Combined Neuro-Humoral Modulation and Outcomes in Patients with Chronic Heart Failure and Mildly Reduced or Preserved Ejection Fraction.

Pharmacotherapy of chronic heart failure with mildly reduced (HFmrEF) and preserved ejection fraction (HFpEF) remains challenging. We aimed to assess whether combined neuro-humoral modulation (NHM) (renin−angiotensin system inhibitors, betablockers, mineralocorticoid receptor antagonists) was differentially associated with outcome according to phenotype and age groups. Between 1999 and 2018 we recruited in a nationwide cardiology registry 4707 patients (HFmrEF n = 2298, HFpEF n = 2409) from three age groups: <65, 65−79 and 80+ years old. We analyzed clinical characteristics and 1 year all-cause mortality/cardiovascular hospitalization according to none/single, any double, or triple NHM. Prescription rates of no/single and triple NHM were 25.1% and 26.7% for HFmrEF; 36.5% and 17.9% for HFpEF patients, respectively. Older age was associated with higher prescription of no/single NHM in HFmrEF (ptrend = 0.001); the reverse was observed among HFpEF (ptrend = 0.005). Triple NHM increased over time in both phenotypes (all p for trend < 0.0001). Compared to no/single NHM, triple, but not double, NHM was associated with better outcomes in both HFmrEF (HR 0.700, 95%CI 0.505−0.969, p = 0.032) and HFpEF (HR 0.700, 95%CI 0.499−0.983, p = 0.039), with no interaction between NHM treatment and age groups (p = 0.58, p = 0.80, respectively). In a cardiology setting, among HF outpatients with EF > 40%, triple NHM treatment increased over time and was associated with better patient outcomes.

Temporal trends in characteristics, treatment, and outcomes of heart failure in octogenarians over two decades.

INTRODUCTION AND OBJECTIVES: Octogenarians represent the most rapidly expanding population segment in Europe. The prevalence of heart failure (HF) in this group exceeds 10%. We assessed changes in clinical characteristics, therapy, and 1-year outcomes over 2 decades in chronic HF outpatients aged ≥ 80 years enrolled in a nationwide cardiology registry. METHODS: We included 2520 octogenarians with baseline echocardiographic ejection fraction measurements and available 1-year follow-up, who were recruited at 138 HF outpatient clinics (21% of national hospitals with cardiology units), across 3 enrolment periods (1999-2005, 2006-2011, 2012-2018). RESULTS: At recruitment, over the 3 study periods, there was an increase in age, body mass index, ejection fraction, the prevalence of obesity, diabetes, dyslipidemia, pre-existing hypertension, and atrial fibrillation history. The proportion of patients with preserved ejection fraction rose from 19.4% to 32.7% (P for trend <.0001). Markers of advanced disease became less prevalent. Prescription of beta-blockers and mineralocorticoid receptor antagonists increased over time. During the 1-year follow-up, 308 patients died (12.2%) and 360 (14.3%) were admitted for cardiovascular causes; overall, 591 (23.5%) met the combined primary endpoint of all-cause mortality or cardiovascular hospitalization. On adjusted multivariable analysis, enrolment in 2006 to 2011 (HR, 0.70; 95%CI, 0.55-0.90; P=.004) and 2012 to 2018 (HR, 0.61; 95%CI, 0.47-0.79; P=.0002) carried a lower risk of the primary outcome than recruitment in 1999 to 2005. CONCLUSIONS: Among octogenarians, over 2 decades, risk factor prevalence increased, management strategies improved, and survival remained stable, but the proportion hospitalized for cardiovascular causes declined. Despite increasing clinical complexity, in cardiology settings the burden of hospitalizations in the oldest old with chronic HF is declining.

[ANMCO Position paper: Care pathway for advanced heart failure patients candidate for heart transplantation/ventricular assist device]. / Position paper ANMCO: Percorso assistenziale del paziente con insufficienza cardiaca avanzata candidabile a trapianto/assistenza ventricolare meccanica.

Heart failure is a complex clinical syndrome with a severe prognosis, despite therapeutic progress. The management of the advanced stages of the syndrome is particularly complex in patients who are referred to palliative care as well as in those who are candidates for cardiac replacement therapy. For the latter group, a prompt recognition of the transition to the advanced stage as well as an early referral to the centers for cardiac replacement therapy are essential elements to ensure that patients follow the most appropriate diagnostic-therapeutic pathway. The aim of this document is to focus on the main diagnostic and therapeutic aspects related to the advanced stages of heart failure and, in particular, on the management of patients who are candidates for cardiac replacement therapy.

Age-related changes in clinical characteristics and outcomes of chronic heart failure outpatients in a cardiology setting. A report from the Italian Network on Heart Failure.

AIMS: Ageing and comorbidities are increasing frailty/complexity of heart failure (HF) patients globally. We assessed evolving trends over two decades according to patients' age and time of recruitment in a nationwide cardiology setting in Italy. METHODS AND RESULTS: Chronic HF outpatients recruited between 1999 and 2018 (N = 14,823) were divided into 3 cohorts: 1999-2005 (N = 5404); 2006-2011 (N = 3971); 2012-2018 (N = 5448). We analyzed temporal changes in clinical characteristics, therapies, and outcome (1-year all-cause mortality/cardiovascular hospitalization), overall and by age group: <65 (n = 5465); 65-79 (n = 6838); ≥80 (n = 2520) years old. Across enrolment epochs, comorbidities (atrial fibrillation, hypertension, obesity) increased by both epoch/age groups (p < 0.001), whereas the prevalence of ischemic etiology declined among patients ≥65 years (p = 0.05). Accordingly, the preserved LVEF phenotype (HFpEF) increased in all age categories (p < 0.001) over time. Moreover, the use of betablockers, mineralocorticoid-receptor antagonists and loop-diuretics rose by enrolment epoch in all age groups (p < 0.05). In parallel with these epidemiologic/treatment changes, age-adjusted survival free from cardiovascular hospitalization improved over time (p < 0.0001). However, divergent trends in the end-point components were apparent according to age groups: mortality decreased in patients<80 years, although hospitalizations remained stable in the youngest group, while subjects ≥65 years were less likely to be admitted for cardiovascular causes (all p < 0.005). CONCLUSIONS: Over two decades in a cardiology outpatient setting, the prevalence of comorbid HFpEF increased in all age categories. Mortality improved among patients<80 years and cardiovascular hospitalizations decreased in patients≥65 years. These findings point to the value of cardiologist' input in the management of adult chronic HF patients at all ages.

[Sodium-glucose co-transporter 2 inhibitors: mechanisms of renal action. Implications for diabetes and heart failure]. / Inibitori del co-trasportatore sodio-glucosio di tipo 2: meccanismi d'azione renale. Le implicazioni nel diabete e nello scompenso cardiaco.

The liver is not the exclusive site of glucose production in humans in the post-absorption state. Experimental data showed that the kidney is able of carrying out gluconeogenesis. Renal glucose production accounts for 20% of systemic glucose production. Evidence indicates that the kidney is able to reabsorb glucose from the glomerular filtrate through the sodium-glucose co-transporters (SGLT) 1 and 2 placed under the Bowman's capsule, in the thick portion of the proximal convoluted tubule, preserving this essential energy substrate for the organism. The maximal renal glucose reabsorption capacity (TmG), as well as the threshold for the spillover of glucose in the urine, are higher in diabetics than normal subjects and contribute to the hyperglycemic state in the absence of glycosuria. The administration of SGLT2 inhibitors in diabetics improves the excretion of sodium and glucose, reducing the threshold of glycosuria and TmG. This also restores the sodium concentration in the filtrate that reaches the macula densa (juxtaglomerular apparatus), which signals the appropriate perfusion of the kidney, defusing the secretion of renin and the activation of the neurohormonal axis that leads to the production of angiotensin II.Large clinical trials conducted with SGLT2 inhibitors in subjects with type 2 diabetes mellitus have demonstrated the great ability of this new class of drugs to achieve cardiac and renal benefits. All studies have shown SGLT2 inhibitors reduce the risk of hospitalizations for heart failure and the progression of kidney damage. A part of the favorable mechanisms is mediated by the natriuretic effect that is associated with the glycosuric effect, which reduces the activation of the renin-angiotensin-aldosterone system together with glomerular hyperfiltration.The aim of this review is to expand the knowledge among general cardiologists on the role of SGLT2 and SGLT1 in renal glucose homeostasis in healthy and diabetic subjects in the light of a potent class of drugs counteracting heart failure.

[Primary aldosteronism: from diagnosis to therapy in clinical practice]. / Iperaldosteronismo primitivo: dalla diagnosi alla terapia nella pratica clinica.

Primary aldosteronism (PA) is the single most common cause of secondary hypertension and is associated with increased target organ injury. It can be can either surgically cured or treated with targeted pharmacotherapy. PA is frequently undiagnosed and untreated, leading to aldosterone-specific cardiovascular morbidity and nephrotoxicity. Thus, clinicians should perform case detection testing for PA at least once in all patients with hypertension. The diagnostic work-up of PA is a sequence of three phases comprising screening tests, confirmatory tests and the differentiation of unilateral from bilateral forms. With appropriate surgical expertise, laparoscopic unilateral adrenalectomy is safe, efficient and curative in patients with unilateral adrenal disease. In patients who have bilateral aldosterone hypersecretion, the optimal management is a low sodium diet and lifelong treatment with a mineralocorticoid receptor antagonist administered at a dosage to maintain a high-normal serum potassium concentration without the aid of oral potassium supplements. In patients with PA, specific treatment provides prognostic benefit over optimal antihypertensive therapy and is therefore crucial to reduce mortality and morbidity in this subgroup of patients with hypertension.