From Structural to Functional Hypertension Mediated Target Organ Damage—A Long Way to Heart Failure with Preserved Ejection Fraction

Arterial hypertension (AH) is a major risk factor for the development of heart failure (HF) which represents one of the leading causes of mortality and morbidity worldwide. The chronic hemodynamic overload induced by AH is responsible for different types of functional and morphological adaptation of the cardiovascular system, defined as hypertensive mediated target organ damage (HMOD), whose identification is of fundamental importance for diagnostic and prognostic purposes. Among HMODs, left ventricular hypertrophy (LVH), coronary microvascular dysfunction (CMVD), and subclinical systolic dysfunction have been shown to play a role in the pathogenesis of HF and represent promising therapeutic targets. Furthermore, LVH represents a strong predictor of cardiovascular events in hypertensive patients, influencing per se the development of CMVD and systolic dysfunction. Clinical evidence suggests considering LVH as a diagnostic marker for HF with preserved ejection fraction (HFpEF). Several studies have also shown that microalbuminuria, a parameter of abnormal renal function, is implicated in the development of HFpEF and in predicting the prognosis of patients with HF. The present review highlights recent evidence on the main HMOD, focusing in particular on LVH, CMD, subclinical systolic dysfunction, and microalbuminuria leading to HFpEF

Severity of Coronary Atherosclerosis and Risk of Diabetes Mellitus

Cardio-vascular target organ damage predicts the onset of type 2 diabetes mellitus (DM) in hypertensive patients. Whether an increased incidence of DM is also in relation to the severity of coronary atherosclerosis is unknown

Determinants of improvement of left ventricular mechano-energetic efficiency in hypertensive patients

BackgroundArterial hypertension, especially when coexisting with other cardiovascular risk factors, could determine an imbalance between myocardial energetic demand and altered efficiency, leading to an early left ventricular (LV) systolic dysfunction, even in terms of echo-derived mechano-energetic efficiency indexed for myocardial mass (MEEi). We aim to analyse an improvement in LV MEEi, if any, in a population of hypertensive patients with a long-term follow-up and to identify clinical, metabolic and therapeutic determinants of LV MEEi amelioration.Materials and methodsIn total, 7,052 hypertensive patients, followed-up for 5.3 ± 4.5 years, enrolled in the Campania Salute Network, underwent echocardiographic and clinical evaluation. LV MEEi was obtained as the ratio between stroke volume and heart rate and normalized per grams of LV mass and ΔMEEi was calculated as difference between follow-up and baseline MEEi. Patients in the highest ΔMEEi quartile (≥0.0454 mL/s/g) (group 1) were compared to the merged first, second and third quartiles (<0.0454 mL/s/g) (group 2). METS-IR (Metabolic Score for Insulin Resistance), an established index of insulin sensitivity, was also derived.ResultsPatients with MEEi improvement experienced a lower rate of major cardiovascular events (p = 0.02). After excluding patients experiencing cardiovascular events, patients in group 1 were younger (p < 0.0001), less often diabetic (p = 0.001) and obese (p = 0.035). Group 1 experienced more frequently LV mass index reduction, lower occurrence of LV ejection fraction reduction, and had a better metabolic control in terms of mean METS-IR during the follow-up (all p < 0.0001). Beta-blockers were more often used in group 1 (p < 0.0001) than group 2. A logistic regression analysis showed that younger age, lower mean METS-IR values, more frequent LV mass index reduction and therapy with beta-blockers were significantly associated with LV MEEi improvement, independently of presence of diabetes and obesity.ConclusionMetabolic control and therapy with beta-blockers could act in a synergic way, determining an improvement in LV MEEi in hypertensive patients over time, possibly confining cardiac damage and hampering progression toward heart failure

Ribociclib in newly diagnosed hepatitis B infection: A case report

Breast cancer is the most frequently diagnosed cancer in women worldwide. Actually CDK4/6 inhibitor Ribociclib is approved for the treatment of metastatic hormone-positive and human epidermal growth factor receptor 2 (HER 2)-negative breast cancer, but comorbidities like infectious or cardiovascular diseases may limit its use.Case reportA 45-year-old woman was diagnosed with metastatic breast cancer in September 2021; also, her hepatitis screening resulted positive for hepatitis B infection. Patient assumed eradicative therapy for hepatitis and bit after started oncological therapy with Ribociclib.OutcomeFrequent check of hepatological function was observed since start of eradicative therapy; liver transaminases and bilirubin kept to not rise despite start of oncological treatment with Ribociclib. Patient’s Performance Status was also not compromised and revaluation at 4, 9 and 13 months showed partial response and then stable disease.Discussionhepatotoxicity of Ribociclib is reported as a possible side effect, and often positivity for hepatitis is cause of exclusion from therapy; in our case, no hepatotoxicity was noted and patient obtained response in terms of control of both infectious and oncological diseases

Insulin resistance and cardiovascular risk: New insights from molecular and cellular biology.

Insulin resistance has been described in several diseases that increase cardiovascular risk and mortality, such as diabetes, obesity, hypertension, metabolic syndrome, and heart failure. Abnormalities of insulin signaling account for insulin resistance. Insulin mediates its action on target organs through phosphorylation of a transmembrane-spanning tyrosine kinase receptor, the insulin receptor (IR). Several mechanisms have been described as responsible for the inhibition of insulin-stimulated tyrosine phosphorylation of IR and the IR substrate (IRS) proteins, including proteasome-mediated degradation, phosphatase-mediated dephosphorylation, and kinase-mediated serine/threonine phosphorylation. In particular, phosphorylation of IRS-1 on serine Ser612 causes dissociation of the p85 subunit of phosphatidylinositol 3-kinase, inhibiting further signaling. On the other hand, phosphorylation of IRS-1 on Ser307 results in its dissociation from the IR and triggers proteasome-dependent degradation. Dysregulation of sympathetic nervous and renin-angiotensin systems resulting in enhanced stimulation of both adrenergic and angiotensin II receptors is a typical feature of several cardiovascular diseases and, at the same time, is involved in the pathogenesis of insulin resistance. The characterization of molecular mechanisms involved in the pathogenesis of insulin resistance may help to design efficacious pharmacologic molecules to treat endothelial and metabolic dysfunction associated with insulin resistance states to reduce the cardiovascular risk and to ameliorate the prognosis of patients with cardiovascular diseases

Fractional flow reserve (FFR) as a guide to treat coronary artery disease

The presence and extent of myocardial ischemia are the major determinants of prognosis in patients with coronary artery disease (CAD). Unlike coronary angiography alone, fractional flow reserve (FFR) has enabled interventional cardiologists to accurately determine whether coronary atherosclerotic plaques are responsible for myocardial ischemia, and therefore deserve to be revascularized. Areas covered: An overview on the role of FFR in the diagnosis and treatment of coronary artery disease, as well as the potential related controversies is provided. Authors describe the coronary physiology underneath this technique and all the procedural aspects in the catheterization laboratory. The landmark trials and the current applications in different coronary lesions and syndromes are also described and potential future research involving FFR and comparisons with other methodologies for the evaluation of coronary physiology are introduced. Expert commentary: FFR is still unsurpassed in diagnostic performance when compared to non-hyperemic indices and noninvasive techniques, and remains the gold standard for the detection of ischemia-inducing coronary stenoses. FFR-guided PCI has been demonstrated superior to an angiography-guided PCI and over medical therapy alone, and ongoing investigation will clarify whether it could perform better, or at least equalize the results of cardiac surgery in patients with severe multivessel disease

Il trattamento dell'infarto miocardico acuto nel 2017

Acute myocardial infarction is a clinical cardiac emergency associated with potential and substantial morbidity and mortality. This disorder is triggered by an acute coronary syndrome caused by episodes of plaque ulceration, fissuration, or rupture with subsequent production of thrombogenic material and intravascular thrombus formation. The presence or absence of ST-segment elevation on the ECG defines the two main clinical spectrum of ST-segment elevation or non-ST-segment elevation myocardial infarction. In the last three decades, pharmacological and interventional management as well as in-hospital care have dramatically improved. Recent advances in antithrombotic strategies, percutaneous access (radial versus femoral), timing of revascularization, new generation coronary stents, lipid profile management, and cardiac rehabilitation programs at discharge have lead the European Task Force on ST-Elevation Myocardial Infarction to revise the 2012 guidelines and to release, in the current year, an updated version