Diagnostic performance of a point of care high-sensitivity cardiac troponin I assay and single measurement evaluation to rule out and rule in acute coronary syndrome.

OBJECTIVES: About 10 million individuals in USA presented annually in the emergency department (ED) with chest pain or with signs and symptoms of acute coronary syndrome (ACS). The advent of point of care (POC) devices, able to measure high sensitivity troponin, are a very interesting tool in the ED setting for its rapid turnaround time (<10 min). METHODS: The present study evaluates the diagnostic performance of the Atellica VTLi (Siemens) in real life setting using the clinical data derived from integrated diagnoses of emergency room staff and cardiologist and in comparison with standard laboratory hs-cTnT assay (Cobas 8000, Elecsys, Roche). 966 patients admitted to the emergency department of "G. Mazzini Hospital" in Teramo, Italy, from July 27, 2022, through June 09, 2023, were enrolled. RESULTS: The diagnostic performance of POC hs-cTnI was evaluated. An appropriate POC hs-cTnI threshold values <4 ng/L supplied a sensitivity and an NPV of 100 % (95 % CI: 99.5-100) in order to achieve rapid rule out for MI through a single measurement at patient presentation in the ED. Furthermore, a derivation POC hs-cTnI concentration >54 ng/L provided a specificity of 97.2 % (95 % CI: 95.9-98.1) and a PPV of 43.5 % (95 % CI: 40.3-46.7) for ruling in MI. CONCLUSIONS: This platform showed comparable diagnostic performance for myocardial infarction to the central laboratory. Our data suggest the possible use of the Atellica VTLi hs-cTnI POC assay either in emergency department of urban medical centre, either in rural hospital for triage and patient management.

Hyperkalaemia in Cardiological Patients: New Solutions for an Old Problem.

Hyperkalaemia is one of the most common electrolyte disorders in patients with cardiovascular disease (CVD). The true burden of hyperkalaemia in the real-world setting can be difficult to assess, but in population-based cohort studies up to 4 in 10 patients developed hyperkalaemia. In addition to drugs interfering with potassium metabolism and food intake, several conditions can cause or worsen hyperkalaemia, such as advanced age, diabetes, and chronic kidney disease. Mortality, cardiovascular morbidity, and hospitalisation are higher in patients with hyperkalaemia. Hyperkalaemia represents a major contraindication or a withholding cause for disease-modifying therapies like renin-angiotensin-aldosterone inhibitors (RAASi), mainly mineralocorticoid receptor antagonists. Hyperkalaemia can be also classified as acute and chronic, according to the onset. Acute hyperkalaemia is often a life-threatening emergency requiring immediate treatment to avoid lethal arrhythmias. Therapy goal is cell membrane stabilisation by calcium administration, cellular intake, shift of extracellular potassium to the intracellular space (insulin, beta-adrenergic agents, sodium bicarbonate), and increased elimination with diuretics or dialysis. Chronic hyperkalaemia was often managed with dietary counselling to prevent potassium-rich food intake and tapering of potassium-increasing drugs, mostly RAASi. Sodium polystyrene sulphonate, a potassium binder, was the only therapeutic option. Recently, new drugs such as patiromer and sodium zirconium cyclosilicate give new opportunities for the treatment of hyperkalaemia, as they proved to be safe, well tolerated, and effective. Aim of this review is to describe the burden of hyperkalaemia in cardiovascular patients, its direct and indirect effects, and the therapeutic options now available in the acute and chronic setting.

[Renal effects of sodium-glucose cotransporter 2 inhibitors in patients with cardiovascular disease with and without chronic kidney disease]. / Gli effetti renali degli inibitori del cotrasportatore sodio-glucosio di tipo 2 in pazienti con malattia cardiovascolare con e senza insufficienza renale cronica.

The kidney plays an important role in maintaining glucose homeostasis which is used as a metabolic substrate, generated through the mechanism of gluconeogenesis and reabsorbed in the glomerular filtrate through the action of sodium-glucose cotransporters 1 and 2 (SGLT1/2) located in the proximal tubule. Recent studies have shown that inhibition of renal glucose reabsorption, achieved through the administration of sodium-glucose cotransporter inhibitors, significantly reduces renal adverse events and exacerbations of heart failure, not only in diabetic patients, with and without confirmed cardiovascular damage, but also in patients with advanced chronic renal failure and in patients with heart failure with reduced ejection fraction regardless of the presence of diabetes. The extent of the benefit was relevant in the various clinical conditions studied, and led to a significant reduction in the major adverse cardiovascular outcomes recorded in each study. In all controlled studies, the efficacy of sodium-glucose cotransporter inhibitors was strongly associated with the reduction in progression of renal damage, as evidenced by the significant reduction in overall mortality obtained in the two studies that enrolled populations of diabetic and non-diabetic patients with advanced chronic renal failure. Both studies were stopped early at the interim analysis due to the evident superiority of the therapy in the treated arm.The purpose of this review is to examine the role of SGLT2/1 both in physiological conditions that in the course of cardio-nephropathy associated or not with type 2 diabetes mellitus and the effect of SGLT2/1 inhibition on clinical outcomes in different cardiovascular risk population enrolled in different randomized controlled clinical trials.

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.

[The mechanisms mediating the favorable effects of sodium-glucose cotransporter 2 inhibitors on cardiorenal function]. / I meccanismi d'azione degli inibitori del cotrasportatore sodio-glucosio di tipo 2 ed i loro effetti benefici sull'assetto funzionale di cuore e rene.

In several clinical investigations performed in patients with type 2 diabetes mellitus and in diabetic and non-diabetic patients with heart failure or chronic kidney disease, sodium-glucose cotransporter 2 inhibitors (SGLT2i) proved their benefit on cardiac and renal adverse outcomes. Although there is clear evidence regarding the clinical benefits achieved, the pathophysiological mechanisms underlying their efficacy are still poorly understood. Some favorable mechanisms are likely related to the induced glycosuria and natriuresis. Both have been observed since the early stages of the molecule action and can drive beneficial hemodynamic changes, resulting in a decline of glomerular hyperfiltration and activation of the renin-angiotensin-aldosterone system. In addition to the improvement of cardiocirculatory regimen and renal performance, SGLT2i have an important role in cardio-renal protection by improving the metabolism of cardiomyocytes, carrying out anti-fibrotic and anti-inflammatory action and increasing the expression of cardio-protective adipokines. Further studies are needed to better understand the molecular mechanisms underlying the favorable effects of these drugs in diabetic and non-diabetic patients. The purpose of this review article is to analyze the molecular mechanisms underlying the cardiovascular benefits of SGLT2i in each of the main organs involved in the cardio-renal axis. Furthermore, the manuscript aims to analyze the extent of the beneficial effects of SGLT2i on heart failure in the different populations investigated in the most recent clinical studies.

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.

Lifestyles and Cardiovascular Prevention in Childhood and Adolescence.

Pathology studies demonstrated that coronary fatty streaks develop early in life and that even more advanced fibrous plaques are present in a proportion of adolescents. The presence and extent of atherosclerosis in children and adolescents can be correlated with the same risk factors present in adults; as well as, childhood levels of these risk factors predict adult cardiovascular diseases. Children are born with ideal cardiovascular health but, unfortunately, most of them develop over time modifiable behavioral risk factors. Achieving sustained lifestyle changes initiated too late in adults is difficult, and pharmacologic risk factor control cannot fully restore a low-risk state. Therefore, it seems eminently reasonable to initiate healthful lifestyle training as early in life, decreasing the prevalence of cardiovascular risk factors to retard atherogenic processes and reduce the future burden of cardiovascular diseases. Many guideline recommendations encourage universal adoption of healthier lifestyles, identification of children with cardiovascular risk factors, and their treatment using targeted lifestyle modification and, rarely, pharmacotherapy. Major gains will likely accrue from public health strategies targeting incorrect diet, physical activity, and cigarette smoking. Individualized strategies, however, will initially focus on the highest risk children such as those with familial hyperlipidaemia, diabetes, hypertension, and obesity. The primary purpose of this article is to provide a broad overview on the long-term cardiovascular effects of risk factors in children and youth and to outline various lines of evidence for the efficacy of primordial and primary prevention in young people, as well as recommendations for population- and individual-level strategies and evidence-based interventions.

Remote monitoring: Doomed to let down or an attractive promise?

Device interrogation and management are time consuming, representing a relevant burden for pacing centers. In several situations, patients' management requires additional follow up visits. Remote Monitoring (RM) allows an optimal recall management and a rapid diagnosis of device or lead failure, without the need of additional in office visits. Further it allows a significant delay reduction between the adverse event and the reaction to the alarm, shortening the time needed to make a clinical decision. A role in risk-predicting patient-related outcomes has also been shown. RM permits detection of the arrhythmia from 1 to 5 months in advance compared to in-office visits. Importantly, by using specific algorithms with multiparametric analysis, RM has been studied as a potential instrument to identify early patients on risk of worsening HF using specific algorithms. Although the use of RM in HF setting remains controversial, it has been proposed to improve HF clinical outcomes and survival in clinical trials. In this sense, RM success could require a standardization of process within a management model, that may involve different health care professionals. In this review, we examine recent advances of RM providing an update of this tool through different clinical scenarios.

Major bleeding with old and novel oral anticoagulants: How to manage it. Focus on general measures.

In the last decade, the introduction of non-vitamin K antagonist oral anticoagulants (NOACs) in clinical practice has changed the therapeutic landscape in the prevention of thromboembolic events. Although NOACs compared to vitamin K antagonists (VKAs) have demonstrated a similar or slightly lower rate of major bleeding and a lower rate of intracranial or fatal bleeding, hemorrhaging still represents the main adverse effect of anticoagulant treatment. This review reports data on the rates of major bleeding with old and new oral anticoagulants. It analyses laboratory tests that can be used to assess the intensity of anticoagulation in patients treated with oral anticoagulants and discusses general measures to implement in managing major bleeding.

Major bleeding with old and novel oral anticoagulants: How to manage it. Focus on reversal agents.

Even though vitamin K antagonists (VKAs) have been employed for >50 years, there is still some uncertainty about the best strategy to reverse anticoagulation due to VKAs in cases of major bleeding. Furthermore, there is also scarce evidence about the most appropriate way to treat serious bleeding associated with non-vitamin K antagonist oral anticoagulants. This review analyses the main advantages and disadvantages of the various forthcoming therapeutic options to restore a normal coagulation status in anticoagulated patients with ongoing serious bleeding. It discusses the role of fresh frozen plasma, prothrombin complex concentrates and recombinant factor VII activated. Moreover, we report updated evidence on antidotes currently available or in development. Finally, this article proposes a comprehensive algorithm that summarizes major bleeding management during treatment with oral anticoagulants.

[Primary prevention of sudden cardiac death through a wearable cardioverter-defibrillator]. / Prevenzione primaria della morte cardiaca improvvisa mediante defibrillatore indossabile.

Nowadays, the implantable cardioverter-defibrillator is the gold standard for the prevention of sudden cardiac death due to tachyarrhythmias. However, its use is not free from short and long-term risks. In the last years, the wearable cardioverter-defibrillator (WCD) has become a widespread option for patients who need a safe and reversible protection against ventricular tachyarrhythmias. Notwithstanding this, its everyday application is restricted by several limitations, including the risk of inappropriate shocks, the device size and the need for strict compliance of both patients and caregivers. In this review, we report the most relevant literature data on WCD usage along with the main fields of applications and future perspectives.