A case of extensive biatrial clot straddling the patent foramen ovale.

Patent foramen ovale (PFO) is a common abnormality that occurs in about 25% of the adult population. In most cases is a benign finding, but sometimes the communication between the right and the left atria can be a conduit for thrombi.

Mutual relationship between heart failure and atrial fibrillation.

Atrial fibrillation (AF) and heart failure (HF) are evolving epidemies, together responsible for substantial human suffering and health-care expenditure. The simultaneous co-hexistence of the two conditions is associated with mortality rates higher than those observed in individuals with only one or none of them. Patients with concomitant HF and AF suffer from even worse symptoms and poorer prognosis, yet evidence-based evaluation and management of this group of patients is lacking. In this review, we evaluate the common mechanisms for the development of AF in HF patients and vice versa, focusing on the evidence for potential treatment strategies. Recent data have suggested that these patients may respond differently if compared to those with HF or AF alone. These results highlight the clear clinical need to identify and treat these diseases according to best evidence, in order to prevent adverse outcomes and reduce the huge burden that HF and AF are expected to have on global healthcare systems in the future.

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.

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).

Nemaline myopathy and heart failure: role of ivabradine; a case report.

BACKGROUND: Nemaline myopathy (NM) is a rare congenital myopathy characterized by muscle weakness, hypotonia and the presence in muscle fibers of inclusions known as nemaline bodies and a wide spectrum of clinical phenotypes, ranging from severe forms with neonatal onset to asymptomatic forms. The adult-onset form is heterogeneous in terms of clinical presentation and disease progression. Cardiac involvement occurs in the minority of cases and little is known about medical management in this subgroup of NM patients. We report a rare case of heart failure (HF) in a patient with adult-onset NM in whom ivabradine proved to be able to dramatically improve the clinical picture. CASE PRESENTATION: We report a case of a 37-year-old man with adult-onset NM, presenting with weakness and hypotonia of the proximal limb muscles and shoulder girdle, severely limiting daily activities. He developed progressive HF over a period of 6 months while attending a rehabilitation program, with reduced left ventricular ejection fraction (LVEF = 20%), manifested by dyspnea and signs of systemic congestion. The patient was started HF therapy with enalapril, carvedilol, spironolactone and loop diuretics. Target HF doses of these drugs (including carvedilol) were not reached because of symptomatic hypotension causing a high resting heart rate (HR) ≥70 beats per minute (bpm). Further deterioration of the clinical picture occurred with several life-threatening arrhythmic episodes requiring external defibrillation. An implantable cardioverter defibrillator (ICD) was then implanted. Persistent high resting HR was successfully treated with ivabradine with HR lowering from 90 bpm to 55 bpm at 1 month follow up, LVEF rising to 50% at 3 month follow up and to 54% at 2,5 year follow up. To date no more hospitalizations for heart failure occurred. A single hospitalization due to aspiration pneumonia required insertion of a tracheostomy tube to protect airways from further aspiration. At present, the patient is attending a regular rehabilitation program with net improvement in neuromotor control and less limitations in daily activities. CONCLUSIONS: HF is a rare feature of NM, but it can negatively influence prognosis. Conventional HF therapy and/or heart transplant are the only reasonable strategy in these patients. Ivabradine is a useful, effective and safe drug for therapy in NM patients with HF and should be considered when resting HR remains high despite beta-blockers' full titration or beta-blockers' underdosing due to intolerance or side effects.

Effects of Sacubitril/Valsartan on Exercise Capacity in Patients with Heart Failure with Reduced Ejection Fraction and the Role of Percentage of Delayed Enhancement Measured by Cardiac Magnetic Resonance in Predicting Therapeutic Response: A Multicentre Study.

Background: This study aims to evaluate the cardiopulmonary effects of sacubitril/valsartan therapy in patients with heart failure with reduced ejection fraction (HFrEF), investigating a possible correlation with the degree of myocardial fibrosis, as assessed by cardiac magnetic resonance. Methods: A total of 134 outpatients with HFrEF were enrolled. Results: After a mean follow-up of 13.3 ± 6.6 months, an improvement in ejection fraction and a reduction in E/A ratio, inferior vena cava size and N-terminal pro-B-type natriuretic peptide levels were observed. At follow-up, we observed an increase in VO2 peak of 16% (p<0.0001) and in O2 pulse of 13% (p=0.0002) as well as an improvement in ventilatory response associated with a 7% reduction in the VE/VCO2 slope (p=0.0001). An 8% increase in the ΔVO2/Δ work ratio and an 18% increase in exercise tolerance were also observed. Multivariate logistic regression analysis showed that the main predictors of events during follow-up were VE/VCO2 slope >34 (OR 3.98; 95% CI [1.59-10.54]; p=0.0028); ventilatory oscillatory pattern (OR 4.65; 95% CI [1.55-16.13]; p=0.0052); and haemoglobin level (OR 0.35; 95% CI [0.21-0.55]; p<0.0001). In patients who had cardiac magnetic resonance, when delayed enhancement >4.6% was detected, a lower response after sacubitril/valsartan therapy was observed as expressed by improvement in ΔVO2 peak, O2 pulse, LVEF and N-terminal pro-B-type natriuretic peptide. No significant differences were observed in ΔVO2/Δ work and VE/VCO2 slope. Conclusion:Sacubitril/valsartan improves cardiopulmonary functional capacity in HFrEF patients. The presence of myocardial fibrosis on cardiac magnetic resonance is a predictor of response to therapy.

The old and new tests for celiac disease: which is the best test combination to diagnose celiac disease in pediatric patients?

BACKGROUND: In the diagnosis of celiac disease (CD), serum assays for anti-endomysium (EMA) and anti-transglutaminase (anti-tTG) antibodies have excellent diagnostic accuracy. However, these assays are less sensitive in young pediatric patients. Recently, a new ELISA test using deamidated gliadin peptides (DGP) as antigen has proved to be very sensitive and specific even in pediatric patients. In addition, anti-actin IgA antibodies (AAA) is another test that can be used in CD patients because antibody concentrations correlate with the degree of villous atrophy. This study evaluated the clinical accuracy of anti-tTG, EMA, AGA, anti-DGP and AAA and the effectiveness of these in different combinations for diagnosing CD in a large cohort of pediatric patients. METHODS: Sera of 150 children under 6 years of age were tested: 95 patients had a diagnosis of CD, while 55 patients who did not suffer from CD were used as controls. Anti-DGP IgA/IgG and AAA were assayed with ELISA kits, while anti-tTG IgA/IgG and AGA IgG/IgA were assayed using a quantitative fluoroimmunoassay. The EMA test was conducted by indirect immunofluorescence. RESULTS: Seventy-six of 95 (80%) CD patients were positive for DGP IgA and/or tTG IgA. Eighty of 95 (84.2%) patients were positive for DGP IgG and/or tTG IgA. None of the controls were positive for these antibodies. Eighty-four of 95 (88.4%) patients and 8/55 (14.5%) controls were positive for AAA and/or anti-tTG IgA. CONCLUSIONS: In very young children, association of anti-tTG IgA with anti-DGP IgG is the best test combination for diagnosing CD, yielding a cumulative sensitivity of 84.2% and a specificity of 100%.

Inhibitors of Protein Convertase Subtilisin/Kexin 9 (PCSK9) and Acute Coronary Syndrome (ACS): The State-of-the-Art.

Acute Coronary Syndrome (ACS) remains one of the most frequent causes of morbidity and mortality in the world. Although the age- and gender-adjusted incidence of ACS is decreasing, the mortality associated with this condition remains high, especially 1-year after the acute event. Several studies demonstrated that PCSK9 inhibitors therapy determine a significant reduction of major adverse cardiovascular events (MACE) in post-ACS patients, through a process of plaque modification, by intervening in lipid metabolism and platelet aggregation and finally determining an improvement in endothelial function. In the EVACS (Evolocumab in Acute Coronary Syndrome) study, evolocumab allows >90% of patients to achieve LDL-C < 55 mg/dL according to ESC/EAS guidelines compared to 11% of patients who only receive statins. In the EVOPACS (EVOlocumab for Early Reduction of low-density lipoprotein (LDL)-cholesterol Levels in Patients With Acute Coronary Syndromes) study, evolocumab determined LDL levels reduction of 40.7% (95% CI: 45.2 to 36.2; p < 0.001) and allowed 95.7% of patients to achieve LDL levels <55 mg/dL. In ODYSSEY Outcome trial, alirocumab reduced the overall risk of MACE by 15% (HR = 0.85; CI: 0.78-0.93; p = 0.0003), with a reduced risk of all-cause mortality (HR = 0.85; CI: 0.73-0.98: nominal p = 0026), and fewer deaths for coronary heart disease (CHD) compared to the control group (HR = 0.92; CI: 0.76-1.11; p = 0.38). The present review aimed at describing the beneficial effect of PCSK9 inhibitors therapy early after ACS in reducing LDL circulating levels (LDL-C) and the risk of major adverse cardiovascular events, which was very high in the first year and persists higher later after the acute event.

The core components of cardio-oncology rehabilitation.

The increased efficacy of cancer therapy has resulted in greater cancer survival and increasing number of people with cancer and cardiovascular diseases. The sharing of risk factors, the bidirectional relationship between cancer and cardiovascular diseases and the cardiotoxic effect of chemotherapy and radiotherapy, are the cause of the rapid expansion of cardio-oncology. All strategies to preserve cardiovascular health and mitigate the negative effect of cancer therapy, by reducing the cardiovascular risk, must be pursued to enable the timely and complete delivery of anticancer therapy and to achieve the longest remission of the disease. Comprehensive cardiac rehabilitation is an easy-to-use model, even in cancer care, and is the basis of Cardio-Oncology REhabilitation (CORE), an exercise-based multi-component intervention. In addition, CORE, besides using the rationale and knowledge of cardiac rehabilitation, can leverage the network of cardiac rehabilitation services to offer to cancer patients exercise programs, control of risk factors, psychological support, and nutrition counseling. The core components of CORE will be discussed, describing the beneficial effect on cardiorespiratory fitness, quality of life, psychological and physical well-being, and weight management. Furthermore, particular attention will be paid to how CORE can counterbalance the negative effect of therapies in those at heightened cardiovascular risk after a cancer diagnosis. Barriers for implementation, including personal, family, social and of the health care system barriers for a widespread diffusion of the CORE will also be discussed. Finally, there will be a call-to-action, for randomized clinical trials that can test the impact of CORE, on morbidity and mortality.

Frailty in Acute and Chronic Coronary Syndrome Patients Entering Cardiac Rehabilitation.

Worldwide population ageing is partly due to advanced standard of care, leading to increased incidence and prevalence of geriatric syndromes such as frailty and disability. Hence, the age at the onset of acute coronary syndromes (ACS) keeps growing as well. Moreover, ageing is a risk factor for both frailty and cardiovascular disease (CVD). Frailty and CVD in the elderly share pathophysiological mechanisms and associated conditions, such as malnutrition, sarcopenia, anemia, polypharmacy and both increased bleeding/thrombotic risk, leading to a negative impact on outcomes. In geriatric populations ACS is associated with an increased frailty degree that has a negative effect on re-hospitalization and mortality outcomes. Frail elderly patients are increasingly referred to cardiac rehabilitation (CR) programs after ACS; however, plans of care must be tailored on individual's clinical complexity in terms of functional capacity, nutritional status and comorbidities, cognitive status, socio-economic support. Completing rehabilitative intervention with a reduced frailty degree, disability prevention, improvement in functional state and quality of life and reduction of re-hospitalization are the goals of CR program. Tools for detecting frailty and guidelines for management of frail elderly patients post-ACS are still debated. This review focused on the need of an early identification of frail patients in elderly with ACS and at elaborating personalized plans of care and secondary prevention in CR setting.

Exercise for slowing the progression of atherosclerotic process: effects on inflammatory markers.

Atherosclerosis is a dynamic process driven by all cardiovascular risk factors that can be briefly divided into an early and a late phase. Inflammation is one of the fundamental substrates that initiates the atherosclerotic process in the early stages and promotes and maintains it in the final stages. In the last decades, clinical and experimental data have shown that inflammation is supported by mediators that respond to physical activity. The present review aimed at investigating the effect of physical exercise on inflammatory mediators, both the positive ones that have a proinflammatory effect (interleukin 6, c-reactive protein and tumor necrosis factor α, interferon γ, high-mobility group box-1), and the negative ones which have an anti-inflammatory effect (interleukin 10). Pooled data support the evidence that physical exercise can directly modulate the activity of inflammatory cytokines slowing down or preventing the formation of the atherosclerotic stage.

Heart rate turbulence for guiding electric therapy in patients with cardiac failure.

BACKGROUND: It is well-known that a reduction of the cardiac frequency variability, measurable with the Heart Rate Variability (HRV) system, is an indirect expression of the sympathetic-autonomic tone. Another index, Heart Rate Turbulence (HRT), has been recently suggested as a possible unit of measurement for the sympathetic-autonomic tone: this system allows to estimate the baro-reflex response of the carotid arteries to an early ventricular extra-systole by analysing heart rate variations induced by a premature beat. METHODS AND RESULTS: In our research we have analyzed this phenomenon in patients affected by moderate or severe cardiac failure. In particular, we divided 110 patients into two arms: subjects with or without a history of resuscitated arrhythmic death, that is, patients with high or low arrhythmic potential. In a detailed analysis of the sympathetic-autonomic tone, using both the above-mentioned parameters, HRV showed an irrelevant statistical difference between the two arms; on the contrary, HRT showed a significant statistical difference. CONCLUSIONS: If our conclusions will be confirmed by next larger reports, HRT could become a reliable index for screening the arrhythmic potential of patients affected by cardiac failure, to select the ones who need a defibrillator implantation.

Tako-tsubo cardiomyopathy and microcirculation.

BACKGROUND: Takotsubo cardiomyopathy was described for the first time in Japan in the 1990s. It is very similar to the ischemic cardiopathy both for clinical and instrumental characteristics. His peculiarity is an alteration of the ventricular contraction mechanism with hypo-akinesis of the apex and lateral segments of the left ventricle, associated with hyper-kinesis of the heart base which is responsible for the typical echocardiographic aspect of a cruet during the systole. However, the etiology of this cardiomyopathy is still unknown despite the fact that numerous hypothesis have been made. A single study of 16 patients proved multivasal damage by a BLASH SCORE analysis of the coronary radiography. In our study, performed on 24 patients, we intended to assess the actual implication of the microcirculation by analyzing the TIMI frame count (TFC), so as reporting correlations between alterations of each single artery and its respective myocardial area. METHODS AND RESULTS: Six Cardiology Centres performed an International multi-centre collection of a consecutive series of 24 patients, of which 20 were women and four men. The average age was 67.4 years. All patients admitted to one of the Cardiology divisions were previously listed for symptoms and signs of Takotsubo cardiomyopathy. An electrocardiographic (ECG), echocardio-gram and a hemodynamic study were carried out on each patient. The patients were evaluated with a follow up lasting 7 weeks. On the coronary radiography film, the microcirculation was examined by an analysis of the TFC according to the Gibson technique. The value obtained was considered pathological if it was >30 frames. The evaluation of the microcirculation by the TFC analysis showed that in 23 of the 24 patients there was a pathological slow down of the flow in the coronary micro- circulation. By analysing the number of involved vessels it was noted that nine patients had a slowdown of the general flow in all three vessels, six patients in only two vessels and the remaining nine in one vessel. In particular: in 14 patients there was an abnormal TFC in left anterior descending coronary artery (LAD), 16 in the right coronary artery (RCA) and 18 in the left circumflex coronary artery (LCX), while in one patient the picture quality in the acute phase did not allow an evaluation of the score in the RCA and in another patient in the LDA. None of the explored vessels that was responsible for the disorder of the microcirculation showed any stenosis. CONCLUSION: From the data evaluated by us, microcirculatory dysfunction seems to be present very often during acute phases of Takotsubo illness, but it is not the only determining factor of the illness.

Rhabdomyolysis induced by co-administration of fluvastatin and colchicine.

A case of fluvastatin-induced rhabdomyolysis after coadministration of colchicine is reported. A 77 year old man with ischemic heart disease, chronic pericardial effusion, diabetes mellitus, dyslipidemia, arterial hypertension, chronic renal failure (stage 2 of classification of chronic kidney disease of National Kidney Foundation) and chronic gout presented with a generalized muscle pain. The patient had been taking 80 mg/day of fluvastatin for 4 years, and, for four weeks before presentation, he had also been taking a dose of colchicine (1.0 mg daily) for an exacerbation of gout. Investigations confirmed the diagnosis of rhabdomyolysis. Discontinuation of fluvastatin and colchicine therapy and adequate fluid administration resulted in the resolution of clinical and biochemical features of rhabdomyolysis. Although neuromuscular adverse effects of fluvastatin and colchicine are well recognized, rhabdomyolysis is rare, making this is only the second case reported of fluvastatin and colchicine co-administration induced rhabdomyolysis in literature.

The MECKI score initiative: Development and state of the art.

The high morbidity and poor survival rates associated with chronic heart failure still represent a big challenge, despite improvements in treatments and the development of new therapeutic opportunities. The prediction of outcome in heart failure is gradually moving towards a multiparametric approach in order to obtain more accurate models and to tailor the prognostic evaluation to the individual characteristics of a single subject. The Metabolic Exercise test data combined with Cardiac and Kidney Indexes (MECKI) score was developed 10 years ago from 2715 patients and subsequently validated in a different population. The score allows an accurate evaluation of the risk of heart failure patients using only six variables that include the evaluation of the exercise capacity (peak oxygen uptake and ventilation/CO2 production slope), blood samples (haemoglobin, Na+, Modification of Diet in Renal Disease) and echocardiography (left ventricular ejection fraction). Over the following years, the MECKI score was tested taking into account therapies and specific markers of heart failure, and it proved to be a simple, useful tool for risk stratification and for therapeutic strategies in heart failure patients. The close connection between the centres involved and the continuous updating of the data allow the participating sites to propose substudies on specific subpopulations based on a common dataset and to put together and develop new ideas and perspectives.

Clinical Evidence for Q10 Coenzyme Supplementation in Heart Failure: From Energetics to Functional Improvement.

Oxidative stress and mitochondrial dysfunction are hallmarks of heart failure (HF). Coenzyme Q10 (CoQ10) is a vitamin-like organic compound widely expressed in humans as ubiquinol (reduced form) and ubiquinone (oxidized form). CoQ10 plays a key role in electron transport in oxidative phosphorylation of mitochondria. CoQ10 acts as a potent antioxidant, membrane stabilizer and cofactor in the production of adenosine triphosphate by oxidative phosphorylation, inhibiting the oxidation of proteins and DNA. Patients with HF showed CoQ10 deficiency; therefore, a number of clinical trials investigating the effects of CoQ10 supplementation in HF have been conducted. CoQ10 supplementation may confer potential prognostic advantages in HF patients with no adverse hemodynamic profile or safety issues. The latest evidence on the clinical effects of CoQ10 supplementation in HF was reviewed.

Sacubitril/Valsartan Improves Autonomic Function and Cardiopulmonary Parameters in Patients with Heart Failure with Reduced Ejection Fraction.

BACKGROUND: Heart rate recovery (HRR) is a marker of vagal tone, which is a powerful predictor of mortality in patients with cardiovascular disease. Sacubitril/valsartan (S/V) is a treatment for heart failure with reduced ejection fraction (HFrEF), which impressively impacts cardiovascular outcome. This study aims at evaluating the effects of S/V on HRR and its correlation with cardiopulmonary indexes in HFrEF patients. METHODS: Patients with HFrEF admitted to outpatients' services were screened out for study inclusion. S/V was administered according to guidelines. Up-titration was performed every 4 weeks when tolerated. All patients underwent laboratory measurements, Doppler-echocardiography, and cardiopulmonary exercise stress testing (CPET) at baseline and at 12-month follow-up. RESULTS: Study population consisted of 134 HFrEF patients (87% male, mean age 57.9 ± 9.6 years). At 12-month follow-up, significant improvement in left ventricular ejection fraction (from 28% ± 5.8% to 31.8% ± 7.3%, p < 0.0001), peak exercise oxygen consumption (VO2peak) (from 15.3 ± 3.7 to 17.8 ± 4.2 mL/kg/min, p < 0.0001), the slope of increase in ventilation over carbon dioxide output (VE/VCO2 slope )(from 33.4 ± 6.2 to 30.3 ± 6.5, p < 0.0001), and HRR (from 11.4 ± 9.5 to 17.4 ± 15.1 bpm, p = 0.004) was observed. Changes in HRR were significantly correlated to changes in VE/VCO2slope (r = -0.330; p = 0.003). After adjusting for potential confounding factors, multivariate analysis showed that changes in HRR were significantly associated to changes in VE/VCO2slope (Beta (B) = -0.975, standard error (SE) = 0.364, standardized Beta coefficient (Bstd) = -0.304, p = 0.009). S/V showed significant reduction in exercise oscillatory ventilation (EOV) detection at CPET (28 EOV detected at baseline CPET vs. 9 EOV detected at 12-month follow-up, p < 0.001). HRR at baseline CPET was a significant predictor of EOV at 12-month follow-up (B = -2.065, SE = 0.354, p < 0.001). CONCLUSIONS: In HFrEF patients, S/V therapy improves autonomic function, functional capacity, and ventilation. Whether these findings might translate into beneficial effects on prognosis and outcome remains to be elucidated.

Comparison of ivabradine versus metoprolol in early phases of reperfused anterior myocardial infarction with impaired left ventricular function: preliminary findings.

BACKGROUND: beta-blockers in ST-segment elevation myocardial infarction (STEMI) are indicated for patients without a contraindication, particularly in patients with high heart rates (HR) or blood pressures. Epidemiological studies have shown that elevated HR represents a risk factor for cardiovascular morbidity. The study investigates the feasibility, tolerability, and the effects after 30 days of follow-up of ivabradine (IVA) versus metoprolol (METO) in early phases of anterior STEMI reperfused by percutaneous coronary intervention (PCI). METHODS AND RESULTS: Patients with a first anterior STEMI, Killip class I-II, an acceptable echocardiographic window, and admitted within 4hours of the onset of symptoms, with an ejection fraction <50%. METO or IVA, 12hours after PCI (double blind), were administered twice per day. Blood pressure (BP), heart rate (HR), electrocardiogram (ECG), and laboratory parameters were monitored during the study. At entry, day 10, day 30, and day 60, by echocardiography, the ESV, EDV, E/A ratio, E wave deceleration time, isovolumetric relaxation time were measured. A total of 155 (50 females, 105 males) patients were randomized in 2 groups: a group received METO (76 patients) 12hours after PCI and a group received IVA (79 patients) 12hours after PCI. The 2 groups were similar for clinical characteristics. No difference was evidenced in HR, systolic blood pressure, diastolic blood pressure, age (range, 39-73 years), sex, ejection fraction (EF), creatine kinase peak, between the 2 groups at entry. Both groups were similar for time to angiography and interventional procedures and number of vessels diseased. IVA group: the 79 patients showed 2 side effects and 5 readmissions: 4 for ischemic events and 1 for heart failure, and 1 sudden death; METO group: the 76 patients had 4 ischemic events, 2 side effects, and 1 patient died during re-acute MI (intrastent thrombosis) and 8 readmissions for heart failure signs. The systolic blood pressure and diastolic blood pressure showed a significant reduction in both groups, P < .0001, respectively), and significant lower values were observed in METO group, P=.0001). The HR was significantly reduced in both groups, P < .0001). IVA group showed a significant increase in EF, P=.0001, with concomitant reduction in ESV and EDV (P=.0001, and .048, respectively). The diastolic parameters were similar in both groups during study period. CONCLUSIONS: Our results suggest that ivabradine may be administered early (12hours after PCI) to patients with successful PCI for anterior STEMI with an impaired left ventricular function and high HR and sinus rhythm. A larger sample of patients and further studies are required to evaluate the effects of ivabradine on clinical end points.