A Multistep Approach to Deal With Advanced Heart Failure: A Case Report on the Positive Effect of Cardiac Contractility Modulation Therapy on Pulmonary Pressure Measured by CardioMEMS

During the last years, the management of heart failure (HF) made substantial progress, focusing on device-based therapies to meet the demands of this complex syndrome. In this case report, we present a multistep approach to deal with HF. Specifically, we report the first patient subjected to the implantation of both Optimizer Smart(R) (Impulse Dynamics Inc., Marlton, NJ, USA) and CardioMEMS devices. A 72-year-old male patient with HF and reduced ejection fraction (HFrEF) was admitted to our cardiology department in January 2021, following a progressive shortening of the time between hospitalizations for levosimendan infusions. Specifically, the patient was monitored daily by CardioMEMS, and a strategy of levosimendan infusions guided by the device had been adopted. He was also a carrier of MitraClips and cardiac resynchronization therapy defibrillator (CRT-D) and had optimized HF medical therapy. In January 2021, the patient implanted Optimizer Smart(R) device for cardiac contractility modulation (CCM) therapy because of poor response to therapy and elevated pulmonary artery pressure (PAP). CCM significantly reduced PAP values following discharge (systolic PAP 33.67 & PLUSMN; 2.92 vs. 40.6 & PLUSMN; 3.37 mmHg, diastolic PAP 14.5 & PLUSMN; 2.01 vs. 22.5 & PLUSMN; 2.53 mmHg, mean PAP 22.87 & PLUSMN; 2.20 vs. 30.9 & PLUSMN; 2.99 mmHg, HR 60.93 & PLUSMN; 1.53 vs. 80.83 & PLUSMN; 3.66 bpm; p < 0.0001), with persisting effect at 9 months. The usefulness of CCM is objectively demonstrated for the first time by continuous invasive monitoring of PAP by CardioMEMS, which can suggest the correct timing for CCM implantation

Bioprosthetic Valve Fracture After TAVR Complicated by Balloon Rupture: Bail-Out TAVR in TAVR in SAVR

Transcatheter aortic valve replacement in surgical aortic valve is a safe and effective procedure to treat patients with failed bioprosthetic surgical valves at high risk for reoperation. Performing bioprosthetic valve fracture has been shown to improve postprocedural hemodynamics of TAVR in surgical aortic valve replacement. However, specific complications related to valve fracture are becoming more common. (Level of Difficulty: Advanced.)

A novel missense mutation for Fabry disease detected by echocardiographic screening in left ventricular hypertrophy patients

Fabry disease is an X-linked lysosomal storage disease caused by mutations in the a-galactosidase A gene (GLA), leading to the absence or a reduction of the enzymatic activity of the encoded enzyme and subsequent progressive tissue accumulation of glycosphingolipids through-out all the body, with consequent multiorgan failure. Here, we report the case of a 57-year-old woman with Fabry disease due to a novel GLA gene mutation

The proliferation marker Chromatin Assembly Factor-1 is of clinical value in predicting the biological behaviour of salivary gland tumours.

Salivary gland tumours (SGT) constitute a diagnostically challenging group of neoplasms with frequently unpredictable clinical outcome. The proliferation rate facilitates the identification of aggressive SGT. The Chromatin Assembly Factor-1 (CAF-1) is a major epigenetic regulator of nuclear chromatin organization during DNA replication. It plays a critical function in human tumourigenesis and has been proposed as a new proliferation and prognostic marker for some malignancies. This study focused on the role of CAF-1/p60 protein as a marker of clinical value for SGT. The expression of CAF-1/p60 was evaluated by immunohistochemistry on a retrospective series of 362 surgically excised benign and malignant SGT with different histogenesis and, when available, on fine-needle pre-surgical cytological biopsies. The resulting data were compared with traditional prognostic parameters, including the expression of the routine proliferation marker ki67/MIB1. CAF-1/p60 was detectable in all SGT, with highest degree of expression in metastasizing malignant tumours. Moreover, the cases of benign tumours which progressed to carcinoma during the follow-up, showed significantly higher CAF-1/p60 expression than non-progressing benign SGT, both on histological sections and cytological smears of the primary tumour. Cox's multiple regression analysis selected CAF-1/p60 expression as the best independent predictor of cancer development for benign SGT (p<0.0001), and the best independent predictor of metastasis onset for malignant tumours (p<0.0004). Overexpression of CAF-1/p60, on histological and/or cytological samples, characterizes malignant SGT with aggressive behaviour, irrespective of their specific histotype, and allows the early diagnosis of progression toward malignancy of morphologically benign tumours

Lipoprotein(a) levels and risk of adverse events after myocardial infarction in patients with and without diabetes

Introduction: The aim of this study was to evaluate the association of lipoprotein(a) [Lp(a)] levels with long-term outcome in patients with recent history of myocardial infarction (MI), and to investigate if diabetes may influence this association. Methods: Consecutive MI patients who underwent urgent/emergent coronary angiography from February 2013 to June 2019 were prospectively collected. The primary outcome was the composite of MI recurrence and all-cause death. The propensity score weighting technique was used to account for covariates potentially influencing the relationship between Lp(a) levels and the study outcomes. Results: The study population consisted of 1018 post-MI patients (median age 63 years). Diabetes was reported in 280 patients (27.5%), who showed lower Lp(a) levels than patients without diabetes (p = 0.026). At a median follow-up of 1121 days, the primary outcome was reported in 182 patients (17.9%). At univariable Cox regression analysis, Lp(a) was associated with the risk of the primary outcome in the overall population and in non-diabetic patients, but not in diabetics. The adjusted Cox regression analysis confirmed the independent association between Lp(a) values and the primary outcome in non-diabetic patients, but not in diabetics. Lp(a) levels &gt; 70 mg/dL were independently associated with the risk of the primary outcome in non-diabetic patients (adjusted HR: 2.839; 95% CI, 1.382-5.832), but not in diabetics. Conclusions: In this real-world post-MI population, increasing Lp(a) levels were significantly associated with the risk of recurrent MI and all-cause death, and very high Lp(a) serum concentration independently predicted long-term outcome in non-diabetic patients, but not in diabetics

A Novel Combination of High-Load Omega-3 Lysine Complex (AvailOm®) and Anthocyanins Exerts Beneficial Cardiovascular Effects

Omega-3 fatty acids have been shown to exert several beneficial effects in the prevention of cardiovascular and cerebrovascular diseases. The objective of the present study was to analyze the effects of a novel high-load omega-3 lysine complex, AvailOm®, its related constituents and a novel mixture of AvailOm® with specific vasoactive anthocyanins on vascular function in mice resistance artery. Pressure myograph was used to perform vascular reactivity studies. Nitric oxide and oxidative stress were assessed by difluorofluorescein diacetate and dihydroethidium, respectively. Increasing doses of AvailOm® exerted a dose-response vasorelaxation via AMPK-eNOS-mediated signaling. Omega-3 Ethyl Ester was identified as the main bioactive derivative of AvailOm®, being capable of inducing vasorelaxant action to the same extent of entire product. The combination of AvailOm® with a mix of potent vasoactive anthocyanins (C3-glu + DP3-glu + Mal3-glu + Mal3-gal + PEO3-gal), strongly protected mesenteric arteries from vascular dysfunction and oxidative stress evoked by oxidized-LDL. These data demonstrate for the first time the direct effects of AvailOm® on resistance arteries. The evidence that the combination of specific vasoactive anthocyanins and AvailOm® further enhanced the vasculoprotective properties of these compounds, may offer new promising perspectives for preventing the onset of cardiovascular and cerebrovascular events

Importance of Echocardiography and Clinical "Red Flags" in Guiding Genetic Screening for Fabry Disease

Aim of this study was to evaluate, in a metropolitan area not already explored, the prevalence of Anderson-Fabry disease, by genetic screening, in patients with echocardiographic evidence of left ventricular hypertrophy (LVH) of unknown origin and "clinical red flags"

Prevalence and Predictors of Out-of-Target LDL Cholesterol 1 to 3 Years After Myocardial Infarction. A Subanalysis From the EYESHOT Post-MI Registry

Background: There is an incomplete understanding of the prevalence and predictors of attainment of low-density lipoprotein cholesterol (LDL-C) goal after myocardial infarction (MI). Aim: To evaluate the prevalence of achievement of LDL-C goal of 70 mg/dL, to identify the baseline features associated with suboptimal lipid control, and to assess the use of LDL-C-lowering drug therapies (LLT) beyond the first year after MI. Methods: The EYESHOT Post-MI was a prospective, cross-sectional, Italian registry, which enrolled patients presenting to cardiologist 1 to 3 years after MI. In this retrospective post-hoc analysis, patients were categorized in 2 groups according to the achievement or not of the LDL-C goal of 70 mg/dL. Univariable and multivariable logistic regression analyses were performed to identify the baseline features associate with LDL-C &gt;= 70 mg/dL. Results: The study population included 903 patients (mean age 65.5 +/- 11.5 years). Among them, LDL-C was &gt;= 70 mg/dL in 474 (52.5%). Male sex (p = 0.031), hypertension (p = 0.024), prior percutaneous coronary intervention (p = 0.016) and high education level (p = 0.008) were higher in the LDL-C &lt; 70 group. At multivariable analysis, low education level was an independent predictor of LDL-C &gt;= 70 mg/dL (OR:1.582; 95%CI, 1.156-2.165; p = 0.004). Conversely, hypertension increased the probability to achieve the LDL-C goal (OR:0.650; 95%CI, 0.443-0.954; p = 0.028). Among off-target patients, LLT was not modified in the majority of cases (67.3%), intensified in 85 (18.6%), and actually reduced in 63 patients (13.8%). Conclusions: In patients presenting to cardiologists 1 to 3 years from the last MI event, LDL-C is not under control in a large proportion of patients, particularly in those with a low education level or without hypertension. LLT is underused in this very-high-risk setting

Protection from angiotensin II–mediated vasculotoxic and hypertensive response in mice lacking PI3Kγ

Hypertension affects nearly 20% of the population in Western countries and strongly increases the risk for cardiovascular diseases. In the pathogenesis of hypertension, the vasoactive peptide of the renin-angiotensin system, angiotensin II and its G protein–coupled receptors (GPCRs), play a crucial role by eliciting reactive oxygen species (ROS) and mediating vessel contractility. Here we show that mice lacking the GPCR-activated phosphoinositide 3-kinase (PI3K)γ are protected from hypertension that is induced by administration of angiotensin II in vivo. PI3Kγ was found to play a role in angiotensin II–evoked smooth muscle contraction in two crucial, distinct signaling pathways. In response to angiotensin II, PI3Kγ was required for the activation of Rac and the subsequent triggering of ROS production. Conversely, PI3Kγ was necessary to activate protein kinase B/Akt, which, in turn, enhanced L-type Ca2+ channel–mediated extracellular Ca2+ entry. These data indicate that PI3Kγ is a key transducer of the intracellular signals that are evoked by angiotensin II and suggest that blocking PI3Kγ function might be exploited to improve therapeutic intervention on hypertension

Predictors of sacubitril/valsartan high dose tolerability in a real world population with HFrEF

Abstract Aims The angiotensin receptor‐neprilysin inhibitor (ARNI) sacubitril/valsartan (Sac/Val) demonstrated to be superior to enalapril in reducing hospitalizations, cardiovascular and all‐cause mortality in patients with ambulatory heart failure and reduced ejection fraction (HFrEF), in particular when it is maximally up‐titrated. Unfortunately, the target dose is achieved in less than 50% of HFrEF patients, thus undermining the beneficial effects on the outcomes. In this study, we aimed to evaluate the role of Sac/Val and its titration dose on reverse cardiac remodelling and determine which echocardiographic index best predicts the up‐titration success. Methods and results From January 2020 to June 2021, we retrospectively identified 95 patients (65.6 [59.1–72.8] years; 15.8% females) with chronic HFrEF who were prescribed Sac/Val from the HF Clinics of 5 Italian University Hospitals and evaluated the tolerability of Sac/Val high dose (the ability of the patient to achieve and stably tolerate the maximum dose) as the primary endpoint in the cohort. We used a multivariable logistic regression analysis, with a stepwise backward selection method, to determine the independent predictors of Sac/Val maximum dose tolerability, using, as candidate predictors, only variables with a P‐value < 0.1 in the univariate analyses. Candidate predictors identified for the multivariable backward logistic regression analysis were age, sex, body mass index (BMI), chronic kidney disease (CKD), chronic obstructive pulmonary disease (COPD), dyslipidaemia, atrial fibrillation, systolic blood pressure (SBP), baseline tolerability of ACEi/ARBs maximum dose, left ventricle global longitudinal strain (LVgLS), LV ejection fraction (EF), tricuspid annulus plane systolic excursion (TAPSE), right ventricle (RV) fractional area change (FAC), RV global and free wall longitudinal strain (RVgLS and RV‐FW‐LS). After the multivariable analysis, only one categorical (ACEi/ARBs maximum dose at baseline) and three continuous (younger age, higher SBP, and higher TAPSE), resulted significantly associated with the study outcome variable with a strong discriminatory capacity (area under the curve 0.874, 95% confidence interval (CI) (0.794–0.954) to predict maximum Sac/Val dose tolerability. Conclusions Our study is the first to analyse the potential role of echocardiography and, in particular, of RV dysfunction, measured by TAPSE, in predicting Sac/Val maximum dose tolerability. Therefore, patients with RV dysfunction (baseline TAPSE <16 mm, in our cohort) might benefit from a different strategy to titrate Sac/Val, such as starting from the lowest dose and/or waiting for a more extended period of observation before attempting with the higher doses