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.

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.

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.

Predicted Skeletal Muscle Mass and 4-Year Cardiovascular Disease Incidence in Middle-Aged and Elderly Participants of IKARIA Prospective Epidemiological Study: The Mediating Effect of Sex and Cardiometabolic Factors.

The sex-specific effect of skeletal muscle mass (SMM) index (SMI) on 4-year first fatal/non-fatal cardiovascular disease (CVD) event in free-of-disease individuals was examined. In 2009, n = 1411 inhabitants (mean age = 64(12)) from Ikaria were selected. Follow-up was performed in 2013. SMI was created to reflect SMM through appendicular skeletal muscle mass (indirectly calculated through formulas) divided by body mass index (BMI). Fifteen and six tenths percent of participants exhibited CVD (19.8% in men/12% in women, p = 0.002). Significant U-shape trends were observed in participants >65 years old and women irrespective to age confirmed through multi-adjusted Cox regression analysis; in age >65 years, Hazard Ratio (HR)(2nd vs. 1st SMI tertile) = 0.80, 95% Confidence Interval (95%CI) (0.45, 0.96) and in women HR(2nd vs. 1st SMI tertile) = 0.71, 95% CI (0.33, 0.95), while, as for the 3rd SMI tertile, no significant trends were observed. Mediation analysis revealed that mediators of the aforementioned associations in men were the arterial distensibility and total testosterone, while, in women, inflammation, insulin resistance, and arterial distensibility. High SMM accompanied by obesity may not guarantee lower CVD risk. Specific cardiometabolic factors seem to explain this need for balance between lean and fat mass.

Rotatripsy: A Hybrid "Drill and Disrupt" Approach for Treating Heavily Calcified Coronary Lesions.

In balloon-uncrossable calcified lesions, rotational atherectomy (RA) is the first-line modality to enable operators to advance balloons and stents over the stenosis. If the lesion is undilatable after RA, a hybrid approach with additional intracoronary lithotripsy (rotatripsy) can be an effective approach that further modifies the calcified plaque and enables stent delivery.

Aortic wall stiffness as a side-effect of anti-cancer medication.

Introduction: Malignancies and cardiovascular disease are the two leading causes of mortality worldwide. There is a growing concern that anti-cancer drugs may lead to increased cardiovascular morbidity among cancer survivors. This may be the result of direct effects of the cancer treatment on heart function, or due to an indirect acceleration of atherosclerosis.Areas covered: We searched two bibliographic databases [PubMed, Scopus] and one full-text database (Google Scholar) for publications on chemotherapy and arterial stiffness since 1970. Anthracyclines, alkylating agents and tyrosine kinase inhibitors seem to affect arterial elastic properties. These effects can be non-reversible and may appear after treatment termination. Monoclonal antibodies may induce either a temporary increase or no change on arterial stiffness of patients with malignancies. Anti-microtubule agents and antimetabolites have not been extensively studied so far.Expert opinion: This literature review suggests that certain anticancer medications may impair arterial stiffness, and that assessment of arterial elastic properties before and after initiation of anti-neoplasmatic therapy may be clinically useful in order to develop protective strategies against chemotherapy-induced vascular effects. Further research is warranted to confirm the effects of anti-cancer agents on arterial stiffness, as well as their potential clinical implications. Future research lies in finding new targeted biomarkers identifying arterial stiffness such as micro RNAs while imaging techniques could also be implemented in assessment of vascular toxicity.

Statins in Stroke.

BACKGROUND: Stroke is a major cause of mortality and disability in modern societies. Statins are effective medications in decreasing cardiovascular events through lipid lowering and pleiotropic effects. OBJECTIVE: To summarize current evidence regarding the role of statins in the prevention and management of stroke. METHODS: A narrative review of current evidence regarding the effect of statins in stroke management. Electronic searches of MEDLINE, EMBASE and Cochrane Databases were performed. RESULTS: In primary prevention of stroke in patients with risk factors but no established cardiovascular disease, potent statins such as atorvastatin and rosuvastatin have shown some benefits, but the clinical relevance of this effect is questionable. In populations at higher risk of stroke, such as patients with established coronary heart disease, the majority of relevant studies have shown a beneficial effect of statins in preventing stroke. Similarly, in patients with a previous cerebrovascular event, there is a clear benefit of statins for the prevention of recurrent events. The use of statins is not associated with an increased risk of intracranial bleeding in primary prevention studies. There may be an increased incidence of non-fatal hemorrhagic stroke with high dose statins in patients with a previous cerebrovascular event. Patients who experience a stroke while on statins should not discontinue statins. In addition, statins are associated with better survival and improved functional outcome when administered during the acute phase of stroke in statin-naive patients. In contrast, statins do not confer any benefit in patients with acute ischemic stroke who receive thrombolysis. CONCLUSION: Treatment with statins prevents ischemic stroke, especially in patients with high cardiovascular risk and established atherosclerotic disease. It seems that both lipid lowering and pleiotropic effects contribute to these effects.

Ibrutinib-related atrial fibrillation: Therapeutic challenges.

Ibrutinib is a drug used in several lymphohyperplastic diseases. Its use is associated with an increased risk of atrial fibrillation. New-onset atrial fibrillation in this setting is a true challenge as several antiarrhythmic drugs are not indicated and long-term anticoagulation has several limitations. Herein, we describe our experience in treating a 55-year-old patient receiving ibrutinib who presented with new-onset atrial fibrillation and borderline arterial pressure. Since first-line therapies, electrical cardioversion and ablation, could not be performed, rhythm control with intravenous administration of amiodarone was attempted and led to prompt sinus rhythm restoration. We discuss the therapeutic challenges related to sinus rhythm restoration and anticoagulation in this group of atrial fibrillation patients.

Inadvertent cardiac phlebography.

We are reporting a case of a 80-year-old lady with effort angina who underwent coronary angiography through the right radial artery, using a dedicated radial multipurpose 5 French Optitorque Tiger catheter. The catheter was advanced into the left ventricle and a left ventriculogram was obtained, while the catheter appeared optimally placed at the centre of the ventricle and the pressure waveform was normal. A large posterior interventricular vein draining into the right atrium was opacified, presumably because the catheter's end hole inadvertently cannulated an endocardial opening of a small thebesian vein, with subsequent retrograde filling of the epicardial vein. Our case suggests that caution is needed when a dedicated radial catheter with both an end-hole and a side hole is used for a ventriculogram, as a normal left ventricular pressure waveform does not exclude malposition of the end-hole against the ventricular wall.

Bilateral symmetry of local inflammatory activation in human carotid atherosclerotic plaques.

INTRODUCTION: Only a few studies have investigated the structural and functional characteristics of carotid arteries bilaterally. Furthermore, there is controversy as to whether inflammation in paired vascular beds is a local or systemic phenomenon. We aimed to examine, in patients with coronary artery disease, whether intra-subject left and right carotid arteries have similar inflammatory status, as determined non-invasively by microwave radiometry (MWR). METHODS: Consecutive patients (n=200) with significant coronary artery disease were evaluated via an ultrasound echo-colour Doppler (US-ECD) study of both carotid arteries and temperature measurements with MWR. During thermography, thermal heterogeneity (ΔT) was defined as the maximum temperature along the carotid artery minus the minimum temperature. RESULTS: Mean T was similar between the left and right carotid arteries (0.78 ± 0.48 vs. 0.84 ± 0.52°C, p=0.12). Mean right intima-media thickness (IMT) was greater compared to mean left IMT (2.16 ± 1.20 vs. 1.93 ± 0.94 mm, p<0.01). In all carotids, there was a correlation between left and right carotid plaque ΔT (R=0.38, p<0.001) and between left and right IMT (R=0.48, p<0.001). Independent predictors for the presence of bilateral carotid plaques were found to be the extent of coronary artery disease, high ΔT, and therapy with angiotensin II receptor blockers; predictors for the presence of high ΔT bilaterally were bilateral carotid plaques, male sex, diabetes mellitus, and hypertension. CONCLUSIONS: There is bilateral inflammatory activation in the carotid atherosclerotic lesions of patients with coronary artery disease. At this stage of carotid disease, arterial hypertension and diabetes mellitus are more strongly correlated with bilateral functional abnormalities in carotid plaques than with structural changes.

Statin therapy and risk of diabetes in patients with heterozygous familial hypercholesterolemia or familial combined hyperlipidemia.

OBJECTIVE: Controversial findings exist regarding potential influence of statin therapy on diabetic incidence. Aim of this study was to investigate the role of long duration statin treatment on diabetes mellitus (DM) incidence of Heterozygous Familial Hypercholesterolemia (hFH) and Familial Combined Hyperlipidemia (FCH) patients. METHODS: Study population consisted of 212 hFH and 147 FCH patients that visited Lipid Outpatient Department (mean follow up of 11 and 10 years respectively). Several clinical data such as history of DM, cardiovascular disease, thyroid function, metabolic syndrome, glucose levels, lipid profile and lifestyle data were obtained. In order to compare the effects of different doses of different types of statins, a "statin treatment intensity product" was used. RESULTS: 14% of FCH and only 1% of hFH patients developed DM during follow up. Although univariate analysis showed a statistical trend (p = 0.06) in the association between new onset DM and statin treatment intensity (STI) in the FCH subgroup of patients with normal baseline glucose levels, this was no longer significant after adjusting for several confounders. Furthermore, the type of statins used did not seem to play a role in the development of DM either in hFH or FCH patients. CONCLUSION: Long duration of high STI does not seem to be associated with diabetic risk in hFH patients. High STI used in the FCH population is not associated with increased risk of new onset DM compared to low STI. Further studies are required in order to clarify the potential diabetogenic effects of statins in these high risk populations.

Morphological and functional assessment of carotid plaques have similar predictive accuracy for coronary artery disease.

BACKGROUND AND PURPOSE: Microwave radiometry allows noninvasive in vivo measuring of internal temperature of tissues reflecting inflammation. In the present study, we evaluated the predictive accuracy of this method for the diagnosis of coronary artery disease (CAD). METHODS: Consecutive patients (n=287) scheduled for coronary angiography were included in the study. In carotid arteries of both groups, the following measurements were performed: (1) intima-media thickness (IMTmax) and (2) temperature measurements by microwave radiometry (ΔTmax). C-statistic and net reclassification improvement were used to compare the prediction ability of the markers IMTmax and ΔTmax for the presence of CAD and multivessel CAD. RESULTS: Of 287 patients, 239 had stenoses ≥50% (CAD group), and 48 did not have significant stenoses (NO-CAD group). ΔTmax was an independent predictor for the presence of CAD and multivessel CAD, showing similar predictive accuracy to intima-media thickness, as assessed by c-statistic and net reclassification improvement. CONCLUSIONS: Local inflammatory activation, as detected by microwave radiometry, has similar predictive accuracy to intima-media thickness for the presence and extent of CAD.

Predictive factors of vascular complications after transcatheter aortic valve implantation in patients treated with a default percutaneous strategy.

BACKGROUND: Percutaneous approach techniques with closure device after transcatheter aortic valve implantation (TAVI) have diminished vascular complications (VC). In this retrospective study, we will report incidence and angiographic factors predisposing to major VC in patients undergoing TAVI using Prostar® XL closure device as a default strategy. METHODS: Consecutive patients, who underwent TAVI transfemorally using Prostar® XL, were evaluated for the incidence of VC according to VARC criteria. Using arterial angiography, the femoral-iliac arterial tortuosity was adjusted for large arterial diameters and expressed as the ratio total tortuosity/arterial diameter (TT/AD). Arterial calcification, the combination of angulation and atheromatosis at the puncture site and ideal puncture were evaluated too. In all patients, 30 days of follow-up was available. RESULTS: Eighty-four patients (80.2 ± 5.86 years, 39 males [46.4%]), who were consecutively treated with the transfemoral approach, were evaluated. In patients with major VC (17/84 [20.23%]) comparing to those without, arterial calcification (11 [64.7%] vs. 8 [11.9%], P < 0.01) and the TT/AD (30.2 ± 11.25 vs. 22.06 ± 8.64, P < 0.01) were independent predictors. Ideal puncture was achieved more frequently among patients without VC comparing to those with major (94.1% vs. 70.6%, P = 0.01). Blood transfusions (1.48 ± 0.37 vs. 2.45 ± 0.59, P = 0.023) were more frequent among patients with major VC. Finally, minimum creatinin clearance after TAVI predicted all-cause 30-day mortality (P = 0.021). CONCLUSIONS: Major VC after TAVI with the use of Prostar closure device can be predicted by arterial calcification at the puncture site and TT/AD ratio. Minimum creatinin clearance after TAVI predicted 30-day mortality.

Large left atrial myxoma in an oligosymptomatic young woman.

We present the case of a young female with a large sporadic left atrial myxoma. Interestingly, despite the tumor's large size, this patient had only mild exertional dyspnea without any embolic events or constitutional symptoms.

Impact of cardiometabolic risk factors on major cardiovascular events in patients with familial combined hyperlipidemia.

BACKGROUND: Familial combined hyperlipidemia (FCH) is an inherited lipid disorder associated with premature cardiovascular disease. It has not been established whether the cardiometabolic risk factors, which frequently accompany FCH, such as diabetes, metabolic syndrome (MetS) and hypertension, modulate cardiovascular risk in FCH patients. METHODS AND RESULTS: In this single-center, retrospective study, 695 FCH patients with adequate follow-up were enrolled (mean age, 48.9 years; 455 male). Risk factors including lipid levels were evaluated before the initiation of treatment. Acute myocardial infarction (AMI) and cardiovascular death were recorded during a mean follow-up of 9 years. The combined endpoint (AMI and/or cardiovascular death) occurred in 41 patients (5.9% of the total). Those FCH patients who reached the combined endpoint had lower high-density lipoprotein cholesterol (HDL-C) than those who did not, but levels of other lipid variables were similar. Presence of hypertension, diabetes or MetS was a predictor of the combined endpoint on univariate Kaplan-Meier analysis (all P<0.005). Multivariate Cox proportional analysis showed that hypertension and MetS were associated with the combined endpoint independently of age, gender, HDL-C and presence of coronary artery disease at enrollment (adjusted hazard ratios [HRs], 3.00; 95% confidence interval [CI]: 1.46-6.17, P=0.003; HR, 2.43; 95CI%: 1.11-5.33, P=0.026, respectively). CONCLUSIONS: Cardiometabolic risk factors such as hypertension and MetS are independent predictors of major cardiovascular events in FCH patients.