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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.

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.

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.

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

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

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.

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.

Background In idiopathic pulmonary arterial hypertension (IPAH) treatment goals include improving right ventricular (RV) function, hemodynamics and symptoms to move patients to a low-risk category for adverse clinical outcomes. No data are available on the effect of upfront combination therapy on RV improvement as compared with monotherapy. The aim of this study was to evaluate echocardiographic RV morphology and function in patients affected by IPAH and treated with different strategies. Methods Sixty-nine consecutive, treatment-naive IPAH patients treated with first-line upfront combination therapy at 10 centers were retrospectively evaluated and compared with 2 matched cohorts treated with monotherapy after short-term follow-up. Evaluation included clinical, hemodynamic and echocardiographic parameters. Results At 155 ± 65 days after baseline evaluation, patients in the oral+prostanoid group (Group 1) had the most clinical and hemodynamic improvement compared with the double oral group (Group 2), the oral monotherapy group (Group 3) and the prostanoid monotherapy group (Group 4). The more extensive reduction of pulmonary vascular resistance in Groups 1, 2 and 4 was associated with significant improvement in all RV echocardiographic parameters compared with Group 3. Considering the number of patients who reached the target goals suggested by established guidelines, 8 of 27 (29.6%) and 7 of 42 (16.7%) patients in Groups 1 and 2, respectively, achieved low-risk status, as compared with 2 of 69 (2.8%) and 6 of 27 (22.2%) in Groups 3 and 4, respectively. Conclusions In advanced treatment-naive IPAH patients, an upfront combination therapy strategy seems to significantly improve hemodynamics and RV morphology and function compared with oral monotherapy. The most significant results seem to be achieved with prostanoids plus oral drug, whereas the use of the double oral combination and prostanoids as monotherapy seem to produce similar results.

AIMS Mineralocorticoid receptor antagonists (MRAs) have been demonstrated to improve outcomes in reduced ejection fraction heart failure (HFrEF) patients. However, MRAs added to conventional treatment may lead to worsening of renal function and hyperkalaemia. We investigated, in a population-based analysis, the long-term effects of MRA treatment in HFrEF patients. METHODS AND RESULTS We analysed data of 6046 patients included in the Metabolic Exercise Cardiac Kidney Index score dataset. Analysis was performed in patients treated (n = 3163) and not treated (n = 2883) with MRA. The study endpoint was a composite of cardiovascular death, urgent heart transplantation, or left ventricular assist device implantation. Ten years' survival was analysed through Kaplan-Meier, compared by log-rank test and propensity score matching. At 10 years' follow-up, the MRA-untreated group had a significantly lower number of events than the MRA-treated group (P

Background Right ventricular (RV) failure is a major determinant of symptoms and shortened survival in pulmonary arterial hypertension (PAH). This study assessed the prognostic relevance of increased right heart (RH) dimensions determined by echocardiography and RH reverse remodeling (RHRR) with targeted therapies in idiopathic PAH (IPAH). Methods The study prospectively monitored 102 therapy-naive IPAH patients for the presence of clinical worsening. Baseline evaluation included RH catheterization and echocardiography. RHRR at the 1-year follow-up was defined by a decrease in RV end-diastolic area, right atrial area, and the left ventricular systolic eccentricity index. Results At the 1-year follow-up, 18 of 102 patients (17.6%) presented with RHRR. A decrease in pulmonary vascular resistance was the only independent determinant of RHRR. The 94 surviving patients were monitored for 995 ± 529 days. RHRR was an independent prognostic factor and significantly improved the power of the prognostic model based on traditional clinical and hemodynamic parameters. The respective event-free survival rates at 1, 3, and 5 years were 94%, 94%, and 94% in patients with RHRR and 75%, 55%, and 24% in those without RHRR (p = 0.0001). Interestingly, RHRR was able to further stratify patients’ risk assessment through the Registry to Evaluate Early And Long-term PAH Disease Management risk score. Conclusions RHRR after 1 year of treatment is an independent predictor of prognosis in IPAH. The likelihood of RHRR is proportional to decreased pulmonary vascular resistance.

AIMS The two main symptoms referred by chronic heart failure (HF) patients as the causes of exercise termination during maximal cardiopulmonary exercise testing (CPET) are muscular fatigue and dyspnoea. So far, a physiological explanation why some HF patients end exercise because of dyspnoea and others because of fatigue is not available. We assessed whether patients referring dyspnoea or muscular fatigue may be distinguished by different ventilator or haemodynamic behaviours during exercise. METHODS AND RESULTS We analysed exercise data of 170 consecutive HF patients with reduced left ventricular ejection fraction in stable clinical condition. All patients underwent maximal CPET and a second maximal CPET with measurement of cardiac output by inert gas rebreathing at peak exercise. Thirty-eight (age 65.0 ± 11.1 years) and 132 (65.1 ± 11.4 years) patients terminated CPET because of dyspnoea and fatigue, respectively. Haemodynamic and cardiorespiratory parameters were the same in fatigue and dyspnoea patients. VO2 was 10.4 ± 3.2 and 10.5 ± 3.3 mL/min/kg at the anaerobic threshold and 15.5 ± 4.8 and 15.4 ± 4.3 at peak, in fatigue and dyspnoea patients, respectively. In fatigue and dyspnoea patients, peak heart rate was 110 ± 22 and 114 ± 22 beats/min, and VE/VCO2 and VO2 /work relationship slopes were 31.2 ± 6.8 and 30.6 ± 8.2 and 10.6 ± 4.2 and 11.4 ± 5.5 L/min/W, respectively. Peak cardiac output was 6.68 ± 2.51 and 6.21 ± 2.55 L/min (P = NS for all). CONCLUSIONS In chronic HF patients in stable clinical condition, fatigue and dyspnoea as reasons of exercise termination do not highlight different ventilatory or haemodynamic patterns during effort.

Aims Risk stratification in heart failure (HF) is crucial for clinical and therapeutic management. A multiparametric approach is the best method to stratify prognosis. In 2012, the Metabolic Exercise test data combined with Cardiac and Kidney Indexes (MECKI) score was proposed to assess the risk of cardiovascular mortality and urgent heart transplantation. The aim of the present study was to compare the prognostic accuracy of MECKI score to that of HF Survival Score (HFSS) and Seattle HF Model (SHFM) in a large, multicentre cohort of HF patients with reduced ejection fraction. Methods and results We collected data on 6112 HF patients and compared the prognostic accuracy of MECKI score, HFSS, and SHFM at 2- and 4-year follow-up for the combined endpoint of cardiovascular death, urgent cardiac transplantation, or ventricular assist device implantation. Patients were followed up for a median of 3.67 years, and 931 cardiovascular deaths, 160 urgent heart transplantations, and 12 ventricular assist device implantations were recorded. At 2-year follow-up, the prognostic accuracy of MECKI score was significantly superior [area under the curve (AUC) 0.781] to that of SHFM (AUC 0.739) and HFSS (AUC 0.723), and this relationship was also confirmed at 4 years (AUC 0.764, 0.725, and 0.720, respectively). Conclusion In this cohort, the prognostic accuracy of the MECKI score was superior to that of HFSS and SHFM at 2- and 4-year follow-up in HF patients in stable clinical condition. The MECKI score may be useful to improve resource allocation and patient outcome, but prospective evaluation is needed.

Aims: The use of β-blockers represents a milestone in the treatment of heart failure with reduced ejection fraction (HFrEF). Few studies have compared β-blockers in HFrEF, and there is little data on the effects of different doses. The present study aimed to investigate in a large database of HFrEF patients (MECKI score database) the association of β-blocker treatment with a composite outcome of cardiovascular death, urgent heart transplantation or left ventricular assist device implantation, addressing the role of β-selectivity and dosage regimens. Methods and results: In 5242 HFrEF patients, we investigated the role of: (i) β-blocker treatment vs. non-β-blocker treatment, (ii) β1-/β2-receptor-blockers vs. β1-selective blockers, and (iii) daily β-blocker dose. Patients were followed for 3.58 years, and 1101 events (18.3%) were observed; 4435 patients (86.8%) were on β-blockers, while 807 (13.2%) were not. At 5 years, β-blocker-patients showed a better outcome than non-β-blocker-subjects [hazard ratio (HR) 0.48, P 2 5 mg carvedilol equivalent daily dose, n = 1005) patients than in both medium dose (12.5–25 mg, n = 1431) and low dose (

The right ventricle (RV) adapts in pulmonary arterial hypertension (PAH) by an increased contractility to preserve its coupling to the pulmonary circulation but relies on increased dimensions when this homeometric adaptation gets exhausted ([1][1]). We therefore investigated on the added value of

BACKGROUND >Despite advances in drug development, life expectancy in idiopathic pulmonary arterial hypertension (IPAH) remains unacceptable. Contemporary IPAH characterization is based on criteria that may not adequately capture disease heterogeneity and may be proposed as a possible explanation for why patient outcome is still unfavorable. The aim of this study was to apply cluster analysis to improve phenotyping of patients with IPAH and analyze long-term clinical outcome of derived clusters. METHODS Patients with IPAH from 2 referral centers (n = 252) were evaluated with clinical, hemodynamic, and echocardiographic assessment and cardiopulmonary exercise test. Patients were classified according to cluster analysis and followed for clinical worsening occurrence. RESULTS The cluster analysis identified 4 IPAH phenotypes. Cluster 1 was characterized by young patients, mild pulmonary hypertension (PH), mild right ventricular (RV) dilation and high oxygen (O2) pulse; Cluster 2 by severe PH and RV dilation and high O2 pulse; and Cluster 3 by male patients, severe PH and RV dilation, and low O2 pulse. Cluster 4 patients were older and overweight, with mild PH and RV dilation and low O2 pulse. After a mean follow-up of 995 ± 623 days, 123 (48.8%) patients had clinical worsening. Cluster 1 patients presented the best prognosis, whereas Cluster 3 had the highest rates of clinical worsening. Compared with Cluster 1, risk of clinical worsening ranged from 4.12 (confidence interval [CI] 1.43–11.92; p = 0.009) for Cluster 4 to 7.38 (CI 2.80–19.40) for Cluster 2 and 13.8 (CI 5.60–34.0; p = 0.0001) for Cluster 3. CONCLUSIONS Cluster analysis of clinical variables identified 4 distinct phenotypes of IPAH. Our findings underscore the high degree of disease heterogeneity that exists within patients with IPAH and the need for advanced clinical testing to define phenotypes to improve treatment strategy decision-making. CONDENSED ABSTRACT Idiopathic pulmonary arterial hypertension (IPAH) characterization is based on criteria that may not adequately capture disease heterogeneity. The aim of this study was to apply cluster analysis to improve phenotyping of IPAH. Patients with IPAH (n = 252) were evaluated with clinical, hemodynamic, and echocardiographic assessment and cardiopulmonary exercise test. Within the umbrella category of IPAH, it was the combination of mean pulmonary arterial pressure, right ventricular size, and oxygen pulse that further stratified patients into novel IPAH phenotypes that significantly associate with clinical worsening. These findings underscore the need for novel multidimensional IPAH phenotyping for improved patient care and trial quality.

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.

In chronic heart failure, minute ventilation (V′E) for a given carbon dioxide production (V′CO2) might be abnormally high during exercise due to increased dead space ventilation, lung stiffness, chemo- and metaboreflex sensitivity, early metabolic acidosis and abnormal pulmonary haemodynamics. The V′Eversus V′CO2 relationship, analysed either as ratio or as slope, enables us to evaluate the causes and entity of the V′E/perfusion mismatch. Moreover, the V′E axis intercept, i.e. when V′CO2 is extrapolated to 0, embeds information on exercise-induced dead space changes, while the analysis of end-tidal and arterial CO2 pressures provides knowledge about reflex activities. The V′Eversus V′CO2 relationship has a relevant prognostic power either alone or, better, when included within prognostic scores. The V′Eversus V′CO2 slope is reported as an absolute number with a recognised cut-off prognostic value of 35, except for specific diseases such as hypertrophic cardiomyopathy and idiopathic cardiomyopathy, where a lower cut-off has been suggested. However, nowadays, it is more appropriate to report V′Eversus V′CO2 slope as percentage of the predicted value, due to age and gender interferences. Relevant attention is needed in V′Eversus V′CO2 analysis in the presence of heart failure comorbidities. Finally, V′Eversus V′CO2 abnormalities are relevant targets for treatment in heart failure.

PURPOSE To assess whether atrial fibrillation (AF) in heart failure (HF) affects oxygen uptake at anaerobic threshold ((Equation is included in full-text article.)O2 AT) and heart rate (HR) kinetics. METHODS A total of 15 patients with HF and AF and 18 with HF and sinus rhythm (SR) performed a maximal incremental and 2 constant workload cycle ergometer cardiopulmonary exercise tests (below and above AT, at 25% and 75% of maximal workload, respectively). At constant workload tests, kinetics of (Equation is included in full-text article.)O2 and HR were assessed by calculating time constant (τ). RESULTS HF patients with AF showed a similar peak (Equation is included in full-text article.)O2 to those with SR (16.7 ± 4.5 mL/kg/min vs 16.6 ± 3.9 mL/kg/min). However, (Equation is included in full-text article.)O2 AT (11.3 ± 2.9 mL/kg/min vs 9.3 ± 2.8 mL/kg/min; P < .05), peak HR (149 ± 18.8 bpm vs 116.4 ± 20.4 bpm; P < .001), HR AT (125.3 ± 19.1 bpm vs 90.3 ± 15.5 bpm; P < .001), and HR increase during exercise were greater in HF patients with AF. Finally, τHR and τ(Equation is included in full-text article.)O2 below and above AT were not significantly different. CONCLUSIONS In HF patients with AF, despite a similar peak (Equation is included in full-text article.)O2 compared with patients with HF and SR, (Equation is included in full-text article.)O2 AT is higher because of a higher HR and a greater HR increase during exercise. One postulated mechanism would be a greater cardiac output increase at the beginning of exercise in HF patients with AF. The delayed AT generates uncertainty about the meaning of a (Equation is included in full-text article.)O2 value at AT in HF patients with AF, because a higher AT is usually associated with better performance and a better prognosis.

Management of patients presenting to the Emergency Department with chest pain is continuously evolving. In the setting of acute coronary syndrome, the availability of high-sensitivity cardiac troponin assays (hs-cTn) has allowed for the development of algorithms aimed at rapidly assessing the risk of an ongoing myocardial infarction. However, concerns were raised about the massive application of such a simplified approach to heterogeneous real-world populations. As a result, there is a potential risk of underdiagnosis in several clusters of patients, including women, for whom a lower threshold for hs-cTn was suggested to be more appropriate. Implementation in clinical practice of sex-tailored cut-off values for hs-cTn represents a hot topic due to the need to reduce inequality and improve diagnostic performance in females. The aim of this review is to summarize current evidence on sex-specific cut-off values of hs-cTn and their application and usefulness in clinical practice. We also offer an extensive overview of thresholds reported in literature and of the mechanisms underlying such differences among sexes, suggesting possible explanations about debated issues.

Background We evaluated the prognostic meaning of the simple presence or absence of identifiable anaerobic threshold (AT) and respiratory compensation point (RCP) at cardiopulmonary exercise tests (CPETs) performed with a maximal incremental exercise protocol. Methods In the present multicenter study, we retrospectively analyzed data in 1,995 patients with heart failure with reduced ejection fraction (HFrEF). All underwent clinical and laboratory evaluation, echocardiography, and maximal CPET at baseline. The analysis was performed according to absence of identified AT and RCP (group 1: n = 292; 15%), presence of AT but absence of identified RCP (group 2: n = 920; 46%), and presence of both AT and RCP (group 3: n = 783; 39%). The study end point was the composite of cardiovascular mortality, urgent heart transplant, and left ventricular assist device implantation. Results Median follow-up was 2.97 years (interquartile range, 1.50-5.35 years). Eighty-seven (30%), 169 (18%), and 111 (14%) events were observed in groups 1, 2, and 3, respectively (P = .025). Compared with results in group 3 (patients with the best survival), the likelihood of reaching the study end point increased 2.7 times when neither AT nor RCP were identified (hazard ratio, 2.74) and 1.4 times when only AT was identified (hazard ratio, 1.4). Moreover, adding the presence or absence of identified AT and RCP improved the prognostic power of peak oxygen uptake because a significant reclassification was obtained. Conclusions AT and RCP identification has a potential role in the prognostic stratification of HFrEF.

Despite cardiovascular disease (CVD) now being the leading cause of morbidity and mortality in women worldwide, this problem is still dramatically underestimated. The disparities in diagnosis, treatment, and prognosis between men and women are rooted in basic biological differences, as well as in the complex interactions of cultural and socioeconomic problems. This is why an up-to-date and gender-based revision of current guidelines is highly desirable.

BACKGROUND The added value of cardiopulmonary exercise testing (CPET) in the follow-up of patients with stable pulmonary arterial hypertension (PAH) remains undefined. METHODS Idiopathic, heritable, and drug-induced PAH patients free from clinical worsening (CW) after 1 year of treatment were enrolled in derivation (n = 80) and validation (n = 80) cohorts at an interval of 6 years and followed for 3 years. Prognostic models were constructed and validated in low-risk patients in World Health Organization (WHO) Functional Class I or II with cardiac index (CI) ≥2.5 liters/min/m2 and right atrial pressure (RAP)

Objectives: The aim of this study was to determine the prevalence of right intraventricular dyssynchrony, its determinants and prognostic impact in idiopathic, heritable, and anorexigen-ind...

Background Although increased pulmonary pressure is caused by changes in the pulmonary vasculature, prognosis in idiopathic pulmonary arterial hypertension (IPAH) is strongly associated with right ventricular (RV) function. The aim of this study was to describe the best RV adaptive remodeling pattern to increased afterload in IPAH. Methods In 60 consecutive patients with IPAH, RV morphologic and functional features were evaluated by echocardiography and cardiac magnetic resonance imaging. To address the question of the best RV adaptation pattern, we divided the study population into two groups by the median value of RV mass/volume ratio (0.46) because this parameter allows the distinction between RV eccentric (≤0.46) and concentric hypertrophy (>0.46). The two groups were compared for RV remodeling and systolic function parameters, World Health Organization class, pulmonary hemodynamics, and 6-minute walk test. Results Despite similar pulmonary vascular resistance, mean pulmonary pressure, and compliance, patients with eccentric hypertrophy had advanced World Health Organization class and worse 6-minute walk test, hemodynamics, RV remodeling, and systolic function parameters compared with patients with concentric hypertrophy. The group with concentric hypertrophy had higher RV to pulmonary arterial coupling compared with the group with eccentric hypertrophy (1.24 ± 0.26 vs 0.83 ± 0.33, p = 0.0001), indicating higher RV efficiency. A significant correlation was found between pulmonary vascular resistance and RV to pulmonary arterial coupling ( r = −0.55, r 2 = 0.31, p = 0.0001), with patients with RV mass/volume ratio > 0.46 at the higher part of the scatterplot, confirming more adequate RV function. Conclusions Concentric hypertrophy might represent a more favorable RV adaptive remodeling pattern to increased afterload in IPAH because it is associated with more suitable systolic function and mechanical efficiency.

Introduction: NYHA is the most used classification for heart failure (HF), but it does not include patient’s clinical features. We proposed a new staging system for HF, named HLM (JACC 2014;20;63(19):1959-60), analogous to the TNM classification used in Oncology. HLM refers to heart damage (H), lung involvement (L), and malfunction (M) of peripheral organs (i.e. kidney, liver, hematopoiesis and central nervous system). Hypothesis: The aim was a preliminary comparison between HLM and NYHA at 6 and 12 months to assess the most accurate prognosis of HF patients in terms of rehospitalization for major adverse cardiovascular and cerebrovascular events (MACCE) and mortality. Methods: We enrolled 1064 consecutive patients with the diagnosis of or at risk for HF. According to HLM classification, all parameters for heart, lungs and peripheral organs function were collected and each patient was classified according to NYHA and HLM. At 6 and 12 months patients were followed up for rehospitalization for MACCE and cardiac death rates were calculated. Results: At 6 and 12 months follow-up, comparing to NYHA, HLM showed a greater area under the ROC curve (AUC) for rehospitalization as well as for cardiac death (Fig. 1). MACCE and cardiac death rates have been assessed separately for each parameter (H, L and M): L and M showed the most accurate prognostic power; at 1 year follow-up, L2 was significantly correlated (p=0.004) with rehospitalization as well as L3 (p=0.000), M1 (p=0.004), M2 (p=0.008) and M3 (p=0.003). M2 was significantly correlated (p=0.02) with cardiovascular mortality as well as M3 (p=0.004 ). Conclusions: Our preliminary data suggest that, compared to NYHA, HLM better stratifies risk of rehospitalization for MACCE and of cardiac death in HF patients. Regarding HLM, lung involvement (L2-3) and two or more organs dysfunction (M2-3) presented the most accurate prognostic power. Those preliminary results need to be confirmed in a greater population with a longer follow up.

Purpose Aim of this study was to describe strain-derived right ventricular (RV) diastolic patterns by speckle-tracking echocardiography (STE) and its clinical impact in idiopathic pulmonary arterial hypertension (IPAH).STE of the RV has been extensively described in PAH. However, diastolic function has been yet underlooked (neglected) for no reason. Methods In 108 consecutive IPAH patients we identified three distinct strain-derived patterns from the mid-basal RV free wall segments. Each patient underwent baseline clinical, hemodynamic and complete echocardiographic evaluation and followed-up for clinical worsening occurrence. Results The three strain-derived diastolic patterns were characterized by high reproducibility (Cohen's κ=0.64, p=0.0001). Pattern 1 was associated with mild pulmonary hypertension and preserved clinical and RV function (preserved RV phenotype). This pattern was repetitively found in a cohort of 30 healthy subjects. Pattern 2 was associated with moderate to severe pulmonary hypertension, WHO functional class II and III, still preserved RV function (RV adaptive phenotype). Pattern 3 was associated with advanced stage of IPAH, characterized by high right atrial pressure, low cardiac index and severe RV remodeling (RV maladaptive phenotype). Multivariable models for clinical worsening (CW) prediction demonstrated that the addition of RV diastolic patterns to clinical and hemodynamic variables significantly increased the prognostic power of the model (0.79 vs 0.66; p Conclusion The results of the present study suggest that using speckle tracking echocardiography we can identify three phenotypically distinct, reproducible and clinically meaningful RV strain-derived diastolic patterns.

Although in the past years a reduced mortality in peri-operative care has been observed, cardiovascular mortality and morbidity still is a major burden in patients undergoing noncardiac surgery and its evaluation is still a difficult task. An accurate risk stratification can improve quality of peri-operative care and may improve survival, while reducing healthcare costs. In clinical practice, we make our assessment of a patient's cardiac status based on history, examination and investigations, together with risks related to the surgical procedure, to generate an 'individualized cardiac risk assessment'. At the present, risk stratification with clinical risk score and cardiac testing have been shown to be suboptimal in identifying high-risk patients. Surgery, like exercise, increases oxygen consumption. Indeed, one of the key elements in determining risk assessment is exercise intolerance, but future research in this field is needed to clarify this statement. Cardiopulmonary exercise testing (CPET) provides a global assessment of functional capacity involving and integrating the physiological measurement during incremental exercise. The pattern of CPET's variables identifies the abnormal exercise capacity, often providing an objective evaluation of cause and, moreover, predicting outcomes in both apparently healthy and chronic disease populations. An anaerobic threshold VO2 above 11 ml/kg per min seems to identify individuals with a very low surgical risk even if undergoing major surgery. This review is focused on tools of risk assessment in patients undergoing noncardiac surgery and on the physiological basis for CPET in detecting patients 'at risk'.

Peak exercise cardiac output (CO) increase is associated with an increase of peak oxygen uptake (VOFifteen of 20 patients bearing LVAD (Jarvik 2000) enrolled in the study successfully performed peak exercise evaluation. All patients had severe HF as shown by clinical evaluation, laboratory tests, echocardiography, spirometry with alveolar-capillary diffusion, and maximal cardiopulmonary exercise testing (CPET). CPETs with non-invasive CO measurements at rest and peak exercise were done on 2days at LVAD pump speed set randomly at 2 and 4.Increasing LVAD pump speed from 2 to 4 increased CO from 3.4±0.9 to 3.8±1.0L/min (ΔCO 0.4±0.6L/min, p=0.04) and from 5.3±1.3 to 5.9±1.4L/min (ΔCO 0.6±0.7L/min, p0.01) at rest and peak exercise, respectively. Similarly, VOIn HF, an increase in CO with a higher LVAD pump speed is associated with increased peak VO

Background— Primary aldosteronism (PA) causes excess left ventricular (LV) hypertrophy and diastolic dysfunction; whether this occurs also in secondary aldosteronism (SA) without hypertension is unknown. We investigated the cardiac modifications in patients with preserved LV ejection fraction who had PA or SA. Methods and Results— We measured several Doppler echocardiography–derived variables, including tissue Doppler imaging (TDI) parameters and strain rate analysis, in 262 patients with PA, 117 with SA because of liver cirrhosis, and in 61 control healthy subjects. SA and PA patients showed markedly elevated aldosterone levels (67 versus 39 ng/dL, respectively; normal values P P =P =0.001) were lower in PA than in SA patients. Conclusions— Primary and secondary hyperaldosteronism correlate with LV enlargement and high prevalence of LV hypertrophy and diastolic dysfunction; a subclinical systolic dysfunction is evident only in PA. In SA, the high rate of LV hypertrophy, in spite of low peripheral resistances and low-to-normal blood pressure, could be accounted for the high renin and aldosterone values, and the work overload associated with a hyperdynamic circulatory state.

In chronic heart failure (HF), the alveolar-capillary membrane undergoes a remodeling process that negatively affects gas exchange. In case of alveolar-capillary gas diffusion impairment, arterial desaturation (SaO2) is rarely observed in HF patients. At play are 3 factors: overall pulmonary diffusing capacity (assessed as lung diffusion for CO, DLCO), global O2 consumption (VO2) and alveolar (A) to arterial (a) pO2 gradient (AaDO2). In 100 consecutive stable HF patients, DLCO, resting respiratory gases and arterial blood gases were measured to determine VO2, paO2, pAO2 and AaDO2. DLCO was poorly but significantly related to AaDO2. The correlation improved after correcting AaDO2 for VO2 (p