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.

[Gender differences of at risk patients with overt heart failure in the real world of general practice. Data from the GIPSI (Gestione Integrata Progetto Scompenso in Italia) registry]. / Differenze tra la popolazione maschile e femminile a rischio ed affetta da insufficienza cardiaca nel mondo reale della medicina generale. I dati del registro GIPSI (Gestione Integrata Progetto Scompenso in Italia).

BACKGROUND: Controlled clinical trials have defined the characteristics of specialized world populations, different from the real world population. On this basis, the GIPSI registry was created, aiming to collect data from heart failure populations managed by general practitioners, focusing on gender differences. METHODS: The registry was based on family history, clinical and laboratory data collection from general practitioners. Patients were considered as being at risk for heart failure if data applied to stage A/B, or presenting overt heart failure if data applied to stage C/D of the American College of Cardiology/American Heart Association classification. RESULTS: From June 2006 to October 2007, 757 consecutive patients (475 male, 62.7%) were enrolled from 260 general practitioner's practices; 227 patients (143 male, 63.0%) had overt heart failure. In the female population at risk, higher systolic and diastolic blood pressure values were observed, whereas males showed more frequently ischemic heart disease, hypercholesterolemia and hypertriglyceridemia, and were more often prescribed with statins and antiplatelet drugs. There were more heart failure females with diabetes and of advanced age. Moreover, females showed a higher pulse pressure and a significantly lower estimated glomerular filtration rate (by simplified MDRD equation) than males. CONCLUSIONS: The data collected in a real world population show that heart failure has significantly different gender characteristics, especially for risk factors, age, blood pressure and renal function. This kind of investigation should be extended to larger patient populations for a better understanding of the disease.

Insulin-treated type 2 diabetes is associated with a decreased survival in heart failure patients after cardiac resynchronization therapy.

BACKGROUND: Cardiac resynchronization therapy (CRT) improves cardiac performance and survival in patients with congestive heart failure. Recent observations suggest that diabetes is associated with a worse outcome in these patients. The aim of the study was to investigate the effect of diabetes and insulin treatment on outcome after CRT. METHODS: Diabetic status and insulin treatment were assessed in 447 patients who underwent CRT (males 80.8%, mean age 65.7 +/- 9.7 years, ejection fraction 29.9 +/- 6.11%). Patients were stratified in three groups according to the presence or absence of diabetes and insulin treatment. RESULTS: Nondiabetic patients were 366 (79.6%), noninsulin-treated diabetic patients 62 (13.9%), insulin-treated diabetic patients 29 (6.5%). The estimated death rate was 5.15 per 100 patients-year in the nondiabetic group, 8.63 in noninsulin-treated diabetics (HR 1.59, P = 0.240), and 15.84 in insulin-treated diabetics (HR 3.05, P = 0.004). Cardiac mortality accounted for 81% of deaths in nondiabetic patients and for 56% of deaths in diabetic patients. Diabetic patients tended to have a worse recovery of left ventricular ejection fraction over time (P = 0.057) and of the distance at 6-minute walking test (6MWT) (P = 0.018). CONCLUSIONS: Insulin-treated diabetes is associated with a worse functional recovery and a higher mortality in patients with advanced heart failure after CRT. While cardiac death accounts for the majority of deaths in nondiabetic patients, a relevant proportion of the mortality in diabetic patients seem to result from noncardiac causes.

Drug-eluting stents for the percutaneous treatment of the anastomosis of the left internal mammary graft to left anterior descending artery.

BACKGROUND: Data on the treatment of left internal mammary to left anterior descending artery (LIMA-to-LAD) anastomotic disease are scarce and not homogeneous. Both surgery and percutaneous interventions (PCI) have been attempted, but the most effective treatment has not yet been established. In particular, should PCI be performed, the role of stenting seems to be limited by less favorable results than in other subsets of lesions. OBJECTIVE: To assess the clinical impact of drug-eluting stent (DES) use in this particular subset of lesions. METHODS: We describe a cohort of patients treated with PCI on LIMA-to-LAD anastomoses, reporting acute 1-year clinical and angiographic outcomes. The clinical impact of DES use was evaluated as the requirement for target lesion revascularizations (TLR). RESULTS: Fifty-six consecutive patients were evaluated. Acute procedural success was achieved in 52 patients (92.8%). Plain balloon angioplasty allowed acute procedural success in 15 patients (28.8%), whereas stenting was required in 37 patients (71.2%) with suboptimal results or to treat complications. Bare-metal stents (BMS) were used in 17 and DES in 20 patients, without differences in acute results. One-year clinical follow-up was available in 96.1% of patients. TLR were needed in 17.3% of patients. No significant differences were detected in TLR rates after treatment with BMS and DES (26.6% vs. 25%; P=0.99). Two late stent thromboses were observed after DES deployment. CONCLUSION: PCI of the stenoses of LIMA-to-LAD anastomoses with DES did not provide any clinical improvement over BMS use in long-term outcomes; DES use was associated with some cases of late thrombosis.

Hydrotherapy in advanced heart failure: the cardio-HKT pilot study.

BACKGROUND: In-water exercise, hydrotherapy, may offer an attractive alternative to conventional training in markedly compromised patients with advanced HF. This Pilot Study evaluates the safety and efficacy of Cardio-Hydrokinesitherapy (Cardio-HKT) in patients with advanced HF on optimal medical therapy. Cardio-HKT is a novel rehabilitation program that includes training sessions in warm water (31 degrees C), integrated by educational and psycho-behavioural sessions to promote healthy life style modifications. METHODS: We studied 18 adult patients with advanced HF, LVEF < 35%, NYHA functional class > II and peak oxygen uptake (peak VO2) < 18 ml/kg/min. Cardio-HKT consisted of a 3 weeks daily in-water training, combined to educational and psycho-behavioural sessions. Patients underwent a six-minute-walking-test (6mWT), a cardiopulmonary exercise test at baseline and after 3 weeks of Cardio-HKT. Quality of life was assessed with the Minnesota Living with Heart Failure Questionnaire (MLHF). RESULTS: All patients completed the Cardio-HKT rehabilitation program without complications. The 6mWT improved from 453 +/- 172 m to 571 +/- 120 m (p < 0.01), peak VO2 from 13.0 +/- 3.1 to 14.5 +/- 2.9 ml/kg/min (p = 0.03), whereas VE/ CO2 slope declined from 37 +/- 10 to 33 +/- 9 (p = 0.01). MLHF markedly improved from 56 (68-27) to 18 (40-7) (p < 0.01). CONCLUSIONS: Our results support the safety and efficacy of the innovative Cardio-HKT rehabilitation program in patients with advanced HF.

Aspergillus left ventricular assist device endocarditis.

Left ventricular assist device (LVAD) support is an established therapy for patients with end-stage heart failure as a bridge to transplant; its usage as an alternative for those patients not eligible for transplant is not an established therapy yet. A 68-year-old male had a Thoratec-Heartmate LVAD implanted as destination therapy. After an uneventful (apart from early fever) recovery in the intensive care unit, the patient developed an intractable high temperature, and generalized sepsis and died 21 days following implant. The white cell blood count never exceeded the guard limits, and the patient succumbed with severe LVAD valve malfunction. At post-mortem examination friable material consisting of fungal hyphae was found on the inflow and outflow valves. According to published clinical trials, infection accounts for more than 40% of mortality in LVAD supported patients. Fungal LVAD endocarditis is a particularly deadly disease. Successful management requires a high level of suspicion and timely institution of antifungal therapy to control the infection. This has led some authors to recommend empiric antifungal therapy in LVAD recipients with culture-negative sepsis unresponsive to broad-spectrum antibiotics.

Cross-sectional multiplane transesophageal echocardiographic measurements: comparison with standard transthoracic values obtained in the same setting.

BACKGROUND: Several algorithms developed for cost-effective use of transesophageal echocardiography (TEE) propose elimination of "screening" transthoracic echocardiographic (TTE) studies. Cross-sectional measurements obtained by TTE (left atrial diameter [LAD], left ventricular internal dimensions in diastole and systole [LVIDd, LVIDs], septal and posterior wall thickness in diastole [VSTd, PWTd], LV end-diastolic and end-systolic volumes [LVEDV and LVESV], and LV ejection fraction [LVEF]) have not been standardized for TEE. METHODS: Forty-six patients (age 27 to 85 years, 60 +/- 13 years, 25 [54%] women) underwent TEE and TTE studies. TTE was performed while the TEE probe was in place and the patient was still sedated. Standard TTE measurements were compared with corresponding TEE values obtained from mid-esophageal and transgastric views. RESULTS: Standard TTE measurements compared favorably with those obtained by TEE at the mid-esophageal three-chamber view for LAD (3.9 +/- 0.6 cm vs 4.0 +/- 0.7 cm, P = NS) and at the transgastric long-axis view for LVIDd (4.6 +/- 0.8 cm vs 4.7 +/- 0.8 cm, P = NS), LVIDs (3.1 +/- 0.9 cm vs 3.1 +/- 0.9 cm, P = NS), and VSTd (0.95 +/- 0.18 cm vs 0.98 +/- 0.19 cm, P = NS). Biplane TTE and TEE measurements of LVEDV (106 +/- 35 ml vs 112 +/- 38 ml, P = NS), LVESV (37 +/- 23 ml vs 37 +/- 25 ml, P = NS), and LVEF (67 +/- 14% vs 69 +/- 14%, P = NS) also correlated closely. The negative predictive values of TEE measurements for excluding abnormal LAD, LVIDd, VSTd, PWTd, and LVEF as defined by TTE were 83%, 94%, 95%, 97%, and 97%, respectively. CONCLUSION: Cross-sectional TEE measurements as obtained in this study are equivalent to standard TTE dimensions and provide reliable information that may facilitate interpretation of TEE studies in the absence of TTE information.

A population-based study on overt heart failure in Lombardy (survey of hospitalization in 1996 and 1997).

BACKGROUND: The aim of this study was to get updated information about the incidence and outcome of heart failure hospital admission in the whole population of the largest Italy region. METHODS: The Lombardy regional database of hospital records (Information System and Quality Control Bureau) provided the requested information: all the heart failure cases admitted to all the institutions of the region were selected by the ICD9 code of congestive heart failure (428-) as the principal or secondary diagnosis. The available data included: diagnosis and surgical procedures (up to four), date of birth, dates of admission and discharge, outcome, DRG code, discharge unit code, gender. The data so obtained concern the hospital discharges in 1996 and 1997. RESULTS: 32,093 cases were selected. The mean ages were 74.1 +/- 11.5 years for males and 80.6 +/- 10.7 for females in 1996, and 71.8 +/- 11.7 for males and 78.3 +/- 10.6 for females in 1997. Most of the cases were classified as appertaining to DRG 127--pure heart failure (56.7%). Heart failure associated with myocardial infarction accounted for 7.3% of cases. The remaining cases (36.0%) were classified as appertaining to heterogeneous medical and surgical DRGs. In 1997, the in-hospital mortality was 14.7% for patients aged > 80 years; 9.7% for patients aged between 71 and 80 years; 7.4% for patients aged between 61 and 70 years and 6.9% for patients < 61 years of age with the exclusion of pediatric cases. The in-hospital mortality was different between discharge units: 2.8% of in-patients discharged from cardiology units, and 10.3% of in-patients discharged from general medicine units. The readmission rate at 1 month was 5.49% whereas that within 1 year was 14.3%. CONCLUSIONS: Heart failure mortality differences between hospital units are not explained by age and by comorbidity. The readmission rate was lower than in previous reports.