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

TEVAR for Iatrogenic Injury of the Distal Aortic Arch after Pacemaker Implantation

Introduction We report the endovascular treatment of aortic arch injury due to direct puncture during pacemaker implantation. Report After pacemaker implantation a 74-year-old woman showed a progressive decrease in haematocrit with elevation of cardiac troponin-I. Coronary angiography revealed the malposition of the catheters introduced through the aortic wall. The atrial lead was placed in the left circumflex coronary artery. Computed tomography scan confirmed distal aortic arch perforation. A Medtronic-Valiant stent–graft was implanted in the distal aortic arch while the two catheters were removed. A new VVI pacemaker was implanted and, 3 days later, the patient underwent percutaneous coronary intervention (PCI) on the dissected left circumflex artery. Four days later the patient was discharged. One-year computed tomography scan showed successful repair of the injured aorta. Discussion Endovascular stent grafting has emerged as a less invasive therapeutic alternative to treat traumatic or iatrogenic injuries of the distal aortic arch

Effects of inhibition of the renin-angiotensin system on hypertension-induced target organ damage: clinical and experimental evidence.

The dysregulation of renin-angiotensin-system (RAS) plays a pivotal role in hypertension and in the development of the related target organ damage (TOD). The main goal of treating hypertension is represented by the long-term reduction of cardiovascular (CV) risk. RAS inhibition either by angiotensin converting enzyme (ACE)-inhibitors or by type 1 Angiotensin II receptors blockers (ARBs), reduce the incidence of CV events in hypertensive patients. Actually, ACE-inhibitors and ARBs have been demonstrated to be effective to prevent, or delay TOD like left ventricular hypertrophy, chronic kidney disease, and atherosclerosis. The beneficial effects of RAS blockers on clinical outcome of hypertensive patients are due to the key role of angiotensin II in the pathogenesis of TOD. In particular, Angiotensin II through an inflammatory-mediated mechanism plays a role in the initiation, progression and vulnerability of atherosclerotic plaque. In addition, Angiotensin II can be considered the hormonal transductor of the pressure overload in cardiac myocytes, and through an autocrine-paracrine mechanism plays a role in the development of left ventricular hypertrophy. Angiotensin II by modulating the redox status and the immune system participates to the development of chronic kidney disease. The RAS blocker should be considered the first therapeutic option in patients with hypertension, even if ACE-inhibitors and ARBs have different impact on CV prevention. ARBs seem to have greater neuro-protective effects, while ACE-inhibitors have greater cardio-protective action

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

Insulin Resistance Predicts Severity of Coronary Atherosclerotic Disease in Non-Diabetic Patients

Background: Insulin resistance (IR) in patients with type 2 diabetes mellitus (T2DM) represents a predictor of coronary artery disease (CAD). However, how IR is able to impact the severity of coronary atherosclerosis in non-diabetic patients is unknown. Objectives. We investigated the relation between the IR and the extent and severity of coronary atherosclerosis in non-diabetic patients referred to coronary angiography (CA) Methods: Consecutive patients undergoing to CA for acute coronary syndromes or stable angina were analyzed. The IR was assessed by mean of the homeostasis model assessment of insulin resistance (HOMA-IR) whereas the SYNTAX score (SS) was used as index of the severity of coronary atherosclerosis Results: Overall, 126 patients were included, with a median SS of 12 (IQR 5.25–20.5). Patients were divided in four groups according to the distribution in quartiles of SS (SS1-2-3-4). A significant correlation between HOMA-IR and SS was observed, especially in women. A progressive increase of HOMA-IR was observed in parallel with the increasing severity (from SS1 to SS4) and extension (1-2-3-vessel disease) of coronary atherosclerosis. Multivariable analysis showed that the HOMA-IR was the strongest independent predictor of severe (SS4) and extensive (three-vessel disease) coronary atherosclerosis. Conclusion: Insulin resistance goes hand in hand with the extension and severity of coronary atherosclerosis in non-diabetic patients. The HOMA index is an independent predictor of three-vessel disease at CA. The HOMA index could be useful for risk stratification of CAD even in absence of T2D

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

Cost Effectiveness of a CYP2C19 Genotype-Guided Strategy in Patients with Acute Myocardial Infarction:Results from the POPular Genetics Trial

INTRODUCTION: The POPular Genetics trial demonstrated that a CYP2C19 genotype-guided P2Y12 inhibitor strategy reduced bleeding rates compared with standard treatment with ticagrelor or prasugrel without increasing thrombotic event rates after primary percutaneous coronary intervention (PCI). OBJECTIVE: In this analysis, we aimed to evaluate the cost effectiveness of a genotype-guided strategy compared with standard treatment with ticagrelor or prasugrel. METHODS: A 1-year decision tree based on the POPular Genetics trial in combination with a lifelong Markov model was developed to compare costs and quality-adjusted life-years (QALYs) between a genotype-guided and a standard P2Y12 inhibitor strategy in patients with myocardial infarction undergoing primary PCI. The cost-effectiveness analysis was conducted from a Dutch healthcare system perspective. Within-trial survival and utility data were combined with lifetime projections to evaluate lifetime cost effectiveness for a cohort of 1000 patients. Costs and utilities were discounted at 4 and 1.5%, respectively, according to Dutch guidelines for health economic studies. Besides deterministic and probabilistic sensitivity analyses, several scenario analyses were also conducted (different time horizons, different discount rates, equal prices for P2Y12 inhibitors, and equal distribution of thrombotic events between the two strategies). RESULTS: Base-case analysis with a hypothetical cohort of 1000 subjects demonstrated 8.98 QALYs gained and €725,550.69 in cost savings for the genotype-guided strategy (dominant). The deterministic and probabilistic sensitivity analysis confirmed the robustness of the model and the cost-effectiveness results. In scenario analyses, the genotype-guided strategy remained dominant. CONCLUSION: In patients undergoing primary PCI, a CYP2C19 genotype-guided strategy compared with standard treatment with ticagrelor or prasugrel resulted in QALYs gained and cost savings. TRIAL REGISTRATION: Clinicaltrials.gov number: NCT01761786, Netherlands trial register number: NL2872