Comprehensive Evaluation of Left Ventricle Dysfunction by a New Computed Tomography Scanner: The E-PLURIBUS Study.

BACKGROUND: Although cardiac magnetic resonance (CMR) is considered the gold standard for myocardial fibrosis detection, cardiac computed tomography (CCT) is emerging as a promising alternative. OBJECTIVES: The purpose of this study was to assess feasibility and diagnostic accuracy of a comprehensive functional and anatomical evaluation with CCT as compared with CMR in patients with newly diagnosed left ventricular dysfunction (LVD). METHODS: A total of 128 consecutive patients with newly diagnosed LVD were screened. Based on the exclusion criteria, 28 cases were excluded. CCT was performed within 10 days from CMR. Biventricular volumes and ejection fraction, and presence and pattern of delayed enhancement (DE), were determined, along with evaluation of coronary arteries among patients undergoing invasive angiography in the 6 months after CCT. RESULTS: Six cases were excluded because of claustrophobia at CMR. Among the 94 patients who formed the study population, the concordance between CCT and CMR in suggesting the cause of the LVD was high (94.7%, 89/94 patients) in the overall population and was 100% for identifying ischemic cardiomyopathy. The CCT diagnostic rate for DE assessment was also high (96.7%, 1,544/1,598 territories) and similar to that of CMR (97.4%; P = 0.345, CCT vs CMR). Moreover, CCT showed high diagnostic accuracy in the detection of DE (94.8%, 95% CI: 93.6%-95.8%) in a territory-based analysis. Biventricular volumes and function parameters as measured by CCT and CMR were similar, without significant differences with the exception of a modest difference in RV volume. CCT was confirmed to be accurate for assessing arterial coronary circulation. The mean radiation exposure of the whole CCT was 7.78 ± 2.53 mSv (0.84 ± 0.24 mSv for DE). CONCLUSIONS: CCT performed with low-dose whole-heart coverage scanner and high-concentration contrast agent appears an effective noninvasive tool for a comprehensive assessment of patients with newly diagnosed LVD.

Revisiting a Prognosticating Algorithm from Cardiopulmonary Exercise Testing in Chronic Heart Failure (from the MECKI Score Population).

Cardiopulmonary exercise testing is a prognostic tool in heart failure with reduced left ventricular ejection fraction (HFrEF). Prognosticating algorithms have been proposed, but none has been validated. In 2017, a predictive algorithm, based on peak oxygen consumption (VO2), ventilatory response to exercise (ventilation [VE] carbon dioxide production [VCO2], the VE/VCO2 slope), exertional oscillatory ventilation (EOV), and peak respiratory exchange ratio, was recommended, according treatment with ß blockers: patients with HFrEF registered in the metabolic exercise test data combined with cardiac and kidney indexes (MECKIs) database were used to validated this algorithm. According to the inclusion/exclusion criteria, 4,683 MECKI patients with HFrEF were enrolled. At 3 years follow-up, the end point was cardiovascular death and urgent heart transplantation (cardiovascular events [CV]). CV events occurred in 25% in patients without ß blockers, whereas those with ß-blockers had 11% (p <0.0001). In patients without ß blockers, 36%, 24%, and 7% CV events were observed in those with peak VO2 ≤10, with peak VO2 >10 <18, and with peak VO2 ≥18 ml/kg/min (p = 0.0001), respectively; in MECKI patients with peak VO2 ≤10 and patients with intermediate exercise capacity, a peak respiratory exchange ratio (≥1.15) and VE/VCO2 slope (≥35) were diriment, respectively (p = 0.0001). EOV, when occurred, increased risk. In MECKI patients on ß blockers, 29%, 17%, and 8% CV events were noticed in those with a peak VO2 ≤8, with peak VO2 = 8 to 12, and patients with peak VO2 ≥12 ml/kg/min, respectively (p = 0.0000); when EOV was monitored an increment of risk was witnessed. In conclusion, the outcome of this algorithm was confirmed with the MECKI cohort.

Evidence of a double anaerobic threshold in healthy subjects.

AIMS: The anaerobic threshold (AT) is an important cardiopulmonary exercise test (CPET) parameter both in healthy and in patients. It is normally determined with three approaches: V-slope method, ventilatory equivalent method, and end-tidal method. The finding of different AT values with these methods is only anecdotic. We defined the presence of a double threshold (DT) when a ΔVO2 > 15 mL/min was observed between the V-slope method (met AT) and the other two methods (vent AT). The aim was to identify whether there is a DT in healthy subjects. METHODS AND RESULTS: We retrospectively analysed 476 healthy subjects who performed CPET in our laboratory between 2009 and 2018. We identified 51 subjects with a DT (11% of cases). Cardiopulmonary exercise test data at rest and during the exercise were not different in subjects with DT compared to those without. Met AT always preceded vent AT. Compared to subjects without DT, those with DT showed at met AT lower carbon dioxide output (VCO2), end-tidal carbon dioxide tension (PetCO2) and respiratory exchange ratio (RER), and higher ventilatory equivalent for carbon dioxide (VE/VCO2). Compared to met AT, vent AT showed a higher oxygen uptake (VO2), VCO2, ventilation, respiratory rate, RER, work rate, and PetCO2 but a lower VE/VCO2 and end-tidal oxygen tension. Finally, subjects with DT showed a higher VO2 increase during the isocapnic buffering period. CONCLUSION: Double threshold was present in healthy subjects. The presence of DT does not influence peak exercise performance, but it is associated with a delayed before acidosis-induced hyperventilation.

Week to week variability of pulmonary capillary blood volume and alveolar membrane diffusing capacity in patients with heart failure.

BACKGROUND: Alveolar-capillary membrane diffusing capacity for carbon monoxide (DMCO) and pulmonary capillary volume (Vcap) can be estimated by the multi-step Roughton and Foster (RF, original method from 1957) or the single-step NO-CO double diffusion technique (developed in the 1980s). The latter method implies inherent assumptions. We sought to determine which combination of the alveolar membrane diffusing capacity for nitric oxide (DMNO) to DMCO ratio, an specific conductance of the blood for NO (θNO) and CO (θCO) gave the lowest week-to-week variability in patients with heart failure. METHODS: 44 heart failure patients underwent DMCO and Vcap measurements on three occasions over a ten-week period using both RF and double dilution NO-CO techniques. RESULTS: When using the double diffusing method and applying θNO = infinity, the smallest week-to-week coefficient of variation for DMCO was 10 %. Conversely, the RF method derived DMCO had a much greater week-to-week variability (2x higher coefficient of variation) than the DMCO derived via the NO-CO double dilution technique. The DMCO derived from the double diffusion technique most closely matched the DMCO from the RF method when θNO = infinity and DMCO = DLNO/2.42. The Vcap measured week-to-week was unreliable regardless of the method or constants used. CONCLUSIONS: In heart failure patients, the week-to-week DMCO variability was lowest when using the single-step NO-CO technique. DMCO obtained from double diffusion most closely matched the RF DMCO when DMCO/2.42 and θNO = infinity. Vcap estimation was unreliable with either method.

Minute ventilation/carbon dioxide production in chronic heart failure.

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'E versus 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'E versus V'CO2 relationship has a relevant prognostic power either alone or, better, when included within prognostic scores. The V'E versus 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'E versus V'CO2 slope as percentage of the predicted value, due to age and gender interferences. Relevant attention is needed in V'E versus V'CO2 analysis in the presence of heart failure comorbidities. Finally, V'E versus V'CO2 abnormalities are relevant targets for treatment in heart failure.

Comparison among different multiparametric scores for risk stratification in heart failure patients with reduced ejection fraction.

Heart failure is a serious condition with high prevalence (about 2% in the adult population in developed countries, and more than 8% in patients older than 75 years). About 3-5% of hospital admissions are linked with heart failure incidents. The guidelines of the European Society of Cardiology for the diagnosis and treatment of acute and chronic heart failure have identified individual markers in patients with heart failure, including demographic data, aetiology, comorbidities, clinical, radiological, haemodynamic, echocardiographic and biochemical parameters. Several scoring systems have been proposed to identify adverse events, such as destabilizations, re-hospitalizations and mortality. This article reviews scoring systems for heart failure prognostication, with particular mention of those models with exercise tolerance objective definition. Although most of the models include readily available clinical information, quite a few of them comprise circulating levels of natriuretic peptides and a more objective evaluation of exercise tolerance. A literature review was also conducted to (a) identify heart failure risk-prediction models, (b) assess statistical approach, and (c) identify common variables.

Sacubitril/valsartan use in a real-world population of patients with heart failure and reduced ejection fraction.

AIMS: Practice guidelines recommend sacubitril/valsartan for heart failure with reduced ejection fraction. The aim of our study was to describe the use of sacubitril/valsartan in real-world clinical practice to help identify patients best able to tolerate titration to higher doses. METHODS: We retrospectively analyzed clinical data for 201 patients with heart failure with reduced ejection fraction prescribed sacubitril/valsartan at our heart failure clinic (Centro Cardiologico Monzino) between September 2016/December 2018. Patients had a mean age of 67.2 years, mean left ventricular ejection fraction of 30.1%, New York Heart Association class II (65%), class III (35%), and poor cardiopulmonary exercise capacity. Median 2-year risk of death/urgent cardiac transplantation was 8.9% [Metabolic Exercise Cardiac Kidney Index (MECKI) score]. RESULTS: After a median follow-up of 230 (interquartile interval: 105-366) days, 57 patients achieved higher-dose sacubitril/valsartan, 103 tolerated medium/low doses, nine died, and 20 interrupted treatment. The highest dose of sacubitril/valsartan was reached by younger patients with better hemoglobin (Hb) levels, renal function, and blood pressure (BP). Patients continuing on sacubitril/valsartan had significantly higher serum Hb and sodium, better BP, and lower MECKI scores than patients who discontinued treatment or died during follow-up. Our patients were older and frailer than those in the pivotal PARADIGM-HF trial. CONCLUSION: In our experience, more than one-third of the patients were able to tolerate the higher dose of sacubitril/valsartan, and these patients were younger, had higher Hb, and better BP and renal function. MECKI score stratification was useful to discriminate patients who continued treatment from those who did not. Future prospective studies should test if these clinical variables can guide the up-titration of sacubitril/valsartan.

Rationale and design of the EPLURIBUS Study (Evidence for a comPrehensive evaLUation of left ventRicle dysfnctIon By a whole-heart coverage cardiac compUted tomography Scanner).

BACKGROUND: Cardiac magnetic resonance (CMR) is the standard of reference for myocardial fibrosis detection by late gadolinium enhancement. Cardiac computed tomography (CCT) is emerging as a promising alternative. The Evidence for a comPrehensive evaLUation of left ventRicle dysfnctIon By a whole-heart coverage cardiac compUted tomography Scanner study will assess the feasibility and diagnostic accuracy of a comprehensive functional and anatomical cardiac evaluation with CCT as compared with CMR and invasive coronary angiography as standard of reference. METHODS: Consecutive patients with a newly diagnosed left ventricle (LV) dysfunction (left ventricular ejection fraction <50%) and a clinical indication to CMR will be screened. Exclusion criteria will be contraindications to contrast agents and impaired renal function. CCT will be performed per protocol within 10 days from CMR. A total of 100 patients will be enrolled within 24 months. We will evaluate with CCT volume and ejection fraction of the LV and right ventricle, presence, extent and pattern of delayed enhancement and cardiac venous system. Moreover, presence and degree of coronary stenoses will be evaluated among patients undergoing invasive coronary angiography in the 6 months following CCT. RESULTS: The primary study endpoints will be: first, to assess the diagnostic performance of CCT vs. CMR to detect the delayed enhancement in a territory-based and patient-based analysis; second, to assess the agreement between CCT and CMR in the discrimination between ischemic vs. nonischemic delayed enhancement patters in a territory-based analysis; third, to assess the correlation between CCT and CMR for LV and right ventricle end-diastolic and end-systolic volumes and ejection fraction measurements. CONCLUSION: The Evidence for a comPrehensive evaLUation of left ventRicle dysfnctIon By a whole-heart coverage cardiac compUted tomography Scanner study will assess the diagnostic performance of CCT using the latest scanner generation for a comprehensive evaluation of patients with new-onset LV dysfunction.

Variability in pulmonary diffusing capacity in heart failure.

BACKGROUND: As pulmonary diffusing capacity is related to mortality risk and prognosis in patients with heart failure (HF), it is measured frequently. As such, it would be essential to know the week-to-week variability (reproducibility) of pulmonary diffusing capacity for carbon monoxide (DLCO) and nitric oxide (DLNO). This variability would let clinicians understand what a clinically measurable change in DLCO and DLNO would be in these patients. METHODS: On three different days spanning over ten weeks, 40 H F patients underwent testing for DLCO and DLNO. DLCO was determined after a 4 s and 10 s breath-hold maneuver, while DLNO was determined after a 4 s breath-hold maneuver. RESULTS: Forty heart failure patients (66 ± 10 years; BMI = 28.4 ± 4.6 kg∙m-2; 28 males), that were referred to our clinic were able to complete the protocol. DLCO (4 s breath-hold) and DLNO (4 s breath-hold) were 79 ± 19 % and 59 ± 14 % predicted, respectively. Fifty percent of patients (n = 20) were below the lower limit of normal (LLN, below the 5th percentile) for predicted DLCO (4 s), while 78 % of patients (n = 31) were below the LLN for predicted DLNO. All 16 patients that were below the LLN for DLCO were also below the LLN for DLNO. Over a ten week period, the reproducibility of DLNO (4 s) DLCO (4 s) and DLCO (10 s) was 18.9, 8.2, and 5.9 mL min mmHg-1, respectively. CONCLUSIONS: The week-to-week fluctuation in DLNO (4 s), as a percentage, is less than DLCO (4 s) in patients with HF. The reproducibility of DLNO in patients with HF is like that of healthy subjects.

Effects of ß2-receptor stimulation by indacaterol in chronic heart failure treated with selective or non-selective ß-blockers: a randomized trial.

Alveolar ß2-receptor blockade worsens lung diffusion in heart failure (HF). This effect could be mitigated by stimulating alveolar ß2-receptors. We investigated the safety and the effects of indacaterol on lung diffusion, lung mechanics, sleep respiratory behavior, cardiac rhythm, welfare, and exercise performance in HF patients treated with a selective (bisoprolol) or a non-selective (carvedilol) ß-blocker. Study procedures were performed before and after indacaterol and placebo treatments according to a cross-over, randomized, double-blind protocol in forty-four patients (27 on bisoprolol and 17 on carvedilol). No differences between indacaterol and placebo were observed in the whole population except for a significantly higher VE/VCO2 slope and lower maximal PETCO2 during exercise with indacaterol, entirely due to the difference in the bisoprolol group (VE/VCO2 31.8 ± 5.9 vs. 28.5 ± 5.6, p < 0.0001 and maximal PETCO2 36.7 ± 5.5 vs. 37.7 ± 5.8 mmHg, p < 0.02 with indacaterol and placebo, respectively). In carvedilol, indacaterol was associated with a higher peak heart rate (119 ± 34 vs. 113 ± 30 bpm, with indacaterol and placebo) and a lower prevalence of hypopnea during sleep (3.8 [0.0;6.3] vs. 5.8 [2.9;10.5] events/hour, with indacaterol and placebo). Inhaled indacaterol is well tolerated in HF patients, it does not influence lung diffusion, and, in bisoprolol, it increases ventilation response to exercise.

Gender and age normalization and ventilation efficiency during exercise in heart failure with reduced ejection fraction.

AIMS: Ventilation vs. carbon dioxide production (VE/VCO2 ) is among the strongest cardiopulmonary exercise testing prognostic parameters in heart failure (HF). It is usually reported as an absolute value. The current definition of normal VE/VCO2 slope values is inadequate, since it was built from small groups of subjects with a particularly limited number of women and elderly. We aimed to define VE/VCO2 slope prediction formulas in a sizable population and to test whether the prognostic power of VE/VCO2 slope in HF was different if expressed as a percentage of the predicted value or as an absolute value. METHODS AND RESULTS: We calculated the linear regressions between age and VE/VCO2 slope in 1136 healthy subjects (68% male, age 44.9 ± 14.5, range 13-83 years). We then applied age-adjusted and sex-adjusted formulas to predict VE/VCO2 slope to HF patients included in the metabolic exercise test data combined with cardiac and kidney indexes score database, which counts 6112 patients (82% male, age 61.4 ± 12.8, left ventricular ejection fraction 33.2 ± 10.5%, peakVO2 14.8 ± 4.9, mL/min/kg, VE/VCO2 slope 32.7 ± 7.7) from 24 HF centres. Finally, we evaluated whether the use of absolute values vs. percentages of predicted VE/VCO2 affected HF prognosis prediction (composite of cardiovascular mortality + urgent transplant or left ventricular assist device). We did so in the entire cardiac and kidney indexes score population and separately in HF patients with severe (peakVO2 < 14 mL/min/kg, n = 2919, 61.1 events/1000 pts/year) or moderate (peakVO2 ≥ 14 mL/min/kg, n = 3183, 19.9 events/1000 pts/year) HF. In the healthy population, we obtained the following equations: female, VE/VCO2 = 0.052 × Age + 23.808 (r = 0.192); male, VE/VCO2 = 0.095 × Age + 20.227 (r = 0.371) (P = 0.007). We applied these formulas to calculate the percentages of predicted VE/VCO2 values. The 2-year survival prognostic power of VE/VCO2 slope was strong, and it was similar if expressed as absolute value or as a percentage of predicted value (AUCs 0.686 and 0.690, respectively). In contrast, in severe HF patients, AUCs significantly differed between absolute values (0.637) and percentages of predicted values (0.650, P = 0.0026). Moreover, VE/VCO2 slope expressed as a percentage of predicted value allowed to reclassify 6.6% of peakVO2 < 14 mL/min/kg patients (net reclassification improvement = 0.066, P = 0.0015). CONCLUSIONS: The percentage of predicted VE/VCO2 slope value strengthens the prognostic power of VE/VCO2 in severe HF patients, and it should be preferred over the absolute value for HF prognostication. Furthermore, the widespread use of VE/VCO2 slope expressed as percentage of predicted value can improve our ability to identify HF patients at high risk, which is a goal of utmost clinical relevance.

Exercise oscillatory ventilation and prognosis in heart failure patients with reduced and mid-range ejection fraction.

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 (<40%, HFrEF) and with HF with preserved 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.

Isocapnic buffering period: From physiology to clinics.

BACKGROUND: During cardiopulmonary exercise test, the isocapnic buffering period ranges between anaerobic threshold (AT) and respiratory compensation point (RCP). We investigated whether oxygen uptake (VO2) increase during the isocapnic buffering period (ΔVO2AT-RCP) is related to heart failure severity and prognosis. METHODS: We retrospectively analysed reduced ejection fraction heart failure patients who attained RCP at cardiopulmonary exercise test. The study endpoint was the composite of cardiovascular mortality and urgent heart transplantation/left ventricular assist device implantation. Hazard ratio was assessed to identify the increase of risk associated with ΔVO2AT-RCP (below and above the median of ΔVO2AT-RCP). RESULTS: AT and RCP were both identified in 782 (39.2%) out of 1995 reduced ejection fraction heart failure cases. Left ventricular ejection fraction and peak VO2 were 33 ± 9% and 16.5 ± 4.5 mL/kg per min (61 ± 16% of predicted value), suggesting moderate heart failure. At five years, endpoint did not vary between patients below and above the median ΔVO2AT-RCP (3.85 mL/min per kg (25-75th interquartile range = 2.69-5.46)). ΔVO2AT-RCP correlated with several parameters associated to heart failure prognosis, such as peak VO2, VE/VCO2 slope, brain natriuretic peptide and left ventricular ejection fraction. The ΔVO2AT-RCP value was associated with prognosis at univariate but not at multivariable analysis, where only VE/VCO2 slope endured. CONCLUSION: ΔVO2AT-RCP correlates with several parameters linked to heart failure severity. Isocapnic buffering period stratifies heart failure patients, but not more than other prognostic indices.

Alveolar-capillary membrane diffusion measurement by nitric oxide inhalation in heart failure.

BACKGROUND: In heart failure, lung diffusion is reduced, it correlates with prognosis and exercise capacity, and it is a therapy target. DESIGN: Diffusion is measured as CO total diffusion (DL(CO)), which has two components: membrane diffusion (Dm) and capillary volume, the latter related to CO and O2 competition for hemoglobin. DL(CO) needs to be corrected for hemoglobin. Diffusion can also be measured with NO (DL(NO)), which has a very high affinity for hemoglobin, and thus, the resistance of hemoglobin being trivial, it directly represents Dm. Therefore, Dm is directly calculated from DL(NO) through a correction factor. DL(NO) has never been measured in heart failure. The study aims at determining, in heart failure, DL(NO), Dm correction factor, and whether Dm(NO) provides Dm estimates comparable to Dm(CO). METHODS: We measured DL(CO), Dm(CO) by multi-maneuver Roughton-Forster method, and DL(CO) and DL(NO) by single-breath maneuver in 50 heart failure and 50 healthy subjects. RESULTS: DL(CO) was 21.9 ± 4.8 ml/mmHg per min and 16.8 ± 5.1 in healthy subjects and heart failure subjects, respectively (p < 0.001). DL(NO) was 88.6 ± 20.5 ml/mmHg per min and 72.5 ± 22.3, respectively (p < 0.001). The correction factors to obtain Dm from DL(NO) were 2.68 (entire population), 2.63 (healthy subjects) and 2.75 (heart failure subjects). Dm(CO) and Dm(NO) were 34.7 ± 10.9 ml/mmHg per min and 33.8 ± 7.6 in healthy subjects and 25.9 ± 2.0 and 26.4 ± 8.1 in heart failure subjects. CONCLUSIONS: DL(NO) and Dm(NO) measurements are feasible in heart failure. Dm(CO) and Dm(NO) provide comparable results. The correction factor to calculate Dm from DL(NO) in heart failure is 2.75, which is little different from the 2.63 value we observed in healthy subjects.

Chronotropic incompentence and functional capacity in chronic heart failure: no role of ß-blockers and ß-blocker dose.

AIM: To assess the effect of chronotropic incompetence on functional capacity in chronic heart failure (CHF) patients, as evaluated as NYHA and peak oxygen consumption (pVO(2) ), focusing on the presence and dose of ß-blocker treatment. METHODS: Nine hundred and sixty-seven consecutive CHF patients were evaluated, 328 of whom were discarded because they failed to meet the study criteria. Of the 639 analyzed, 90 were not treated with ß-blockers whereas the other 549 were. The latter were further subdivided in high (n = 184) and low (n = 365) ß-blockers daily dose group in accordance with an arbitrary cut-off of 25 mg for carvedilol and of 5 mg for bisoprolol. Failure to achieve 80% of the percentage of maximum age predicted peak heart rate (%Max PHR) or of HR reserve (%HRR) constituted chronotropic incompetence. RESULTS: No differences were found in NYHA or pVO2 between patients with and without ß-blockers and, similarly, between high and low ß-blocker dose groups. Twenty and sixty-nine percent of not ß-blocked patients showed chronotropic incompetence according to %Max PHR and %HRR, respectively, whereas this prevalence rose to 61% and 84% in those on ß-blocker therapy. Patients taking ß-blockers without chronotropic incompetence, as inferable from both %Max PHR and %HRR, showed higher NYHA and pVO2 regardless of drug dose, whereas, in not ß-blocked patients, only %HRR revealed a difference in functional capacity. At multivariable analysis, HR increase during exercise (ΔHR) was the variable most strongly associated to pVO2 (ß: 0.572; SE: 0.008; P < 0.0001) and NYHA class (ß: -0.499; SE: 0.001; P < 0.0001). CONCLUSIONS: ΔHR is a powerful predictor of CHF severity regardless of the presence of ß-blocker therapy and of ß-blocker daily dose.

Sildenafil improves the alveolar-capillary function in heart failure patients.

BACKGROUND: Sildenafil is used for pulmonary hypertension treatment and its use is safe in chronic heart failure (HF) patients. AIMS: To analyze the effects of sildenafil on lung mechanics, gas diffusion, exhaled nitric oxide (eNO) at rest and during exercise in chronic HF. We did so to evaluate if sildenafil prevents exercise-induced pulmonary edema formation. METHODS: We studied 22 chronic HF males. We measured after a single dose of placebo, sildenafil (25 mg) and sildenafil (100 mg), lung diffusion (DLCO), molecular diffusion (DM), pulmonary capillary volume (VC), eNO, all at rest and during exercise, standard pulmonary function, and maximal cardiopulmonary exercise. RESULTS: At rest sildenafil improved pulmonary mechanics and DLCO from 23.1+/-6.3 ml/mmHg/min to 23.9+/-6.4 (25 mg, p<0.05) and to 25.3+/-6.7 100 mg, p<0.02). Sildenafil (100 mg) prevents edema formation (highest DM/VC during exercise). At rest eNO was low and not affected by tested drugs. With light exercise eNO was higher with sildenafil 100 mg. Peak VO(2) increased with sildenafil from 1376+/-331 ml/min to 1471+/-375 (25 mg, p<0.01) and 1524+/-461 (100 mg, p<0.02). Peak VO(2) increase was related to DLCO improvement. CONCLUSION: In chronic HF sildenafil increases exercise performance, improves lung mechanics and gas diffusion and prevents exercise-induced pulmonary edema formation probably by restoring NO pathways.

Diagnostic accuracy of multidetector computed tomography coronary angiography in patients with dilated cardiomyopathy.

OBJECTIVES: The purpose of this work was to assess the safety, feasibility, and diagnostic accuracy of multidetector computed tomography (MDCT) in dilated cardiomyopathy (DCM) of unknown etiology. BACKGROUND: Multidetector computed tomography is an appropriate noninvasive tool for coronary artery disease (CAD) detection, particularly in patients with low probability of the disease, such as patients with DCM of unknown origin. METHODS: We studied 61 unknown origin DCM patients (ejection fraction: 33.9 +/- 8.6%, group 1) and 139 patients with normal cardiac function with indications for coronary angiography (group 2, control population). All underwent coronary MDCT and angiography. Multidetector computed tomography images were acquired by light speed 16-slice computed tomography. The degree of stenosis was estimated in 15 coronary artery segments according to the American Heart Association model. RESULTS: In group 1, no MDCT-related complications were found, while 10 complications were associated with conventional angiography (p = 0.001). Overall feasibility of coronary artery visualization was 97.2% (863 of 888 segments). The most frequent cause of artifacts was interference from a hypertrophic cardiac venous system (10 artifacts, 40%). In group 2, overall feasibility was 96.1% (p = NS vs. group 1). In group 1, all cases with normal (44 cases) or pathological (17 cases) coronary arteries by conventional coronary angiography were correctly detected by MDCT, with, in 1 case, disparity of stenosis severity. In group 1, sensitivity, specificity, and positive and negative predictive values of MDCT for the identification of >50% stenosis were 99%, 96.2%, 81.2%, and 99.8%, respectively. In group 2, sensitivity and negative predictive values were lower than in group 1 (86.1% vs. 99% and 96.4% vs. 99.8%, respectively); specificity (96.4%) and positive predictive value (86.1%) were not significantly different versus group 1. CONCLUSIONS: Multidetector computed tomography is feasible, safe, and accurate for identification of idiopathic versus ischemic DCM, and may represent an alternative to coronary angiography.