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Cardiac involvement has been frequently reported in COVID-19 as responsible of increased morbidity and mortality. Given the importance of right heart function in acute and chronic respiratory diseases, its assessment in SARS-CoV-2 infected patients may add prognostic accuracy. Transthoracic echocardiography has been proposed to early predict myocardial injury and risk of death in hospitalized patients. This systematic review presents the up-to-date sum of literature regarding right ventricle ultrasound assessment. We evaluated commonly used echocardiographic parameters to assess RV function and discussed their relationship with pathophysiological mechanisms involved in COVID-19. We searched Medline and Embase for studies that used transthoracic echocardiography for right ventricle assessment in patients with COVID-19.

Objectives The DETECT algorithm has been developed to identify SSc patients at risk for pulmonary arterial hypertension (PAH) yielding high sensitivity but low specificity, and positive predictive value. We tested whether cardiopulmonary exercise testing (CPET) could improve the performance of the DETECT screening strategy. Methods Consecutive SSc patients over a 30-month period were screened with the DETECT algorithm and positive subjects were referred for CPET before the execution of right-heart catheterization. The predictive performance of CPET on top of DETECT was evaluated and internally validated via bootstrap replicates. Results Out of 314 patients, 96 satisfied the DETECT application criteria and 54 were positive. PAH was ascertained in 17 (31.5%) and pre-capillary pulmonary hypertension in 23 (42.6%) patients. Within CPET variables, the slope of the minute ventilation to carbon dioxide production relationship (VE/VCO2 slope) had the best performance to predict PAH at right-heart catheterization [median (interquartile range) of specificity 0.778 (0.714–0.846), positive predictive value 0.636 (0.556–0.750)]; exploratory analysis on pre-capillary yielded a specificity of 0.714 (0.636–0.8) and positive predictive value of 0.714 (0.636–0.8). Conclusion In association with the DETECT algorithm, CPET may be considered as a useful tool in the workup of SSc-related pulmonary hypertension. The sequential determination of the VE/VCO2 slope in DETECT-positive subjects may reduce the number of unnecessary invasive procedures without any loss in the capability to capture PAH. This strategy had also a remarkable performance in highlighting the presence of pre-capillary pulmonary hypertension.

Early risk stratification for complications and death related to Coronavirus disease 2019 (COVID-19) infection is needed. Because many patients with COVID-19 who developed acute respiratory distress syndrome have diffuse alveolar inflammatory damage associated with microvessel thrombosis, we aimed to investigate a common clinical tool, the CHA(2)DS(2)-VASc, to aid in the prognostication of outcomes for COVID-19 patients. We analyzed consecutive patients from the multicenter observational CORACLE registry, which contains data of patients hospitalized for COVID-19 infection in 4 regions of Italy, according to data-driven tertiles of CHA(2)DS(2)-VASc score. The primary outcomes were inpatient death and a composite of inpatient death or invasive ventilation. Of 1045 patients in the registry, 864 (82.7%) had data available to calculate CHA(2)DS(2)-VASc score and were included in the analysis. Of these, 167 (19.3%) died, 123 (14.2%) received invasive ventilation, and 249 (28.8%) had the composite outcome. Stratification by CHA(2)DS(2)-VASc tertiles (T1: ≤1; T2: 2 to 3; T3: ≥4) revealed increases in both death (8.1%, 24.3%, 33.3%, respectively; p

Introduction: Myocardial injury is commonly observed in patients (pts) with Coronarvirus disease 2019 (Covid-19) but its anatomical correlate has not been elucidated. We evaluated the association between presence of transthoracic echocardiographic (TTE) left ventricular (LV) regional wall motion abnormalities (RWMA), myocardial injury and outcomes in Covid-19 pts. Methods: We conducted a cohort study including 7 hospitals in New York City (US) and Milan (Italy) of hospitalized pts with confirmed Covid-19 who had a TTE during their index hospitalization. Myocardial injury was defined as any elevation in cardiac troponin (cTn) during the hospitalization. Using multivariable logistic regression, we analyzed the association between RWMA, myocardial injury and in-hospital death. Results: Among 305 total pts included in the study, 49 (16%) had RWMA and 44 (14%) had global LV systolic dysfunction. Among those with RWMA, 31/49 (63%) had LV ejection fraction Figure 1 ). Conclusion: In Covid-19 pts, RWMA are associated with typical ACS presentation: chest pain, ST changes and cTn elevations. Accordingly, a large proportion of pts with RWMA who underwent LHC had confirmed ACS warranting PCI. Though myocardial injury was associated with increased risk of in-hospital death regardless of the presence of RWMA, LHC should be considered for pts with RWMA and myocardial injury to rule-out obstructive disease.

Background Myocardial injury is frequent among patients hospitalized with coronavirus disease-2019 (COVID-19) and is associated with a poor prognosis. However, the mechanisms of myocardial...

Pulmonary capillary stress failure is potentially involved in exercise-induced hypoxemia i.e. a significant fall in hemoglobin O2 saturation (SpO2) during sea level exercise in endurance-trained athletes. Whether there may be specific properties of the pulmonary vascular function in athletes exhibiting O2 desaturation is unknown., info:eu-repo/semantics/published

Knowledge of preoperative right heart function of adult patients with cystic fibrosis (CF) awaiting lung transplant (LUTX) is limited. The echocardiography of adult patients with CF enlisted for LUTX was retrospectively analyzed and compared with standards and invasive analyses (right heart catheterization, multigated radionuclide ventriculography). We included 49 patients (reported as mean ± standard deviation; 29 ± 9 years of age; forced expiratory volume in first second of expiration, 31% ± 11% predicted; lung allocation score, 36 ± 5; invasive mean pulmonary artery pressure, 17 ± 5 mm Hg; multigated radionuclide ventriculography right ventricle [RV] ejection fraction, 50% ± 9%). Patients had increased RV end-diastolic area, RV wall thickness, and increased pulmonary artery acceleration time with subnormal tricuspid annular plane systolic excursion, tissue Doppler positive peak systolic velocity, and fraction area change. Subnormal tricuspid annular plane systolic excursion (23 mm), tissue Doppler positive peak systolic velocity (14 cm/s), and fraction area change (49%) had high sensitivity and negative predictive value in predicting impaired RV. EJECTION FRACTION: A good correlation between echocardiographic estimated and invasively measured systolic pulmonary artery pressure was observed (R

Expanding from China around the World, COVID-19 is the disease caused by the Severe Acute Respiratory Syndrome Related Coronavirus 2 (SARS-CoV-2). COVID-19 primarily manifests by hypoxic normo-hypocapnia with preserved lung compliance [1]. In the absence of targeted treatment, sub-intensive clinicians support patients with non-invasive ventilation and anti-inflammatory/anti-viral agents waiting for status improvement. Angiotensin-converting enzyme 2 (ACE2), highly expressed on the external membrane of lungs, heart, kidney and gastrointestinal tract cells, displays the binding site for the spike protein of SARS-CoV-2 [2]. ACE2, identified as counterpart of the Renin-Angiotensin-Aldosterone System (RAAS), converts Angiotensin (Ang) II to Ang-(1-7) and Ang I to Ang-(1-9). ACE2 activity induces vasodilatation and reduces cell growth and inflammatory response. In experimental models that mimic the viral acute respiratory distress syndrome (ARDS), the absence of Ace2 led to inflammation, vascular permeability and lung injury via activation of Ang II pathway [3, 4]. The decrease in ACE2 activity by SARS-CoV-2 can unleash a cascade of injurious effects through a heightened imbalance in the actions of the products of ACE versus ACE2. Moving to a clinical setting, the ACE2 downregulation may be one of the pathways sustaining arterial hypertension [5] and pulmonary arterial hypertension [6]. Therefore, it is conceivable that in COVID-19 a cleavage of membrane ACE2 along with its circulatory levels could impact on the disease progression and clinical worsening [7]. Thus, to support a pathophysiological role of ACE2, the present report shares clinical data from an observational study conducted on 40 patients with a diagnosis of COVID-19, hospitalised in the Cardiorespiratory Sub-Intensive COVID-19 Unit at the Fondazione IRCCS Ca' Granda Policlinico Hospital of Milan., In COVID-19 patients respiratory failure is associated with increase systemic blood pressure conceivably due to the modulation of renin-angiotensin-aldosterone system by SARS-CoV-2 infection.

Uncertainties remain about the diagnostic and therapeutic strategy to prevent left ventricular thrombus formation after myocardial infarction. In particular, the roles of predisposing factors and prophylactic anticoagulation have not been sufficiently considered. We propose an ‘uncertainties flowchart’ with the aim of stimulating research on the topic.

There has been suggestion that a greater "pulmonary vascular reserve" defined by a low pulmonary vascular resistance (PVR) and a high lung diffusing capacity (DL) allow for a superior aerobic exercise capacity. How pulmonary vascular reserve might affect exercise capacity at moderate altitude is not known.Thirty-eight healthy subjects underwent an exercise stress echocardiography of the pulmonary circulation, combined with measurements of DL for nitric oxide (NO) and carbon monoxide (CO) and a cardiopulmonary exercise test at sea level and at an altitude of 2250 m.At rest, moderate altitude decreased arterial oxygen content (CaO2) from 19.1 ± 1.6 to 18.4 ± 1.7 mL·dL, P0.001, and slightly increased PVR, DLNO, and DLCO. Exercise at moderate altitude was associated with decreases in maximum O2 uptake (V˙O2max), from 51 ± 9 to 43 ± 8 mL·kg⋅min, P0.001, and CaO2 to 16.5 ± 1.7 mL·dL, P0.001, but no different cardiac output, PVR, and pulmonary vascular distensibility. DLNO was inversely correlated to the ventilatory equivalent of CO2 (V˙E/V˙CO2) at sea level and at moderate altitude. Independent determinants of V˙O2max as determined by a multivariable analysis were the slope of mean pulmonary artery pressure-cardiac output relationship, resting stroke volume, and resting DLNO at sea level as well as at moderate altitude. The magnitude of the decrease in V˙O2max at moderate altitude was independently predicted by more pronounced exercise-induced decrease in CaO2 at moderate altitude.Aerobic exercise capacity is similarly modulated by pulmonary vascular reserve at moderate altitude and at sea level. Decreased aerobic exercise capacity at moderate altitude is mainly explained by exercise-induced decrease in arterial oxygenation.

Introduction: The presence of pulmonary hypertension (PH) before lung transplantation (LuTx) is a well known risk factor for primary graft dysfunction (PGD). However, the role of the comprehensive cardiopulmonary hemodynamic assessed before LuTx is limited. We aimed to explore if other hemodynamic variables may have a role in PGD, besides absolute PH. Methods: a retrospective study was conducted at Policlinico Hospital of Milan (Italy) on adults who underwent LuTx for any indication other than cystic fibrosis from 2011 to 2017. PGD was defined as PaO2/FIO2 Results: among 67 patients (57% male, median age 58 years), 28 (42%) had PGD. PH was prevalent in PGD+ group (57% vs 33%, p=0.045). PAWP showed the strongest difference (PAWP: 13.0 vs 10.0 mmHg, p=0.036), while RAP was slightly higher in PGD+ group (RAP: 7.0 vs 5.5 mmHg, p=0.048). No differences were observed between PVR or IC (PVR: 2.61 vs 2.62 UW, p=0.622; CI: 3.13 vs 3.07 l/min/mq, p=0.760). Conclusion: our data confirm that PH is an important factor in PGD. However normal median values of PVR together with a higher median PAWP may suggest a predominant role of the post capillary component in this disease. From this point of view, RAP may reflect the overload of the right ventricle caused by higher total afterload. Thus, PAWP should be considered in PGD’s development.

Previous studies showed that transcutaneous vagus nerve stimulation (tVNS) modulates the autonomic nervous system (ANS) in resting condition. However, the autonomic regulation in response to an orthostatic challenge during tVNS in healthy subjects remains unknown. We tested the hypothesis that tVNS reduces heart rate (HR) and alters the responsivity of ANS to orthostatic stress in healthy subjects. In a randomized and cross-over trial, thirteen healthy subjects underwent two experimental sessions on different days: (1) tVNS and (2) control. Using a tVNS device, an auricular electrode was placed on the left cymba conchae of the external ear, an electric current with a pulse frequency of 25 Hz and amplitude between 1 and 6 mA was applied. For the assessment of ANS, the beat-to-beat HR and systolic arterial pressure (SAP) were analyzed using linear and nonlinear approaches during clinostatic and orthostatic conditions. In clinostatic conditions, tVNS reduced HR (p &lt, 0.01), SAP variability (p &lt, 0.01), and cardiac and peripheral sympathetic modulation (p &lt, 0.01). The responsivity of the peripheral sympathetic modulation to orthostatic stress during tVNS was significantly higher when compared to the control session (p = 0.03). In conclusion, tVNS reduces the HR and affects cardiac and peripheral autonomic control and increases the responses of peripheral autonomic control to orthostatic stress in healthy subjects.

Traditional echocardiography is unable to detect neither the early stages of iron overload cardiomyopathy nor myocardial iron deposition. The aim of the study is to determine myocardial systolic strain indices in thalassemia major (TM), and assess their relationship with T2*, a cardiac magnetic resonance index of the severity of cardiac iron overload. 55 TM cases with recent cardiac magnetic resonance (CMR-T2*) underwent speckle tracking analysis to assess regional myocardial strains and rotation. The results were compared with a normal control group (n = 20), and were subsequently analyzed on the basis of the CMR-T2* values. Two TM groups were studied: TM with significant cardiac iron overload (“low” T2*, ≤20 ms; n = 21), and TM with normal T2* values (“normal” T2*, >20 ms; n = 34). TM patients show significant, uniform decrease in circumferential and radial strain (P

Background— The prevalence of heart failure with preserved ejection fraction is increasing. The prognosis worsens with pulmonary hypertension and right ventricular (RV) failure development. We targeted pulmonary hypertension and RV burden with the phosphodiesterase-5 inhibitor sildenafil. Methods and Results— Forty-four patients with heart failure with preserved ejection fraction (heart failure signs and symptoms, diastolic dysfunction, ejection fraction ≥50%, and pulmonary artery systolic pressure >40 mm Hg) were randomly assigned to placebo or sildenafil (50 mg thrice per day). At 6 months, there was no improvement with placebo, but sildenafil mediated significant improvements in mean pulmonary artery pressure (−42.0±13.0%) and RV function, as suggested by leftward shift of the RV Frank-Starling relationship, increased tricuspid annular systolic excursion (+69.0±19.0%) and ejection rate (+17.0±8.3%), and reduced right atrial pressure (−54.0±7.2%). These effects may have resulted from changes within the lung (reduced lung water content and improved alveolar-capillary gas conductance, +15.8±4.5%), the pulmonary vasculature (arteriolar resistance, −71.0±8.2%), and left-sided cardiac function (wedge pulmonary pressure, −15.7±3.1%; cardiac index, +6.0±0.9%; deceleration time, −13.0±1.9%; isovolumic relaxation time, −14.0±1.7%; septal mitral annulus velocity, −76.4±9.2%). Results were similar at 12 months. Conclusions— The multifaceted response to phosphodiesterase-5 inhibition in heart failure with preserved ejection fraction includes improvement in pulmonary pressure and vasomotility, RV function and dimension, left ventricular relaxation and distensibility (structural changes and/or ventricular interdependence), and lung interstitial water metabolism (wedge pulmonary pressure decrease improving hydrostatic balance and right atrial pressure reduction facilitating lung lymphatic drainage). These results enhance our understanding of heart failure with preserved ejection fraction and offer new directions for therapy. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT01156636.

Background Cardiopulmonary exercise testing (CPET) provides powerful information on risk of death in heart failure (HF). We sought to define the relative and additive contribution of the 3 landmark (CPET) prognostic markers—peak oxygen consumption (VO 2 ), minute ventilation/carbon dioxide production (VE/VCO 2 ) slope, and exercise periodic breathing (EPB)—to the overall risk of cardiac death and to develop a prognostic score for optimizing risk stratification in HF patients. Methods and Results A total of 695 stable HF patients (average LVEF: 25 ± 8%) underwent a symptom-limited CPET maximum test after familiarization and were prospectively tracked for cardiac mortality. At multivariable Cox analysis EPB emerged as the strongest prognosticator. Using a statistical bootstrap technique (5000 data resamplings), point estimates, and 95% confidence intervals were obtained. Thirty-two configurations were adopted to classify patients into a given cell, according to EPB presence or absence and values of the 2 other covariates. Configurations without EPB and with VE/VCO 2 slope ≤30 were not significantly different from 0 (reference value). Statistical power of configurations increased with higher VE/VCO 2 slope and lower peak VO 2 . This prompted us to formulate a score including EPB as a discriminating variable, the (P)e(R)i(O)dic (B)reathing during (E)xercise (PROBE), which ranges between -1 and 1, with zero as reference configuration, that would help to optimize the prognostic accuracy of CPET-derived variables. The greatest PROBE score impact was provided by EPB, followed by VE/VCO 2 slope, whereas peak VO 2 added minimal prognostic power. Conclusions EPB with an elevated VE/VCO 2 slope leads to the highest and most precise PROBE score, whereas no additional risk information emerges when EPB is present with a peak VO 2 ≤10 mL O 2 ·kg −1 ·min −1 . PROBE score appears to provide a step forward for optimizing CPET use in HF prognostic definition.

ObjectivesThe purpose of this study was to test the ability of cardiopulmonary exercise testing (CPET)-derived variables as sudden cardiac death (SCD) predictors.BackgroundThe CPET variables, such as peak oxygen uptake (VO2), ventilatory requirement to carbon dioxide (CO2) production (VE/VCO2) slope, and exercise oscillatory breathing (EOB), are strong predictors of overall mortality in chronic heart failure (CHF) patients. Even though up to 50% of CHF patients die from SCD, it is unknown whether any of these variables predicts SCD.MethodsOne hundred fifty-six CHF patients (mean age: 60.9 ± 9.4 years; mean ejection fraction: 34.9 ± 10.6%) underwent CPET. Subjects were tracked for sudden versus pump-failure cardiac mortality over 27.8 ± 25.2 months.ResultsSeventeen patients died from SCD, and 17 died from cardiac pump failure. Survivors showed significantly higher peak VO2(16.8 ± 4.5 ml·kg−1·min−1) and lower VE/VCO2slope (32.8 ± 6.4) and prevalence of EOB (20.3%), compared with subjects who experienced arrhythmic (13.5 ± 3.2 ml·kg−1·min−1; 41.5 ± 11.4; 100%) or nonarrhythmic (14.1 ± 4.7 ml·kg−1·min−1; 38.1 ± 7.3; 47.1%) deaths (p < 0.05). At Cox regression analysis, all variables were significant univariate predictors of both sudden and pump failure death (p < 0.01). Multivariate analysis, including left ventricular (LV) ejection fraction, LV end systolic volume, and LV mass selected EOB, was the strongest predictor of both overall mortality (chi-square: 38.7, p < 0.001) and SCD (chi-square: 44.7, p < 0.001), whereas VE/VCO2slope was the strongest ventilatory predictor of pump failure death (chi-square: 11.8, p = 0.001).ConclusionsExercise oscillatory breathing is an independent predictor of SCD in patients with CHF and might help as an additional marker for prioritization of antiarrhythmic strategies.

Background Statins represent a modern mainstay of the drug treatment of coronary artery disease and acute coronary syndromes. Reduced aerobic work performance and slowed VO2 kinetics are established features of the clinical picture of post-myocardial infarction (MI) patients. We tested the hypothesis that statin therapy improves VO2 exercise performance in normocholesterolaemic post-MI patients. Materials and methods According to a double-blinded, randomized, crossover and placebo-controlled study design, in 18 patients with uncomplicated recent (3 days) MI we investigated the effects of atorvastatin (20 mg day−1) on gas exchange kinetics by calculating VO2 effective time constant (tau) during a 50-watt constant workload exercise, brachial artery flow-mediated dilatation (FMD) as an index of endothelial function, left ventricular function (echocardiography) and C-reactive protein (CRP, as an index of inflammation). Atorvastatin or placebo was given for 3 months each. Results Atorvastatin therapy significantly improved exercise VO2 tau and FMD, and reduced CRP levels. We did not observe changes in cardiac contractile function and relaxation properties during all study periods in either group. Conclusions In post-MI patients exercise performance is a potential additional target of benefits related to statin therapy. Endothelial function improvement is very likely implicated in this newly described therapeutic property.

Patients with pulmonary arterial hypertension (PAH) and with heart failure (HF) have increased ventilatory responses to exercise in proportion to disease severity. Exercise-associated oscillatory ventilation (EOV) predicts poor outcome in HF. Whether EOV occurs in PAH is unknown.We analyzed the initial cardiopulmonary exercise tests (CPETs) and right heart catheterization data of 109 patients with PAH and in 107 patients with HF consecutively referred to our center.The PAH patients were aged 54±16 years and their NYHA functional class was 2.8±0.5. The HF patients were aged 53±13 years and NYHA 2.4±0.6. Hemodynamic data were obtained in only 36 of them. The patients with PAH compared to those with HF had a lower peak VO2 (13±5 vs 17±5 mL/kg/min, p0.001) and a higher ventilatory equivalent for CO2 (VE/VCO2) slope (55±21 vs 34±7, p0.001). Mean pulmonary artery pressure was higher (50±10 vs 29±11 mmHg) and wedge pressure lower (10±3 vs 19±5 mmHg) in PAH patients, but cardiac output was not different (4.0±1.3 vs 4.2±1.2L/min). EOV was present in 22 patients (21%) with HF and in no patient with PAH.Patients with PAH compared to HF with slightly better functional class have a lower aerobic exercise capacity and higher ventilatory responses, but no EOV. An increase in pulmonary artery wedge pressure rather than a low cardiac output may be necessary condition of EOV in HF.

Air pollution has recently been associated with the development of acute decompensated heart failure, but the underlying biological mechanisms remain unclear. A pulmonary vasoconstrictor effect of air pollution, combined with its systemic effects, may precipitate decompensated heart failure. The aim of the present study was to investigate the effects of acute exposure to diesel exhaust (DE) on pulmonary vascular resistance (PVR) under resting and stress conditions but also to determine whether air pollution may potentiate acquired pulmonary hypertension. Eighteen healthy male volunteers were exposed to ambient air (AA) or dilute DE with a particulate matter of 3for 2 h in a randomized, crossover study design. The effects of DE on PVR, on the coefficient of distensibilty of pulmonary vessels (α), and on right and left ventricular function were evaluated at rest ( n = 18), during dobutamine stress echocardiography ( n = 10), and during exercise stress echocardiography performed in hypoxia ( n = 8). Serum endothelin-1 and fractional exhaled nitric oxide were also measured. At rest, exposure to DE did not affect PVR. During dobutamine stress, the slope of the mean pulmonary artery pressure-cardiac output relationship increased from 2.8 ± 0.5 mmHg·min·l−1in AA to 3.9 ± 0.5 mmHg·min·l−1in DE ( P < 0.05) and the α coefficient decreased from 0.96 ± 0.15 to 0.64 ± 0.12%/mmHg ( P < 0.01). DE did not further enhance the hypoxia-related upper shift of the mean pulmonary artery pressure-cardiac output relationship. Exposure to DE did not affect serum endothelin-1 concentration or fractional exhaled nitric oxide. In conclusion, acute exposure to DE increased pulmonary vasomotor tone by decreasing the distensibility of pulmonary resistive vessels at high cardiac output.

We appreciate Dr Jamous' interest in our article1 and his query as to how pulmonary hemodynamics may have changed after vasodilating challenge. This was not a prespecified end point or a quest for testing our hypotheses. Nonetheless, it remains intriguing to understand whether pulmonary capillary wedge pressure and pulmonary vascular resistance under acute challenge may predict benefit. According to Melenowski et al,2 an acute test with sildenafil can be very appropriate in left-sided pulmonary hypertension (PH), given the high responsiveness rate in heart failure (HF) patients with elevated pulmonary vascular resistance who are unresponsive to standard challenge with prostacyclin. As to mean pulmonary artery pressure differences between our study and the Sildenafil Use in Pulmonary Arterial Hypertension (SUPER-1) trial, performed in patients with pulmonary arterial hypertension, we would avoid, according to current literature, the comparison of pulmonary arterial hypertension with nonpulmonary forms, such as group 2 PH.3 Differences in pathobiology and drug dose may, per se, explain variability in outcomes. We agree that changes in the precapillary contribution to the pulmonary artery pressure rise are attributable to mechanisms other than vasodilation. Indeed, in a transaortic constriction rat model of left ventricular (LV) hypertrophy and diastolic HF, a clear biological activity of sildenafil on lung arterial microvasculature and endothelial function has been documented.4 This fully supports our findings and may represent …

Background— In heart failure (HF), a defective nitric oxide signaling is involved in left ventricular (LV) diastolic abnormalities and remodeling. PDE5 inhibition, by blocking degradation of nitric oxide second-messenger cyclic guanosine monophosphate, might be beneficial. In a cohort of systolic HF patients, we tested the effects of PDE5 inhibition (sildenafil) on LV ejection fraction, diastolic function, cardiac geometry, and clinical status. Methods and Results— Forty-five HF patients (New York Heart Association class II-III) were randomly assigned to placebo or sildenafil (50 mg three times per day) for 1 year, with assessment (6 months and 1 year) of LV ejection fraction, diastolic function, geometry, cardiopulmonary exercise performance, and quality of life. In the sildenafil group only, at 6 months and 1 year, LV ejection fraction, early diastolic tissue Doppler velocities (E′) at the mitral lateral (from 4.62 to 5.20 and 5.19 m/s) and septal (from 4.71 to 5.23 and 5.24 m/s) annuli significantly increased, whereas the ratio of early transmitral (E) to E′ lateral decreased (from 13.1 to 9.8 to 9.4) ( P 2 ; P 2 ; P o 2 ), ventilation efficiency (ventilation to CO 2 production slope), and quality of life ( P Conclusions— Findings confirm that in HF, sildenafil improves functional capacity and clinical status and provide the first human evidence that LV diastolic function and cardiac geometry are additional targets of benefits related to chronic PDE5 inhibition. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00975494.

The assessment of aerobic exercise capacity is an important component in the clinical management of patients with heart failure (HF). Although a significant percentage of patients diagnosed with HF also present with chronic obstructive pulmonary disease (COPD) comorbidity, the combined impact of these chronic conditions on the aerobic exercise response is unknown and is therefore the purpose of the present investigation.Sixty-nine subjects with HF and COPD were matched to 69 subjects solely diagnosed with HF according to age, sex, and HF etiology. All subjects underwent resting pulmonary function and diffusion capacity testing, echocardiography with tissue Doppler imaging, and cardiopulmonary exercise testing (CPX).Subjects with COPD comorbidity had significantly lower pulmonary function testing and diffusion capacity values versus HF alone (P.05). In addition, subjects with both HF and COPD had significantly higher pulmonary artery systolic pressures (51.9 ± 9.0 vs 37.0 ± 7.8 mm Hg, P.001) as assessed by pulsed Doppler echocardiography. Cardiopulmonary exercise testing revealed a significantly poorer response in subjects with HF and COPD by all variables that were analyzed, including peak oxygen consumption (12.1 ± 4.3 vs 16.3 ± 4.3 mL kg⁻¹ min⁻¹, P.001), minute ventilation/carbon dioxide production slope (42.7 ± 7.4 vs 33.3 ± 6.6, P.001) and heart rate recovery at 1 minute (12.1 ± 2.5 vs 14.2 ± 2.9 beats, P.001).Patients with HF and the comorbidity of COPD have significantly impaired CPX responses. This novel finding may impact the clinical interpretation of CPX data in patients with HF who also present with this chronic pulmonary condition.

Background— The six-minute walk test (6MWT) and cardiopulmonary exercise testing (CPET) are the 2 testing modalities most broadly used for assessing functional limitation in patients with heart failure (HF). A comprehensive comparison on clinical and prognostic validity of the 2 techniques has not been performed and is the aim of the present investigation. Methods and Results— Two hundred fifty-three patients diagnosed with systolic (n=211) or diastolic (n=42) HF (age: 61.9�10.1 years; New York Heart Association Class: 2.2�0.78) underwent a 6MWT and a symptom-limited CPET evaluation and were prospectively followed up. During the 4-year tracking period, there were 43 cardiac-related deaths with an annual cardiac mortality rate of 8.7%. The 6MWT distance correlated with CPET-derived variables (ie, peak V o 2 , V o 2 at anaerobic threshold, and V e /V co 2 slope) and was significantly reduced in proportion with lower peak V o 2 and higher V e /V co 2 slope classes and presence of an exercise oscillatory breathing (EOB) pattern ( P P =NS). At univariate and multivariate Cox proportional analyses, the association of the 6MWT distance with survival was not significant either as a continuous or dicotomized variable (≤300 m). Conversely, CPET-derived variables emerged as prognostic with the strongest association found for EOB (systolic HF) and V e /V co 2 slope (entire population with HF and patients with a 6MWT≤300 m). Conclusions— The 6MWT is confirmed to be a simple and reliable first-line test for quantification of exercise intolerance in patients with HF. However, there is no supportive evidence for its use as a prognostic marker in alternative to or in conjunction with CPET-derived variables.

Some studies suggest that the sympathetic nervous system and the renin-angiotensin system are activated in patients with chronic obstructive pulmonary disease (COPD), potentially resulting in negative cardiopulmonary and muscular effects. The aim of this pilot study was to evaluate the efficacy of an angiotensin converting enzyme (ACE) inhibitor on cardiopulmonary exercise performance in COPD patients. Primary outcome was the effect of treatment on the ventilatory response to exercise (VE/VCO(2) slope). Secondary outcomes were exercise variables evaluated by the cardiopulmonary exercise test, and pulmonary function according to ACE genotyping.4 weeks treatment with enalapril (10 mg od) or placebo was evaluated in 21 COPD patients (FEV(1)60%) and without cardiovascular disease in a double-blind, cross-over study.18 patients completed the study. Enalapril did not exert a significant effect on exercise VE/VCO(2) slope or on peak O(2) consumption. However enalapril significantly improved peak O(2) pulse and work rate compared to placebo. A mild but significant worsening of the diffusion capacity of the lung was observed. ACE genotype did not significantly affect patients' response to treatment, except for a trend toward a more evident effect of treatment in patients with II ACE genotype in terms of O(2) pulse and gas diffusion.In this pilot study, ACE inhibition did not affect the ventilatory response to exercise in COPD patients. However, treatment resulted in improvement in work rate and O(2) pulse, suggesting that ACE inhibitor therapy warrants consideration and may provide beneficial effect on the cardiovascular response to exercise in COPD.

Aims The influence of permanent atrial fibrillation on exercise tolerance and cardio-respiratory function during exercise in heart failure (HF) is unknown. Methods and results We retrospectively compared the results of 942 cardiopulmonary exercise tests, performed consecutively at seven Italian laboratories, in HF patients with atrial fibrillation ( n = 180) and sinus rhythm ( n = 762). By multivariable logistic regression analysis, peak VO2 (OR 0.376, 95% CI 0.240–0.588, P < 0.0001), O2pulse (VO2/heart rate, HR) (OR 0.236, 95% CI 0.152–0.366, P < 0.0001), VCO2 (OR 3.97, 95% CI 2.163–7.287, P < 0.0001), and ventilation (OR 1.38, 95% CI 1.045–1.821, P = 0.0231) were independently associated with atrial fibrillation. Anaerobic threshold (AT) was identified in 132 of 180 (73%) atrial fibrillation and in 649 of 762 (85%) sinus rhythm patients ( P = 0.0002). By multivariable logistic regression analysis, only peak VO2 (OR 0.214, 95% CI 0.155–0.296, P < 0.0001) was independently associated with unidentified AT. At AT, atrial fibrillation HF patients had higher HR ( P < 0.0001) and higher VO2 ( P < 0.001) compared with sinus rhythm HF patients. Among AT variables, by multivariable logistic regression analysis, only HR was an independent predictor of atrial fibrillation. Conclusion In HF patients with permanent atrial fibrillation, exercise performance is reduced as reflected by reduced peak VO2. The finding of unidentified AT is associated with a poor performance. In atrial fibrillation patients, VO2 is higher at AT whereas lower at peak. This last observation raises uncertainties about the use of AT data to define performance and prognosis of HF patients with atrial fibrillation.

Background Risk stratification for subsequent cardiovascular events following a myocardial infarction (MI) is an important area of research. Previous findings indicate flow-mediated dilatation (FMD) may be a valuable prognostic indicator. This study investigates the prognostic value of FMD in patients suffering an uncomplicated MI. Methods One hundred and seventy nine post-MI patients [110male/69 female, mean age: 64.8±10.0 years, ejection fraction: 51.9±12.2%] were included in this analysis. Ultrasound images of the brachial artery were used to determine FMD following reactive hyperemia. Subjects were tracked for subsequent cardiovascular events [myocardial infarction, heart failure, additional interventions (percutaneous coronary intervention, coronary artery bypass)] following data collection via medical chart review. Results There were 45 subsequent cardiovascular events during a mean tracking period of 13.7 (±9.5) months. Receiver operating characteristic (ROC) curve analysis revealed a diagnosis of diabetes (ROC area: 0.67, p =0.001, 95% confidence interval: 0.58–0.77) and percent change in arterial diameter (ROC area: 0.63, p =0.01, 95% confidence interval: 0.53–0.73, optimal threshold: ≤/>4.5%) were prognostically significant. Kaplan–Meier analysis revealed the event-free survival rate for subjects without diabetes and an arterial diameter change >4.5%, without diabetes and percent change in arterial diameter ≤4.5%, with diabetes and percent change in arterial diameter >4.5% and with diabetes and percent change in arterial diameter ≤4.5% was 88.7%, 78.4%, 67.7% and 38.5%, respectively (Log-rank: 24.9, p Conclusions Non-invasive FMD is a potential risk factor after MI and may add information to conventional risk stratification. This will need to be tested in further studies.

Background Ventilatory efficiency, commonly assessed by the minute ventilation (VE)-carbon dioxide production (VCO 2 ) slope, has proven to be a strong prognostic marker in the heart failure (HF) population. Recently, the oxygen uptake efficiency slope (OUES) has demonstrated prognostic value, but additional comparisons to established cardiopulmonary exercise test (CPET) variables are required. Methods and Results A total of 341 subjects were diagnosed with HF participated in this analysis. The VE/VCO 2 slope and the OUES were calculated using 50% (VE/VCO 2 slope 50 or OUES 50 ) and 100% (VE/VCO 2 slope 100 or OUES 100 ) of the exercise data. Peak oxygen consumption (VO 2 ) was also determined. There were 47 major cardiac-related events during the 3-year tracking period. Receiver operating characteristic (ROC) curve analysis demonstrated the classification schemes for both VE/VCO 2 slope and OUES calculations as well as peak VO 2 were statistically significant (all areas under the ROC curve: ≥0.74, P 2 slope 100 was, however, significantly greater than OUES 50 , OUES 100 , and peak VO 2 ( P Conclusions Although the OUES was a significant predictor of mortality, the VE/VCO 2 slope maintained optimal prognostic value. An elevated VE/VCO 2 slope may be the single best indicator of increased risk for adverse events.