Association Between Aldosterone and Parathyroid Hormone Levels in Patients With Adrenocortical Tumors.

OBJECTIVE: Patients with primary aldosteronism (PA) can present with high PTH levels and negative calcium balance, with some studies speculating that aldosterone could directly stimulate PTH secretion. Either adrenalectomy or mineralocorticoid receptor blockers could reduce PTH levels in patients with PA. The aim of this study was to assess the relationship between aldosterone levels and parathyroid hormone (PTH)-vitamin D-calcium axis in a cohort of patients with PA, compared with patients with nonsecreting adrenocortical tumors in conditions of vitamin D sufficiency. METHODS: We enrolled a series of 243 patients retrospectively, of whom 66 had PA and 177 had nonsecreting adrenal tumors, and selected those with full mineral metabolism evaluation and 25(OH) vitamin D levels >20 ng/mL at the time of initial endocrine screening. The final cohort was composed of 26 patients with PA and 39 patients, used as controls, with nonsecreting adrenal tumors. The relationships between aldosterone, PTH levels, and biochemistries of mineral metabolism were assessed. RESULTS: Aldosterone was positively associated with PTH levels (r = 0.260, P < .05) in the whole cohort and in the PA cohort alone (r = 0.450; P = .02). In the multivariate analysis, both aldosterone concentrations and urinary calcium excretion were significantly related to PTH levels, with no effect of 25(OH) vitamin D or other parameters of bone metabolism. CONCLUSION: PTH level is associated with aldosterone, probably independent of 25(OH) vitamin D levels and urinary calcium. Whether aldosterone interacts directly with the parathyroid glands remains to be established.

Effects of sacubitril valsartan on clinical and echocardiographic parameters of outpatients with heart failure and reduced ejection fraction.

AIM: Sacubitril valsartan (SV) has revolutionized disease history in patients with heart failure and reduced ejection fraction (HFrEF). Our study assessed SV impact on clinical and echocardiographic parameters in HFrEF outpatients previously treated with optimized therapy. METHODS: Forty-nine HFrEF outpatients were retrospectively included in the study. We collected data from transthoracic echocardiography and clinical assessment at baseline and after 3 ± 1 and 12 ± 1 months of treatment with SV. Results were also stratified by sex to analyse possible sex-based differences in reverse remodelling response to SV. RESULTS: After 3 months of treatment we observed a significative improvement of both systolic and diastolic function with a reduction of left ventricular mass and relative wall thickness (RWT). At 12 months we observed a further improvement of all previous parameters, plus systolic pulmonary artery pressure (PAP) and left atrial (LA) diameter. In women, most of the echocardiographic parameters improved after SV initiation, but did not reach the statistical significance, except for left ventricular ejection fraction (LVEF), PAP and LA diameter. As for clinical parameters, SV improved New York Heart Association (NYHA) Class, systolic blood pressure and loop diuretic dosage with a mild but significative increase in serum creatinine and potassium. CONCLUSION: Our study showed significative reverse remodelling properties of SV with an improvement of LV volumes, mass and systo-diastolic function. NYHA Class, systolic blood pressure and loop diuretic dosage also improved with only mild increase in serum creatinine and potassium. Women showed a lesser extent of reverse remodelling compared with men.

Prevalence and Incidence of Atrial Fibrillation in a Large Cohort of Adrenal Incidentalomas: A Long-Term Study.

CONTEXT: Chronic glucocorticoids excess leads to morphological and functional cardiac alterations, a substrate for arrhythmias. Autonomous cortisol secretion (ACS) in adrenal incidentalomas is a model of chronic endogenous hypercortisolism. OBJECTIVE: To investigate prevalence and incidence of atrial fibrillation (AF) in a large cohort of patients with ACS. DESIGN: Retrospective study. SETTING: University hospital. PATIENTS: Patients evaluated between 1990 and 2018 for adrenal incidentalomas (n = 632), without pheochromocytoma, primary aldosteronism, Cushing syndrome, congenital adrenal hyperplasia, and adrenal malignancy. Cortisol after 1-mg dexamethasone suppression test < or > 50 nmol/L defined nonsecreting tumors (NST) (n = 420) and ACS (n = 212), respectively. INTERVENTION: Assessment of AF at baseline (n = 632) and during a median follow-up of 7.7 years retrospectively (NST, n = 249; ACS, n = 108). Comparison with general population. MAIN OUTCOME MEASURE: Prevalence and incidence of AF. RESULTS: AF prevalence was higher in patients with ACS (8.5%) than NST (3.1%, P = 0.003) and the general population (1.7%; P < 0.001 vs ACS, P = 0.034 vs NST). The age-adjusted rate ratio to the general population was 1.0 for NST and 2.6 for ACS. AF was associated with ACS (odds ratio, 2.40; 95% confidence interval [CI], 1.07-5.39; P = 0.035). The proportion of patients with AF at last evaluation was higher in ACS (20.0%) than NST (11.9%; P = 0.026). ACS showed a higher risk of incident AF than NST (hazard ratio, 2.95; 95% CI, 1.27-6.86; P = 0.012), which was associated with post-dexamethasone cortisol (hazard ratio, 1.15; 95% CI, 1.07-1.24; P < 0.001), independently of known contributing factors. CONCLUSIONS: Patients with adrenal incidentalomas and ACS are at risk of AF. Electrocardiogram monitoring may be recommended during follow-up.

Glyco-metabolic control, inflammation markers, and cardiovascular outcomes in type 1 and type 2 diabetic patients on insulin pump or multiple daily injection (italico study).

BACKGROUND: To evaluate if the positive effects recorded on glycaemic control with continuous subcutaneous insulin infusion (CSII) were maintained on the long-term compared with multiple daily injection (MDI). The secondary objective was to evaluate if there is a reduction of type and number of cardiovascular events (CV). METHODS: This retrospective, observational study evaluated glycaemic control and the number of CV in 104 patients with type 1 or 2 diabetes previously treated with MDI and initiating CSII therapy with tubed insulin pumps compared with 109 patients previously treated with MDI continuing MDI. RESULTS: After 8 years, the glycaemic control including glycated haemoglobin (HbA1c ), fasting plasma glucose (FPG), and prandial plasma glucose (PPG) improved with both CSII and MDI compared with baseline; however, HbA1c , FPG, and PPG recorded with CSII were lower than data recorded with MDI. During the 8 years, there were fewer CV events with CSII, compared with MDI, and in particular, there were fewer cases of atrial fibrillation, premature ventricular contractions, acute coronary infarction, angina pectoris, heart failure, and peripheral vascular ischemia. We did not record any reduction of ischemic stroke events. CONCLUSION: Our preliminary data suggest that CSII treatment seems to reduce the rates of CV compared with MDI therapy. Moreover, CSII also improved glycaemic control, without increasing the number of hypoglycaemia. However, given the observational design of this trial, our data should be validated in a randomized clinical trial; if they will be confirmed, CSII could be chosen for fully informed and motivated patients at higher risk of developing CV.

Hyperuricemia: a novel old disorder-relationship and potential mechanisms in heart failure.

Uric acid, the metabolic mediator of gout and urate renal stones, is associated with increased cardiovascular risk burden. Hyperuricemia is an old emerging metabolic disorder, and interaction among uric acid and cardiovascular diseases has been clearly described. Several illness including hypertension, myocardial infarction, metabolic syndrome, and heart failure, are related with uric acid levels increase. In this review, we will discuss the pathophysiology of hyperuricemia and describe the biological plausibility for this metabolite to participate in the pathogenesis of cardiovascular disorders. In particular, we will focus on the implications of hyperuricemia in the onset and progression of heart failure, paying special attention to the pathophysiology and the possible clinical implications. We will conclude by discussing the effects of lowering plasma uric acid concentration on the prognosis of heart failure by reviewing most of available data on the different classes of drugs directly or indirectly involved in the hyperuricemia management.

Beneficial Effects of Listening to Classical Music in Patients With Heart Failure: A Randomized Controlled Trial.

BACKGROUND: Practical recommendations on nonpharmacologic non-device/surgical interventions in patients with heart failure (HF) are well known. Although complementary treatments may have beneficial effects, there is no evidence that these on their own improve mortality, morbidity, or quality of life. We examined the effects of listening to recorded classical music on HF-specific quality of life (QOL), generic QOL, sleep quality, anxiety, depression, and cognitive state in patients with HF in the home-care setting. METHODS AND RESULTS: Multicenter randomized controlled trial. One hundred fifty-nine patients with HF were randomized on a 1:1 basis in 2 groups: experimental (music) and control. Patients were evaluated after 30, 60, 90 days (experimental period) and at 6 months. Patients randomized to the music group listened to music from a large preselected playlist, at least 30 minutes per day, for 3 months on an MP3 player. Patients in the control group received standard care. HF-specific QOL, generic QOL, self-care, somatic perception of HF symptoms, sleep quality, anxiety and depression, and cognitive abilities were assessed throughout the use of specific scales. On average, patients in the music group showed greater improvements in terms of HF-specific QOL (P < .001), generic-QOL (P = .005), quality of sleep (P = .007), anxiety and depression levels (P < .001 for both), and cognitive performances (P = .003). CONCLUSIONS: Listening to recorded classical music is a feasible, noninvasive, safe, and inexpensive intervention, able to improve QOL in patients with HF in the home-care setting.

The Steroid Profile of Adrenal Incidentalomas: Subtyping Subjects With High Cardiovascular Risk.

CONTEXT: Steroid profiling by mass spectrometry has shown implications for diagnosis and subtyping of adrenal tumors. OBJECTIVES: To investigate steroid profiles and their cardiovascular correlates in a large cohort of patients with nonsecreting (NS) adrenal incidentalomas and autonomous cortisol secretion (ACS). DESIGN: Cohort study. SETTING: University hospital. PATIENTS: Patients (n = 302) with incidentally discovered adrenal masses, divided into unilateral adenoma and hyperplasia with ACS (n = 46 and n = 52, respectively) and NS (n = 120 and n = 84, respectively). Post-dexamethasone suppression test (DST) cortisol <50 or >50 nmol/L defined NS and ACS, respectively. INTERVENTION: Analysis of 10-steroid panel by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and clinical data (mean follow-up 39 months). MAIN OUTCOME MEASURES: Difference in baseline and post-DST steroid profiles between groups. Correlation with cardiovascular profile. RESULTS: Patients with unilateral adenomas and ACS showed higher cortisol, 11-deoxycortisol, and corticosterone and lower dehydroepiandrosterone than those with NS adenomas. Patients with ACS hyperplasia showed higher cortisol and lower androgens in women than those with NS. Patients with ACS had reduced suppression of post-DST cortisol, 11-deoxycortisol, and corticosterone, irrespective of adrenal morphology. Post-DST cortisol and corticosterone were associated with higher prevalence of severe/resistant hypertension. Patients with ACS unilateral adenomas showed higher incidence of worsening of hypertensive disease and novel cardiovascular events than those with NS, with post-DST cortisol [hazard ratio (HR) 1.02; 95% CI, 1.01 to 1.03; P < 0.001] and baseline corticosterone (HR 1.06; 95% CI, 1.01 to 1.12; P = 0.031) among the main predictors. CONCLUSIONS: Patients with adrenal incidentalomas showed different steroid profiles, depending on functional status and adrenal morphology, with implications for their cardiovascular status.

Sclerosing Angiomatoid Nodular Transformation of the Adrenal Gland: A Case Report of a Novel Histopathological Entity.

The finding of an indeterminate adrenal mass at radiological investigations is a challenge for physicians. Complex diagnostic work-up, periodic follow-up, or surgical intervention are therefore needed to rule out malignant lesions. Tertiary care hospitals are provided with 18F-fludeoxyglucose (18F-FDG) positron emission tomography (PET) and 18F-dihydroxyphenylalanine (18F-DOPA) PET, which aid in the characterization of indeterminate adrenal masses. Nevertheless, the histopathological examination may be required to exclude malignancy or rare etiologies. A 54-year-old woman presented to our clinic 6 months after a cerebral hemorrhage. She was hypertensive and had recently discovered a left adrenal mass of 15 mm during an abdominal ultrasound. Contrast-enhanced CT, following adrenal protocol, revealed a 14-mm adrenal mass without characteristics suggestive of an adrenal adenoma. Tumor markers were negative. Functional tests excluded hormone hypersecretion. An 18F-DOPA PET was negative. An 18F-FDG PET showed mild uptake of both the adrenal glands, with a more circumscribed pattern in the left one (maximum standardized uptake value = 4). As the clinical diagnosis was still indeterminate, we performed laparoscopic left adrenalectomy. The histopathological examination described a sclerosing angiomatoid nodular transformation (SANT) of the adrenal gland, a benign lesion already described as a rare occurrence only in the spleen. IgG4 levels were reduced. In conclusion, this is a report of a SANT of the adrenal gland, a novel entity that should be taken into consideration in the differential diagnosis of indeterminate adrenal masses at CT scan.

Effects of allopurinol and febuxostat on cardiovascular mortality in elderly heart failure patients.

Hyperuricemia is an emerging risk factor for the development of heart failure (HF) and is associated with a worsen prognosis of the disease. The effect of urate lowering drugs (ULT) and, in particular, the xanthine oxidase inhibitor in patients with HF is controversial. The aim of the study is to compare the effects of treatment with two different xanthine oxidase inhibitors (allopurinol or febuxostat) on cardiovascular mortality in elderly patients with chronic HF in a setting of clinical practice. In this observational trial, 255 elderly patients affected by chronic HF and treated with ULT on top of optimal medical treatment for HF. The sample included only outpatients with mild-to-moderate HF mainly secondary to chronic arterial hypertension or coronary artery disease and not previously hospitalized for HF. Patient treated with febuxostat (N. 120) and allopurinol (N. 135) were balanced for most of the baseline variables. In particular age, NYHA class distribution, drug treatment and renal function were comparable at the baseline and during the observation in both groups (p > 0.05). After a mean follow-up period of 5.1 years, the cumulative cardiovascular survival was 0.96 (95% CI 0.93-0.99) in febuxostat-treated patients and 0.89 (95% CI 0.84-0.93) in those treated with allopurinol. The between group difference, adjusted for the main confounding risk factors, was statistically significant (p = 0.04). Our study results suggest that possibility that febuxostat, a selective XO inhibitor, may favorably affect cardiovascular mortality in comparison with allopurinol in elderly patients with mild-to-moderate HF. This preliminary observation deserves further evaluation in the next future.

Sacubitril/valsartan improves both functional and echocardiographic parameters in patients with chronic heart failure with reduced ejection fraction.

OBJECTIVE: We evaluated the clinical efficacy of sacubitril/valsartan in a group of ambulatory patients with heart failure (HF) with reduced ejection fraction (HFrEF) referred to our HF clinic. METHODS: Patients (n = 29; 72% males; mean age 76 years) with HFrEF in New York Heart Association (NYHA) classes II-III were included in the present study. We evaluated clinical as well as echocardiographic parameters (e.g. haemodynamics, such as blood pressure and heart rate, metabolic status, echocardiographic ventricular volumes and ejection fraction [EF]), at baseline and after 6 months of treatment with sacubitril/valsartan. RESULTS: After 6 months of sacubitril/valsartan treatment, several parameters were significantly improved. For example, EF and ventricular volumes (both diastolic and systolic) and atrial dimensions, as well as NYHA functional class (only 1 patient was still in NYHA class III) and renal impairment improved. There was no hospitalization for HF or other causes during the 6 month follow-up and no patient died. CONCLUSIONS: Based on our real-life experience, in HFrEF patients with NYHA class II-III, the new angiotensin receptor-neprilysin inhibitor (ARNi) sacubitril/valsartan was effective in improving HF management, both from the clinical and the echocardiographic perspective.

Morbidity and mortality in a population of patients affected by heart failure and chronic obstructive pulmonary disease: an observational study.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) and heart failure (HF) often coexist. Moreover, elderly patients suffering from HF have a higher incidence of COPD, which further complicates their clinical condition. Indacaterol/glycopirronium has shown benefits in the treatment of COPD, with few cardiologic adverse effects. We evaluated the safety and efficacy of this therapy in patients with history of HF. METHODS: We enrolled 56 patients with a history of HF (New York Heart Association [NYHA] classes II and III) and stable COPD. We evaluated blood samples, clinical assessment, echocardiograms and basal spirometry at baseline and after 6 months of therapy with indacaterol/glycopirronium. In addition, the number of re-hospitalizations during the treatment period was evaluated. RESULTS: The treatment was well tolerated. Brain natriuretic peptide (BNP) levels were significantly reduced compared with baseline (p < 0.001) after 6 months of treatment, and a higher percentage of patients improved their clinical status compared with baseline (p < 0.001). Minor changes were noted in the hemodynamic and metabolic parameters. Significant improvements in the echocardiographic parameters were noted in HF with reduced ejection fraction (HFrEF) patients. All respiratory parameters (forced expiratory volume in 1 s [FEV1], FEV1/forced vital capacity [FVC] ratio and COPD Assessment Test [CAT] scores) improved significantly (p < 0.001). No hospitalizations owing to HF or COPD exacerbation occurred. One patient died of respiratory failure. CONCLUSION: Indacaterol/glycopirronium was well-tolerated and effective in the treatment of COPD in this cohort of patients with a history of HF. Further studies are needed to clarify whether this compound can have a direct role in improving overall cardiovascular function.

Canrenone on cardiovascular mortality in congestive heart failure: CanrenOne eFFects on cardiovascular mortality in patiEnts with congEstIve hearT failure: The COFFEE-IT study.

AIM: To evaluate canrenone effects compared to other therapies on cardiovascular mortality in patients with chronic heart failure (CHF) and preserved systolic function after 10 years of evaluation. METHODS: We enrolled 532 patients with CHF and preserved systolic function. Patients were followed with a mean follow-up of 10 years: 166 patients were in therapy with canrenone, while 336 patients were in conventional therapy. We re-evaluated these data after 10 years, together with the rate of death and survival. RESULTS: Systolic and diastolic blood pressure were lower with canrenone compared to the group not treated with canrenone, both in supine and orthostatism. In the group treated with canrenone we recorded a lower value of fasting plasma glucose and glycated hemoglobin. Uric acid was lower in the group treated with canrenone, no differences were observed regarding creatinine, sodium, potassium, brain natriuretic peptide (BNP), pro-BNP or plasma renin activity (PRA), while aldosterone levels were reduced in canrenone group compared to control. After 10 years, left ventricular mass was lower in canrenone group. We recorded a more pronounced progression of NYHA class in controls compared to patients treated with canrenone, with also a higher number of deaths. A higher number of deaths was recorded in control group in the 68-83 years range compared to canrenone. A higher incidence of death was reported among patients without hypercholesterolemia in control group; this was not significant in patients treated with canrenone. A longer survival was observed in patients treated with canrenone. CONCLUSION: Administered to patients with CHF and preserved systolic fraction, reduced mortality and extended the life.

Coexisting Heart Failure and Chronic Obstructive Pulmonary Disease: Report of Two Cases Treated with Indacaterol/Glycopyrronium.

Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality worldwide, and it is associated with a high economic burden. Heart failure shares some general symptoms with COPD; thus, diagnosing COPD is difficult in subjects with a history of heart failure, and spi-rometry is mandatory for confirmation. Moreover, COPD is a highly prevalent comorbidity negatively impacting the outcome of heart failure patients. We document here the treatment with indacaterol/glycopyrronium in 2 patients with concomitant COPD and heart failure. Overall, the combination of indacaterol and glycopyrronium resulted in a reciprocal potentiation with a maximal bronchodilatory effect.

Sacubitril/Valsartan in Clinical Practice: A Report of 2 Cases.

Following the results of the PARADIGM-HF trial, the European Society of Cardiology (ESC) guidelines recommend sacubitril/valsartan to replace ACE inhibitors in ambulatory patients with heart failure with reduced ejection fraction (HFrEF) who remain symptomatic despite optimal therapy and who fit trial criteria. However, the optimal use of sacubitril/valsartan in clinical practice needs further investigation. We report here the cases of 2 patients with HFrEH successfully treated with sacubitril/valsartan in our daily practice. Both subjects presented multiple comorbidities and received an implantable cardioverter defibrillator in primary prevention. In both patients, therapy with sacubitril/valsartan led to prompt (30 days) amelioration of heart function, with a corresponding decrease in NHYA class and without any relevant safety issue.

Management of a Multicomorbid Patient with Heart Failure.

The optimal use of sacubitril/valsartan in clinical practice needs further investigation, in particular for patients with multiple comorbidities, as such patients are usually poorly represented in clinical trials. To this end, well-documented case reports may add further evidence to the bulk of "field practice" experience on sacubitril/valsartan. We report here the case of a patient with heart failure with reduced ejection refraction with multiple comorbidities treated with sacubitril/valsartan. Overall, sacubitril/valsartan led to a prompt (within a few months) improvement in LVEF (+15%, from 38 to 53%), without any noticeable adverse events. This therapy also allowed the patient to discontinue furosemide.

Continuous ultrafiltration for congestive heart failure: the CUORE trial.

Background: There are limited data comparing ultrafiltration with standard medical therapy as first-line treatment in patients with severe congestive heart failure (HF). We compared ultrafiltration and conventional therapy in patients hospitalized for HF and overt fluid overload.Methods and Results: Fifty-six patients with congestive HF were randomized to receive standard medical therapy (control group; n = 29) or ultrafiltration (ultrafiltration group; = 27). The primary endpoint of the study was rehospitalizations for congestive HF during a 1-year follow-up. Despite similar body weight reduction at hospital discharge in the 2 groups (7.5 ± 4.5 and 7.9 ± 5.0 kg, respectively;P = .75), a lower incidence of rehospitalizations for HF was observed in the ultrafiltration-treated patients during the following year (hazard ratio 0.14, 95% confidence interval 0.04-0.48; P = .002).Ultrafiltration-induced benefit was associated with a more stable renal function, unchanged furosemide dose, and lower B-type natriuretic peptide levels. At 1 year, 7 deaths (30%) occurred in the ultrafiltration group and 11 (44%) in the control group (P = .33).Conclusions: In HF patients with severe fluid overload, first-line treatment with ultrafiltration is associated with a prolonged clinical stabilization and a greater freedom from rehospitalization for congestive HF.

Uricaemia and ejection fraction in elderly heart failure outpatients.

BACKGROUND: Preliminary data suggest that serum uric acid (SUA) could be involved in the prognosis of chronic heart failure (HF). The aim of our study was to test the relationship between SUA and left ventricular ejection fraction (EF%) in a cohort of elderly hypertensive outpatients with chronic HF. DESIGN: We consecutively enrolled 487 elderly outpatients (M = 59·8%; F = 40·2%; mean age: 72 ± 11 years old) affected by mild-to-moderate hypertensive and/or ischaemic HF, evaluating the relationship between SUA and EF%. RESULTS: In an univariate analysis, SUA was inversely related with EF%: B = -4·392, 95% CI -5·427 to -3·357, P < 0·001. After adjustment for a large number of variables in a multivariate analysis, the value of EF% was best predicted by SUA (B = -3·005, 95% CI -4·386 to -1·623, P < 0·001), log brain natriuretic peptide (BNP: B = -2·341, 95% CI -3·137 to -1·248, P < 0·001) and mean arterial pressure (MAP: B = 0·241, 95% CI 0·047 to 0·435, P = 0·015). A separate analysis by estimated glomerular filtration rate (eGFR) levels confirmed the inverse relationship between SUA and EF% in patients with normal renal function. A separate analysis by sex confirmed that SUA and log BNP were significant strong predictors of EF% in men, but not in women where the best predictors were log BNP, MAP and body mass index. The predicting role of SUA was apparently independent of eGFR and use of diuretics. CONCLUSION: Serum uric acid seems to be inversely related to EF% in male elderly patients with HF after adjustment for the several confounding factors. This observation supports a primary negative effect of SUA on left ventricular function that warrants further investigations.