Iron deficiency from the standpoint of cardiac rehabilitation : Novel therapeutic opportunities

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

Association between loop diuretic dose changes and outcomes in chronic heart failure: observations from the ESC-EORP Heart Failure Long-Term Registry

[Abstract] Aims. Guidelines recommend down-titration of loop diuretics (LD) once euvolaemia is achieved. In outpatients with heart failure (HF), we investigated LD dose changes in daily cardiology practice, agreement with guideline recommendations, predictors of successful LD down-titration and association between dose changes and outcomes. Methods and results. We included 8130 HF patients from the ESC-EORP Heart Failure Long-Term Registry. Among patients who had dose decreased, successful decrease was defined as the decrease not followed by death, HF hospitalization, New York Heart Association class deterioration, or subsequent increase in LD dose. Mean age was 66±13 years, 71% men, 62% HF with reduced ejection fraction, 19% HF with mid-range ejection fraction, 19% HF with preserved ejection fraction. Median [interquartile range (IQR)] LD dose was 40 (25–80) mg. LD dose was increased in 16%, decreased in 8.3% and unchanged in 76%. Median (IQR) follow-up was 372 (363–419) days. Diuretic dose increase (vs. no change) was associated with HF death [hazard ratio (HR) 1.53, 95% confidence interval (CI) 1.12–2.08; P = 0.008] and nominally with cardiovascular death (HR 1.25, 95% CI 0.96–1.63; P = 0.103). Decrease of diuretic dose (vs. no change) was associated with nominally lower HF (HR 0.59, 95% CI 0.33–1.07; P = 0.083) and cardiovascular mortality (HR 0.62 95% CI 0.38–1.00; P = 0.052). Among patients who had LD dose decreased, systolic blood pressure [odds ratio (OR) 1.11 per 10 mmHg increase, 95% CI 1.01–1.22; P = 0.032], and absence of (i) sleep apnoea (OR 0.24, 95% CI 0.09–0.69; P = 0.008), (ii) peripheral congestion (OR 0.48, 95% CI 0.29–0.80; P = 0.005), and (iii) moderate/severe mitral regurgitation (OR 0.57, 95% CI 0.37–0.87; P = 0.008) were independently associated with successful decrease. Conclusion. Diuretic dose was unchanged in 76% and decreased in 8.3% of outpatients with chronic HF. LD dose increase was associated with worse outcomes, while the LD dose decrease group showed a trend for better outcomes compared with the no-change group. Higher systolic blood pressure, and absence of (i) sleep apnoea, (ii) peripheral congestion, and (iii) moderate/severe mitral regurgitation were independently associated with successful dose decrease

Association of kidney disease measures with risk of renal function worsening in patients with type 1 diabetes

Background: Albuminuria has been classically considered a marker of kidney damage progression in diabetic patients and it is routinely assessed to monitor kidney function. However, the role of a mild GFR reduction on the development of stage 653 CKD has been less explored in type 1 diabetes mellitus (T1DM) patients. Aim of the present study was to evaluate the prognostic role of kidney disease measures, namely albuminuria and reduced GFR, on the development of stage 653 CKD in a large cohort of patients affected by T1DM. Methods: A total of 4284 patients affected by T1DM followed-up at 76 diabetes centers participating to the Italian Association of Clinical Diabetologists (Associazione Medici Diabetologi, AMD) initiative constitutes the study population. Urinary albumin excretion (ACR) and estimated GFR (eGFR) were retrieved and analyzed. The incidence of stage 653 CKD (eGFR < 60 mL/min/1.73 m2) or eGFR reduction > 30% from baseline was evaluated. Results: The mean estimated GFR was 98 \ub1 17 mL/min/1.73m2 and the proportion of patients with albuminuria was 15.3% (n = 654) at baseline. About 8% (n = 337) of patients developed one of the two renal endpoints during the 4-year follow-up period. Age, albuminuria (micro or macro) and baseline eGFR < 90 ml/min/m2 were independent risk factors for stage 653 CKD and renal function worsening. When compared to patients with eGFR > 90 ml/min/1.73m2 and normoalbuminuria, those with albuminuria at baseline had a 1.69 greater risk of reaching stage 3 CKD, while patients with mild eGFR reduction (i.e. eGFR between 90 and 60 mL/min/1.73 m2) show a 3.81 greater risk that rose to 8.24 for those patients with albuminuria and mild eGFR reduction at baseline. Conclusions: Albuminuria and eGFR reduction represent independent risk factors for incident stage 653 CKD in T1DM patients. The simultaneous occurrence of reduced eGFR and albuminuria have a synergistic effect on renal function worsening

Sex- and age-related differences in the management and outcomes of chronic heart failure: an analysis of patients from the ESC HFA EORP Heart Failure Long-Term Registry

Aims: This study aimed to assess age- and sex-related differences in management and 1-year risk for all-cause mortality and hospitalization in chronic heart failure (HF) patients. Methods and results: Of 16 354 patients included in the European Society of Cardiology Heart Failure Long-Term Registry, 9428 chronic HF patients were analysed [median age: 66 years; 28.5% women; mean left ventricular ejection fraction (LVEF) 37%]. Rates of use of guideline-directed medical therapy (GDMT) were high (angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, beta-blockers and mineralocorticoid receptor antagonists: 85.7%, 88.7% and 58.8%, respectively). Crude GDMT utilization rates were lower in women than in men (all differences: P\ua0 64 0.001), and GDMT use became lower with ageing in both sexes, at baseline and at 1-year follow-up. Sex was not an independent predictor of GDMT prescription; however, age >75 years was a significant predictor of GDMT underutilization. Rates of all-cause mortality were lower in women than in men (7.1% vs. 8.7%; P\ua0=\ua00.015), as were rates of all-cause hospitalization (21.9% vs. 27.3%; P\ua075 years. Conclusions: There was a decline in GDMT use with advanced age in both sexes. Sex was not an independent predictor of GDMT or adverse outcomes. However, age >75 years independently predicted lower GDMT use and higher all-cause mortality in patients with LVEF 6445%

Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes

BACKGROUND: Data are lacking on the long-term effect on cardiovascular events of adding sitagliptin, a dipeptidyl peptidase 4 inhibitor, to usual care in patients with type 2 diabetes and cardiovascular disease. METHODS: In this randomized, double-blind study, we assigned 14,671 patients to add either sitagliptin or placebo to their existing therapy. Open-label use of antihyperglycemic therapy was encouraged as required, aimed at reaching individually appropriate glycemic targets in all patients. To determine whether sitagliptin was noninferior to placebo, we used a relative risk of 1.3 as the marginal upper boundary. The primary cardiovascular outcome was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina. RESULTS: During a median follow-up of 3.0 years, there was a small difference in glycated hemoglobin levels (least-squares mean difference for sitagliptin vs. placebo, -0.29 percentage points; 95% confidence interval [CI], -0.32 to -0.27). Overall, the primary outcome occurred in 839 patients in the sitagliptin group (11.4%; 4.06 per 100 person-years) and 851 patients in the placebo group (11.6%; 4.17 per 100 person-years). Sitagliptin was noninferior to placebo for the primary composite cardiovascular outcome (hazard ratio, 0.98; 95% CI, 0.88 to 1.09; P<0.001). Rates of hospitalization for heart failure did not differ between the two groups (hazard ratio, 1.00; 95% CI, 0.83 to 1.20; P = 0.98). There were no significant between-group differences in rates of acute pancreatitis (P = 0.07) or pancreatic cancer (P = 0.32). CONCLUSIONS: Among patients with type 2 diabetes and established cardiovascular disease, adding sitagliptin to usual care did not appear to increase the risk of major adverse cardiovascular events, hospitalization for heart failure, or other adverse events

Asymptomatic aortic dissection associated with a mitral prosthetic leak: a clinical case report

A case of aortic dissection ("DeBakey type III") in an asymptomatic 78-year-old woman is described. The patient underwent a mitral valve replacement (bioprosthesis Sorin) in June 1990 for severe mitral stenosis; in October 1990 she was admitted to our hospital for severe dyspnea and cardiac failure with good response to medical treatment. The routine echo color Doppler examination showed only a hint of paraprosthetic leak, which required further investigation by transesophageal echocardiography. This approach revealed the presence of a regurgitant jet extending from the prosthetic mitral valve toward the atrial septum. The examination of the thoracic aorta revealed the presence of a dissection flap; the color Doppler technique showed a bidirectional flow through the site of communication between the two lumina. The extension of the dissection from the aortic arch to the origin of the renal branches was confirmed by computerized axial tomography. We emphasize the importance of the transesophageal approach in elderly patients with aortic dissection, often asymptomati

The role of mitral regurgitation in the neurovegetative regulation of mitral valve prolapse

To define the role of mitral regurgitation (MR) on sympatho-vagal balance in mitral valve prolapse (MVP) patients, we analyzed 41 ambulatory MVP symptomatic patients. Twenty-seven patients (4 males, 23 females, aged 34 +/- 3 years) had significative MR assessed color Doppler, while 14 patients (5 males, 9 females, aged 29 +/- 3 years) had no MR; 36 age- and sex-matched subjects were studied as controls (C). Spectral analysis of heart rate variability (HRV) was performed at rest and during sympathetic activation (tilt). In the whole group of MVP patients spectral components did not differ significantly from C at rest and during tilt. When patients were subdivided in relation to the presence (+) or absence (-) of MR, HRV revealed in MR+ patients at rest an increased high frequency (HF) and a diminished low frequency (LF) component (47 +/- 5 and 41 +/- 5 normalized units, nu) with respect to C (34 +/- 3 and 54 +/- 3 nu, p < 0.05, respectively). Viceversa during tilt, in MR+ patients it was possible to observe a LF increase greater than in C (delta LF: 36 +/- 4 versus 25 +/- 3 nu, p < 0.05). As HF component is currently interpreted as a marker of vagal modulation of HRV, our results suggest an increased vagal tone associated with MR possibly due to stimulation of atrial vagal receptors; moreover, an increased sympathetic responsiveness to tilt seems to characterize MR+ patients

Hemodynamic response to somatostatin at rest and during sympathetic activation in idiopathic orthostatic hypotension

Idiopathic orthostatic hypotension (IOH) represents a degenerative disorder of the peripheral nervous system characterized by low values of arterial blood pressure during orthostatism, with reduction in serum catecholamines. Since treatment of symptomatic IOH has been unsatisfactory till now, we studied the hemodynamic response to somatostatin (S) (Octreotide, 100 micrograms sc) at rest (R) and during sympathetic activation (tilting, T) by means of 2D and/or color Doppler echocardiography, in 5 ambulatory IOH patients (4M, 1F; aged 65 +/- 5 years), with simultaneous recording of blood pressure and heart rate. Post-S, an increased blood pressure was evident during T without heart rate modifications (pre- vs post-S, SAP: 92 +/- 9 vs 148 +/- 12; DAP: 61 +/- 4 vs 90 +/- 9 mmHg; p less than 0.05), while systolic echo parameters did not change significantly. Doppler aortic velocity curve showed during T a reduction of Vmax (pre- vs post-S: 0.98 +/- 0.09 vs 0.73 +/- 0.03 m/s; p less than 0.05) and of cardiac output, due to unchanged preload. Pre-S, at rest, Doppler mitral velocity curve presented a normal E/A ratio as in normal subjects, with a reduced E peak and an increased A peak post-S, indirect signs of increased afterload. Pre-S, E and A peak velocities underwent progressive decrease during T, markedly more evident post-S. Total peripheral resistance, at rest and during T, increased post-S too (pre- vs post-S, rest: 2406 +/- 267 vs 3162 +/- 599; T: 1634 +/- 201 vs 2784 +/- 425 dyne*s/cm-5; p less than 0.05