Primary and secondary prevention protocols aim at reducing the plasma levels of lipids - with particular reference to low-density lipoprotein cholesterol (LDL-C) plasma concentrations – in order to ...improve the overall survival and reduce the occurrence of major adverse cardiovascular events. The use of statins has been widely considered as the first-line approach in lipids management as they can dramatically impact on the cardiovascular risk profile of individuals. The introduction of ezetimibe and proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors overcame the adverse effects of statins and ameliorate the achievement of the target lipids levels. Indeed, advances in therapies promote the use of specific molecules – i.e. short strands of RNA named small-interfering RNAs (siRNAs) – to suppress the transcription of genes related to lipids metabolism. Recently, the inclisiran has been developed: this is a siRNA able to block the mRNA of the PCSK9 gene. About 50% reduction in low-density lipoprotein cholesterol levels have been observed in randomized controlled trials with inclisiran. The aim of this review was to summarize the literature regarding inclisiran and its possible role in the general management of patients with lipid disorders and/or in primary/secondary prevention protocols.
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•The LDL-C targets in primary and secondary prevention are challenging.•Inclisiran is a short strands RNA able to selectively inhibit PCSK9 synthesis.•Inclisiran provides about 50% reduction in LDL-C plasma concentrations.•No significant adverse event rates are compared to placebo.•The need for a twice-yearly administration of Inclisiran may improve compliance.
In the essential homeostatic role of kidney, two intrarenal mechanisms are prominent: the glomerulotubular balance driving the process of Na+ and water reabsorption in the proximal tubule, and the ...tubuloglomerular feedback which senses the Na+ concentration in the filtrate by the juxtaglomerular apparatus to provide negative feedback on the glomerular filtration rate. In essence, the two mechanisms regulate renal oxygen consumption. The renal hyperfiltration driven by increased glomerular filtration pressure and by glucose diuresis can affect renal O2 consumption that unleashes detrimental sympathetic activation. The sodium-glucose co-transporters inhibitors (SGLTi) can rebalance the reabsorption of Na+ coupled with glucose and can restore renal O2 demand, diminishing neuroendocrine activation. Large randomized controlled studies performed in diabetic subjects, in heart failure, and in populations with chronic kidney disease with and without diabetes, concordantly address effective action on heart failure exacerbations and renal adverse outcomes.
The need for anticoagulation in patients with atrial fibrillation (AF) is fundamental to prevent thromboembolic events. Direct oral anticoagulants (DOACs) recently demonstrated to be superior, or at ...least equal, to Warfarin in reducing the risk for stroke/systemic embolism and preventing major bleeding and intracranial hemorrhages. The AF population often suffers from chronic kidney disease (CKD). Indeed, the relationship between AF and renal function is bidirectional: AF can trigger kidney failure, while kidney impairment can promote alterations able to enhance AF. Therefore, there are concerns regarding prescriptions of anticoagulants to patients with AF and CKD. The worsening in kidney function can be effectively due to anticoagulants administration. Warfarin has been recognized to promote acute kidney injury in case of excessive anticoagulation levels. Nevertheless, further mechanisms can induce the chronic worsening of renal function, thus leading to terminal kidney failure as observed in post-hoc analysis from registration trials and dedicated observational studies. By contrast, DOACs seem to protect kidneys from injuries more efficiently than Warfarin, although they still continue to play a role in promoting some kidney lesions. However, the exact mechanisms remain unknown. This narrative review aimed to discuss the influence of oral anticoagulants on renal impairment as well as to overview potential pathophysiological mechanisms related to this clinical complication.
•Congestion in acute heart failure affects survival curves and length of stay.•Our comparisons revealed that the higher the hydration status, the longer the LOS.•BIVA measurements are independent ...predictor of length of stay in acute HF patients.
Congestion in acute heart failure (AHF) affects survival curves and hospital length of stay (LOS). The evaluation of congestion, however, is not totally objective. The aim of this study was to verify the accuracy of bioelectrical impedance vector analysis (BIVA) in predicting the LOS in AHF patients.
This is a retrospective study. A total of 706 patients (367 male; mean age: 78 ± 10 y) who had been admitted to hospital with an AHF event were enrolled. All underwent anthropometric and clinical evaluation, baseline transthoracic echocardiography, and biochemical and BIVA evaluations.
The comparison among the clinical characteristics of congestion, LOS, and hyperhydration status revealed that the higher the hydration status, the longer the LOS (from 7.36 d interquartile range: 7.34–7.39 d in normohydrated patients to 9.04 d interquartile range: 8.85– 9.19 d in severe hyperhydrated patients; P < 0.05). At univariate analysis, brain natriuretic peptide, blood urea nitrogen, New York Heart Association class, hemoglobin, hydration index, and peripheral edema all had a statistically significant influence on LOS. At multivariate analysis, only brain natriuretic peptide (P < 0.0001), blood urea nitrogen (P = 0.011), and hydration index (P < 0.0001) were significantly associated to LOS.
Congestion evaluated by BIVA is an independent predictor of length of total hospital stay in HF patients with acute decompensation. The quick and reliable detection of congestion permits the administration of target therapy for AHF, thus reducing LOS and treatment costs.
•Congestion is a marker of adverse prognosis in patients with heart failure (HF).•BNP, ePVS, BIVA, and BUN/Cr ratio are independent prognostic biomarkers in HF.•Combining BNP, eVPS, BIVA, and BUN/Cr ...explain the 40% risk of death in HF.
Congestion is a marker of adverse prognosis in patients with heart failure (HF). In addition to brain natriuretic peptide (BNP), estimated plasma volume status (ePVS), bioimpedance vector analysis (BIVA), and blood urea nitrogen/creatinine ratio (BUN/Cr) are emerging as new markers for congestion. The aim of this study was to evaluate the prognostic value of BNP, ePVS, BIVA, and BUN/Cr in HF.
We analyzed the data from 436 patients with acute or chronic heart failure (AHF, n=184, and CHF, n=252, respectively). BNP, ePVS, hydration index (HI%), and BUN/Cr were collected from all patients at admission. The endpoint was all-cause mortality.
Ninety-two patients died after a median follow-up of 463 days (IQR: 287–669). The cumulative mortality of all of the patients was 21% (31% and 13% in AHF and CHF, respectively, p<0.0001). The optimal cut-offs for death occurrence were BNP: >441pg/mL, ePVS: >5.3dL/gr, HI: >73.8%, BUN/Cr: >25. Multivariate Cox regression analysis maintained an independent predictive value for mortality (HR 2. 1, HR 2.2, HR 2.1, and HR 1.7; C-index 0.756). AHF status was no longer associated with death. Together, these variables explained 40% of the risk of death (R2 adjusted=0.40). Patients with all four parameters below or above their optimal cut-off had mortality rates of 4% and 59%, respectively.
BNP, ePVS, BIVA, and BUN/Cr at admission provide independent and complementary prognostic information in patients with HF and, when combined, explain the 40% risk of death in these patients independent from the acute or chronic HF condition.
Clinical presentation of Takotsubo syndrome (TTS) may range from acute chest pain to dyspnea: the prognostic role of clinical onset is still controversial. Aim of this study was therefore to ...investigate the prognostic relevance of dyspnea at presentation in patients with TTS. We analyzed 1,071 TTS patients (median age 72 years, 90% female) enrolled in the international multicenter GEIST registry. Patients were divided according to the presence or absence of dyspnea at hospital admission, as clinically assessed by the accepting physician. The primary endpoint was occurrence of in-hospital complications defined as a composite of pulmonary edema, cardiogenic shock and death. Overall, 316 (30%) patients presented with dyspnea at hospital admission. Diabetes, lower left ventricular ejection fraction and presence of pulmonary disease or atrial fibrillation were independently associated with dyspnea. In-hospital pulmonary edema, cardiogenic shock and death (17% vs. 3%, p < 0.001; 12% vs. 7%, p = 0.009; 5% vs. 2%, p = 0.004 respectively) and long-term overall mortality (22% vs. 11%, p < 0.001) occurred more frequently in patients with dyspnea than in those without. At multivariable analysis, dyspnea at presentation remained independently associated to both the composite primary endpoint odds ratio 2.98 (95% confidence interval (CI) 1.95-4.59, p < 0.001 and all-cause mortality hazard ratio 2.03 (95% CI 1.37-2.99), p < 0.001. Dyspnea at presentation is common in TTS and is independently associated with in-hospital complications and impaired long-term prognosis. Thorough symptom assessment including dyspnea therefore represents a valuable tool to potentially optimize risk-stratification models for TTS patients.
One important complication related to takotsubo syndrome (TTS) is adverse rhythm disorders. Our study was conducted to determine the incidence and management of adverse rhythm disorders in TTS and ...its long-term prognostic impact. We analyzed 906 TTS patients from 9 European centers. Patients were divided into the adverse rhythm disorders group (encompassing ventricular tachycardia, ventricular fibrillation, torsade de pointes, and asystole or complete atrioventricular block) and non-adverse rhythm disorders group. In our study cohort, we identified 67 (7.4%) patients with presence of adverse rhythm disorders. TTS patients were followed up over a period of 2.8 years. In the adverse rhythm disorders group, 18% of patients presented adverse rhythm disorders before hospital admission. Asystole and/or AV block were significantly more presented before admission (13 patients versus 8 patients;
p
< 0.01), whereas ventricular tachyarrhythmias were more presented in-hospital (4 patients versus 42 patients;
p
< 0.01). Adverse rhythm disorders patients suffered more frequently from cardiogenic shock (31% versus 7.6%,
p
< 0.01) and in-hospital death (10.9% versus 3.6%;
p
< 0.01). Furthermore, the long-term survival was significantly impaired in adverse rhythm disorders patients as compared with non-adverse rhythm disorders patients; (log-rank
p
< 0.01). Using multivariate Cox regression analysis, cardiogenic shock (HR 2.86, 95% CI 1.1–6.9;
p
= 0.02) was identified as independent predictors of adverse rhythm disorders. The short- and long-term mortality rate of TTS patients presenting with adverse rhythm disorders was significantly higher than in TTS patients presenting without it. Therefore, TTS patients with adverse rhythm disorders should be carefully monitored during hospital stay and at long-term follow-up.
Background
Left ventricular (LV) thrombi during Takotsubo syndrome represent a potential complication and can be associated with cerebrovascular embolic events. The aim of this study was to evaluate ...the exact incidence, predictors, and management strategies of LV thrombi in patients with Takotsubo syndrome.
Methods and Results
We enrolled 541 consecutive patients in a multicenter international registry. Clinical features and echocardiographic data at admission, during hospitalization, and after 3 months were evaluated. Survival rates for long‐term follow‐up (mean 984±908 days) were recorded. Twelve Takotsubo syndrome patients (2.2%) developed LV thrombi (all female presenting with apical ballooning pattern). All patients with LV thrombi were treated with oral anticoagulation therapy; however, 2 (17%) had a stroke before treatment initiation. These patients were characterized by a higher prevalence of ST‐elevation (56% versus 16%; P<0.001) and higher troponin I levels (10.8±18.3 ng/mL versus 3.5±4.3 ng/mL; P=0.001) as compared with those without LV thrombi. At multivariate analysis including age, sex, LV ejection fraction, ST‐elevation at admission, and apical ballooning pattern, troponin I level >10 ng/mL was the only predictor for LV thrombosis (hazard ratio 6.6, confidence interval, 1.01–40.0; P=0.04). After 3 months all LV thrombi disappeared. Oral anticoagulation therapy was interrupted in all patients except 1. At long‐term follow‐up, the survival rate was not different between patients with and without LV thrombi (84% versus 85%; P=0.99).
Conclusions
LV thrombi have a relatively low incidence among patients with Takotsubo syndrome and were detected in female patients with apical ballooning pattern and increased troponin levels. Oral anticoagulation therapy for 3 months seems reasonable in these high‐risk patients.
The whole-body bioelectrical phase-angle (PhA) is emerging as a new tool in stratifying prognosis in patients with both acute (AHF) and chronic heart failure (CHF).
To evaluate the determinants of ...PhA in HF patients.
We analyzed data from 900 patients with AHF or CHF (mean age: 76±10 years, 54% AHF). Clinical, serum biochemical, echocardiographic and bioelectrical measurements were collected from all of patients. PhA was quantified in degrees. Congestion was assessed by a multiparametric approach, including the presence of peripheral edema, brain natriuretic peptides (BNP) plasma levels, blood urea nitrogen to creatinine ratio (BUN/Cr), and relative plasma volume status (PVS) calculated by Kaplan-Hakim's formula. Geriatric Nutritional Risk Index (GNRI) was adopted as indicator for nutritional status.
At univariate analysis, PhA was significantly lower in females, in patients with peripheral edema, and AHF. PhA significantly correlates age, BNP, PVS, BUN/Cr, and GNRI. At multivariate analysis, congestion biomarkers emerged as the major determinant of PhA as they explained the 34% of data variability, while age, GNRI, and gender only explained 6%, 0.5%, and 0.5%, respectively (adjusted R2 = 0.41). In particular, PVS (regression of coefficient B=−0.17) explained the 20% of PhA variability, while peripheral congestion (B=−0.27) and BNP (B=−0.15) contributed to 10% and 2%, respectively.
The main determinant of bioelectrical PhA in patients with HF is congestion and PVS in particular, while nutritional status has marginal impact.
Abstract Objective To evaluate the role of bioelectrical impedance vector analysis (BIVA) and brain natriuretic peptide (BNP) in detecting peripheral congestion in heart failure (HF). Background ...BIVA/BNP are biomarkers for congestion in acute (ADHF) and chronic HF. Methods 487 ADHF and 413 chronic HF patients underwent BIVA and BNP tests. Results BIVA was more accurate than BNP in detecting peripheral congestion both in ADHF (AUC 0.88 vs 0.57 respectively; p < 0.001) and chronic HF patients (AUC 0.89 vs 0.68, respectively; p < 0.001). In ADHF patients, the optimal BNP cut-off for discriminating presence or absence of edema was >870 pg/mL (PPV = 48% and NPV = 58%) whereas in chronic HF it was >216 pg/mL (PPV = 18% and NPV = 95%). The BIVA detected edema when the vector fell into the lower pole of 75th percentile tolerance ellipse (PPV = 84% and NPV = 78%) in ADHF, the lower pole of 50% (PPV = 68% and NPV = 95%) in chronic HF. Conclusions In HF patients, BIVA is an easy, fast technique to assess peripheral congestion, and is even more accurate than BNP.
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