Real-World Data from the Use of Ranolazine in Patients with Stable Angina Pectoris: The RANGER Study.

Background: Although ranolazine has been available for years as a second-line treatment to reduce angina attacks in patients with stable angina pectoris, real-world data on the effectiveness, tolerability, and safety of ranolazine are limited. Methods: A non-interventional, prospective study was conducted to assess the effectiveness and safety of ranolazine. Patients eligible for enrolment had a baseline assessment between one and fourteen days after initiating ranolazine for the first time and a follow-up visit three months later. The primary endpoints comprised the weekly frequency of angina attacks, total adverse events, and ranolazine discontinuation rate. The secondary endpoints included the use of short-acting nitrates, changes on the Canadian Cardiovascular Society (CCS) angina classification score and quality of life scale score (QoL). Results: In total, 1101 patients were enrolled at 214 sites. Mean weekly angina attacks were reduced from 3.6 ± 2.9 to 0.4 ± 0.9 (p < 0.0001) and the mean weekly consumption of short-acting nitrates decreased by 1.7 ± 2.2 (p < 0.0001). CCS class and QoL were also improved (p < 0.0001). Adverse events were reported by 11 (1%) patients in total, while 2 of them (0.2%) were characterised as serious. Treatment was discontinued for various reasons in 23 patients (2.1%) after the follow-up period. Ranolazine treatment was equally effective in all subgroups tested, with larger benefits observed in patients with more frequent angina and CCS angina class III and IV. Up-titration of ranolazine during the study improved the outcomes. Conclusions: Ranolazine was well tolerated and effectively reduced angina attacks, with simultaneous improvement of the CCS class and QoL score in patients with stable angina.

Left atrial strain and ventricular global longitudinal strain in cirrhotic patients using the new criteria of Cirrhotic Cardiomyopathy Consortium.

BACKGROUND: The new criteria of Cirrhotic Cardiomyopathy Consortium (CCC) propose the use of left ventricular global longitudinal strain (LV-GLS) for evaluation of systolic function in patients with cirrhosis. The aim of this study was to evaluate LV-GLS and left atrial (LA) strain in association with the severity of liver disease and to assess the characteristics of cirrhotic cardiomyopathy (CCM). METHODS: One hundred and thirty-five cirrhotic patients were included. Standard echocardiography and speckle tracking echocardiography (2D-STE) were performed, and dual X-ray absorptiometry was used to quantify the total and regional fat mass. CCM was defined, based on the criteria of CCC, as having advanced diastolic dysfunction, left ventricular ejection fraction ≤50% and/or a GLS <18%. RESULTS: LV-GLS lower or higher than the absolute mean value (22.7%) was not associated with mortality (logrank, p = 0.96). LV-GLS was higher in patients with Model for end stage liver disease (MELD) score ≥15 compared to MELD score <15 (p = 0.004). MELD score was the only factor independently associated with systolic function (LV-GLS <22.7% vs. ≥22.7%) (Odds Ratio:1.141, p = 0.032). Patients with CCM (n = 11) had higher values of estimated volume of visceral adipose tissue compared with patients without CCM (median: 735 vs. 641 cm3 , p = 0.039). On multivariable Cox regression analysis, MELD score [Hazard Ratio (HR):1.26, p < 0.001] and LA reservoir strain (HR:0.96, p = 0.017) were the only factors independently associated with the outcome. CONCLUSION: In our study, absolute LV-GLS was higher in more severe liver disease, and LA reservoir strain was significantly associated with the outcome in patients with end-stage liver disease.

The association of insulin resistance measured through the estimated glucose disposal rate with predictors of micro-and macrovascular complications in patients with type 1 diabetes.

BACKGROUND AND AIM: Insulin resistance (IR) is associated with a higher rate of type 1 diabetes (T1D) complications. We aimed to examine the relationship between estimated glucose disposal rate (eGDR), a readily available marker of IR in clinical practice and early predictor biomarkers of macrovascular and microvascular complications in patients with T1D. DESIGN: A cross-sectional study. METHODS: A total of 165 consecutive patients with T1D free of cardiovascular, eye, and renal complications were included in the study from 2016 to 2020. Participants were characterized as insulin resistant if their eGDR value was ≤ 8 mg/kg/min. Pulse wave velocity (PWV) and global longitudinal strain (GLS) were used as surrogates for subclinical atherosclerosis and left ventricular systolic dysfunction (LVSD), respectively. Four previously standardized tests based on the calculation of heart rate variability (HRV) were used to evaluate subclinical cardiac autonomic neuropathy (CAN). Early nephropathy was assessed by assessing urinary albumin to creatinine ratio (ACR). RESULTS: The population sample (n = 165) included a majority of female patients (63%) and had a median age of 32 years (24-43), median disease duration of 14 years ( ± 9.5-21.5), a median BMI value of 23.7 kg/m2 (21.4-26.6), an HbA1C of 7.2% (6.7-8.2) and median eGDR (lower values indicate higher insulin resistance) of 9.2 mg/kg/min (8.2-9.9), while 21.8% (n = 36) of the participants were characterized as insulin resistant. After adjustment for age, gender, and the duration of diabetes, the presence of IR was significantly associated with higher prevalence of subclinical atherosclerosis (OR:2.59, 95% CI: 1.06-6.30, p = 0.036), CAN (OR:3.07, 95% CI: 1.02-9.32, p = 0.047) and subclinical LVSD (OR: 4.9, 95% CI: 1.94-12.79, p = 0.001). No association was shown with ACR. CONCLUSIONS: In patients with T1D, insulin resistance, as measured by eGDR, correlates well with early CVD predictors and CAN. These associations appear independent of the effects of gender, aging, and disease duration.

Antihypertensive Drugs and Risk of Bone Fractures.

Antihypertensive drugs are among the most documented regimens worldwide with an overall survival and cardioprotective benefit. However, there is evidence that they cause symptoms of orthostatic hypotension (i.e., dizziness and syncope) placing patients at risk for falls and fall-related injuries such as bone fractures. Moreover, it seems that they might impact bone metabolism and architecture impairing bone health. The aim of this review was to summarize the accumulative literature exploring any potential association between several antihypertensive medications including diuretics, renin-angiotensin-aldosterone system inhibitors, beta-blockers and calcium channel blockers and the risk of fractures.

Subclinical Left Ventricular Systolic Dysfunction in HIV Patients: Prevalence and Associations with Carotid Atherosclerosis and Increased Adiposity.

BACKGROUND: Human immunodeficiency virus (HIV) is mainly detected in young, otherwise healthy, individuals. Cardiomyopathy and peripheral artery disease affecting these patients appears to be multifactorial. Prompt and potentially more effective implementation of therapeutic measures could be enabled by pre-symptomatic diagnosis of myocardial dysfunction and peripheral artery damage. However, limited data is available to date on this specific topic. Μethods: We investigated the association between global longitudinal strain (GLS), an established index of subclinical left ventricular systolic dysfunction (LVSD) assessed by two-dimensional speckle-tracking echocardiography, and: (a) patient history; (b) demographic and clinical baseline characteristics; (c) carotid intima-media thickness (IMT) and the presence of carotid atherosclerotic plaque(s), measured by ultrasonography; (d) temperature difference (ΔT) along each carotid artery, measured by microwave radiometry; and (e) basic blood panel measurements, including high-sensitivity troponin-T (hsTnT) and NT-proBNP in people living with HIV (PLWH) and no history of cardiovascular disease. RESULTS: We prospectively enrolled 103 consecutive PLWH (95% male, age 47 ± 11 years, anti-retroviral therapy 100%) and 52 age- and sex-matched controls. PLWH had a significantly higher relative wall thickness (0.38 ± 0.08 vs. 0.36 ± 0.04, p = 0.048), and higher rate of LVSD (34% vs. 15.4%, p = 0.015), and carotid artery atherosclerosis (28% vs. 6%, p = 0.001) compared with controls. Among PLWH, LVSD was independently associated with the presence of carotid atherosclerosis (adj. OR:3.09; 95%CI:1.10-8.67, p = 0.032) and BMI (1.15; 1.03-1.29, p = 0.017), while a trend for association between LVSD and left ventricular hypertrophy was also noted (3.12; 0.73-13.33, p = 0.124). No differences were seen in microwave radiometry parameters, NT-proBNP, hs-TnT and c-reactive protein between PLWH with and without LVSD. CONCLUSIONS: Subclinical LVSD and carotid atherosclerosis were significantly more frequent in PLWH compared to a group of healthy individuals, implying a possible link between HIV infection and these two pathological processes. Carotid atherosclerosis and increased adiposity were independently associated with impaired GLS in HIV-infected individuals.

Multichamber Involvement of Metastatic Cardiac Melanoma.

A 30-year-old man with a history of an in-situ melanoma of the forehead was referred for cardiac evaluation because of tachycardia and elevated levels of serum troponin. The transthoracic echocardiogram revealed multiple masses attached to the walls of both ventricles and the right atrium (RA). A large mass was occupying almost one third of the right ventricle (RV), resulting in reduction of the end-diastolic RV volume and tachycardia. A cardiac magnetic resonance imaging confirmed multifocal myocardial infiltration and intracavitary masses and excluded the presence of thrombus in any of the cardiac chambers. Diffuse metastatic involvement in the liver, the spleen, and the brain by computed tomography precluded surgical management. Being BRAF-unmutated, the patient was initially treated with a combination of nivolumab and ipilimumab. One month later, the cardiac metastases in RA and left ventricle were unchanged on echocardiogram, while the tumor in RV was enlarged occupying the majority of the chamber, resulting in further reduction of the cardiac output and tachycardia. The treatment was changed to a combination of dacarbazine and carboplatin, but the patient eventually died two months later. Heart is not a common metastatic site of melanoma and cardiac involvement is usually clinically silent making ante mortem diagnosis difficult. Multimodalidy imaging plays a pivotal role in the diagnostic work up. Cardiac melanoma metastases indicate an advance stage disease with poor prognosis.

Association of loop diuretics use and dose with outcomes in outpatients with heart failure: a systematic review and meta-analysis of observational studies involving 96,959 patients.

There is ongoing controversy regarding the association between loop diuretics (LD), especially in high doses, and adverse clinical outcomes in outpatients with heart failure (HF). We performed a systematic review of the evidence for LD in outpatients with HF. We searched MEDLINE, EMBASE, and Cochrane Clinical Trial Collection to identify controlled studies, evaluating the association between LD and morbidity and mortality in patients with HF. The primary endpoint was all-cause mortality and secondary endpoint HF hospitalizations. Quantitative analysis was performed by generating forest plots and pooling adjusted risk estimates across studies using random effects models. Between-study heterogeneity was assessed through Q and I2 statistics. Twenty-four studies with a total of 96,959 patients were included. No randomized studies were identified. Use of LD was associated with increased all-cause mortality compared with non-use (pooled adjusted risk estimates, 1.18; P = 0.001) and increased HF hospitalization rates (pooled adjusted risk estimates, 1.81; P < 0.001). These associations remained significant after excluding studies that included HF patients at discharge from hospital (pooled adjusted risk estimates, 1.31 and 1.89, respectively; P < 0.001 for both). High-dose LD (median dose 80 mg) were also associated with increased all-cause mortality (pooled adjusted risk estimates, 1.99; P < 0.001) compared with low-dose LD. Again, this association remained significant after excluding studies that included HF patients at discharge from hospital (pooled adjusted risk estimates, 1.33; P < 0.001). Existing evidence indicates that LD, especially in high doses, are associated with increased all-cause mortality and HF hospitalization rates. For this reason, prospective, randomized studies are warranted to clarify whether these associations indicate causality or are merely an epiphenomenon due to disease severity. Systematic review registration: PROSPERO database registration number CRD42020153239. Date of registration: 28 April 2020.

Inadequate management of cardiovascular risk factors prior to admission for an acute coronary event.

Objectives: Optimal regulation of modifiable risk factors has been proposed as the standard of care both for primary and secondary prevention of cardiovascular disease (CVD). The aim of this study was to assess primary and secondary cardiovascular risk management received before admission for an acute coronary event. Methods: Data were analyzed for 185 consecutive hospitalized patients with a diagnosis of acute coronary syndrome (ACS) in the Cardiology department of a University hospital during an annual period (1/7/2019 until 30/6/2020). The study population was divided into two groups, the primary and secondary prevention subgroups, according to previous medical history of cardiovascular disease (CVD). Results: The mean age of the participants was 65.5 ±12.2 years and most patients were male (81.6%). Previous CVD was present in 51 patients (27.9%). Fifty-seven patients (30.8%) had a history of diabetes mellitus (DM) and 97 (52.4%) had a history of dyslipidemia. Hypertension was present in 101 (54.6%) patients. In the secondary prevention group, the LDL-C was on target in only 33.3% of the patients, while 20% patients did not use statins. The use of antiplatelet/anticoagulant agents was 94.5%. Among patients with diabetes, only 20% had been using a GLP-1 receptor agonist or/and an SGLT-2 inhibitor, while the HbA1c was on target in 47.8%. Twenty-five percent of the patients were active smokers. In the primary prevention group, the use of statins was overall low (25.8%) but more frequent in patients with diabetes and those without diabetes at very high-risk for CVD (47.1% and 32.1% respectively). The LDL-C was on target in less than 23.1% of the patients. The use of antiplatelet/anticoagulant agents was low (20.1%), but higher in those with diabetes (52.9%). In the diabetic group, HbA1c was on target in 61.8%. Active smoking was practiced by 46.3% of the patients. Conclusions: Our data show that in a substantial proportion of patients presenting with ACS, previous CVD prevention, both primary and secondary, fails to meet the current recommendations provided by scientific societies.

Cardiac adiposity as a modulator of cardiovascular disease in HIV.

BACKGROUND: With the number of people living with human immunodeficiency virus (HIV) steadily increasing, cardiovascular disease has emerged as a leading cause of non-HIV related mortality. People living with HIV (PLWH) appear to be at increased risk of coronary artery disease and heart failure (HF), while the underlying mechanism appears to be multifactorial. In the general population, ectopic cardiac adiposity has been highlighted as an important modulator of accelerated coronary artery atherosclerosis, arrhythmogenesis and HF with preserved ejection fraction (HFpEF). Cardiac adiposity is also strongly linked with obesity, especially with visceral adipose tissue accumulation. AIMS: This review aims to summarize the possible role of cardiac fat depositions, assessed by imaging modalities,as potential contributors to the increased cardiac morbidity and mortality seen in PLWH, as well as therapeutic targets in the current ART era. MATERIALS & METHODS: Review of contemporary literature on this topic. DISCUSSION: Despite antiretroviral therapy (ART), PLWH have evidence of persistent, HIV-related systemic inflammation and body fat alterations. Cardiac adiposity can play an additional role in the pathogenesis of cardiovascular disease in the HIV setting. Imaging modalities such as echocardiography, cardiac multidetector computed tomography and cardiac magnetic resonance have demonstrated increased adipose tissue. Studies show that high cardiac fat depots play an additive role in promoting coronary artery atherosclerosis and HFpEF in PLWH. Systemic inflammation due to HIV infection, metabolic adverse effects of ART, adipose alterations in the ageing HIV population, inflammation and immune activation are likely important mechanisms for adipose dysfunction and disproportionately occurrence of ectopic fat depots in the heart among PLWH. CONCLUSIONS: High cardiac adiposity seems to plays an additive role in promoting coronary artery atherosclerosis and HFpEF in PLWH. The underlying mechanisms are multiple and warrant further investigation. Improved understanding of the regulating mechanisms that increase cardiovascular risk in HIV infection may give rise to more tailored therapeutic strategies targeting cardiac fat depots.

Pulmonary Embolism Prophylaxis in Patients With COVID-19: An Emerging Issue.

Severe acute respiratory syndrome (SARS)-CoV-2 virus disease (coronavirus disease 2019; COVID-19) is associated with increased coagulation activity, resulting in an excessive risk of venous thromboembolism (VTE) and poor prognosis. The most common manifestation of VTE is pulmonary embolism (PE), with approximately one in five hospitalised patients being at risk. These reports led to the empirical use of prophylactic anticoagulation, even in the absence of established or clinically suspected disease. This review summarises current aspects and recommendations regarding the use of thromboprophylaxis for PE in patients with COVID-19.

Early left ventricular systolic dysfunction in asymptomatic patients with type 1 diabetes: a single-center, pilot study.

AIMS: Prevalence and risk factors of pre-symptomatic left ventricular systolic dysfunction (LVSD) in individuals with type 1 diabetes (T1D) have not been adequately studied. The present cross-sectional study assessed the prevalence of early LVSD in asymptomatic patients with type 1 diabetes and investigated potential risk factors. METHODS: Consecutive patients with T1D, free of cardiovascular disease and significant evident microvascular complications were examined. LVSD was assessed by speckle-tracking echocardiography and calculation of global longitudinal strain (GLS). Abnormal GLS was defined as a value>-18.7%. We looked for possible associations between the presence of LVSD and patient demographic, clinical and laboratory characteristics, as well as with autonomic nervous system (ANS) function and arterial stiffness. RESULTS: We enrolled 155 T1D patients (29.7% men, age 36.7 ±â€¯13.1 years, diabetes duration 19.1 ±â€¯10.0 years, HbA1c 7.5 ±â€¯1.4% [58 ±â€¯15 mmol/mol]). Early LVSD was prevalent in 53 (34.2%) patients. Multivariable analysis identified male gender (OR:4.14; 95% CI:1.39-12.31, p = 0.011), HbA1c (OR:1.59 per 1% increase; 95% CI:1.11-2.28, p = 0.011), glomerular filtration rate (GFR, OR:0.97; 95% CI:0.95-0.99, p = 0.010) and BMI (OR:1.19; 95% CI:1.06-1.34, p = 0.003) as independent predictors of LVSD presence. CONCLUSIONS: Early subclinical LVSD is a common finding in asymptomatic patients with T1D, free of macrovascular and significant microvascular complications. Apart from chronic hyperglycemia, increased adiposity may be implicated in its etiology. Further investigation is warranted to identify patients at high risk for whom early screening is required and to determine possible associations between risk markers identified in the present analysis and long-term outcomes.

Renin Angiotensin Aldosterone System Inhibitors in Chronic Kidney Disease: A Difficult Equation.

Chronic kidney disease (CKD) is a global health problem and is strongly associated with hypertension (HTN) and impaired quality of life. Managing HTN with agents that block the renin angiotensin aldosterone system (RAAS) remains the gold standard, however there is a misleading impression that patients with impaired renal function or those receiving hemodialysis should not be treated with RAAS inhibitors. To date, only a few data in this field are available, given that this population subset is systematically excluded from many major clinical trials. The purpose of this review was to solve the difficult equation regarding the optimal use of RAAS blockade in patients with CKD.

Cardiac Adiposity and Arrhythmias: The Role of Imaging.

Increased cardiac fat depots are metabolically active tissues that have a pronounced pro-inflammatory nature. Increasing evidence supports a potential role of cardiac adiposity as a determinant of the substrate of atrial fibrillation and ventricular arrhythmias. The underlying mechanism appears to be multifactorial with local inflammation, fibrosis, adipocyte infiltration, electrical remodeling, autonomic nervous system modulation, oxidative stress and gene expression playing interrelating roles. Current imaging modalities, such as echocardiography, computed tomography and cardiac magnetic resonance, have provided valuable insight into the relationship between cardiac adiposity and arrhythmogenesis, in order to better understand the pathophysiology and improve risk prediction of the patients, over the presence of obesity and traditional risk factors. However, at present, given the insufficient data for the additive value of imaging biomarkers on commonly used risk algorithms, the use of different screening modalities currently is indicated for personalized risk stratification and prognostication in this setting.

Imaging modalities for cardiovascular phenotyping in asymptomatic people living with HIV.

Cardiovascular disease (CVD) has emerged as a leading cause of non-HIV-related mortality among people living with HIV (PLWH). Despite the growing CVD burden in PLWH, there is concern that general population risk score models may underestimate CVD risk in these patients. Imaging modalities have received mounting attention lately to better understand the pathophysiology of subclinical CVD and provide improved risk assessment in this population. To date, traditional and well-established techniques such as echocardiography, pulse wave velocity, and carotid intima thickness continue to be the basis for the diagnosis and subsequent monitoring of vascular atherosclerosis and heart failure. Furthermore, novel imaging tools such as cardiac computed tomography (CT) and cardiac CT angiography (CCTA), positron emission tomography/CT (PET/CT), and cardiac magnetic resonance (CMR) have provided new insights into accelerated cardiovascular abnormalities in PLWH and are currently evaluated with regards to their potential to improve risk stratification.

Preoperative Evaluation of Coronary Artery Disease in Liver Transplant Candidates: Many Unanswered Questions in Clinical Practice.

Cardiovascular (CV) complications represent the first non-graft-related cause of death and the third overall cause of death among patients undergoing liver transplantation (LT). History of coronary artery disease is related to increased CV mortality following LT. Although it is of paramount importance to stratify CV risk in pre-LT patients, there is no consensus regarding the choice of the optimal non-invasive cardiac imaging test. Algorithms proposed by scientific associations include non-traditional risk factors, which are associated with increased cardiac risk profiles. Thus, an individualized pre-LT evaluation protocol should be followed. As the average age of patients undergoing LT and the number of candidates continue to rise, the "3 W" questions still remain unanswered, Who, Which and When? Who should be screened for coronary artery disease (CAD), which screening modality should be used and when should the asymptomatic waitlisted patients repeat cardiac evaluation? Prospective studies with large sample sizes are warranted to define an algorithm that can provide better risk stratification and more reliable survival prediction.

Blood Pressure-Lowering Effect of Newer Antihyperglycemic Agents (SGLT-2 Inhibitors, GLP-1 Receptor Agonists, and DPP-4 Inhibitors).

The prevalence of arterial hypertension is high in patients with diabetes mellitus (DM). When DM and hypertension coexist, they constitute a dual cardiovascular threat and should be adequately controlled. Novel antihyperglycemic agents, including sodium-glucose co-transporter 2 (SGLT-2) inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1 RAs), and dipeptidyl peptidase-4 (DPP-4) inhibitors, have recently been used in the treatment of DM. Beyond their glucose-lowering effects, these drugs have shown beneficial pleiotropic cardiovascular effects, including lowering of arterial blood pressure (BP), as acknowledged in the 2019 European Society of Cardiology/European Association for the Study of Diabetes guidelines on diabetes, prediabetes, and cardiovascular diseases. The purpose of this review was to summarize the available information on the BP-reducing effects of these new glucose-lowering drug classes and provide a brief report on underlying pathophysiological mechanisms. We also compare the three drug classes (SGLT-2 inhibitors, GLP-1 RAs, and DPP-4 inhibitors) in terms of their BP-lowering effect and show that the greater BP reduction seems to be achieved with SGLT-2 inhibitors, whereas DPP-4 inhibitors have probably the mildest antihypertensive effect.

Unusual Complications of Infective Endocarditis.

BACKGROUND Despite advances in management, infective endocarditis remains a condition with high in-hospital and post-discharge mortality, especially when it is complicated by perivalvular extension and heart failure (HF). CASE REPORT Herein we describe two illustrative cases of endocarditis. The first case was complicated by left ventricle to right atrial fistula. The second cased was complicated by valvular perforation with a "windsock" appearance. Both patients developed acute HF. CONCLUSIONS Fistulas and severe valvular regurgitation are among the major causes of acute HF in the setting of infective endocarditis. In such cases, surgery should be considered to decrease mortality.