrial fibrillation on short period repolarization variables in decompensated CHF patients. METHOD: We used 5 min ECG recordings to assess the mean, standard deviation (SD), and normalized variance (NV) of the following variables: QT end (QTe), QT peak (QTp), and T peak to T end (Te) in 121 decompensated CHF, of whom 40 had permanent atrial fibrillation, too. We reported also the 30-day mortality. RESULTS: QTpSD (p < .01), TeSD (p < .01), QTpVN (p < .01), and TeVN (p < .01) were higher in the atrial fibrillation than among sinus rhythm CHF subjects. Multivariable logistic analysis selected only TeSD (odd ratio, o.r.: 1.32, 95% confidence interval, c.i.: 1.06-1.65, p: .015) associated with atrial fibrillation. A total of 27 patients died during the 30-days follow-up (overall mortality rate 22%), 7 (18%), and 20 (25%) respectively in the atrial fibrillation and sinus rhythm patients. Furthermore, the following variables were associated to the morality risk: NT-pro Brain Natriuretic Peptide (o.r.: 1.00, 95% c.i.: 1.00-1.00, p: .041), left ventricular end diastolic diameter (o.r.: 0.81, 95% c.i.: 0.67-0.96, p: .010), and Te mean (o.r.: 1.04, 95% c.i.: 1.02-1.09, p: .012). CONCLUSION: In decompensated CHF subjects, Te mean seems be associated to mortality and TeSD to the permanent atrial fibrillation. We could hypothesize that, during severe CHF, the multi-level ionic CHF channel derangement could be critical in influencing these non-invasive markers. (ClinicalTrials.gov number, NCT04127162).

Time- and frequency-domain analysis of repolarization phase during recovery from exercise in healthy subjects.

BACKGROUND/AIM: Recently, data from temporal dispersion of myocardial repolarization analysis have gained a capital role in the sudden cardiac death risk stratification. Aim of this study was to evaluate the influence of heart rate, autonomic nervous system, and controlled breathing on different myocardial repolarization markers in healthy subjects. METHOD: Myocardial repolarization dispersion markers from short-period (5 minutes) electrocardiogram (ECG) analysis (time and frequency domain) have been obtained in 21 healthy volunteers during the following conditions: free breathing (rest); controlled breathing (resp); the first 5 minutes of postexercise recovery phases (exercisePeak ), maximum sympathetic activation; and during the second 5 minutes of postexercise recovery phases (exerciseRecovery ), intermediate sympathetic activation. Finally, we analyzed the whole repolarization (QTe), the QT peak (QTp), and T peak - T end intervals (Te). RESULTS: During the exercisePeak , major part of repolarization variables changed in comparison to the rest and resp conditions. Particularly, QTe, QTp, and Te standard deviations (QTeSD , QTpSD , and TeSD ); variability indexes (QTeVI and QTpVI), normalized variances (QTeVN, QTpVN, and TeVN); and the ratio between short-term QTe, QTp, and Te variability RR (STVQTe/RR , STVQTp/RR, and STVTe/RR ) increased. During exerciseRecovery , QTpSD (P < .05), QTpVI (P < .05), QTeVN (P < .05), QTpVN (P < .001), TeVN (P < .05), STVQTe/RR (P < .05), STVQTp/RR (P < .001), and STVTe/RR (P < .001) were significantly higher in comparison to the rest. The slope between QTe (0.24 ± 0.06) or QTp (0.17 ± 0.06) and RR were significantly higher than Te (0.07 ± 0.06, P < .001). CONCLUSION: Heart rate and sympathetic activity, obtained during exercise, seem able to influence the time domain markers of myocardial repolarization dispersion in healthy subjects, whereas they do not alter any spectral components.

A new pathophysiology in heart failure patients.

In the treatment of patients with severe heart failure, left ventricle assist device plays an important role, especially as a destination therapy. Nevertheless, even in successful cases, patients' progressive weaning is rarely taken into consideration. The recovery of more physiological circulation conditions is not a main goal. This hypothesis is discussed in this article.

Age, gender and drug therapy influences on Tpeak-tend interval and on electrical risk score.

BACKGROUND AND OBJECTIVES: Electrical risk score (ERS) has been proposed as easy, inexpensive test to stratify of sudden cardiac death (SCD) risk in subjects with normal left ventricular function. Potentially, aging, gender and drugs can influence ERS affecting two on six electrical markers, particularly, those based on the repolarization. Aim of this study was to establish aging, gender and drug therapy possible influences on ERS and mortality in elderly patients. METHOD: 237 consecutive, low SCD risk-outpatients with asymptomatic and treated cardiovascular risk factors were analyzed. Six simple ECG markers composed ERS: heart rate (>75 bpm); left ventricular hypertrophy (Sokolow-Lyon criteria); delayed QRS transition zone (≥V4), frontal QRS-T angle (>90°), long QTBazett; long T peak to T end interval (Tp-e). We obtained ERS in 237 outpatients, grouped according age (<40 ys, ≥40 to <60 ys and ≥60 ys), gender and drug therapy with or without possible influence on the repolarization phase. RESULTS: Two-hundred-thirty-seven patients were grouped respectively in the following age classes: <40 years old; ≥40 to <60 years old and ≥60 years old. ERS (p < 0.05), QTBazett (p < 0.001), Tp-e (p < 0.001) were higher in older subjects independently from gender, drug therapy and cardiovascular comorbidity. After two years we reported a 7.3% of mortality in the older groups; age (deceased versus survivors: 80 ± 4 versus 73 ± 7 years, p < 0.05) and Tp-e (deceased versus survivors: 117 ± 15 versus 93 ± 21 ms, p < 0.05) were significantly lower in survivors, multivariable logistic regression analysis selected only the Tp-e as significant risk factor for total mortality (odd ratio 1.06, 95% CI: 1.01-1.12, p < 0.05). CONCLUSION: Aging was associated to the ERS and repolarization phase derangement. Tp-e should be considered a marker of total mortality rather than SCD in the over sixty years old patients.

Hospital mortality in decompensated heart failure. A pilot study.

BACKGROUND/AIM: Heart failure is a leading cause of morbidity and mortality worldwide and it is a major cause of emergency department access for cardiovascular disease patients. Aim of this study was to identify the electrocardiographic (ECG) markers, based on short-term temporal repolarization dispersion, capable to individuate decompensated chronic heart failure (CHF) patients at high mortality risk. METHODS: We obtained the following variables from an ECG recording, monitored via mobile phone, during 5-minute recordings in decompensated CHF patients: RR, QT end (QTe), QT peak (QTp) and T peak to T end (Te) and we calculated mean, standard deviation (SD) and normalized index (N). RESULTS: In-hospital mortality occurred for 25 subjects on 101 studied (25%). Deceased patients showed higher QTeSD (p < 0.01), Te mean (p < 0.01), TeSD (p < 0.05), QTeVN (p < 0.05) than the surviving group. Logistic multivariable analysis evidenced that Te mean was a significant predictor of in-hospital mortality (odd ratio: 0.09, 95% confidence limit: 0.02-0.35, p: 0.001). At multiple regression analysis, TeSD was significantly and positively related only to the NT-pro BNP levels (r: 0.540; p < 0.001). The Te mean (AUC: 0.677 p < 0.01) and TeSD (AUC: 0.647, p: 0.05) showed significant sensitivity/specificity for the event. CONCLUSIONS: The Te mean and TeSD seem to be a promising noninvasive clinical marker able to identify patients with decompensated CHF at high risk of in-hospital mortality.

SARS-CoV-2 spread in Northern Italy: what about the pollution role?

The recent epidemic of the new SARS-CoV-2 in the northern regions of Italy is putting the organization of the Italian health system under serious attack. The current emergency requires all possible efforts to stem the spread of the virus. In this context, it is clear that we have the urgent need to rely upon etiopathogenetic data, in order to do all possible efforts to block the epidemic. However, observing the trend of the infections in China and the geographic areas of the main outbreaks, it could be hypothesized that air pollution plays a role. In particular, it has been previously demonstrated, in specific populations, a role of particulate matter in worsening clinical presentation of virus infection in airways. Without prejudice to the ascertained virus spread by air droplets or contaminated surfaces, the factors that could have favored its spread remain to be investigated. Moreover, if these observations were to be confirmed, when the health emergency is resolved, it will be mandatory to redesign an economic-productive model in balance with the environment.

Anemia and Iron Deficiency in Heart Failure: Clinical and Prognostic Role.

Anemia and iron deficiency (ID) represent 2 prevalent, often interrelated, comorbidities in heart failure (HF). Both of them are significantly related to functional capacity and are undoubted predictors of poor prognosis in patients with HF. Although anemia and ID both have "global" detrimental effects, these 2 conditions are too often overlooked in cardiology daily clinical practice. The present review sought to summarize briefly the prevalence and the underlying pathophysiologic mechanisms of anemia and ID as regards HF severity (ie, exercise capacity) and prognosis.

Hidden in the heart: A peculiar type of left ventricular remodeling after acute myocardial infarction.

We reported an unusual case of left ventricular pouch, in a 72-year-old man who had an acute coronary syndrome treated with percutaneous revascularization. The echocardiogram showed a sort of pouch, delimited by epicardium and endocardium, confirmed by 3D echo. This finding appeared as an echo free area, with a really slight color flow inside. We consequently supposed it would be a dissecting hematoma, a rare complication of the ischemic disease, due to the rupture of the intramyocardial vessels among the spiral myocardial fibers. This would produce a hemorrhagic pouch contained by epicardial and endocardial layers, which could evolve into mural thrombi.

[QT Variability Index as a tool for risk stratification of sudden cardiac death]. / Il QT Variability Index come strumento per la stratificazione del rischio di morte improvvisa.

Sudden cardiac death is the leading cause of mortality in patients with chronic heart failure (CHF) and history of myocardial infarction. Selection of patients at risk of sudden cardiac death is dramatically important to choose the correct therapeutic approach. The QT Variability Index (QTVI) is a non-invasive measure of repolarization lability that has been applied to a wide variety of subjects with cardiovascular disease. It is a ratio of normalized QT variability to normalized heart rate variability, and therefore includes an assessment of the autonomic nervous system tone. As opposed to T wave alternans, QTVI assesses variance in repolarization at all frequencies. Recent studies suggest that QTVI may help clinicians choosing the appropriate implantable cardiovester defibrillator timing implantation, in patients with dilated or hypertrophic cardiomyopathy or CHF because of its efficacy in patient evaluation and follow-up.

Climate change versus Mediterranean diet: A hazardous struggle for the women's heart.

Climate change impacts food systems, causing nutritional deficiencies and increasing cardiovascular diseases (CVD). Regulatory frameworks like the European Farm-to-Fork Strategy aim to mitigate these effects, but current EU food safety regulations inadequately address health risks from poor diet quality and contaminants. Climate change adversely affects food quality, such as nutrient depletion in crops due to higher CO2 levels, leading to diets that promote chronic diseases, including CVD. Women, because of their roles in food production and their unique physiological responses to nutrients, face distinct vulnerabilities. This review explores the interplay between climate change, diet, and cardiovascular health in women. The review highlights that sustainable diets, particularly the Mediterranean diet, offer health benefits and lower environmental impacts but are threatened by climate change-induced disruptions. Women's adherence to the Mediterranean diet is linked to significant reductions in CVD risk, though sex-specific responses need further research. Resilient agricultural practices, efficient water management, and climate-smart farming are essential to mitigate climate change's negative impacts on food security. Socio-cultural factors influencing women's dietary habits, such as traditional roles and societal pressures, further complicate the picture. Effective interventions must be tailored to women, emphasizing education, community support, policy changes, and media campaigns promoting healthy eating. Collaborative approaches involving policymakers, health professionals, and the agricultural sector are crucial for developing solutions that protect public health and promote sustainability. Addressing the multifaceted challenges posed by climate change to food quality and cardiovascular health in women underscores the need for integrated strategies that ensure food security, enhance diet quality, and mitigate environmental impacts.

Sex- and gender-related disparities in chest pain syndromes: the feminine mystique of chest pain.

Chest pain syndromes encompass a wide range of different clinical conditions, being coronary artery disease one of the most important and feared aetiology. Sex and gender disparities have been reported in pathophysiology, clinical presentations, diagnostic work-up and outcomes of patients admitted for chest pain. Biological differences in sexual hormones and neurological pain procession pathways have been proposed as contributors to disparities between men and women; however, gender-related disparities in socio-economic and psychological status have emerged as additional factors involved in these conditions. A better understanding of gender- and sex-related disparities will lead to improved clinical care and management of chest pain syndromes in both men and women. In this comprehensive review, we describe the existing knowledge regarding sex and gender-based differences in management and outcomes of chest pain syndromes in order to stimulate and promote the development of a more sex- and gender-oriented approach to these conditions.

Maternal-fetal dyad beyond the phenomenology of pregnancy: from primordial cardiovascular prevention on out, do not miss this boat!

Pregnancy represents a stress test for every woman's cardiovascular (CV) system, and a pre-existing maternal unfavorable cardio-metabolic phenotype can uncover both adverse pregnancy outcomes and the subsequent development of cardiovascular disease (CVD) risk factors during and after pregnancy. Moreover, the maternal cardiac and extracardiac environment can affect offspring's cardiovascular health through a complex mechanism called developmental programming, in which fetal growth can be influenced by maternal conditions. This interaction continues later in life, as adverse developmental programming, along with lifestyle risk factors and genetic predisposition, can exacerbate and accelerate the development of CV risk factors and CVD in childhood and adolescence. The aim of this narrative review is to summarize the latest evidences regarding maternal-fetal dyad and its role on primordial, primary and secondary CV prevention.

Artificial Intelligence Applied to Electrical and Non-Invasive Hemodynamic Markers in Elderly Decompensated Chronic Heart Failure Patients.

OBJECTIVES: The first aim of this study was to assess the predictive power of Tend interval (Te) and non-invasive hemodynamic markers, based on bioimpedance in decompensated chronic heart failure (CHF). The second one was to verify the possible differences in repolarization and hemodynamic data between CHF patients grouped by level of left ventricular ejection fraction (LVEF). Finally, we wanted to check if repolarization and hemodynamic data changed with clinical improvement or worsening in CHF patients. METHODS: Two hundred and forty-three decompensated CHF patients were studied by 5 min ECG recordings to determine the mean and standard deviation (TeSD) of Te (first study). In a subgroup of 129 patients (second study), non-invasive hemodynamic and repolarization data were recorded for further evaluation. RESULTS: Total in-hospital and cardiovascular mortality rates were respectively 19 and 9%. Te was higher in the deceased than in surviving subjects (Te: 120 ± 28 vs. 100 ± 25 ms) and multivariable logistic regression analysis reported that Te was related to an increase of total (χ2: 35.45, odds ratio: 1.03, 95% confidence limit: 1.02-1.05, p < 0.001) and cardiovascular mortality (χ2: 32.58, odds ratio: 1.04, 95% confidence limit: 1.02-1.06, p < 0.001). Subjects with heart failure with reduced ejection fraction (HFrEF) reported higher levels of repolarization and lower non-invasive systolic hemodynamic data in comparison to those with preserved ejection fraction (HFpEF). In the subgroup, patients with the NT-proBNP reduction after therapy showed a lower rate of Te, heart rate, blood pressures, contractility index, and left ventricular ejection time in comparison with the patients without NT-proBNP reduction. CONCLUSION: Electrical signals from ECG and bioimpedance were capable of monitoring the patients with advanced decompensated CHF. These simple, inexpensive, non-invasive, easily repeatable, and transmissible markers could represent a tool to remotely monitor and to intercept the possible worsening of these patients early by machine learning and artificial intelligence tools.

A matter of sex-persistent predictive value of MECKI score prognostic power in men and women with heart failure and reduced ejection fraction: a multicenter study.

Background: A sex-based evaluation of prognosis in heart failure (HF) is lacking. Methods and results: We analyzed the Metabolic Exercise test data combined with Cardiac and Kidney Indexes (MECKI) score registry, which includes HF with reduced ejection fraction (HFrEF) patients. A cross-validation procedure was performed to estimate weights separately for men and women of all MECKI score parameters: left ventricular ejection fraction (LVEF), hemoglobin, kidney function assessed by Modification of Diet in Renal Disease, blood sodium level, ventilation vs. carbon dioxide production slope, and peak oxygen consumption (peakVO2). The primary outcomes were the composite of all-cause mortality, urgent heart transplant, and implant of a left ventricle assist device. The difference in predictive ability between the native and sex recalibrated MECKI (S-MECKI) was calculated using a receiver operating characteristic (ROC) curve at 2 years and a calibration plot. We retrospectively analyzed 7,900 HFrEF patients included in the MECKI score registry (mean age 61 ± 13 years, 6,456 men/1,444 women, mean LVEF 33% ± 10%, mean peakVO2 56.2% ± 17.6% of predicted) with a median follow-up of 4.05 years (range 1.72-7.47). Our results revealed an unadjusted risk of events that was doubled in men compared to women (9.7 vs. 4.1) and a significant difference in weight between the sexes of most of the parameters included in the MECKI score. S-MECKI showed improved risk classification and accuracy (area under the ROC curve: 0.7893 vs. 0.7799, p = 0.02) due to prognostication improvement in the high-risk settings in both sexes (MECKI score >10 in men and >5 in women). Conclusions: S-MECKI, i.e., the recalibrated MECKI according to sex-specific differences, constitutes a further step in the prognostic assessment of patients with severe HFrEF.

Depression, anxiety and alexithymia symptoms are major determinants of health related quality of life (HRQoL) in cirrhotic patients.

HRQoL is impaired in cirrhosis. Establishing the relevance of depression, anxiety, alexithymia and cirrhosis stage on the patients' HRQoL. Sixty cirrhotics underwent a neuropsychological assessment, including ZUNG-SDS, STAI Y1-Y2 and TAS-20. Minimal hepatic encephalopathy (MHE) was detected by PHES, HRQoL by Short-Form-36 (SF-36). Depression was detected in 34 patients (57 %, 95%CI = 44-70 %), state-anxiety in 16 (27 %, 95%CI = 15-38 %), trait-anxiety in 17 (28 %, 95%CI = 17-40 %), alexithymia in 14 (31 % 95%CI = 16-46 %) and MHE in 22 (37 %, 95%CI = 24-49 %). Neuropsychological symptoms were unrelated to cirrhosis stage, hepatocellular carcinoma or MHE. A significant correlation was observed among psychological test scores and summary components of SF-36. At multiple linear regression analysis including Child-Pugh and MELD scores, previous-HE and the psychological test scores as possible covariates, alexithymia and depression as well as to the Child-Pugh score were significantly related to the SF-36 mental component; while trait-anxiety was the only variable significantly and independently related to the SF-36 physical component. Depression, state and trait-anxiety and alexithymia symptoms are frequent in cirrhotics and are among the major determinants of the altered HRQoL.

The Impact of Physical Activity and Inactivity on Cardiovascular Risk across Women's Lifespan: An Updated Review.

Physical inactivity (PI) represents a significant, modifiable risk factor that is more frequent and severe in the female population worldwide for all age groups. The physical activity (PA) gender gap begins early in life and leads to considerable short-term and long-term adverse effects on health outcomes, especially cardiovascular (CV) health. Our review aims to highlight the prevalence and mechanisms of PI across women's lifespan, describing the beneficial effects of PA in many physiological and pathological clinical scenarios and underlining the need for more awareness and global commitment to promote strategies to bridge the PA gender gap and limit PI in current and future female generations.

Effect of Head-Up/-Down Tilt on ECG Segments and Myocardial Temporal Dispersion in Healthy Subjects.

The head-up/-down tilt test acutely modifies the autonomic nervous system balance throughout a deactivation of the cardiopulmonary reflexes. The present study examines the influence of head-up/-down tilt on a number of ECG segments. A total of 20 healthy subjects underwent a 5 min ECG and noninvasive hemodynamic bio-impedance recording, during free and controlled breathing, lying at (a) 0°; (b) -45°, tilting up at 45°, and tilting up at 90°. Heart rate variability power spectral analysis was obtained throughout some ECG intervals: P-P (P), P-Q (PQ), PeQ (from the end of P to Q wave), Q-R peak (QR intervals), Q-R-S (QRS), Q-T peak (QTp), Q-T end (QTe), STp, STe, T peak-T end (Te), and, eventually, the TeP segments (from the end of T to the next P waves). Results: In all study conditions, the Low Frequency/High FrequencyPP and LFPP normalized units (nu) were significantly lower than the LF/HFRR and LFRRnu, respectively. Conversely, the HFPP and HFPPnu were significantly higher in all study conditions. STe, QTp, and QTe were significantly related to the PP and RR intervals, whereas the T wave amplitude was inversely related to the standard deviations of all the myocardial repolarization variables and to the left ventricular end-systolic volume (LVEDV). The T wave amplitude diminished during head-up tilt and significantly correlated with the LVEDV.