Search

Since 50 years, cardiopulmonary exercise testing (CPET) plays a central role in heart failure (HF) assessment. Oxygen uptake (VO2) is one of the main HF prognostic indicators, then paralleled by ventilation to carbon dioxide (VE/VCO2) relationship slope. Also anaerobic threshold retains a strong prognostic power in severe HF, especially if expressed as a percent of maximal VO2 predicted value. Moving beyond its absolute value, a modern approach is to consider the percentage of predicted value for peak VO2 and VE/VCO2 slope, thus allowing a better comparison between genders, ages, and races. Several VO2 equations have been adopted to predict peak VO2, built considering different populations. A step forward was made possible by the introduction of reliable non-invasive methods able to calculate cardiac output during exercise: the inert gas rebreathing method and the thoracic electrical bioimpedance. These techniques made possible to calculate the artero-venous oxygen content differences (ΔC(a-v)O2), a value related to haemoglobin concentration, pO2, muscle perfusion, and oxygen extraction. The role of haemoglobin, frequently neglected, is however essential being anaemia a frequent HF comorbidity. Finally, peak VO2 is traditionally obtained in a laboratory setting while performing a standardized physical effort. Recently, different wearable ergo-spirometers have been developed to allow an accurate metabolic data collection during different activities that better reproduce HF patients’ everyday life. The evaluation of exercise performance is now part of the holistic approach to the HF syndrome, with the inclusion of CPET data into multiparametric prognostic scores, such as the MECKI score.

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.

Background: The prognostic role of moderate hyperkalemia in reduced ejection fraction (HFrEF) patients is still controversial. Despite this, it affects the use of renin–angiotensin–aldosterone system inhibitors (RAASi) with therapy down-titration or discontinuation. Objectives: Aim of the study was to assess the prognostic impact of moderate hyperkalemia in chronic HFrEF optimally treated patients. Methods and results: We retrospectively analyzed MECKI (Metabolic Exercise test data combined with Cardiac and Kidney Indexes) database, with median follow-up of 4.2 [IQR 1.9–7.5] years. Data on K+ levels were available in 7087 cases. Patients with K+ plasma level ≥ 5.6 mEq/L and < 4 mEq/L were excluded. Remaining patients were categorized into normal >4 and < 5 mEq/L (n = 4826, 68%) and moderately high ≥5.0 and ≤ 5.5 mEq/L (n = 496, 7%) K+. Then patients were matched by propensity score in 484 couplets of patients. MECKI score value was 7% [IQR 3.1–14.1%] and 7.3% [IQR 3.4–15%] (p = 0.678) in patients with normal and moderately high K+ values while cardiovascular mortality events at two years follow-up were 41 (4.2%) and 33 (3.4%) (p = 0.333) in each group respectively. Conclusions: Moderate hyperkalemia does not influence patients' outcome in a large cohort of ambulatory HFrEF patients.

Background: The role of risk scores in heart failure (HF) management has been highlighted by international guidelines. In contrast with HF, which is intrinsically a dynamic and unstable syndrome, all its prognostic studies have been based on a single evaluation. We investigated whether time-related changes of a well-recognized risk score, the MECKI score, added prognostic value. MECKI score is based on peak VO2, VE/VCO2 slope, Na+, LVEF, MDRD and Hb. Methods: A multi-centre retrospective study was conducted involving 660 patients who performed MECKI re-evaluation at least 6 months apart. Based on the difference between II and I evaluation of MECKI values (MECKI II - MECKI I = ∆ MECKI) the study population was divided in 2 groups: those presenting a score reduction (∆ MECKI 0, clinical deterioration). Results: The prognostic value of MECKI score is confirmed also when re-assessed during follow-up. The group with improved MECKI (366 patients) showed a better prognosis compared to patients with worsened MECKI (294 patients) (p < 0.0001). At 1st evaluation, the two groups differentiated by LVEF, VE/VCO2 slope and blood Na+ concentration, while at 2nd evaluation they differentiated in all 6 parameters considered in the score. The patients who improved MECKI score, improved in all components of the score but hemoglobin, while patients who worsened the score, worsened all parameters. Conclusions: This study shows that re-assessment of MECKI score identifies HF subjects at higher risk and that score improvement or deterioration regards several MECKI score generating parameters confirming the holistic background of HF.

Background Heart failure (HF) in women often assumes extremely peculiar characteristics. The risk stratification and prognostic evaluation of HF in women is a challenge for clinicians. The actual prognostic scores are, in fact, lacking a specific sex-oriented assessment. In HF women show better survival despite a comparatively low peak oxygen consumption (VO2) at cardiopulmonary exercise testing: this raises doubt about the accuracy of risk assessment in women. Previous studies on MECKI score database have demonstrated that female prognostic advantage is lost when sex-specific differences are correctly considered. The present analysis has the aim to identify parameters which could be differently associated to prognosis in men and women and to re-calibrate the MECKI score according to these differences. Methods The new weights of the MECKI score variables according to gender, were calculated using the means of the 200 repetitions obtained to cross-validation procedure. The primary outcome of the study was the composite of all-cause mortality, urgent heart transplant and LVAD implant. The difference in predictive ability between the native and gender re-calibrated MECKI was calculated with the ROC curve at 2 years follow-up and calibration plot. Results We retrospectively analyzed 7900 HF patients with reduced ejection fraction included in the MECKI score registry (61±13 years, 6456 M/ 1444 F, LVEF 33±10%, VO2 /kg 14.9±4.9 mL/min Kg). Patients follow up was: 4.05 years [1.72-7.47]. Table 1 presents the weights of the individual MECKI variables for males and females. The main differences have been detected for the intercept value, hemoglobin and Na+. We used these variables to recalibrate the algorithm of MECKI score. We obtained higher AUC for MECKI re-calibrated by gender than for Native MECKI (0.7893 vs. 0.7799, p=0.0194, Fig. 1 left panel). Moreover, the gender MECKI was better calibrated (Fig. 1, right panels). Conclusions The calibration of MECKI Score according to gender specific differences improves the prognostic power and accuracy of mortality prediction at two years follow up.

La menopausa costituisce un momento cruciale della vita della donna non solo dal punto di vista riproduttivo ma anche dal punto di vista fisiopatologico. Il calo della produzione ovarica di estrogeni determina una ridotta stimolazione di beta recettori endoteliali e miocardici che sono alla base di processi patologici quali le alterazioni del microcircolo coronarico o lo scompenso cardiaco a frazione d’eiezione preservata. Tali alterazioni si associano a quelle indotte da altri fattori di rischio cardiovascolare. È fondamentale in tale contesto prendere coscienza e trattare i fattori di rischio classici e quelli genere-specifici per non favorire l’insorgenza di patologie che incidono sugli eventi, sulla qualità della vita e sui costi sanitari.

Cardiopulmonary exercise test (CPET) has an important role in assessing heart failure (HF) patients. Among CPET parameters, a pivotal role is attributed to the anaerobic threshold (AT), normally determined by V-slope, ventilatory equivalent and end-tidal methods. In about 10% of healthy subjects, a lack of concordance between these methods has been reported. This event was named double AT (DT). We hypothesized that DT was due to a delay in chemoreflex response.We reanalyzed CPET data of two cross-over studies in which we compared CPET in stable HF patients treated for two months with bisoprolol and carvedilol. In chronic HF, carvedilol has a greater sympathetic inhibition than bisoprolol, as shown by a lower chemoreflex response.In 87 patients, we identified DT in 46% and 66% of cases during bisoprolol and carvedilol treatment, respectively (p 0.01). Compared with bisoprolol, carvedilol treatment was associated to a lower peak oxygen uptake (from 17.4 ± 4.3 to 16.4 ± 4.1 mL/min/kg) and oxygen pulse (from 11.8 ± 2.9 to 11.1 ± 2.9 mL/min/kg) suggestive of lower peak cardiac output.DT is frequent in HF and more often with carvedilol than bisoprolol treatment, may be due to a greater inhibition of sympathetic tone and prolonged circulatory time. These findings open an unexplored research field.

Objectives The purpose of this study was to explore speckle tracking echocardiographic right ventricular (RV) post-systolic strain patterns and their clinical relevance in idiopathic pulmonary arterial hypertension (PAH). Background The imaging of RV diastolic function in PAH remains incompletely understood. Methods Speckle tracking echocardiography of RV post-systolic strain recordings were examined in 108 consecutive idiopathic patients with PAH. Each of them underwent baseline clinical, hemodynamic, and complete echocardiographic evaluation and follow-up. Results In total, 3 post-systolic strain patterns derived from the mid-basal RV free wall segments were identified. Pattern 1 was characterized by prompt return of strain-time curves to baseline after peak systolic negativity, like in normal control subjects. Pattern 2 was characterized by persisting negativity of strain-time curves well into diastole, before an end-diastolic returning to baseline. Pattern 3 was characterized by a slow return of strain-time curves to baseline during diastole. The 3 patterns corresponded respectively to mild PH, more advanced PH but with still preserved RV function, and PH with obvious end-stage right heart failure. Patterns were characterized by optimal reproducibility when complementary to quantitative measurement of right ventricular longitudinal early diastolic strain rate (RVLSR-E), and right ventricular longitudinal late diastolic strain rate (RVLSR-A) (Cohen's κ = 0.88; p = 0.0001). Multivariable models for clinical worsening prediction demonstrated that the addition of RV post-systolic patterns to clinical and hemodynamic variables significantly increased their prognostic power (0.78 vs. 0.66; p Conclusions Speckle tracking echocardiography allows for the identification of 3 phenotypically distinct, reproducible, and clinically meaningful RV strain-derived post-systolic patterns.

The prognostic stratification of heart failure remains an urgent need for correct clinical management of the affected patients. In fact, due to the high mortality and morbidity rates, heart failure constantly requires an updated and careful management of all aspects that characterise the disease. In addition to the well-known clinical, laboratory and instrumental characteristics that affect the prognosis of heart failure, gender, age and body mass index have a different impact and deserve specific insights and clarifications. At this scope, the metabolic exercise cardiac kidney index score research group has produced several works in the past, trying to identify the role of these specific factors on the prognosis of heart failure. In particular, the different performances in the cardiopulmonary exercise test of specific categories of heart failure patients, such as women, elderly and obese or overweight individuals, have requested dedicated evaluations of metabolic exercise cardiac kidney index score power.

Background: In clinical practice, anaerobic threshold (AT) is used to guide training and rehabilitation programs, to define risk of major thoracic or abdominal surgery, and to assess prognosis in heart failure (HF). AT of oxygen uptake (V.O2; V.O2AT) has been reported as an absolute value (V.O2ATabs), as a percentage of predicted peak V.O2 (V.O2AT%peak_pred), or as a percentage of observed peak V.O2 (V.O2AT%peak_obs). A direct comparison of the prognostic power among these different ways to report AT is missing. Research question: What is the prognostic power of these different ways to report AT? Study design and methods: In this observational cohort study, we screened data of 7,746 patients with HF with a history of reduced ejection fraction (< 40%) recruited between 1998 and 2020 and enrolled in the Metabolic Exercise Combined With Cardiac and Kidney Indexes register. All patients underwent a maximum cardiopulmonary exercise test, executed using a ramp protocol on an electronically braked cycle ergometer. Results: This study considered 6,157 patients with HF with identified AT. Follow-up was median, 4.2 years (25th-75th percentiles, 1.9-5.0 years). Both V.O2ATabs (mean ± SD, 823 ± 305 mL/min) and V.O2AT%peak_pred (mean ± SD, 39.6 ± 13.9%), but not V.O2AT%peak_obs (mean ± SD, 69.2 ± 17.7%), well stratified the population regarding prognosis (composite end point: cardiovascular death, urgent heart transplant, or left ventricular assist device). Comparing area under the receiver operating characteristic curve (AUC) values, V.O2ATabs (0.680) and V.O2AT%peak_pred (0.688) performed similarly, whereas V.O2AT%peak_obs (0.538) was significantly weaker (P < .001). Moreover, the V.O2AT%peak_pred AUC value was the only one performing as well as the AUC based on peak V.O2 (0.710), with an even a higher AUC (0.637 vs 0.618, respectively) in the group with severe HF (peak V.O2 < 12 mL/min/kg). Finally, the combination of V.O2AT%peak_pred with peak V.O2 and V. per CO2 production shows the highest prognostic power. Interpretation: In HF, V.O2AT%peak_pred is the best way to report V.O2 at AT in relationship to prognosis, with a prognostic power comparable to that of peak V.O2 and, remarkably, in patients with severe HF.

As recently reported, elevated fasting glucose plasma level constitutes a risk factor for 30-day total mortality in acutely decompensated chronic heart failure (CHF). Aim of this study was to evaluate the 30-day mortality risk in decompensated CHF patients by fasting glucose plasma level and some repolarization ECG markers.A total of 164 decompensated CHF patients (M/F: 94/71; mean age, 83 ± 10 years) were studied; Tend (Te), QT interval (QT) and 5 min of ECG recordings were obtained, studying mean, SD and normalized index of the abovementioned ECG intervals. These repolarization variables and fasting glucose were analyzed to assess the 30-day mortality risk among these patients.Thirty-day mortality rate was 21%, deceased subjects showed a significant increase in N terminal-pro-brain natriuretic peptide (Data suggest that two simple, inexpensive, noninvasive markers, as fasting glucose and Te, were capable to stratify the short-term total and cardiovascular mortality risk in acutely decompensated CHF.

Cardiopulmonary exercise testing is a prognostic tool in heart failure with reduced left ventricular ejection fraction (HFrEF). Prognosticating algorithms have been proposed, but none has been validated. In 2017, a predictive algorithm, based on peak oxygen consumption (VO2), ventilatory response to exercise (ventilation [VE] carbon dioxide production [VCO2], the VE/VCO2 slope), exertional oscillatory ventilation (EOV), and peak respiratory exchange ratio, was recommended, according treatment with β blockers: patients with HFrEF registered in the metabolic exercise test data combined with cardiac and kidney indexes (MECKIs) database were used to validated this algorithm. According to the inclusion/exclusion criteria, 4,683 MECKI patients with HFrEF were enrolled. At 3years follow-up, the end point was cardiovascular death and urgent heart transplantation (cardiovascular events [CV]). CV events occurred in 25% in patients without β blockers, whereas those with β-blockers had 11% (p 10

n/a.

Aims Risk assessment in pulmonary arterial hypertension (PAH) is essential for prognostication. However, the majority of patients end-up in an intermediate risk status despite targeted-therapy, offering insufficient guidance in clinical practice. The added value of cardiopulmonary exercise testing (CPET) in this setting remains undefined. Methods and results Two independent cohorts with idiopathic PAH at intermediate risk were used to develop (n = 124) and externally validate (n = 143) the prognostic model. Risk assessment was based on the simplified version of the ESC/ERS guidelines score. The same definition of clinical worsening (CW) was used for both cohorts. Discrimination and calibration were assessed. Seventy-four derivation cohort patients experienced CW (51.2%) during a median of 34 months. Stroke volume index (SVI) and 6-min walk-distance (6MWD) were independent predictors of CW. With addition of CPET variables, SVI and VO2 peak independently improved the power of the prognostic model, determined by the integrated discrimination integral (IDI) index. ROC-derived cut-off values for SVI and VO2 peak were 34 and 14 ml/kg/min, respectively. Forty-eight validation cohort patients experienced CW (33.5%) during a median of 27 months follow-up. Different combinations of cut-off values of SVI and VO2 peak defined three meaningful groups showing good discrimination and calibration. The event-free survival rates at 1, 2, and 3 years were, respectively, 96%, 89%, and 89% for high SVI/high VO2 peak combination; 85%, 73%, and 61% for high SVI/low VO2 peak; and 80%, 70%, and 56% for low SVI/low VO2 peak. Conclusions Combinations of VO2 peak and SVI during follow-up is important in the prognostication of intermediate-risk prevalent patients with idiopathic PAH.

Aims Complications associated with iron accumulation were highly recurrent in thalassemia patients, who underwent frequent blood transfusions, in particular hemosiderotic cardiomyopathy which could lead to heart failure and arrhythmias. Nowadays, the better iron chelation therapy has improved cardiovascular morbidity in these patients; nevertheless, mild impairment should be seek for and eventually treated. The objective of our study was to evaluate the possibility of using early electrocardiographic markers of myocardial damage and predictors of mortality, such as the Electric Risk Score (ERS). Methods and results 73 patients with thalassemia major were enrolled in this study, which were divided into two groups, with 45 years old as cut off. Anamnestic, clinical, electrocardiographic, and echocardiographic data were collected. From ECG, ERS was obtained. over 45 yrs-old group of pts, in addition to a predictable increase in the prevalence of traditional cardiovascular risk factors and drug intake, an alteration of the QRS-T angle (14[30] vs. −4[28], p value: Conclusions From the data in our study it emerged that an appropriate iron-chelation therapy is able to effectively counteract the hemosiderotic cardiomyopathy of thalassemic patients so as to detect electro- and echocardiographic anomalies only in patients of more advanced age, a result that we think both the consequence, not so much of iron overload, but of an increase in the prevalence of age- and gender-related cardiovascular risk factors. The initial changes in cardiac electromechanics, which can be assessed with the aforementioned methods, we believe, can become a very early sign of specific myocardial damage. 329 Figure 1Electrical risk score parameters.

Aims Pulmonary arterial hypertension (PAH) is a rare, progressive disease with a poor prognosis. It is characterized by the presence of mean pulmonary arterial pressure (mPAP) ≥25 mmHg along with a pulmonary arterial wedge pressure (PAWP) ≤15 mmHg and pulmonary vascular resistance (PVR) >3 Wood units at right heart catheterization, in the absence of other causes of pre-capillary PH such as PH due to lung diseases, chronic thromboembolic PH, or other rare diseases. Hypoxaemia is a frequent finding in patients with PAH and could be related to ventilation–perfusion mismatch, reduced diffusing capacity, decreased cardiac output, or the opening of intrapulmonary (IP) or intracardiac shunt. Purpose of the present study is to detect IP shunts in PAH patients and its determinants. Methods and results We retrospectively enrolled 29 PAH patients, collecting clinical parameters, haemodynamic and blood gas analysis at baseline and after specific therapies at follow-up. Shunt fraction was calculated by the formula (Cc—Ca)/(Cc—Cv) during oxygen supplementation (FiO2 100%). Intracardiac defects were excluded by echo contrast examination. As expected, after treatments our results showed a significant decrease of PAPm (−7.2 ± 11.6 mmHg) and a significant decrease of PVR (−2.1 ± 3.9 WU). However, it was reported a statistically significant decrease in Hb value (−1.2 ± 1.7 g/dl), in SpO2 (−2.1 ± 3.8%) and in the alveolar–arterial oxygen gradient (a-ADO2) (+54.5 ± 113.1 mmHg). 6MWT and NYHA decreased at follow-up but not statistically significance was detected. IP shunt increase was detected at follow-up after specific treatments (delta Shunt +6.9 ± 6.5%). At multivariate analysis delta PVR remains the only independent determinants of delta Shunts with a significative increment of shunts when PVR are reduced by more than three WU. Conclusions Specific PAH treatments determine a decrease of PVR, but a reverse correlation with IP shunt was noticed. Increase of IP shunt could be not a favourable clinical feature. In fact high IP shunt fraction could determine hypoxaemia and the need of a chronic oxygen supply therapy. Although a not statistically significant decrease of 6MWT and NYHA was found, it is reasonable that a long-standing hypoxaemia could reduce the aerobic function capacity. Ours results unfortunately were deeply influenced by the loss of a great part of elective patients during the pandemic, with the most part of data coming from patients needing hospitalization. This could explain why the delta shunt fraction is higher than expected.

Aims Cardiopulmonary exercise test (CPET) and 6-min walking test (6MWT) are frequently used in heart failure (HF). CPET is a maximal exercise, whereas 6MWT is a self-selected constant load test usually considered a submaximal, and therefore safer, exercise but this has not been tested previously. The aim of this study was to compare the cardiorespiratory parameters collected during CPET and 6MWT in a large group of healthy subjects and patients with HF of different severity. Methods and results Subjects performed a standard maximal CPET and a 6MWT wearing a portable device allowing breath-by-breath measurement of cardiorespiratory parameters. HF Patients were grouped according to their CPET peak oxygen uptake (peakṼO2). One-hundred and fifty-five subjects were enrolled, of whom 40 were healthy (59 ± 8 years; male 67%) and 115 were HF patients (69 ± 10 years; male 80%; left ventricular ejection fraction 34.6 ± 12.0%). CPET peakṼO2 was 13.5 ± 3.5 ml/kg/min in HF patients and 28.1 ± 7.4 ml/kg/min in healthy (P 110% of CPET peakṼO2 in 42% of more severe HF patients (peakṼO2 Conclusions 6MWT must be perceived as a maximal or even supra-maximal exercise activity at least in patients with severe exercise limitation from HF. Our findings should influence the safety procedures needed for the 6MWT in HF.

Background The pivotal role of cardiopulmonary exercise testing (CPET) in the assessment of functional capacity and prognosis of patients with heart failure with reduced ejection fraction (HFrEF), either as a single CPET parameter (i.e. peak oxygen uptake, peak VO2), as a combination of CPET parameters (i.e. oxygen uptake at the anaerobic threshold (AT) and ventilatory efficiency (VE/VCO2 slope), or as a part of more comprehensive scores (i.e. Metabolic Exercise combined with Cardiac and Kidney Indexes, MECKI) is well established. Just few studies are available with respect a possible role of CPET in risk stratification of patients in HF with midrange EF (HFmrEF) subset, namely HF patients with LVEF between 40% and 49%. Purpose The aim of the present large Italian multicenter study was to characterize and to compare stable HFmrEF and HFrEF patients in terms of exercise capacity as well as of instrumental and laboratory variables. We analyzed a possible independent and incremental prognostic value of CPET parameters in identifying those HFmrEF patients at high cardiovascular death risk. Methods We retrospectively analyzed clinical and CPET data of stable HF patients with HFrEF and HFmrEF from the MECKI Score database. Five-thousand-seven-hundred-eleven patients, 4,535 with HFrEF and 1,176 with HFmrEF, were considered for the study. The end-point was cardiovascular death at 5 years. The median follow-up was 1343 days (25th–75th range, 627–2403 days). Results Cardiovascular death occurred in 552 HFrEF (12.2% event rate) and 61 HFmrEF (5.2% event rate) patients. At multivariate analysis, an independent role of variables included in the MECKI score (age, atrial fibrillation, LVEF, haemoglobin, sodium, MDRD, AT identification, VO2 at AT, peak VO2 also expressed as percentage of the maximum predicted, VE/VCO2 slope) was confirmed in HFrEF group (C-index=0.744) whereas, in the HFmrEF group, only age and peak VO2 remained outcome predictors (C-index=0.745). We identified a peak VO2 31 as the most accurate cut-off values able to identify a HFmrEF subgroup with a cardiovascular mortality rate significantly higher than the overall HFmrEF (5.2% vs 8.5%) (Figure 1). By using both cut-off values contextually, we recognized a relatively small HFmrEF population with a cardiovascular risk quite similar to the HFrEF sample (11.4% vs 12.2%) (Figure 1). Conclusions Present data support the CPET as a useful tool in the HFmrEF management. Besides the peak VO2, which resulted as a strong independent outcome predictor, also a number of other CPET variables were associated to the cardiovascular death risk. Particularly, a peak VO2 ≤55% of the maximum and a VE/VCO2 slope ≥31 identified a HFmrEF subgroup of patients with a high cardiovascular death risk, similar to the one observed in the HFrEF group. Funding Acknowledgement Type of funding sources: None. Figure 1

Chronic thromboembolic pulmonary hypertension (CTEPH) is a severe and under-recognized complication of acute pulmonary embolism (PE). Forty consecutive patients with acute PE (Group 1), predominantly female (22, 55%) with a mean age of 69 ± 15 years, were matched for demographic data with 40 healthy subjects (Group 2), 40 systemic hypertension patients (Group 3) and 45 prevalent idiopathic pulmonary arterial hypertension (IPAH) patients (Group 4). The baseline evaluation included physical examination, NYHA/WHO functional class, right heart catheterization (RHC) limited to IPAH patients, echocardiographic assessment and systemic arterial stiffness measurement by cardio-ankle vascular index (CAVI). Patients with PE underwent an echocardiographic evaluation within 1 month from hospital discharge (median 27 days, IQR 21–30) to assess the echo-derived probability of PH. The CAVI values were significantly higher in the PE and IPAH groups compared with the others (Group 1 vs. Group 2, p &lt, 0.001, Group 1 vs. Group 3, p &lt, Group 1 vs. Group 4, p = ns, Group 4 vs. Group 2, p &lt, Group 4 vs. Group 3, p &lt, Group 2 vs. Group 3, p = ns). The predicted probability of echocardiography-derived high-risk criteria of PH increases for any unit increase of CAVI (OR 9.0, C.I.3.9–20.5, p = 0.0001). The PE patients with CAVI ≥ 9.0 at the time of hospital discharge presented an increased probability of PH. This study highlights a possible positive predictive role of CAVI as an early marker for the development of CTEPH.

Aims: Exercise oscillatory ventilation (EOV) is a pivotal cardiopulmonary exercise test parameter for the prognostic evaluation of patients with chronic heart failure (HF). It has been described in patients with HF with reduced ejection fraction (50%, HFpEF), but no data are available for patients with HF with mid-range ejection fraction (40–49%, HFmrEF). The aim of the study was to evaluate the prognostic role of EOV in HFmrEF patients. Methods and results: We analysed 1239 patients with HFmrEF and 4482 patients with HFrEF, enrolled in the MECKI score database, with a 2-year follow-up. The study endpoint was the composite of cardiovascular death, urgent heart transplant, and ventricular assist device implantation. We identified EOV in 968 cases (16% and 17% of cases in HFmrEF and HFrEF,. respectively). HFrEF EOV+ patients were significantly older, and their parameters suggested a more severe HF than HFrEF EOV− patients. A similar behaviour was found in HFmrEF EOV+ vs. EOV− patients. Kaplan–Meier analysis, irrespective of ejection fraction, showed that EOV is associated with a worse survival, and that patients with HFrEF and HFmrEF EOV+ had a significantly worse outcome than the EOV− of the same ejection fraction groups. EOV-associated survival differences in HFmrEF patients started after 18 months of follow-up. Conclusion: Exercise oscillatory ventilation has a similar prevalence and ominous prognostic value in both HFmrEF and HFrEF patients, indicating a group of patients in need of a more intensive follow-up and a more aggressive therapy. In HFmrEF, the survival curves between EOV+ and EOV− patients diverged only after 18 months.

Aims: Exercise-derived parameters, specifically peak exercise oxygen uptake (peak VO2) and minute ventilation/carbon dioxide relationship slope (VE/VCO2 slope), have a pivotal prognostic value in heart failure (HF). It is unknown how the prognostic threshold of peak VO2 and VE/VCO2 slope has changed over the last 20 years in parallel with HF prognosis improvement. Methods and results: Data from 6083 HF patients (81% male, age 61 ± 13 years), enrolled in the MECKI score database between 1993 and 2015, were retrospectively analysed. By enrolment year, four groups were generated: group 1 1993–2000 (n = 440), group 2 2001–2005 (n = 1288), group 3 2006–2010 (n = 2368), and group 4 2011–2015 (n = 1987). We compared the 10-year survival of groups and analysed how the overall risk (cardiovascular death, urgent heart transplantation, or left ventricular assist device implantation) changed over time according to peak VO2 and VE/VCO2 slope and to major clinical and therapeutic variables. At 10 years, a progressively higher survival from group 1 to group 3 was observed, with no further improvement afterwards. A 20% risk for peak VO2 15 mL/min/kg (95% confidence interval 16–13), 9 (11–8), 4 (4–2) and 5 (7–4) was observed in group 1, 2, 3, and 4, respectively, while the VE/VCO2 slope value for a 20% risk was 32 (37–29), 47 (51–43), 59 (64–55), and 57 (63–52), respectively. Conclusions: Heart failure prognosis improved over time up to 2010 in a HF population followed by experienced centres. The peak VO2 and VE/VCO2 slope cut-offs identifying a definite risk progressively decreased and increased over time, respectively. The prognostic threshold of peak VO2 and VE/VCO2 slope must be updated whenever HF prognosis improves.

The usefulness of β-blockers in heart failure (HF) patients with permanent atrial fibrillation (AF) has been questioned. Background: The usefulness of β-blockers in heart failure (HF) patients with permanent atrial fibrillation (AF) has been questioned. Methods and results: We analyzed data from HF patients (958 patients (801 males, 84%, age 67 ± 11 years)) with AF enrolled in the MECKI score database. We evaluated prognosis (composite of cardiovascular death, urgent heart transplant, or left ventricular assist device) of patients receiving β-blockers (n = 777, 81%) vs. those not treated with β-blockers (n = 181, 19%). We also analyzed the role β1-selectivity and the role of daily β-blocker dose. To account for different HF severity, Kaplan-Meier survival curves were normalized for relevant confounding factors and for treatment strategies. Dose was available in 629 patients. Median follow-up was 1312 (577–2304) days in the entire population, 1203 (614–2420) and 1325 (569–2300) days in patients not receiving and receiving β-blockers. 224 (23%, 54/1000 events/year), 163 (21%, 79/1000 events/year), and 61 (34%, 49/1000 events/year) events were recorded, respectively. At 10-year patients treated with β-blockers had a better outcome (HR 0.447, p < 0.01) with no effects as regards β1selective drugs (53%) vs. β1-β2 blockers (47%). Survival improved in parallel with β-blocker dose increase (HR 0.296, 0.496, 0.490 for the high, medium, and low dose vs. no β-blockers, p < 0.0001). Conclusion: HF patients with AF taking a β-blocker have a better outcome (with a survival improvement in parallel with daily dose but no differences as regards β1 selectivity) but this does not mean that β-blockers improve outcomes in these patients as we cannot control for all the potential confounders associated with β-blocker use.

Risk assessment in pulmonary arterial hypertension (PAH) is essential for prognostication. However, the majority of patients end-up in an intermediate risk status, offering insufficient guidance in clinical practice. The added value of cardiopulmonary exercise testing in this setting remains undefined.Two independent cohorts with idiopathic PAH at intermediate risk were used to develop (n = 124) and externally validate (n = 143) the prognostic model. Cross-validation on the overall population was used to strengthen the results of the analysis. Risk assessment was based on the simplified version of the ESC/ERS guidelines score. Discrimination and calibration were assessed.A risk score was constructed based on the beta-coefficient of the cross-validated model, including the stroke volume index (SVI) and the peak oxygen uptake (VOCombinations of VO

Pulmonary arterial hypertension (PAH) is a rare, progressive disease with a poor prognosis. The pathophysiologic model is mainly characterized by an afterload mismatch in which an increased right ventricle afterload, driven by increased pulmonary vascular resistance (PVR), leads to right heart failure. International guidelines recommend optimization of treatment based on regular risk assessments to achieve or maintain a low-risk status. Current risk scores are based on a multi-modality approach, including demographic, clinical, functional, exercise, laboratory, and hemodynamic parameters, which lack significant echocardiographic parameters. The originality of echocardiography relies on the opportunity to assess in a non-invasive way a physiologically meaningful combination of easy to measure variables tightly related to right ventricle adaptation/maladaptation to increased afterload, the main determinant of a patient’s prognosis. Echo-derived morphological and functional parameters have been investigated in PAH, proving to have prognostic relevance. Different therapeutic strategies proved to have different effects in reducing PVR. An upfront combination of drugs, including a parenteral prostacyclin, has shown to be associated with right heart reverse remodeling in a greater proportion of patients than other treatment strategies as a function of PVR reduction. Adding echocardiographic data to current risk scores would allow better identification of right ventricle (RV) adaptation in PAH patients’ follow-up. This additional information would allow better stratification of the patient, leading to optimized and personalized therapeutic management.

During the COVID-19 pandemic, the use of protective masks has been essential to reduce contagions. However, public opinion is that there is an associated subjective shortness of breath. We evaluated cardiorespiratory parameters at rest and during maximal exertion to highlight any differences with the use of protective masks.12 healthy subjects performed three identical cardiopulmonary exercise tests, one without wearing a protective mask, one wearing a surgical mask and one with a filtering face piece particles class 2 (FFP2) mask. Dyspnoea was assessed using the Borg scale. Standard pulmonary function tests were also performed.All the subjects (40.8±12.4 years; six male) completed the protocol with no adverse events. Spirometry showed a progressive reduction of forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) from no mask to surgical to FFP2 (FEV1: 3.94±0.91 L, 3.23±0.81 L, 2.94±0.98 L; FVC: 4.70±1.21 L, 3.77±1.02 L, 3.52±1.21 L; p2 uptake (V˙O2) and CO2 production (V˙CO2) were progressively lower, with a reduction in respiratory rate. At peak exercise, subjects had a progressively higher Borg scale when wearing surgical and FFP2 masks. Accordingly, at peak exercise, V˙O2 (31.0±23.4 mL·kg−1·min−1, 27.5±6.9 mL·kg−1·min−1, 28.2±8.8 mL·kg−1·min−1; p=0.001), ventilation (92±26 L, 76±22 L, 72±21 L; p=0.003), respiratory rate (42±8 breaths·min−1, 38±5 breaths·min−1, 37±4 breaths·min−1; p=0.04) and tidal volume (2.28±0.72 L, 2.05±0.60 L, 1.96±0.65 L; p=0.001) were gradually lower. There was no significant difference in oxygen saturation.Protective masks are associated with significant but modest worsening of spirometry and cardiorespiratory parameters at rest and peak exercise. The effect is driven by a ventilation reduction due to increased airflow resistance. However, because exercise ventilatory limitation is far from being reached, their use is safe even during maximal exercise, with a slight reduction in performance.

Aims CoV-19/SARS-CoV-2 is a highly pathogenic virus that is causing a global pandemic with a high number of deaths and infected people. To contain the diffusion of infection, several governments have enforced restrictions on outdoor activities or even collective quarantine on the population. The present commentary briefly analyzes the effects of quarantine on lifestyle, including nutrition and physical activity and the impact of new technologies in dealing with this situation. Data synthesis Quarantine is associated with stress and depression leading to unhealthy diet and reduced physical activity. A diet poor in fruit and vegetables is frequent during isolation, with a consequent low intake of antioxidants and vitamins. However, vitamins have recently been identified as a principal weapon in the fight against the Cov-19 virus. Some reports suggest that Vitamin D could exert a protective effect on such infection. During quarantine, strategies to further increase home-based physical activity and to encourage adherence to a healthy diet should be implemented. The WHO has just released guidance for people in self-quarantine, those without any symptoms or diagnosis of acute respiratory illness, which provides practical advice on how to stay active and reduce sedentary behavior while at home. Conclusion Quarantine carries some long-term effects on cardiovascular disease, mainly related to unhealthy lifestyle and anxiety. Following quarantine, a global action supporting healthy diet and physical activity is mandatory to encourage people to return to a good lifestyle routine.

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.

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.

CoV-19/SARS-CoV-2 (coronavirus 2019/severe acute respiratory syndrome coronavirus 2) is a virus that has caused a pandemic with high numbers of deaths worldwide. To contain the diffusion of infection, several governments have enforced restrictions on outdoor activities on the population. Today, we are witnessing the so-called “second wave” COVID-19 (coronavirus disease 2019) with an increasing number of cases similar to the one reported at the beginning of the current year. It is plausible that further restrictions will be applied to contain the “second wave” of infections. The present commentary evaluated the effects of stress on lifestyle during the COVID-19 pandemic in women. We briefly suggest practical recommendations for women to reduce stress and recovery for a healthy lifestyle after quarantine. Quarantine is associated with stress and depression, which lead to unhealthy lifestyle, including unhealthy diet, smoking, alcohol, and reduced physical activity. Women are more likely to suffer from depression and stress and quarantine has acted as a trigger. The prolongation of the COVID-19 pandemic around the world requires decisive action to correct the unhealthy lifestyle that has developed in recent months.

Several large clinical trials showed a favorable effect of β-blocker treatment in patients with chronic heart failure (HF) as regards overall mortality, cardiovascular mortality, and hospitalizations. Indeed, the use of β-blockers is strongly recommended by current international guidelines, and it remains a cornerstone in the pharmacological treatment of HF. Although different types of β-blockers are currently approved for HF therapy, possible criteria to choose the best β-blocking agent according to HF patients’ characteristics and to β-receptors’ location and functions in the cardiopulmonary system are still lacking. In such a context, a growing body of literature shows remarkable differences between β-blocker types (β1-selective blockers versus β1-β2 blockers) with respect to alveolar-capillary gas diffusion and chemoreceptor response in HF patients, both factors able to impact on quality of life and, most likely, on prognosis. This review suggests an original algorithm for choosing among the currently available β-blocking agents based on the knowledge of cardiopulmonary pathophysiology. Particularly, starting from lung physiology and from some experimental models, it focuses on the mechanisms underlying lung mechanics, chemoreceptors, and alveolar-capillary unit impairment in HF. This paper also remarks the significant benefit deriving from the correct use of the different β-blockers in HF patients through a brief overview of the most important clinical trials.