Patients' Clinical and Psychological Status in Different COVID-19 Waves in Italy: A Quanti-Qualitative Study.

BACKGROUND: COVID-19 waves have been characterized by different clinical manifestations, a decrease of functional abilities, and the presence of psychological symptoms. The aims of this study were to investigate differences in physical and psychological symptoms during the three Italian waves of the coronavirus pandemic. METHODS: Patients undergoing a functional, cardiological and pneumological check-up follow-up at ICS Maugeri Institutes, 2-3 months after recovery from COVID-19 were consecutively recruited to participate in the study, completing a quanti-qualitative questionnaire about anxiety, depression, PTSD symptoms, and personal resources. RESULTS: 104 patients were recruited: 44 and 60 during the first and second/third pandemic waves, respectively. Physical comorbidities were more present in the second/third waves compared to the first one, while no significant differences were found in anxious and depressive symptoms, which were significantly higher than normal during the three waves; PTSD symptoms were reported by 56.3% of patients. Family, social support, and a positive mindset were described as resources to cope with the COVID-19 burden. Negative affects arose during outbreaks (panic) and the disease (fear), while positive affect (joy) characterized only the follow-up period. CONCLUSION: This study shows how psychophysical symptoms might change during the pandemic waves and highlights the importance of protective factors to balance the subjective distress.

Heart failure patients with improved ejection fraction: Insights from the MECKI score database.

AIMS: Improvement of left ventricular ejection fraction is a major goal of heart failure (HF) treatment. However, data on clinical characteristics, exercise performance and prognosis in HF patients who improved ejection fraction (HFimpEF) are scarce. The study aimed to determine whether HFimpEF patients have a distinct clinical phenotype, biology and prognosis than HF patients with persistently reduced ejection fraction (pHFrEF). METHODS AND RESULTS: A total of 7948 patients enrolled in the Metabolic Exercise Cardiac Kidney Indexes (MECKI) score database were evaluated (median follow-up of 1490 days). We analysed clinical, laboratory, electrocardiographic, echocardiographic, exercise, and survival data from HFimpEF (n = 1504) and pHFrEF (n = 6017) patients. The primary endpoint of the study was the composite of cardiovascular death, left ventricular assist device implantation, and urgent heart transplantation. HFimpEF patients had lower HF severity: left ventricular ejection fraction 44.0 [41.0-47.0] versus 29.7 [24.1-34.5]%, B-type natriuretic peptide 122 [65-296] versus 373 [152-888] pg/ml, haemoglobin 13.5 [12.2-14.6] versus 13.7 [12.5-14.7] g/dl, renal function by the Modification of Diet in Renal Disease equation 72.0 [56.7-89.3] versus 70.4 [54.5-85.3] ml/min, peak oxygen uptake 62.2 [50.7-74.1] versus 52.6 [41.8-64.3]% predicted, minute ventilation-to-carbon dioxide output slope 30.0 [26.9-34.4] versus 32.1 [28.0-38.0] in HFimpEF and pHFrEF, respectively (p < 0.001 for all). Cardiovascular mortality rates were 26.6 and 46.9 per 1000 person-years for HFimpEF and pHFrEF, respectively (p < 0.001). Kaplan-Meier analysis showed that HFimpEF had better a long-term prognosis compared with pHFrEF patients. After adjustment for variables differentiating HFimpEF from pHFrEF, except echocardiographic parameters, the Kaplan-Meier curves showed the same prognosis. CONCLUSIONS: Heart failure with improved ejection fraction represents a peculiar group of HF patients whose clinical, laboratory, electrocardiographic, echocardiographic, and exercise characteristics parallel the recovery of systolic function. Nonetheless, these patients remain at risk for adverse outcome.

Standardised Exercise Prescription for Patients with Chronic Coronary Syndrome and/or Heart Failure: A Consensus Statement from the EXPERT Working Group.

Whereas exercise training, as part of multidisciplinary rehabilitation, is a key component in the management of patients with chronic coronary syndrome (CCS) and/or congestive heart failure (CHF), physicians and exercise professionals disagree among themselves on the type and characteristics of the exercise to be prescribed to these patients, and the exercise prescriptions are not consistent with the international guidelines. This impacts the efficacy and quality of the intervention of rehabilitation. To overcome these barriers, a digital training and decision support system [i.e. EXercise Prescription in Everyday practice & Rehabilitative Training (EXPERT) tool], i.e. a stepwise aid to exercise prescription in patients with CCS and/or CHF, affected by concomitant risk factors and comorbidities, in the setting of multidisciplinary rehabilitation, was developed. The EXPERT working group members reviewed the literature and formulated exercise recommendations (exercise training intensity, frequency, volume, type, session and programme duration) and safety precautions for CCS and/or CHF (including heart transplantation). Also, highly prevalent comorbidities (e.g. peripheral arterial disease) or cardiac devices (e.g. pacemaker, implanted cardioverter defibrillator, left-ventricular assist device) were considered, as well as indications for the in-hospital phase (e.g. after coronary revascularisation or hospitalisation for CHF). The contributions of physical fitness, medications and adverse events during exercise testing were also considered. The EXPERT tool was developed on the basis of this evidence. In this paper, the exercise prescriptions for patients with CCS and/or CHF formulated for the EXPERT tool are presented. Finally, to demonstrate how the EXPERT tool proposes exercise prescriptions in patients with CCS and/or CHF with different combinations of CVD risk factors, three patient cases with solutions are presented.

Physiological and Psychological Response to Acute Mental Stress in Female Patients Affected by Chronic Pulmonary Arterial Hypertension: An Explorative Controlled Pilot Trial.

Little is known about physiological and psychological responses to mental stress in stable patients affected by pulmonary arterial hypertension (PAH). The current explorative controlled pilot study was conducted to investigate whether heart rate (HR) and perceived stress would differ during standardized mental stress testing in PAH patients compared to healthy subjects. Correlation analysis between HR, perceived stress, participants' psychological status and performance on the mental stress task was also performed. The study included 13 female PAH patients (average age: 44.38 ± 10.88 years; average education: 14 ± 3.07 years; mean duration of illness: 9.15 ± 5.37 years) and 13 female controls similar in age (mean age: 47.85 ± 6.36 years) and education (15.92 ± 1.55 years). Participants performed a standardized 9 min mental stress test (computer based, adaptive math task). HR and perceived stress during the task were compared to resting baseline and correlated with psychological state and task performance. Both HR and perceived stress significantly increased during mental stress in a similar way in both groups. A significant correlation was found between HR and perceived stress. Our data show that moderate mental stress has a comparable effect on HR and perceived stress increase in stable PAH patients and control subjects.

Functional outcome after cardiac rehabilitation and its association with survival in heart failure across the spectrum of ejection fraction.

BACKGROUND: There is limited evidence regarding the effects of cardiac rehabilitation (CR) in patients with heart failure and preserved ejection fraction (HFpEF). METHODS: We studied 1784 patients admitted to inpatient CR. The patients were grouped into HFpEF (EF≥0.50), HF with mildly reduced EF (HFmrEF; EF 41-49), and HF with reduced EF (HFrEF; EF≤0.40). A standardized 6-min walking test was performed at admission and discharge. Measures of functional outcome were: (1) absolute increase in 6-min walking distance (6MWD) from admission to discharge >50 m and (2) increase in 6MWD to ≥300 among the patients who walked <300 m at admission. RESULTS: After adjustment, the patients with HFpEF or HFmrEF were as likely as those with HFrEF to achieve an increase in 6MWD >50 m (odds ratio 0.95 [95%CI 0.71-1.24; p=0.648] and 1.04 [95%CI 0.77-1.41; p=0.769], respectively) or an increase in 6MWD to ≥300 m (odds ratio 0.79 [95%CI 0.51-1.23; p=0.299] and 0.65 [95%CI 0.38-1.12; p=0.118], respectively). The adjusted hazard ratio of 5-year mortality for patients who achieved an increase in 6MWD >50 m was 0.60 (95%CI 0.51-0.71; p<0.001) and that for patients who achieved an increase in 6MWD at discharge to ≥300 m 0.61 (95%CI 0.48-0.79; p<0.001). In each EF group, both outcomes remained independently associated with improved survival. CONCLUSIONS: Our data suggest that patients with HFpEF or HFmrEF are as likely as those with HFrEF to benefit from CR in terms of functional improvement. Functional improvement was independently associated with improved long-term survival, regardless of EF.

Predictors of survival in patients undergoing cardiac rehabilitation after transcatheter aortic valve replacement (TAVR): a multicenter retrospective study.

BACKGROUND: The aim of this study was to evaluate cardiac rehabilitation (CR)-derived predictors of outcome in patients discharged from rehabilitation after transcatheter aortic valve replacement (TAVR). METHODS: We retrospectively analyzed data from 232 TAVR patients (aged 82±6 years, 55% females) discharged following an average 3-week residential CR program in the period January 2009 to December 2017. Comorbidities (cumulative illness rated state-comorbidity index, CIRS-CI), echocardiography on admission, disability (Barthel Index [BI]) and functional capacity (6-min walk distance, 6MWD) at discharge, and maximal training session intensity expressed in METs/min were collected. The endpoint was all-cause mortality. RESULTS: Seventy-four (32%) deaths occurred at 3-year follow-up. At discharge, non-survivors had a higher comorbidity rate (CIRS-CI 5.2±2.3 vs. 4.1±1.9, P=0.000), higher disability level (BI 80.4±24 vs. 88.8±17, P=0.000), and worse renal function (creatinine 1.6±0.9 vs. 1.2±0.4 mg/dL, P=0.000). They were also more often on diuretics (73% vs. 53.2%, P=0.003) and beta-blocker therapy (73% vs. 57.6%, P=0.042) and had a markedly reduced functional capacity (6MWD 221±100m vs. 265±105m, P=0.001). At multivariate Cox proportional hazards regression analysis, independent predictors of survival at follow-up were lower comorbidity rate, a better-preserved renal function, lower use of diuretics, and a higher 6MWD at discharge (Harrell's C = 0.707). CONCLUSIONS: Patients attending residential CR after TAVR are very old with significant comorbidity. The overall 3-year mortality rate after CR discharge is high. Our findings suggest the need for individually tailored follow-up care in patients discharged from CR after TAVR to address their residual exercise capacity, comorbidities, and renal function impairment.

Does moderate hyperkalemia influence survival in HF? Insights from the MECKI score data base.

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

Exploring the Prognostic Performance of MECKI Score in Heart Failure Patients with Non-Valvular Atrial Fibrillation Treated with Edoxaban.

INTRODUCTION: Risk stratification in heart failure (HF) is essential for clinical and therapeutic management. The Metabolic Exercise test data combined with Cardiac and Kidney Indexes (MECKI) score is a validated prognostic model for assessing cardiovascular risk in HF patients with reduced ejection fraction (HFrEF). From the validation of the score, the prevalence of HF patients treated with direct oral anticoagulants (DOACs), such as edoxaban, for non-valvular atrial fibrillation (NVAF) has been increasing in recent years. This study aims to evaluate the reliability of the MECKI score in HFrEF patients treated with edoxaban for NVAF. MATERIALS AND METHODS: This study included consecutive outpatients with HF and NVAF treated with edoxaban (n = 83) who underwent a cardiopulmonary exercise test (CPET). They were matched by propensity score with a retrospective group of HFrEF patients with NVAF treated with vitamin K antagonists (VKAs) from the MECKI score registry (n = 844). The study endpoint was the risk of cardiovascular mortality, urgent heart transplantation, or Left Ventricle Assist Device (LVAD) implantation. RESULTS: Edoxaban patients were treated with a more optimized HF therapy and had different clinical characteristics, with a similar MECKI score. After propensity score, 77 patients treated with edoxaban were successfully matched with the MECKI-VKA control cohort. In both groups, MECKI accurately predicted the composite endpoint with similar area under the curves (AUC = 0.757 vs. 0.829 in the MECKI-VKA vs. edoxaban-treated group, respectively, p = 0.452). The two populations' survival appeared non-significantly different at the 2-year follow-up. CONCLUSIONS: this study confirms the prognostic accuracy of the MECKI score in HFrEF patients with NVAF treated with edoxaban, showing improved predictive power compared to VKA-treated patients.

The Octopus Trap of Takotsubo and Stroke: Genetics, Biomarkers and Clinical Management.

Takotsubo cardiomyopathy (TC) is a reversible cardiomyopathy mimicking an acute coronary syndrome, usually observed in response to acute stress situations. The association between acute ischemic stroke and TC is already known, since it has been previously reported that ischemic stroke can be both a consequence and a potential cause of TC. However, the precise pathophysiological mechanism linking the two conditions is still poorly understood. The aim of our review is to expand insights regarding the genetic susceptibility and available specific biomarkers of TC and to investigate the clinical profile and outcomes of patients with TC and stroke. Since evidence and trials on TC and stroke are currently lacking, this paper aims to fill a substantial gap in the literature about the relationship between these pathologies.

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.

When Outcomes Diverge: Age and Cardiovascular Risk as Determinants of Mortality and ICU Admission in COVID-19.

BACKGROUND: Hospital mortality and admission to the Intensive Care Unit (ICU) are markers of disease severity in COVID-19 patients. Cardiovascular co-morbidities are one of the main determinants of negative outcomes. In this study we investigated the impact of cardiovascular co-morbidities on mortality and admission to the ICU in first-wave COVID-19 patients. METHODS: A multicenter, retrospective, cohort study. A total of 1077 patients were analyzed for mortality and ICU admission. Cardiovascular risk factors were explored as determinants of the outcomes after correction for other confounders. RESULTS: In the multivariable model, after correction for age, only a history of heart failure remained independently associated (p = 0.0013) with mortality (hazard ratio 2.22, 95% confidence interval 1.37 to 3.62). Age showed a mortality risk increase of 8% per year (hazard ratio 1.08, 95% confidence interval 1.05 to 1.10, p = 0.001). The transition from ward to the ICU had, as a single determinant, the age, but in a reversed fashion (hazard ratio 0.96, 95% confidence interval 0.94 to 0.98, p = 0.0002). CONCLUSIONS: Once adjusted for the main determinant of mortality (age) heart failure only remained independently associated with mortality. Admission to the ICU was less likely for elderly patients. This may reflect the catastrophic impact of the first wave of COVID-19 pandemic in terms of ICU bed availability in Lombardy, leading to a selection process for ICU admission.

Pick Your Threshold: A Comparison Among Different Methods of Anaerobic Threshold Evaluation in Heart Failure Prognostic Assessment.

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

Sexual and Reproductive Health in Women with Pulmonary Hypertension: A Qualitative Study.

Pulmonary arterial hypertension (PAH) is a devastating disease characterized by elevation in pulmonary artery pressure causing progressive symptoms: shortness of breath, fatigue, and a decline in functional ability. Research on the impact of PAH on sexual and reproductive health was sparse. The aim of this study is to explore sexual and reproductive health of women with PAH in relation to their illness experience. Twenty-five women with PAH participated in semistructured interviews. A thematic analysis was conducted on the transcripts using the ATLAS.ti software. Four main themes were identified: illness experience, intimate relationship, sexuality, and attitudes toward pregnancy. Results showed that illness changed women's self-perception, couples' relationship, sexuality, and the idea of an eventual pregnancy. The relationship with the partner was usually indicated as an important resource, whereas communication with health care professionals was a critical but also potential key resource for the future. Results point to the need for intervention strategies to support women with PAH and help them make aware choices. Moreover, intervention strategies may inform health care interventions and policies for tackling the challenges posed by this illness.

Association of improvement in functional capacity after rehabilitation with long-term survival in heart failure.

BACKGROUND: The prognostic value of change in six-minute walking distance (6MWD) after treatment to predict mortality in heart failure (HF) remains a controversial issue. We assessed the prognostic value of rehabilitation-induced improvement in 6MWD in predicting mortality in patients with HF. METHODS: We studied 2257 patients admitted to six inpatient rehabilitation facilities after a hospitalization for HF (N. 912) or because of worsening functional capacity and/or deteriorating clinical status (N. 1345). A six-minute walking test was performed at admission and discharge. The primary outcome was 3-year all-cause mortality after discharge from cardiac rehabilitation. We used multivariable Cox proportional hazard modeling to assess the association of increase in 6MWD with 3-year mortality, adjusting for established predictors of mortality. RESULTS: 6MWD significantly increased by 61 m (p < .001) from admission to discharge and 969 patients (42.9%) achieved an increase in 6MWD >50 m. After full adjustment, an increase in 6MWD >50 m was associated with a 22% decreased risk for 3-year mortality (HR 0.78 [95% CI 0.68-0.91]; p = .002). When modeled as a continuous variable, improvement in 6MWD remained independently associated with decreased risk for 3-year mortality (HR per each 50 m increase: 0.92 [95% CI 0.88-0.96]). CONCLUSIONS: Rehabilitation-induced improvement in 6MWD was associated with a significantly reduced risk for 3-year mortality. Our data also suggest that an improvement in 6MWD of more than 50 m could represent a clinically meaningful endpoint of cardiac rehabilitation for patients with heart failure.

Characteristics, Outcomes, and Long-Term Survival of Patients With Heart Failure Undergoing Inpatient Cardiac Rehabilitation.

OBJECTIVE: To investigate the association of cardiac rehabilitation (CR) participation with all-cause mortality after a hospitalization for heart failure (HF) and to describe the characteristics and functional and clinical outcomes of HF patients undergoing inpatient CR. DESIGN: Multicenter cohort study. The association between CR participation and all-cause mortality from discharge from the acute care setting was assessed using Cox regression analysis adjusting for established prognostic factors. SETTING: Six inpatient rehabilitation facilities. PARTICIPANTS: A total of 3219 patients with HF admitted to inpatient CR between January 2013 and December 2016. Of these patients, 1455 had been transferred directly from acute care hospitals after a hospitalization for HF (CR-group 1) and 1764 had been admitted from the community due to worsening functional disability or worsening clinical conditions (CR-group 2). Serving as a control group were 633 patients not referred to CR after a hospitalization for HF served as control group (non-CR group). INTERVENTIONS: Cardiac rehabilitation. MAIN OUTCOME MEASURES: Long-term mortality. Secondary outcomes were: (1) change in functional capacity, as assessed by change in 6-minute walking distance from admission to discharge; (2) clinical outcomes of the index inpatient rehabilitation admission, including in-hospital mortality and unplanned readmission to the acute care. RESULTS: Compared with the non-CR group, the adjusted hazard ratios of mortality at 1, 3, and 5 years for CR-group 1 patients were 0.82 (range, 0.68-0.97), 0.81 (range, 0.71-0.93), and 0.80 (range, 0.70-0.91). The 6-minute walking distance increased from 230-292 meters (P<.001), and 43.4% of the patients gained >50 m improvement. Overall, 2.5% of the patients died in hospital and 4.7% of the patients experienced unplanned readmissions to acute care, with significant differences between group 1 and group 2. CONCLUSIONS: Our data show that inpatient CR is effective in improving functional capacity and suggest that inpatient CR provided in the earliest period after a hospitalization for HF is associated with long-term improved survival.

The Future of Exercise-Based Cardiac Rehabilitation for Patients With Heart Failure.

Cardiac rehabilitation (CR) is a comprehensive program that includes exercise training, titration of medical therapy, lifestyle modification, educational support, and psychosocial assessment. All these components are safe and beneficial resulting in significant improvements in quality of life, functional capacity, mortality, and hospital readmission. Current guidelines support its use in a broad spectrum of cardiac disease. This review focuses on exercise-based CR for heart failure (HF) patients in whom CR is a recommended treatment. Exercise should be prescribed according to a personalized approach, optimizing, and tailoring the rehabilitative program to the patient's characteristics. Specific CR programs are dedicated to older patients, those with HF and preserved ejection fraction, and recipients of cardiac implantable electronic devices or left ventricular assistance device. Telemedicine may increase CR participation and overcome some of the barriers that limit its utilization.

Evidence for Biological Age Acceleration and Telomere Shortening in COVID-19 Survivors.

The SARS-CoV-2 infection determines the COVID-19 syndrome characterized, in the worst cases, by severe respiratory distress, pulmonary and cardiac fibrosis, inflammatory cytokine release, and immunosuppression. This condition has led to the death of about 2.15% of the total infected world population so far. Among survivors, the presence of the so-called persistent post-COVID-19 syndrome (PPCS) is a common finding. In COVID-19 survivors, PPCS presents one or more symptoms: fatigue, dyspnea, memory loss, sleep disorders, and difficulty concentrating. In this study, a cohort of 117 COVID-19 survivors (post-COVID-19) and 144 non-infected volunteers (COVID-19-free) was analyzed using pyrosequencing of defined CpG islands previously identified as suitable for biological age determination. The results show a consistent biological age increase in the post-COVID-19 population, determining a DeltaAge acceleration of 10.45 ± 7.29 years (+5.25 years above the range of normality) compared with 3.68 ± 8.17 years for the COVID-19-free population (p < 0.0001). A significant telomere shortening parallels this finding in the post-COVID-19 cohort compared with COVID-19-free subjects (p < 0.0001). Additionally, ACE2 expression was decreased in post-COVID-19 patients, compared with the COVID-19-free population, while DPP-4 did not change. In light of these observations, we hypothesize that some epigenetic alterations are associated with the post-COVID-19 condition, particularly in younger patients (< 60 years).

Effects of an outpatient service holistic rehabilitation program in a case of pulmonary atresia.

A 42-year-old woman affected by pulmonary atresia came to our attention complaining of dyspnea and fatigue for minimal efforts with important desaturation. After assessing her basal functional capacity with a cardiopulmonary exercise test, the patient was enrolled in an extremely individualized rehabilitation program, which entailed a discreet improvement in the quality of life indices, in the absence of side effects. This paper shows that even patients with extremely severe forms of congenital heart disease, when clinical stable, can undergone a tailored cardiorespiratory rehabilitation program. This must be carried out in a monitored environment and under the supervision of expert personnel.

Standardized exercise training is feasible, safe, and effective in pulmonary arterial and chronic thromboembolic pulmonary hypertension: results from a large European multicentre randomized controlled trial.

AIMS: This prospective, randomized, controlled, multicentre study aimed to evaluate efficacy and safety of exercise training in patients with pulmonary arterial (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH). METHODS AND RESULTS: For the first time a specialized PAH/CTEPH rehabilitation programme was implemented in 11 centres across 10 European countries. Out of 129 enrolled patients, 116 patients (58 vs. 58 randomized into a training or usual care control group) on disease-targeted medication completed the study [85 female; mean age 53.6 ± 12.5 years; mean pulmonary arterial pressure 46.6 ± 15.1 mmHg; World Health Organization (WHO) functional class II 53%, III 46%; PAH n = 98; CTEPH n = 18]. Patients of the training group performed a standardized in-hospital rehabilitation with mean duration of 25 days [95% confidence interval (CI) 17-33 days], which was continued at home. The primary endpoint, change of 6-min walking distance, significantly improved by 34.1 ± 8.3 m in the training compared with the control group (95% CI, 18-51 m; P < 0.0001). Exercise training was feasible, safe, and well-tolerated. Secondary endpoints showed improvements in quality of life (short-form health survey 36 mental health 7.3 ± 2.5, P = 0.004), WHO-functional class (training vs. control: improvement 9:1, worsening 4:3; χ2P = 0.027) and peak oxygen consumption (0.9 ± 0.5 mL/min/kg, P = 0.048) compared with the control group. CONCLUSION: This is the first multicentre and so far the largest randomized, controlled study on feasibility, safety, and efficacy of exercise training as add-on to medical therapy in PAH and CTEPH. Within this study, a standardized specialized training programme with in-hospital start was successfully established in 10 European countries.

Role of gender, age and BMI in prognosis of heart failure.

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