Cardio-oncology rehabilitation: are we ready?

Cardio-oncology rehabilitation (CORE) is not only an essential component of cancer rehabilitation but also a pillar of preventive cardio-oncology. Cardio-oncology rehabilitation is a comprehensive model based on a multitargeted approach and its efficacy has been widely documented; when compared with an 'exercise only' programme, comprehensive CORE demonstrates a better outcome. It involves nutritional counselling, psychological support, and cardiovascular (CV) risk assessment, and it is directed to a very demanding population with a heavy burden of CV diseases driven by physical inactivity, cancer therapy-induced metabolic derangements, and cancer therapy-related CV toxicities. Despite its usefulness, CORE is still underused in cancer patients and we are still at the dawning of remote models of rehabilitation (tele-rehabilitation). Not all CORE is created equally: a careful screening procedure to identify patients who will benefit the most from CORE and a multidisciplinary customized approach are mandatory to achieve a better outcome for cancer survivors throughout their cancer journey. The aim of this paper is to provide an updated review of CORE not only for cardiologists dealing with this peculiar population of patients but also for oncologists, primary care providers, patients, and caregivers. This multidisciplinary team should help cancer patients to maintain a healthy and active life before, during, and after cancer treatment, in order to improve quality of life and to fight health inequities.

Dopamine Pharmacodynamics: New Insights.

Dopamine is a key neurotransmitter involved in physiological processes such as motor control, motivation, reward, cognitive function, and maternal and reproductive behaviors. Therefore, dysfunctions of the dopaminergic system are related to a plethora of human diseases. Dopamine, via different circuitries implicated in compulsive behavior, reward, and habit formation, also represents a key player in substance use disorder and the formation and perpetuation of mechanisms leading to addiction. Here, we propose dopamine as a model not only of neurotransmission but also of neuromodulation capable of modifying neuronal architecture. Abuse of substances like methamphetamine, cocaine, and alcohol and their consumption over time can induce changes in neuronal activities. These modifications lead to synaptic plasticity and finally to morphological and functional changes, starting from maladaptive neuro-modulation and ending in neurodegeneration.

Multimodality imaging in decompensated heart failure.

Heart failure (HF) is usually suspected by clinical history, symptoms, physical examination, electrocardiogram findings, and natriuretic peptides' values. However, echocardiography and other imaging techniques play an essential role in supporting HF diagnosis. Thanks to its non-invasiveness and safety, transthoracic echocardiography is the first-level technique of choice to assess myocardial structure and function, trying to establish the diagnosis of HF with reduced, mildly reduced, and preserved ejection fraction. The role of echocardiography is not limited to diagnosis but it represents a crucial tool in guiding therapeutic decision-making and monitoring response to therapy. Over the last decades, several technological advancements were made in the imaging field, aiming at better understanding the morphofunctional abnormalities occurring in cardiovascular diseases. The purpose of this review article is to summarize the incremental role of imaging techniques (in particular cardiac magnetic resonance and myocardial scintigraphy) in HF, highlighting their essential applications to HF diagnosis and management.

Effect of changes in perfusion defect size during serial stress myocardial perfusion imaging on cardiovascular outcomes in patients treated with primary percutaneous coronary intervention after myocardial infarction.

BACKGROUND: We evaluated the prognostic value of changes in perfusion defect size (PDS) on serial MPS in patients treated with primary percutaneous coronary intervention (PCI) after acute myocardial infarction (AMI). METHODS: We enrolled 112 patients treated with primary PCI after AMI who underwent two stress MPS within 1 month and after 6 months. Improvement in PDS was defined as a reduction ≥5%. Remodeling was defined as an increase in left ventricular (LV) end-diastolic volume index ≥20%. Cardiac events included cardiac death, nonfatal MI, unstable angina, repeated revascularization, and heart failure. RESULTS: During a median follow-up of 86 months, 22 events occurred. Event rate was higher (P < .01) in patients with worsening of PDS compared to those with unchanged or improved PDS. Moreover, patients with remodeling had a higher (P < .001) event rate compared to those without. At Cox analysis, worsening of PDS and remodeling resulted independent predictors of events (both P < .01). Patients with both worsening of PDS and remodeling had the worst event-free survival (P <.001). CONCLUSION: In patients treated with primary PCI after AMI, worsening of PDS and remodeling are associated to higher risk of events at long-term follow-up. Gated stress MPS improves risk stratification in these patients.

Effects of High Intensity Interval Training Rehabilitation Protocol after an Acute Coronary Syndrome on Myocardial Work and Atrial Strain.

Background andObjectives: Current guidelines on cardiac rehabilitation (CR) suggest moderate-intensity physical activity after acute coronary syndrome (ACS). Recent report have shown that high-intensity interval training (HIIT) could be more effective than moderate-intensity continuous training (MCT) in improving cardiac performance. Our aim was to analyze the effects of HIIT protocol after ACS on advanced echocardiographic parameters of myocardial function. Materials and Methods: In total, 75 patients with recent ACS, with or without ST segment elevation, were enrolled and compared with a control group of 50 age- and sex-comparable healthy subjects. Patients were randomized to perform a MCT training or HIIT-based rehabilitation program. A complete echocardiographic evaluation, including left ventricular (LV) and left atrial (LA) global longitudinal strain (GLS) and myocardial work (MW) through speckle-tracking analysis, was performed for all patients, before and after cardiac rehabilitation training. A cardiopulmonary exercise testing (CPET) was also performed at the end of the rehabilitation program. Results: Patients who followed the HIIT rehabilitation program showed improved LV diastolic function compared to the MCT group (E/e': 3.4 ± 3.1 vs. 6.4 ± 2.8, respectively, p < 0.01). Similarly, LV systolic function showed significant improvement in the group of patients performing HIIT (ejection fraction: 53.1 ± 6.4 vs. 52.3 ± 5.4%, p < 0.01; GLS: −17.8 ± 3.8 vs. −15.4 ± 4.3, p < 0.01). In addition, LA strain was improved. MW efficiency was also increased in the HIIT group (91.1 ± 3.3 vs. 87.4 ± 4.1%, p < 0.01), and was closely related to peak effort measurements expressed in peak VO2 by CPET. Conclusions: In patients with recent ACS, the HIIT rehabilitation program determined reverse cardiac remodeling, with the improvement of diastolic and systolic function, assessed by standard echocardiography. In addition, cardiac deformation index as GLS, LA strain and MW efficiency improved significantly after HIIT, and were associated with functional capacity during effort.

Anabolic hormones and heart failure with preserved ejection fraction: looking for Ariadne's thread.

Heart failure with preserved ejection fraction (HFpEF) is a complex clinical syndrome that accounts for more than half of all heart failure patients. Identification, early diagnosis and management of patients are still complex, and no targeted treatment is available, since all tested drugs were not able to lower hard clinical outcomes. A multi-hormonal deficiency syndrome has been described in HFpEF patients suggesting that different hormones may represent new biomarkers of the disease, but their clinical utility is still debated. The natriuretic peptides are the cornerstone biomarker in heart failure, predicting cardiovascular death and heart failure hospitalization. Testosterone and DHEA-S deficiencies have been reported in HFpEF and associated with right ventricular impairment and diastolic dysfunction. IGFBP-1/IGF-1 axis correlates with echocardiographic parameters of HFpEF patients and with several prognostic biomarkers including NT-proBNP and C reactive protein. Low triiodothyronine syndrome is frequently found in HFpEF and thyroid hormones should represent a potential biomarker of risk stratification and prognosis.

Stress Echocardiography and Strain in Aortic Regurgitation (SESAR protocol): Left ventricular contractile reserve and myocardial work in asymptomatic patients with severe aortic regurgitation.

OBJECTIVES: To analyze left ventricular (LV) myocardial deformation and contractile reserve (CR) in asymptomatic patients with severe aortic regurgitation (AR) at rest and during exercise, and their correlation with functional capacity. BACKGROUND: The natural history of chronic AR is characterized by a prolonged silent phase before onset of symptoms and overt LV dysfunction. Assessment of LV systolic function and contractile reserve has an important role in the decision-making of AR asymptomatic patients. METHODS: Standard echo, lung ultrasound, and LV 2D speckle tracking strain were performed at rest and during exercise in asymptomatic patients with severe AR and in age- and sex-comparable healthy controls. RESULTS: 115 AR patients (male sex 58.2%; 52.3 ± 18.3 years) and 55 controls were enrolled. Baseline LV ejection fraction was comparable between the groups. Resting LV global longitudinal strain (GLS) and myocardial work efficiency (MWE) were significantly reduced in AR (GLS-15.8 ± 2.8 vs -21.4 ± 4.4; P < .001). Patients with AR and CR- showed reduced resting LV GLS and MWE and increased B-lines. MWE was closely related to peak effort watts, VO2 , LV E/e', and B-lines, at a multivariable analysis. Both GLS and MWE were strong independent predictors of CR. A resting LV GLS cutoff of -12% differentiated CR+ and CR- (78% sensitivity and 84% specificity). CONCLUSIONS: The lower resting values of LV GLS and MWE in severe AR asymptomatic patients suggest an early subclinical myocardial damage that seems to be closely associated with lower exercise capacity, greater pulmonary congestion, and blunted LV contractile reserve during stress.

Effect of intravenous iron replacement therapy on exercise capacity in iron deficient anemic patients after cardiac surgery.

Iron deficiency (ID) is recognized as an important comorbidity in patients undergoing cardiac surgery; however, it still remains under-diagnosed and under-treated in clinical practice. This study aims at comparing efficacy and the effects on exercise capacity of intravenous ferric carboxymaltose (FCM) versus ferric gluconate (FG) in patients with ID anemia (IDA) resulting from cardiac surgery. We retrospectively analyzed data from our records of in-hospital patients with IDA after cardiac surgery undergoing cardiac rehabilitation. Group I was treated with FG, group II with FCM. Efficacy measures included changes (baseline vs discharge) in hemoglobin (Hb) and in distance traveled at six-minutes walking test (6MWT). Data from 74 in-patients (mean age 67.5±10.4 years, 43% women) were analyzed. At discharge, patients treated with FCM showed higher levels of Hb (11.1±1.2g/dl vs 10.2±1.1 g/dl; p=0.001), greater distance traveled at 6MWT (279.2±108.8 meters vs 236.3±72.7 meters; p=0.048), and lower in-hospital rehabilitation length of stay (20.3±7 vs 25.3±11.7 days; p=0.043) as compared to FG group. At multivariate analysis, the most powerful predictors of Hb increase >1 g/dl at discharge were transferrin levels (p=0.019) and treatment with FCM (p<0.001). FCM replacement therapy and iron serum levels were the most powerful predictors of 6MWT distance improvement (>100 meters) at discharge (p=0.13 and p=0.003, respectively). In patients with IDA following cardiac surgery, intravenous FCM is effective in restoring Hb levels and in improving exercise capacity after cardiac surgery.

The role of echocardiography in SARS-CoV-2 pandemic: a compromise among appropriateness, safety and clinical impact.

SARS-CoV-2 infection, responsible for COVID-19, can determine cardiac events, which require a quick diagnosis and management, and should not be overlooked due to the presence of COVID-19 infection. In some cases, cardiovascular symptoms can also be the first and only manifestation of SARS-CoV-2 infection. In patients with COVID-19, the full cardiovascular disease diagnostic algorithm can be hindered by logistic restrain mainly derived from the difficulty of transporting patients in critical conditions to Radiology or Hemodynamics wards. The echocardiography in SARS-CoV-2 pandemic can help for differential diagnosis of cardiac events, which can be related or unrelated by the infection and can likely impact on short-term prognosis. Indeed, transthoracic echocardiography plays a key role in the screen for CV complications of COVID-19 infection: it must be focused cardiac ultrasound study (FoCUS) performed at bedside. All transthoracic, transesophageal and stress echocardiograms in patients in which test results are unlikely to change the management strategy should be postponed.

Cardiac rehabilitation activities during the COVID-19 pandemic in Italy. Position Paper of the AICPR (Italian Association of Clinical Cardiology, Prevention and Rehabilitation).

The COVID-19 outbreak is having a significant impact on both cardiac rehabilitation (CR) inpatient and outpatient healthcare organization. The variety of clinical and care scenarios we are observing in Italy depends on the region, the organization of local services and the hospital involved. Some hospital wards have been closed to make room to dedicated beds or to quarantine the exposed health personnel. In other cases, CR units have been converted or transformed into COVID-19 units.  The present document aims at defining the state of the art of CR during COVID-19 pandemic, through the description of the clinical and management scenarios frequently observed during this period and the exploration of the future frontiers in the management of cardiac rehabilitation programs after the COVID-19 outbreak.

Use of the North American Nursing Diagnosis Association taxonomies, Nursing Intervention Classification, Nursing Outcomes Classification and NANDA-NIC-NOC linkage in cardiac rehabilitation.

This study aims at creating a standardized language for each patient admitted to Cardiac Rehabilitation Unit (CR) by identifying nursing diagnosis, interventions, results/objectives expected and related correlations. The primary outcome was identifying health needs of all patients admitted to CR. The secondary outcomes were the identification of North American Nursing Diagnosis Association -International diagnoses (NANDA-I), of nursing intervention classification (NIC), of nursing outcomes classification (NOC) and their correlation NANDA-NIC-NOC linkage (NNN linkage) in order to define a standardized language for all nursing staff. This is a retrospective study involving a sample of 168 patients discharged from CR. The NANDA-I, the NIC, the NOC and the most frequently used NNN connections were identified and collected by using structured form including the 11 functional models of Marjory Gordon. Data from 76 patients were analyzed (92.1% male; mean age (± SD) 62.7±9 yrs; IQ range: 42-82). The main NANDA-I nursing diagnosis belongs to psychological sphere, but not to physiological domains. The statement NIC has allowed to put into practice actions of health prevention and education. Nursing care documentation and NNN taxonomic language promotes a wide diffusion of nursing discipline culture and significant qualitative improvement of patient's care, further improving the communication between nurses and other health professionals.

Secondary prevention advices after cardiovascular index event: From drug prescription to risk factors control in real world practice.

The present study aims at evaluating the achievement of blood pressure, lipid and blood glucose targets, healthy lifestyle changes and appropriate drug prescription/adherence in patients attending secondary prevention/CR ambulatory visit after index cardiovascular event in a time period ranging 1 to 5 year. At ambulatory visit, a predetermined set of data collection was used, including demographic data, cardiovascular risk factors and lifestyle habits, type and time of index event, current symptoms, physical sign, biochemistry and current medical treatment (including type and dosage). Cardiovascular risk profile (smoking habits, physical activity and body weight), secondary prevention goals (LDL-cholesterol, blood pressure, resting heart rate, glycated haemoglobin level) and the use of recommended drugs were also evaluated and categorized. Study population consisted of 800 patients [644 men (84.5%), aged 69±10.9 years)]. Cardiovascular index events were coronary artery bypass graft (CABG) (20%) ST segment elevation myocardial infarction (STEMI) (28%), non-ST segment elevation myocardial infarction (NSTEMI) (21%) and stable angina (13%) by unstable angina (13%) and stroke (5%). About 30% of patients was symptomatic (angina or dyspnoea) at the time of ambulatory visit. Major comorbidities were hypertension (73%), dyslipidaemia (64%) and diabetes (40%). More than 80% of patients achieved target levels for blood pressure. Patients that have participated to cardiac rehabilitation programmes after cardiovascular index event showed best achievement in blood pressure target (83.8% vs 76.8%, p=0.02). LDL-cholesterol target (<70 mg/dl) was achieved in about 2/3 of patients; HbA1c target (<7%) was achieved in 56.4% of diabetic population. About 75% of study cohort was treated with RAAS inhibitors, 85% with beta-blockers, 92% with statins and 87% with acetylsalicylic acid. All drugs were increasingly adopted from index event. Implementing secondary prevention guidelines into the 'real world' clinical practice in "late" interval from 1 to 5 years after a cardiovascular event improved risk factors control and appropriate drug prescription. Whether these improvements translated into prognostic advantages remains to be elucidated.

Exercise training in patients with chronic heart failure: A new challenge for Cardiac Rehabilitation Community.

Exercise training (ET) is strongly recommended in patients with chronic stable heart failure (HF). Moderate-intensity aerobic continuous ET is the best established training modality in HF patients. In the last decade, however, high-intensity interval exercise training (HIIT) has aroused considerable interest in cardiac rehabilitation community. In HF patients, HIIT exerts larger improvements in exercise  capacity compared to moderate-continuous ET. Since better functional capacity translates into symptoms relief and improvement in quality of life in patients with HF, this training modality is collecting growing interest and consensus, not revealing major safety issues. HIIT should not replace other training modalities in HF but should rather complement them. Inspiratory muscle training, another promising training modality in patients with HF, exerts beneficial effect on inspiratory muscle strength and inspiratory endurance, on exercise capacity and quality of life. In conclusion, taking into consideration the complecity of HF syndrome, combining and tailoring different ET modalities according to each patient's baseline clinical characteristics (i.e. exercise capacity, comorbidity, frailty status, personal needs, preferences and goals) seem the most wily approach for exercise prescription.

Testosterone treatment in chronic heart failure. Review of literature and future perspectives.

Mounting evidence suggests that hormonal deficiencies (HD) have an important role in chronic heart failure (CHF). In particular, androgen depletion is common in men with CHF and is associated with increased morbidity and mortality. This review summarizes the current understanding of the complex relationship between CHF and testosterone, focusing on evidence derived from clinical trials that have investigated the role of testosterone in the treatment of CHF. A greater comprehension of this area will allow researchers and clinicians to plan future studies that improve current strategies to reduce mortality in this high-risk population. Online databases PubMed (Medline), Web of Science, and Scopus were searched for manuscripts published prior to June 2018 using key words "heart failure" AND "testosterone" OR "anabolism" OR "hormone" OR "replacement treatment". Manuscripts were collated, studied and carried forward for discussion where appropriate. In summary, findings from the literature demonstrate that testosterone treatment in CHF is a promising topic that requires further investigation.

The impairment of the Growth Hormone/Insulin-like growth factor 1 (IGF-1) axis in heart failure: A possible target for future therapy.

Hormonal abnormalities are quite common in chronic heart failure (CHF). The most studied hormonal axis in CHF is the impairment of Growth Hormone (GH)/Insulin Growth Factor-1(IGF-1), which in turn is defined either by a blunted response to GH stimulation test or low serum IGF-1 values.  Several independent groups reported that the presence of an abnormal GH/IGF-1 status in CHF is associated with a more severe disease, impaired functional capacity and reduced Survival rates. After the first encouraging results, double -blind controlled trials showed a neutral effect of the GH administration in patients. However, further studies reported positive results, when a GH-therapy is implemented only in those patients presenting a GH deficiency (replacement therapy).

Cardiac Prevention and Rehabilitation "3.0": From acute to chronic phase. Position Paper of the ltalian Association for Cardiovascular Prevention and Rehabilitation (GICR-IACPR).

Cardiac rehabilitation (CR) is the subspecialty of clinical cardiology dedicated to the treatment of cardiac patients, early and in the long term after an acute event. The aim of CR is to improve both quality of life and prognosis through prognostic stratification, clinical stabilization and optimization of therapy (pharmacological and non), management of comorbidities, treatment of disability, as well as through the provision and reinforcement of secondary prevention interventions and maintenaince of adherence to treatment. The mission of CR has changed over time. Once centered on the acute phase, aimed primarily at short-term survival, the healthcare of cardiac patients now increasingly involves the chronic phase where the challenge is to guarantee continuity and quality of care in the medium and long-term. The aim of the present position paper is to provide the state-of-the-art of CR in Italy, discussing its trengths and weaknesses as well as future perspectives.

Clinical outcomes and glycaemic responses to different aerobic exercise training intensities in type II diabetes: a systematic review and meta-analysis.

AIMS: To establish if aerobic exercise training is associated with beneficial effects on clinical outcomes and glycaemic profile in people with type II diabetes. METHODS: A systematic search was conducted to identify studies through a search of MEDLINE (1985 to Sept 1, 2016, Cochrane Controlled Trials Registry (1966 to Sept 1, 2016), CINAHL, SPORTDiscus and Science Citation Index. The search strategy included a mix of MeSH and free text terms for related key concepts. Searches were limited to prospective randomized or controlled trials of aerobic exercise training in humans with type II diabetes, aged >18 years, lasting >2 weeks. RESULTS: Our analysis included 27 studies (38 intervention groups) totalling 1372 participants, 737 exercise and 635 from control groups. The studies contain data from 39,435 patient-hours of exercise training. Our analyses showed improvements with exercise in glycosylated haemoglobin (HbA1C%) MD: -0.71%, 95% CI -1.11, -0.31; p value = 0.0005. There were significant moderator effects; for every additional week of exercise HbA1C% reduces between 0.009 and 0.04%, p = 0.002. For those exercising at vigorous intensity peak oxygen consumption (peak VO2) increased a further 0.64 and 5.98 ml/kg/min compared to those doing low or moderate intensity activity. Homeostatic model assessment of insulin resistance (HOMA-IR) was also improved with exercise MD: -1.02, 95% CI -1.77, -0.28; p value = 0.007; as was fasting serum glucose MD: -12.53 mmol/l, 95% CI -18.94, -6.23; p value <0.0001; and serum MD: -10.39 IU, 95% CI -17.25, -3.53; p value = 0.003. CONCLUSIONS: Our analysis support existing guidelines that for those who can tolerate it, exercise at higher intensity may offer superior fitness benefits and longer program duration will optimize reductions in HbA1C%.

Serum uric acid is associated with non-dipping circadian pattern in young patients (30-40 years old) with newly diagnosed essential hypertension.

BACKGROUND: We aimed at evaluating the relationship between the circadian blood pressure rhythm and UA level in young patients (30-40 years old) with newly diagnosed essential hypertension. METHODS: The study included 62 essential hypertensive patients and 29 healthy controls (20 men, 35 ± 3 years) divided into two groups according to 24-hour ABPM results: 30 dippers and 32 nondippers. RESULTS: Nondippers showed significantly higher both serum UA levels compared to dippers and controls (6.1 ± 0.7, 5.2 ± 0.9 and 4.1 ± 0.9 mg/dL, p < 0.001, respectively); and high sensitivity C-reactive protein (hsCRP) (4.1 ± 2.2 mg/L, 3.3 ± 1.9 mg/L, and 1.4 ± 0.9 mg/L, p < 0.001, respectively). After adjusting for age, sex, body mass index, smoking, creatinine levels, hsCRP and comorbidity, multivariate logistic regression analysis revealed an independent association between serum UA levels and nondipper pattern (OR 2.44, 95%CIs 1.4-4.1, p = 0.002). CONCLUSION: Serum UA is independently associated with nondipper circadian pattern in young patients with newly diagnosed essential hypertension.

Resistance training and sarcopenia.

Aging is inexorably accompanied by a progressive decline of muscle mass, quality and strength. The resulting condition has been termed sarcopenia. Age-related sarcopenia can be accelerated by a variety of factors including changes in the hormonal milieu, inactivity, poor nutrition, chronic illness, and loss of integrity and function in the peripheral and central nervous systems. The downstream mechanisms by which these risk factors cause sarcopenia are not completely understood. Exercise training (particularly resistance training) has long been identified as the most promising method for increasing muscle mass and strength among older people. New interventions aimed at preventing muscle atrophy, promoting muscle growth and ultimately, maintaining muscle functions during aging are discussed. Understanding how age affects muscle-related gene expression, protein recycling and resynthesis, post-translational modification and turnover will be crucial to identify new treatment options.

Exercise training modalities in chronic heart failure: does high intensity aerobic interval training make the difference?

Exercise training (ET) is strongly recommended in patients with chronic heart failure (CHF). Moderate-intensity aerobic continuous ET is the best established training modality in CHF patients. In the last decade, however, high-intensity interval exercise training (HIIT) has aroused considerable interest in cardiac rehabilitation community. Basically, HIIT consists of repeated bouts of high-intensity exercise alternated with recovery periods. In CHF patients, HIIT exerts larger improvements in exercise capacity compared to moderate-continuous ET. These results are intriguing, mostly considering that better functional capacity translates into an improvement of symptoms and quality of life. Notably, HIIT did not reveal major safety issues; although CHF patients should be clinically stable, have had recent exposure to at least regular moderate-intensity exercise, and appropriate supervision and monitoring during and after the exercise session are mandatory. The impact of HIIT on cardiac dimensions and function and on endothelial function remains uncertain. HIIT should not replace other training modalities in heart failure but should rather complement them. Combining and tailoring different ET modalities according to each patient's baseline clinical characteristics (i.e. exercise capacity, personal needs, preferences and goals) seem the most astute approach to exercise prescription.