Lung Ultrasound in Patients With SARS-COV-2 Pneumonia: Correlations With Chest Computed Tomography, Respiratory Impairment, and Inflammatory Cascade.

OBJECTIVES: Lung ultrasound (LUS) might be comparable to chest computed tomography (CT) in detecting parenchymal and pleural pathology, and in monitoring interstitial lung disease. We aimed to describe LUS characteristics of patients during the hospitalization for COVID-19 pneumonia, and to compare the extent of lung involvement at LUS and chest-CT with inflammatory response and the severity of respiration impairment. METHODS: During a 2-week period, we performed LUS and chest CT in hospitalized patients affected by COVID-19 pneumonia. Dosages of high sensitivity C-reactive protein (HS-CRP), d-dimer, and interleukin-6 (IL-6) were also obtained. The index of lung function (P/F ratio) was calculated from the blood gas test. LUS and CT scoring were assessed using previously validated scores. RESULTS: Twenty-six consecutive patients (3 women) underwent LUS 34 ± 14 days from the early symptoms. Among them, 21 underwent CT on the same day of LUS. A fair association was found between LUS and CT scores (R = 0.45, P = .049), which became stronger if the B-lines score on LUS was not considered (R = 0.57, P = .024). LUS B-lines score correlated with IL-6 levels (R = 0.75, P = .011), and the number of involved lung segments detected by LUS correlated with the P/F ratio (R = 0.60, P = .019) but not with HS-CRP and d-Dimer levels. No correlations were found between CT scores and inflammations markers or P/F. CONCLUSION: In patients with COVID-19 pneumonia, LUS was correlated with both the extent of the inflammatory response and the P/F ratio.

Iron deficiency from the standpoint of cardiac rehabilitation: novel therapeutic opportunities.

Anemia is one of the most frequent comorbidities found in patients with coronary artery disease and chronic heart failure (CHF) who are being followed in cardiac rehabilitation facilities. The more frequent type of anemia is caused by iron deficiency (IDA, iron-deficiency anemia): this review summarizes the state of the art of this topic. First of all, the mechanisms of IDA will be analyzed. Subsequently, a description of the main conditions where IDA can unfavorably affect the clinical course, and of its more frequent complications, will be presented (percutaneous interventions, heart surgery, CHF). Special attention will be paid in the description of anemia in the setting of CHF. To this regard, in recent years a relevant amount of research has been carried out, to determine whether treating anemia (either by directly stimulating erythropoiesis or by correcting iron deficiency by oral or intravenous route) is of any clinical and prognostic relevance in patients with CHF. The results of this research will, therefore, be summarized and critically discussed. Finally, we will outline the promising role of cardiac rehabilitation facilities and of its network of experts in the diagnosis, prognostic stratification, and treatment of anemia and iron deficiency.

Cross-Lagged Relations Between Exercise Capacity and Psychological Distress During Cardiac Rehabilitation.

Background: Poorer mental health is associated with lower exercise capacity, above and beyond the effect of other cardiovascular risk factors. However, the directionality of this relationship remains unclear. Purpose: The main aim of the present study was to clarify, with a cross-lagged panel design, the relationship between psychological status and exercise capacity among patients in a cardiac rehabilitation (CR) program. Methods: A clinical sample of 212 CR patients completed exercise-capacity testing and measures of depression and anxiety (Hospital Anxiety and Depression Scale) pre-CR and post-CR. Demographic and clinical data, including BMI and smoking history, were also collected. Multivariate stepwise regression analysis was performed to identify the best predictors of exercise capacity at discharge. Structural equation modeling was utilized to quantify the cross-lagged effect between exercise capacity and psychological distress. Results: Multivariate regression analysis revealed that higher levels of psychological distress pre-CR are predictively associated with less improvement in exercise capacity post-CR, beyond the effects of age, sex, and baseline functional status. Results from structural equation modeling supported a 1-direction association, with psychological distress pre-CR predicting lower exercise capacity post-CR over and above autoregressive effects. Conclusions: Study results did not support the hypothesis of a bidirectional relationship between psychological distress and EC. High levels of psychological distress pre-CR appeared to be longitudinally associated with lower exercise capacity post-CR, but not vice versa. This finding highlights the importance of assessing and treating both anxiety and depression in the early phase of secondary prevention programs.

Levosimendan in Acute and Advanced Heart Failure: An Appraisal of the Clinical Database and Evaluation of Its Therapeutic Applications.

The use of inotropes for correcting hemodynamic dysfunction in patients with congestive heart failure has been described over many decades. However, negative or insufficient data have been collected regarding the effects of cardiac glycosides, catecholamines, and phosphodiesterase inhibitors on quality of life and survival. More recently, the calcium sensitizer and potassium channel-opener levosimendan has been proposed as a safer inodilator than traditional agents in some heart failure settings, such as advanced heart failure. At the 2017 annual congress of the Heart Failure Association of the European Society of Cardiology (Paris, April 30-May 2), a series of tutorials delivered by lecturers from 8 European countries examined how to use levosimendan safely and effectively in acute and advanced heart failure. The proceedings of those tutorials have been collated in this review to provide an expert perspective on the optimized use of levosimendan in those settings.

A brief period of intensive cardiac rehabilitation improves global longitudinal strain and diastolic function after a first uncomplicated myocardial infarction.

Objectives In patients with abnormal left ventricular ejection fraction (LVEF) after acute myocardial infarction (AMI), cardiac rehabilitation with physical training prevents cardiac remodelling. To define the role of rehabilitation in the recovery of ventricular function in less severe cases, we studied its effects on more refined indexes of left ventricular function in uncomplicated, low-risk patients. Methods and results Fifty-five patients underwent percutaneous coronary revascularization after uncomplicated first AMI. Thirty-four started cardiac rehabilitation with counselling and physical training; 21 patients did not train, followed a counselling program and were taken as controls. Echocardiography was performed at baseline, after rehabilitation or counselling program and at six months follow-up. We measured: global strain (GS%) with speckle tracking analysis, E/e' by tissue Doppler imaging (TDI), left ventricular elastance (KLV) from the deceleration time (DT), LVEF, systolic and diastolic volumes, wall motion score index (WMSI). At baseline, groups had similar GS%, KLV, LVEF, DT, E/e', systolic and diastolic volumes, WMSI. Rehabilitation increased peak VO2 by 18% (P < 0.05) and improved GS%, KLV, LVEF, E/e' and WMSI (P < 0.02) that were unchanged in controls. The improvement persisted at six months. Conclusions After a first uncomplicated AMI, abnormalities of left systolic and diastolic ventricular function may be present persisting over time despite a normal LVEF, which are fully reverted by cardiac rehabilitation.

Blood pressure changes in patients with chronic heart failure undergoing slow breathing training.

BACKGROUND: Slow breathing training (SBT) has been proposed as a new non-pharmacological treatment able to induce favorable effects in patients with chronic heart failure (CHF). However, no information is available regarding its effects on orthostatic blood pressure (BP) changes in these patients, an issue of practical relevance given the reported BP-lowering effect of SBT. The aim of this study is to evaluate the influence of SBT on BP and whether SBT induces orthostatic hypotension (OH) or changes in quality of life (QoL) in CHF patients. METHODS: The analysis was performed as part of an ongoing crossover open trial aimed at assessing the clinical effectiveness of SBT in treated patients with CHF. The patients underwent 10-12 weeks of SBT with the RESPeRATE device and 10-12 week follow-up under usual care. Patients were randomly divided into two groups: group I began with SBT, followed by usual care; group II began with usual care, followed by SBT. Patients undergoing SBT were asked to perform each day two separate 15 min sessions of device-guided SBT at a breathing frequency of 6 breaths/min. In all patients, before the enrollment and after each study phase, clinical data collection and BP measurements in sitting, supine and standing position were performed. OH was defined as a decrease of ≥ 20 mmHg in systolic blood pressure (SBP) or ≥ 10 mmHg in diastolic blood pressure (DBP) within 3 min of standing. QoL was assessed three times at the beginning, and after each phase of the study by the Minnesota Living with Heart Failure (MLHF) questionnaire. RESULTS: Forty patients (two equal groups) completed the study, with the following baseline characteristics: 32 males/eight females, age 63.3 ± 13.4 years, 25 with ischemic CHF, 37 in New York Heart Association class II and three in class III, left ventricular ejection fraction 30.8 ± 6.7%, mean BP 138.7 ± 16.5/83.1 ± 11.5 mmHg, 23 with arterial hypertension and four with a history of stroke. There were no significant differences between the groups in clinical characteristics, SBP and DBP at rest, while seated and before and after standing up. OH prevalence was low and did not change during the study (10% vs 10%). No significant difference in average SBP and DBP changes secondary to body position were found when comparing the two study phases. Decrease in MLHF score was observed in group I during SBT (p = 0.002), but not in group II. CONCLUSIONS: Our data indicate that SBT is safe, does not affect the prevalence of OH in CHF patients and shows a non-significant tendency to improve QoL. These results should be confirmed in a larger sample of patients to support the safety of SBT and its possible benefits as a novel component of cardiorespiratory rehabilitation programs in CHF.

Current activities of Cardiovascular Rehabilitation in the ambulatory setting of the Lombardy Region.

In the present work, the current activities of Cardiovascular Rehabilitation and Prevention (CRP) in the ambulatory setting of the Lombardy Region (Italy) are described. Based on the 2012 Legislation, ambulatory CRP is delivered by means of three programme categories (MAC 6, 7, and 8) with different degrees of intensity. The patient evaluation of global cardiovascular/clinical risk, comorbidity, and disability is the cornerstone for MAC prescription. Following the organization of MAC activities, a survey on 327 patients was carried out by the regional network of the Italian Society of Cardiovascular Rehabilitation (GICR-IACPR). Globally, acute coronary syndromes (with or without coronary revascularization) constituted the main access group to CRP. More than 60% of patients displayed a condition of high risk, comorbidity, and disability. The outcome of ambulatory CRP by means of MAC 6 and 7 was satisfactory, while in the 'less intensive' MAC 8 patients with complete drug up-titration and achievement of secondary prevention targets were no more than 70%.

Cardiovascular Management Self-efficacy: Psychometric Properties of a New Scale and Its Usefulness in a Rehabilitation Context.

BACKGROUND: Self-efficacy beliefs have been shown to affect various effective health-promoting behaviors in patients. Unfortunately, availability of reliable and valid measures of self-efficacy in cardiovascular diseases (CVDs) is still very limited. PURPOSE: The aims of this study were to present a new scale measuring self-efficacy beliefs in managing CVD and to examine its psychometric properties. METHODS: The study involved 172 patients (mean age = 66.4 years; SD = 9.99 years; 76.2% men) undergoing cardiovascular rehabilitation. Various psychological factors and CVD severity indicators were collected. RESULTS: An Exploratory Structural Equation Model showed that the Cardiovascular Management Self-efficacy Scale has three factors: Cardiac Risk Factors, Adherence to Therapy, and Recognition of Symptoms. They all showed high internal consistency, and good convergent, discriminant, and predictive validity. Furthermore, these factors showed significant relations with CVD severity indicators. CONCLUSIONS: The Cardiovascular Management Self-efficacy Scale could be a helpful instrument to monitor differences during interventions to improve good disease management.

Renal function and peak exercise oxygen consumption in chronic heart failure with reduced left ventricular ejection fraction.

BACKGROUND: Chronic kidney disease is associated with sympathetic activation and muscle abnormalities, which may contribute to decreased exercise capacity. We investigated the correlation of renal function with peak exercise oxygen consumption (V̇O2) in heart failure (HF) patients. METHODS AND RESULTS: We recruited 2,938 systolic HF patients who underwent clinical, laboratory, echocardiographic and cardiopulmonary exercise testing. The patients were stratified according to estimated glomerular filtration rate (eGFR). Mean follow-up was 3.7 years. The primary outcome was a composite of cardiovascular death and urgent heart transplantation at 3 years. On multivariable regression, eGFR was predictor of peakV̇O2(P<0.0001). Other predictors were age, sex, body mass index, HF etiology, NYHA class, atrial fibrillation, resting heart rate, B-type natriuretic peptide, hemoglobin, and treatment. After adjusting for significant covariates, the hazard ratio for primary outcome associated with peakV̇O2<12 ml·kg(-1)·min(-1)was 1.75 (95% confidence interval (CI): 1.06-2.91; P=0.0292) in patients with eGFR ≥60, 1.77 (0.87-3.61; P=0.1141) in those with eGFR of 45-59, and 2.72 (1.01-7.37; P=0.0489) in those with eGFR <45 ml·min(-1)·1.73 m(-2). The area under the receiver-operating characteristic curve for peakV̇O2<12 ml·kg(-1)·min(-1)was 0.63 (95% CI: 0.54-0.71), 0.67 (0.56-0.78), and 0.57 (0.47-0.69), respectively. Testing for interaction was not significant. CONCLUSIONS: Renal dysfunction is correlated with peakV̇O2. A peakV̇O2cutoff of 12 ml·kg(-1)·min(-1)offers limited prognostic information in HF patients with more severely impaired renal function.

The influence of illness severity on health satisfaction in patients with cardiovascular disease: the mediating role of illness perception and self-efficacy beliefs.

The importance of psychological factors in improving conditions of cardiovascular disease (CVD) patients is stressed by the guidelines for their prevention and rehabilitation, but little is known about the impact of illness severity on patients' well-being, and on the psychosocial variables that may mediate this association. The aim of this study was to investigate the role of illness perception and self-efficacy beliefs on the relationship between illness severity and health satisfaction in 75 CVD patients undergoing rehabilitation (80% men; mean age = 65.44) at the St. Luca Hospital, Istituto Auxologico Italiano, Milan, Italy. Illness severity was measured in terms of left ventricular ejection fraction; psychological factors were assessed at the beginning and end of rehabilitation. Results from path analyses showed that the relationships among CVD severity and health satisfaction were mediated by illness perception and self-efficacy beliefs. Findings underscored the importance of considering illness representations and self-efficacy beliefs to improve well-being in CVD patients.

The ACTonHEART study: rationale and design of a randomized controlled clinical trial comparing a brief intervention based on Acceptance and Commitment Therapy to usual secondary prevention care of coronary heart disease.

BACKGROUND: Modifiable risk factors, including life-style habits and psychological variables, have been increasingly demonstrated to have an important role in influencing morbidity and mortality in cardiovascular patients, and to account for approximately 90% of the population risk for cardiac events.Acceptance and Commitment Therapy (ACT) has shown effectiveness in promoting healthy behaviors, and improving psychological well-being in patients with chronic physical conditions. Moreover, a first application of an acceptance-based program in cardiac patients has revealed high treatment satisfaction and initial evidences of effectiveness in increasing heart-healthy behaviour. However, no clinical trial to date has evaluated the efficacy of an acceptance-based program for the modification of cardiovascular risk factors and the improvement of psychological well-being, compared to usual secondary prevention care. METHODS: Approximately 168 patients will be recruited from an outpatient cardiac rehabilitation unit and randomly assigned to receive usual care or usual care + a brief ACT-based intervention. The ACT group will be administered five group therapy sessions integrating educational topics on heart-healthy behaviours with acceptance and mindfulness skills. Participants will be assessed at baseline, six weeks later (post treatment for the ACT condition), at six and twelve months follow-up.A partially-nested design will be used to balance effects due to clustering of participants into small therapy groups. Primary outcome measures will include biological indicators of cardiovascular risk and self-reported psychological well-being. Treatment effects will be tested via multilevel modeling after which the mediational role of psychological flexibility will be evaluated. DISCUSSION: The ACTonHEART study is the first randomized clinical trial designed to evaluate the efficacy of a brief group-administered, ACT-based program to promote health behavior change and psychological well-being among cardiac patients. Results will address the effectiveness of a brief treatment created to simultaneously impact multiple cardiovascular risk factors. Conducted in the context of clinical practice, this trial will potentially offer empirical support to alternative interventions to improve quality of life and reduce mortality and morbidity rates among cardiac patients. TRIAL REGISTRATION: clinicaltrials.gov/ (NCT01909102).

[Familial hypercholesterolemia in cardiac rehabilitation: a new field of interest]. / L'ipercolesterolemia familiare: un ambito di sempre maggiore interesse in Cardiologia Riabilitativa e Preventiva.

Familial hypercholesterolemia (FH) is a frequently undiagnosed genetic disease characterized by substantial elevations of low-density lipoprotein cholesterol (LDL-C). The prevalence of heterozygous FH (HeFH) in the general population is 1:500 inhabitants, while the prevalence of homozygous FH (HoFH) is 1:1,000,000. If FH is not identified and aggressively treated at an early age, affected individuals have a 20-fold increased lifetime risk of coronary heart disease compared with the general population. This narrative review provide a concise overview of recommendations for diagnosis and treatment of adults and children with FH, and discuss the utility of considering FH as a comorbidity at the entry of cardiac rehabilitation programmes.

Heart Rate Variability and Cognition: A Narrative Systematic Review of Longitudinal Studies.

BACKGROUND: Heart rate variability (HRV) is a reliable and convenient method to assess autonomic function. Cross-sectional studies have established a link between HRV and cognition. Longitudinal studies are an emerging area of research with important clinical implications in terms of the predictive value of HRV for future cognition and in terms of the potential causal relationship between HRV and cognition. However, they have not yet been the objective of a systematic review. Therefore, the aim of this systematic review was to investigate the association between HRV and cognition in longitudinal studies. METHODS: The review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The Embase, PsycINFO and PubMed databases were searched from the earliest available date to 26 June 2023. Studies were included if they involved adult human subjects and evaluated the longitudinal association between HRV and cognition. The risk of bias was assessed with the Newcastle-Ottawa Scale for Cohort Studies. The results were presented narratively. RESULTS: Of 14,359 records screened, 12 studies were included in this systematic review, with a total of 24,390 participants. Two thirds of the studies were published from 2020 onwards. All studies found a longitudinal relationship between HRV and cognition. There was a consistent association between higher parasympathetic nervous system (PNS) activity and better cognition, and some association between higher sympathetic nervous system activity and worse cognition. Also, higher PNS activity persistently predicted better executive functioning, while data on episodic memory and language were more scant and/or controversial. CONCLUSIONS: Our results support the role of HRV as a biomarker of future cognition and, potentially, as a therapeutic target to improve cognition. They will need confirmation by further, more comprehensive studies also including unequivocal non-HRV sympathetic measures and meta-analyses.

Effects of a brief intervention based on Acceptance and Commitment Therapy versus usual care for cardiac rehabilitation patients with coronary heart disease (ACTonHEART): a randomised controlled trial.

OBJECTIVES: The main objective of the study is to investigate the short-term efficacy of Acceptance and Commitment Therapy (ACT) on the simultaneous modification of biological indicators of risk and psychological well-being in patients with coronary heart disease attending cardiac rehabilitation (CR). DESIGN: This was a two-arm randomised controlled trial comparing a brief, manualised, ACT-based intervention with usual care (UC). SETTING: The study was conducted in an outpatient CR unit in Italy. Data collection took place from January 2016 to July 2017. PARTICIPANTS: Ninety-two patients were enrolled and randomised, following an unbalanced randomisation ratio of 2:1 to the ACT group (n=59) and the control group (n=33). Eighty-five patients completed the ACT (n=54) and the UC (n=31) interventions and were analysed. INTERVENTIONS: The control group received UC, a 6 weeks multidisciplinary outpatient CR programme, encompassing exercise training, educational counselling and medical examinations. The experimental group, in addition to UC, participated in the Acceptance and Commitment Therapy on HEART disease (ACTonHEART) intervention encompassing three group sessions based on ACT. OUTCOMES: The primary outcomes were Low Density Lipoproteins (LDL)cholesterol, resting systolic blood pressure, body mass index (BMI) and psychological well-being measured by the Psychological General Well-Being Index (PGWBI). Outcome measures were assessed at baseline and at the end of CR. RESULTS: Based on linear mixed models, no significant group × time interaction was observed for either the primary outcomes (ß, 95% CI: PGWBI =-1.13, -6.40 to -4.14; LDL cholesterol =-2.13, -11.02 to -6.76; systolic blood pressure =-0.50, -10.76 to -9.76; diastolic blood pressure =-2.73, -10.12 to -4.65; BMI =-0.16, -1.83 to -1.51, all p values >0.05) or the secondary outcomes (all p values >0.05). A significant time effect was found for the PGWBI total (beta=4.72; p=0.03). CONCLUSIONS: Although analyses revealed null findings, the results can inform the design of future ACT-based CR interventions and can help researchers to strike a balance between the idealised implementation of an ACT intervention and the structural limitations of existing CR programmes. TRIAL REGISTRATION NUMBER: NCT01909102.

Effects of cardiac rehabilitation on cardiopulmonary test parameters in heart failure: A real world experience.

Background: Cardio-Pulmonary Exercise Test (CPET) is the gold standard for evaluation of patients with heart failure (HF); however, its use is limited in everyday practice. We analyzed the use of CPET for HF management in the real world. Methods: From 2009 to 2022, 341 patients with HF underwent 12-16 weeks of rehabilitation in our Centre. We present data from 203 patients (60%), excluding those unable to perform CPET, those with anaemia and severe pulmonary disease. Before and after rehabilitation, we performed CPET, blood tests and echocardiography, tailoring individual physical training to the results of baseline test. The following variables were considered: peak Respiratory Equivalent Ratio (RER), peakVO2 (ml/Kg/min), VO2 at aerobic threshold (VO2AT,% maximal), VE/VCO2 slope, P(ET)CO2, VO2 /Work ratio (ΔVO2/ΔWork). Results: Rehabilitation improved peak VO2, pulse O2, VO2 AT and ΔVO2/ΔWork in all patients by about 13% (p < 0.01). Most patients (126, 62%) showed a reduced left ventricular ejection fraction (HFrEF), but rehabilitation was effective also in patients with mildly reduced (HFmrEF: n = 55, 27%) or preserved ejection fraction (HFpEF: n = 22, 11%). Conclusions: Rehabilitation in patients with heart failure induces a significant recovery of cardiorespiratory performance easily assessed by CPET, that is applicable to the majority of them and should be used routinely in the programming and evaluating of cardiac rehabilitation programs.

Intermittent levosimendan infusions in advanced heart failure: favourable effects on left ventricular function, neurohormonal balance, and one-year survival.

The role of repeated infusions of Levosimendan (LEVO) in patients with chronic advanced heart failure is still unclear. Thirty-three patients with chronic heart failure presenting clinical deterioration were randomized 2:1 to receive monthly infusions of LEVO (n = 22) or Furosemide (Controls, n = 11). At the first drug's administration, noninvasive hemodynamic evaluation was performed; before and after each infusion, we assessed NYHA class, systolic and diastolic function, functional mitral regurgitation, and brain natriuretic peptide (BNP) levels. Noninvasive hemodynamic in the LEVO group showed vasodilation and decrease in thoracic conductance (index of pulmonary congestion), whereas in Controls, only a reduced thoracic conductance was observed. In the LEVO group, systolic and diastolic function, ventricular volumes, severity of mitral regurgitation, and BNP levels improved over time from baseline and persisted 4 weeks after the last infusion (P < 0.01). In Controls, no change developed over time in cardiac function and BNP levels. In LEVO-treated patients, 1-year mortality tended to be lower than in those treated with Furosemide. In conclusion, serial LEVO infusions in advanced heart failure improved ventricular performance and favorably modulated neurohormonal activation. Multicenter randomized studies are warranted to test the effect of LEVO on long-term outcome.

Intravenous iron therapy improves the hypercapnic ventilatory response and sleep disordered breathing in chronic heart failure.

AIMS: Intravenous iron therapy can improve symptoms in patients with heart failure, anaemia and iron deficiency. The mechanisms underlying such an improvement might involve chemoreflex sensing and nocturnal breathing patterns. METHODS AND RESULTS: Patients with heart failure, reduced left ventricular ejection fraction, anaemia (haemoglobin <13 g/dl in men; <12 g/dl in women) and iron deficiency (ferritin <100 or 100-299 µg/L with transferrin saturation <20%) were 2:1 randomized to patient-tailored intravenous ferric carboxymaltose dose or placebo. Chemoreflex sensitivity cardiorespiratory sleep study, symptom assessment and cardiopulmonary exercise test were performed before and 2 weeks after the last treatment dose. Fifty-eight patients (38 active arm/20 placebo arm) completed the study. Intravenous iron was associated with less severe symptoms, higher haemoglobin (12.5 ± 1.4 vs. 11.7 ± 1.0 mg/dl, p < 0.05) and improved haematinic parameters. Ferric carboxymaltose improved the central hypercapnic ventilatory response (-25.8%, p < 0.05 vs. placebo), without changes in peripheral chemosensitivity. In particular, the central hypercapnic ventilatory responses passed from 4.6 ± 6.5 to 2.9 ± 2.9 L/min/mmHg after ferric carboxymaltose and from 4.4 ± 4.6 to 4.6 ± 3.9 L/min/mmHg after placebo (ptreatment*condition  = 0.046). In patients presenting with sleep-related breathing disorder, apnoea-hypopnoea index was reduced with active treatment as compared to placebo (12 ± 11 vs. 19 ± 13 events/h, p < 0.05). After ferric carboxymaltose, but not after placebo, both peak oxygen uptake (VO2 ) increased (Δ1.1 ± 2.0 ml/kg/min, p < 0.05) and VO2 /workload slope was steeper (Δ0.67 ± 1.7 L/min/W, p < 0.01). CONCLUSIONS: Intravenous ferric carboxymaltose improves the hypercapnic ventilatory response and sleep-related breathing disorders in patients with heart failure, anaemia and iron deficiency. These newly described findings, along with improved oxygen delivery to exercising muscles, likely contribute to the favourable effects of ferric carboxymaltose in anaemic patients with heart failure.

Low anaerobic threshold and increased skeletal muscle lactate production in subjects with Huntington's disease.

Mitochondrial defects that affect cellular energy metabolism have long been implicated in the etiology of Huntington's disease (HD). Indeed, several studies have found defects in the mitochondrial functions of the central nervous system and peripheral tissues of HD patients. In this study, we investigated the in vivo oxidative metabolism of exercising muscle in HD patients. Ventilatory and cardiometabolic parameters and plasma lactate concentrations were monitored during incremental cardiopulmonary exercise in twenty-five HD subjects and twenty-five healthy subjects. The total exercise capacity was normal in HD subjects but notably the HD patients and presymptomatic mutation carriers had a lower anaerobic threshold than the control subjects. The low anaerobic threshold of HD patients was associated with an increase in the concentration of plasma lactate. We also analyzed in vitro muscular cell cultures and found that HD cells produce more lactate than the cells of healthy subjects. Finally, we analyzed skeletal muscle samples by electron microscopy and we observed striking mitochondrial structural abnormalities in two out of seven HD subjects. Our findings confirm mitochondrial abnormalities in HD patients' skeletal muscle and suggest that the mitochondrial dysfunction is reflected functionally in a low anaerobic threshold and an increased lactate synthesis during intense physical exercise.

Cardiac-specific experiential avoidance predicts change in general psychological well-being among patients completing cardiac rehabilitation.

Previous studies have shown that experiential avoidance (EA) is associated with physical and psychological well-being in medical and non-medical samples. The aims of the present study were to evaluate the reciprocal association between psychological well-being and EA over time among cardiac rehabilitation (CR) patients with moderately to severely low levels of psychological well-being. Pre-CR data on demographic characteristics, measures of psychological well-being, and cardiac-specific EA were collected from 915 CR patients, as well as post-CR psychological well-being and EA data, from 800 of these patients. A cross-lagged model was estimated to examine the relationship between EA and psychological well-being among patients with moderately to severely low levels of psychological well-being based on questionnaire scores. Both EA and psychological well-being significantly changed during CR and were negatively associated with each other at both pre- and post-CR. Results from cross-lagged structural equation modeling supported a nonreciprocal association between EA and psychological well-being during CR. Pre-CR assessment of EA in patients showing low levels of well-being at the beginning of CR could help to identify patients at risk for worse psychological outcomes. EA could be a promising target of psychological treatments administered during CR.

Do the remodeling effects of sacubitril/valsartan treatment depend upon heart failure duration?

AIMS: The angiotensin receptor and neprilysin inhibitor (ARNI) sacubitril/valsartan (LCZ696) is recommended for the treatment of patients with heart failure in New York Heart Association (NYHA) class II-III and left ventricular ejection fraction (LVEF) 35% or less. We examined the effects of sacubitril/valsartan on cardiac remodeling and their correlation with heart failure duration in patients enrolled in our heart failure clinic from March 2017 to December 2019. METHODS: Echocardiographic and clinical/laboratory data were collected at baseline and at 6-month and 12-month follow-up visits in 69 patients (age 67 ±â€Š12 years, disease duration 8.4 ±â€Š5.8 years, 93% men). RESULTS: At both time points, mean NYHA class, NT-proBNP level, LVEF, LV end-systolic volume, and estimated systolic pulmonary pressure significantly (P < 0.05) improved versus baseline, as did the proportion of patients with diastolic dysfunction grade 3 or functional mitral regurgitation grade 3-4. In the subgroup with mean disease duration less than 8.5 years (n = 40), there was a significant improvement in all variables at both time points; in this group, a recovery of right ventricular function was also seen at the 12-month follow-up. On the contrary, patients with heart failure duration of at least 8.5 years (n = 29) showed only a slight improvement in LVEF and mitral regurgitation at 12 months. There were no significant changes in renal function and/or potassium levels in all patients. CONCLUSION: In patients with a relatively short disease duration, sacubitril/valsartan was associated with a strong favorable remodeling of the left ventricle and improvement in pulmonary circulation.