Adverse effects of sodium-glucose cotransporter-2 inhibitors in patients with heart failure: a systematic review and meta-analysis.

Sodium-glucose cotransoporter-2 inhibitors (SGLT-2Is) improve prognosis in heart failure (HF) patients both with reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF). However, these drugs can have some side effects. To estimate the relative risk of side effects in HF patients treated with SGLT-2Is irrespective from left ventricular EF and setting (chronic and non-chronic HF). Five randomized controlled trials (RCTs) enrolling patients with HFrEF, 4 RCTs enrolling non-chronic HF, and 3 RCTs enrolling HFpEF were included. Among side effects, urinary infection, genital infection, acute kidney injury, diabetic ketoacidosis, hypoglycemia, hyperkalemia, hypokalemia, bone fractures, and amputations were considered in the analysis. Overall, 24,055 patients were included in the analysis: 9020 (38%) patients with HFrEF, 12,562 (52%) with HFpEF, and 2473 (10%) with non-chronic HF. There were no differences between SGLT-2Is and placebo in the risk to develop diabetic ketoacidosis, hypoglycemia, hyperkalemia, hypokalemia, bone fractures, and amputations. HFrEF patients treated with SGLT-2Is had a significant reduction of acute kidney injury (RR = 0.54 (95% CI 0.33-0.87), p = 0.011), whereas no differences have been reported in the HFpEF group (RR = 0.94 (95% CI 0.83-1.07), p = 0.348) and non-chronic HF setting (RR = 0.79 (95% CI 0.55-1.15), p = 0.214). A higher risk to develop genital infection (overall 2.57 (95% CI 1.82-3.63), p < 0.001) was found among patients treated with SGLT-2Is irrespective from EF (HFrEF: RR = 1.96 (95% CI 1.17-3.29), p = 0.011; HFpEF: RR = 3.04 (95% CI 1.88-4.90), p < 0.001). The risk to develop urinary infections was increased among SGLT-2I users in the overall population (RR = 1.13 (95% CI 1.00-1.28), p = 0.046) and in the HFpEF setting (RR = 1.19 (95% CI 1.02-1.38), p = 0.029), whereas no differences have been reported in HFrEF (RR = 1.05 (95% CI 0.81-1.36), p = 0.725) and in non-chronic HF setting (RR = 1.04 (95% CI 0.75-1.46), p = 0.806). SGLT-2Is increase the risk of urinary and genital infections in HF patients. In HFpEF patients, the treatment increases the risk of urinary infections compared to placebo, whereas SGLT-2Is reduce the risk of acute kidney disease in patients with HFrEF.

Sacubitril/valsartan and arrhythmic burden in patients with heart failure and reduced ejection fraction: a systematic review and meta-analysis.

The aim of this study was to assess whether angiotensin receptor/neprilysin inhibitor (ARNI) decreases ventricular arrhythmic burden compared to angiotensin-converting enzyme inhibitors or angiotensin receptor antagonist (ACE-I/ARB) treatment in chronic heart failure with reduced ejection fraction (HFrEF) patients. Further, we assessed if ARNI influenced the percentage of biventricular pacing. A systematic review of studies (both RCTs and observational studies) including HFrEF patients and those receiving ARNI after ACE-I/ARB treatment was conducted using Medline and Embase up to February 2023. Initial search found 617 articles. After duplicate removal and text check, 1 RCT and 3 non-RCTs with a total of 8837 patients were included in the final analysis. ARNI was associated with a significative reduction of ventricular arrhythmias both in RCT (RR 0.78 (95% CI 0.63-0.96); p = 0.02) and observational studies (RR 0.62; 95% CI 0.53-0.72; p < 0.001). Furthermore, in non-RCTs, ARNI also reduced sustained (RR 0.36 (95% CI 0.2-0.63); p < 0.001), non-sustained VT (RR 0.67 (95% CI 0.57-0.80; p = 0.007), ICD shock (RR 0.24 (95% CI 0.12-0.48; p < 0.001), and increased biventricular pacing (2.96% (95% CI 2.25-3.67), p < 0.001). In patients with chronic HFrEF, switching from ACE-I/ARB to ARNI treatment was associated with a consistent reduction of ventricular arrhythmic burden. This association could be related to a direct pharmacological effect of ARNI on cardiac remodeling.Trial registration: CRD42021257977.

Sodium nitroprusside for advanced heart failure. A metanalysis of literature data.

Advanced heart failure (HF) is associated with a very poor prognosis and places a big burden on health-care services. The gold standard treatment, i.e. long-term mechanical circulatory support or heart transplantation, is precluded in many patients but observational studies suggest that the use of SNP might be associated with favourable long-term clinical outcomes. We performed a metanalysis of published studies that compared sodium nitroprusside (SNP) with optimal medical therapy to examine the safety and efficacy of SNP as part of the treatment regimen of patients hospitalized for advanced heart failure (HF). We searched PUBMED, EMBASE and WEB OF SCIENCE for studies that compared SNP with optimal medical therapy in advanced HF on July 2022. After screening 700 full-text articles, data from two original articles were included in a combined analysis. The analysis demonstrated a 66% reduction in the odds of death in advanced HF patients treated with SNP. The results show the potential importance of the inclusion of SNP in the treatment regimen of patients hospitalized because of advanced HF and underlines that controlled, randomized studies are still required in this condition.

Beneficial effects of adaptive servo-ventilation on natriuretic peptides and diastolic function in acute heart failure patients with preserved ejection fraction and sleep-disordered breathing.

PURPOSE: Adaptive servo-ventilation (ASV) is a ventilator algorithm able to correct breathing through anticyclic support of breathing in patients with central sleep apnea (CSA). So far, very few data exist regarding the role of ASV on acute heart failure with preserved ejection fraction (HFpEF). METHODS: We performed a single-center prospective, randomized, case-control study in consecutive acute HFpEF (left ventricle ejection fraction, LVEF ≥ 45%) patients with sleep-disordered breathing (SDB, apnea-hypopnea index, AHI > 15/h) and prevalence of CSA. RESULTS: We included ten consecutive patients randomized for ASV on top of standard therapy for acute heart failure (group 1) versus standard care alone (group 2). ASV therapy significantly reduced AHI and CSA. An improvement in cardiac diastolic function was seen in group 1 compared to group 2 (E/E' 17.5 to 9.6, p < 0.02 vs 18.5 to 14.5, p = 0.4). Brain natriuretic peptide (BNP) markedly decreased in cases, but not in controls (298 to 84 pg/ml, p < 0.02 vs 280 to 120 pg/ml, p = 0.06). Right ventricle (RV) function significantly improved in group 1, differently from group 2. CONCLUSIONS: An acute use of ASV seems effective in reducing BNP and improving diastolic and RV function in acute HFpEF patients with SDB and CSA, compared to standard treatment.

Outcome of patients listed for heart transplantation after a failed surgical ventricular restoration procedure.

Patients with end-stage ischemic cardiomyopathy (IHD) and left ventricular (LV) dilatation are increasingly treated by means of surgical ventricular restoration (SVR). In some patients, SVR can delay heart transplantation (HTX). We retrospectively analyzed our experience, trying to ascertain whether HTX after a failed SVR (fSVR) carried a greater mortality risk. Since 1985, we performed 742 HTX. Since June 1999, 133 IHD patients were listed for HTX. We assigned them to 3 groups: (A) not a redo (n=54); (B) redo after coronary artery bypass grafting (n=54); and (C) redo after fSVR (n=25). Respectively, 37, 33, and 12 patients underwent HTX with in-hospital mortality after HTX of 4/37 (10.8%), 12/33 (36.4%), and 2/12 (16.7%). Mortality on the list was 9/54 (16.7%), 11/54 (20.4%), and 7/25 (28.0%) respectively. Removal from the list occurred in 4, 5, and 2 patients, and 4, 5, and 4 patients are still awaiting HTX, respectively. In group C, the mean time from SVR to HTX list was 45.6+/-43.3 months, and list mortality occurred after 5.83+/-5.81 months. In-hospital mortality in both patients of group C was due to the occurrence of multisystem organ failure; 10/12 were extubated after 19.3+/-9.6 hours and discharged from the intensive care unit after 3.9+/-1.6 days. The recorded complications were: 3 acute renal failure, 1 pericardial effusion, and 2 episodes of acute rejection. Since only 5/25 patients with fSVR had undergone SVR at our institution, we cannot establish which patients were really eligible for HTX at the time of SVR. Our experience showed that patients listed for HTX displayed a high list mortality, but that HTX after a failed SVR did not seem to have a poorer outcome than HTX after previous conventional CABG.

Possible role of everolimus in improving renal function in long-term heart transplantation.

Patient survival after heart transplantation has improved dramatically since the availability of calcineurine inhibitor (CNIs); the number of long-term patients is progressively increasing. However, in these patients, nephrotoxicity of CNIs has been largely responsible for the progressive development of renal dysfunction. Since impaired renal function is an important issue that reduces long-term patient survival, it is important to develop strategies to improve renal function while maintaining immunologic safety to preserve graft function. Everolimus is an mTOR inhibitor sirolimus analogue, that has proved, to be highly efficacious to prevent acute myocardial rejection and reduce the severity of cardiac allograft vasculopathy in de novo HTx patients. There is reasonable evidence that, in long term heart transplanted patients, renal function may improve when everolimus is administered associated with a progressive reduction of CNIs. So far there is no evidence to identify which patient may benefit from this therapeutic approach. Indeed everolimus alone may be equally effective to prevent rejection and improve renal function when CNIs are completely discontinued, but data are still lacking on the risks, dosages and side effects of this type of immunosuppression. Ongoing clinical studies will provide further guidance about the possibility to halt or reduce the progression of renal impairment in long term heart transplant patients.

[Lipomatous hypertrophy of the interatrial septum: its assessment with TEE, CT and MRI]. / Ipertrofia lipomatosa del setto interatriale: valutazione con TEE, TAC e RMN.

BACKGROUND: Lipomatous atrial septal hypertrophy (LHS) is an uncommon condition characterized by the deposition of excessive adipose tissue in the atrial septum. The fossa ovalis is spared by this infiltration of fat. A variety of atrial arrhythmia has been associated with this lesion, which is more common in obese, elderly female patients. Because of the lack of specific symptoms, LHS is the outcome of casual observation during echo-Doppler or autopsy studies. METHODS: We describe the case of a 76-year-old woman who came under our observation due to stroke and atrial arrhythmia. Transesophageal echocardiography clearly revealed lipomatous atrial septal hypertrophy. RESULTS: The MRI confirmed the diagnosis, visualizing the typical "dumbbell" interatrial septum. Computed tomography made it possible to define the anatomic substance of the lesion as "fatty". CONCLUSIONS: Transesophageal echocardiography is the method of choice in the diagnosis of LHS. Other techniques such as RMI or CT-scan can be useful only in selected patients with large fatty infiltration of the atrial wall or marked hypertrophy of the interatrial septum.