Hypertriglyceridemia and omega-3 fatty acids: Their often overlooked role in cardiovascular disease prevention.

AIMS: This review aims to describe the pathogenic role of triglycerides in cardiometabolic risk, and the potential role of omega-3 fatty acids in the management of hypertriglyceridemia and cardiovascular disease. DATA SYNTHESIS: In epidemiological studies, hypertriglyceridemia correlates with an increased risk of cardiovascular disease, even after adjustment for low density lipoprotein cholesterol (LDL-C) levels. This has been further supported by Mendelian randomization studies where triglyceride-raising common single nucleotide polymorphisms confer an increased risk of developing cardiovascular disease. Although guidelines vary in their definition of hypertriglyceridemia, they consistently define a normal triglyceride level as <150 mg/dL (or <1.7 mmol/L). For patients with moderately elevated triglyceride levels, LDL-C remains the primary target for treatment in both European and US guidelines. However, since any triglyceride level in excess of normal increases the risk of cardiovascular disease, even in patients with optimally managed LDL-C levels, triglycerides are an important secondary target in both assessment and treatment. Dietary changes are a key element of first-line lifestyle intervention, but pharmacological treatment including omega-3 fatty acids may be indicated in people with persistently high triglyceride levels. Moreover, in patients with pre-existing cardiovascular disease, omega-3 supplements significantly reduce the risk of sudden death, cardiac death and myocardial infarction and are generally well tolerated. CONCLUSIONS: Targeting resistant hypertriglyceridemia should be considered as a part of clinical management of cardiovascular risk. Omega-3 fatty acids may represent a valuable resource to this aim.

The scar: the wind in the perfect storm-insights into the mysterious living tissue originating ventricular arrhythmias.

BACKGROUND: Arrhythmic death is very common among patients with structural heart disease, and it is estimated that in European countries, 1 per 1000 inhabitants yearly dies for sudden cardiac death (SCD), mainly as a result of ventricular arrhythmias (VA). The scar is the result of cardiac remodelling process that occurs in several cardiomyopathies, both ischemic and non-ischemic, and is considered the perfect substrate for re-entrant and non-re-entrant arrhythmias. METHODS: Our aim was to review published evidence on the histological and electrophysiological properties of myocardial scar and to review the central role of cardiac magnetic resonance (CMR) in assessing ventricular arrhythmias substrate and its potential implication in risk stratification of SCD. RESULTS: Scarring process affects both structural and electrical myocardial properties and paves the background for enhanced arrhythmogenicity. Non-uniform anisotropic conduction, gap junctions remodelling, source to sink mismatch and refractoriness dispersion are some of the underlining mechanisms contributing to arrhythmic potential of the scar. All these mechanisms lead to the initiation and maintenance of VA. CMR has a crucial role in the evaluation of patients suffering from VA, as it is considered the gold standard imaging test for scar characterization. Mounting evidences support the use of CMR not only for the definition of gross scar features, as size, localization and transmurality, but also for the identification of possible conducting channels suitable of discrete ablation. Moreover, several studies call out the CMR-based scar characterization as a stratification tool useful in selecting patients at risk of SCD and amenable to implantable cardioverter-defibrillator (ICD) implantation. CONCLUSIONS: Scar represents the substrate of ventricular arrhythmias. CMR, defining scar presence and its features, may be a useful tool for guiding ablation procedures and for identifying patients at risk of SCD amenable to ICD therapy.

Starting dose and dose adjustment of non-vitamin K antagonist oral anticoagulation agents in a nationwide cohort of patients with atrial fibrillation.

This study aims to provide real-world data about starting-dose of NOACs and dose-adjustment in patients with atrial fibrillation (AF). In fact, even if new oral anticoagulation agents (NOACs) have a predictable effect without need for regular monitoring, dose-adjustments should be performed according to the summary of product information and international guidelines. We employed the Italian Medicines Agency monitoring registries comprising data on a nationwide cohort of patients with AF treated with NOACs from 2013 to 2018. Logistic regression analysis was used to evaluate the determinants of dosage choice. During the reference period, treatment was commenced for 866,539 patients. Forty-five percent of the first prescriptions were dispensed at a reduced dose (dabigatran 60.3%, edoxaban 45.2%, apixaban 40.9%, rivaroxaban 37.4%). The prescription of reduced dose was associated with older age, renal disease, bleeding risk and the concomitant use of drugs predisposing to bleeding, but not with CHA2DS2-VASc and HAS-BLED. A relative reduction of the proportion of patients treated with low dosages was evident overtime for dabigatran and rivaroxaban; whereas prescription of low dose apixaban and edoxaban increased progressively among elderly patients. Evidence based on real-world data shows a high frequency of low dose prescriptions of NOACs in AF patients. Except for older age, renal disease, bleeding risk and the concomitant use of drugs predisposing to bleeding, other factors that may determine the choice of reduced dose could not be ascertained. There may be potential under-treatment of AF patients, but further evaluation is warranted.

Non-vitamin K antagonist oral anticoagulation agents in patients with atrial fibrillation: Insights from Italian monitoring registries.

BACKGROUND: Atrial fibrillation (AF) is the most common cardiac arrhythmia associated with an increased risk of stroke and thromboembolism. Anticoagulation with Vitamin K antagonists (VKAs) or with novel oral anti-coagulants (NOACs) represents the cornerstone of the pharmacological treatment to reduce the risk of thromboembolism. This study aims to provide real-world data from a whole large European country about NOAC use in "non-valvular atrial fibrillation" (NVAF). METHODS: We analysed the Italian Medicines Agency (AIFA) monitoring registries collecting data of a nationwide cohort of patients with "NVAF" treated with NOACs. Using logistic regression analysis, baseline characteristics and treatment discontinuation information were compared among initiators of the 4 NOACs. RESULTS: In the reference period, the NOAC database collected data for 683,172 patients. The median age was 78 years with 19.5% aged 85 or older. Overall, the treatments were in accordance with guidelines. About 1/3 of patients switched from a prior VKA treatment; in the 72.3% of cases, these patients had a labile International Normalized Ratio (INR) at first prescription. The most prescribed NOAC was rivaroxaban, followed by apixaban, dabigatran and edoxaban. CONCLUSIONS: This study is the largest European real-world study ever published on NOACs. It includes all Italian patients treated with NOACs since 2013 accounting for about 1/3 of subjects with AF. The enrolled population consisted of very elderly patients, at high risk of ischemic adverse events. The AIFA registries are consolidated tools that guarantee the appropriateness of prescription and provide important information for the governance of National Health System by collecting real-world data.

Cardiac autonomic dysfunction and functional outcome after ischaemic stroke.

ischaemic stroke has been associated with an impairment of cardiac autonomic balance. The aim of this study was to assess the impact of cardiac autonomic derangement on functional outcome after a rehabilitation program in patients with recent ischaemic stroke. The study population included 85 consecutive first-ever stroke survivors (46 men and 39 women; mean age 60.0 +/- 12.4 years), who underwent 24-h Holter monitoring before the beginning of a 60-day rehabilitation program. Time-domain measures of heart-rate variability (HRV) were considered in all cases. By the end of the rehabilitation program an unfavorable functional outcome with dependency (Barthel Index score of <75) was found in 44.7% of patients. Multivariate analysis demonstrated that age [odds ratio (OR) 1.09, 95% CI 1.04-1.19, P = 0.002], stroke severity (OR 1.12, 95% CI 1.01-1.34, P = 0.004), Barthel Index score (OR 0.92, 95% CI 0.87-0.98, P = 0.01) and Rankin Scale score (OR 3.88, 95% CI 2.13-7.56, P = 0.02) on admission, as well as lower values of the standard deviation of normal-to-normal R wave to R wave (RR) intervals (OR 9.67, 95% CI 2.58-18.67, P = 0.006) were independent predictors of an unfavorable functional outcome. Assessment of HRV before a rehabilitation program may provide additional information on the probability of a functional recovery in stroke survivors.

Permanent cardiac pacing versus medical treatment for the prevention of recurrent vasovagal syncope: a multicenter, randomized, controlled trial.

BACKGROUND: This clinical investigation was performed to compare the effects of permanent dual-chamber cardiac pacing with pharmacological therapy in patients with recurrent vasovagal syncope. METHODS AND RESULTS: Patients from 14 centers were randomized to receive either a DDD pacemaker provided with rate-drop response function or the beta-blocker atenolol at the dosage of 100 mg once a day. Inclusion criteria were age >35 years, >/=3 syncopal spells in the preceding 2 years, and positive response to tilt table testing with syncope occurring in association with relative bradycardia. The primary outcome was the first recurrence of syncope after randomization. Enrollment was started in December 1997, and the first formal interim analysis was performed on July 30, 2000. By that time, 93 patients (38 men and 55 women; mean age, 58.1+/-14.3 years) had been enrolled and randomized, although follow-up data were available for all patients (46 patients in the pacemaker arm, 47 patients in the pharmacological arm). The interim analysis showed a significant effect in favor of permanent cardiac pacing (recurrence of syncope in 2 patients [4.3%] after a median of 390 days) compared with medical treatment (recurrence of syncope in 12 patients [25.5%] after a median of 135 days; OR, 0.133; 95% CI, 0.028 to 0.632; P=0.004). Consequently, enrollment and follow-up were terminated. CONCLUSIONS: DDD pacing with rate-drop response function is more effective than beta-blockade for the prevention of syncopal recurrences in highly symptomatic vasovagal fainters with relative bradycardia during tilt-induced syncope.

Assessment of left ventricular hypertrophy in patients with essential hypertension. A rational basis for the electrocardiogram.

There is a large body of evidence that the electrocardiogram (ECG) is insensitive in the recognition of left ventricular hypertrophy (LVH), in comparison with the echocardiogram; however, its specificity is high. In this study we further analyzed the performance of the ECG in detecting LVH in 200 consecutive patients (124 men and 76 women, mean age 50.9 years) with mild to moderate essential hypertension, using echocardiographically determined left ventricular mass (LVM) as the standard for comparison. To test the hypothesis that, owing to the high number of true positive findings, the ECG may still be useful for clinical purposes by selecting subsets of hypertensives with higher degrees of LVH, we compared the mean values of LVM index corresponding to either positive (true positive) or negative (false negative) electrocardiographic signs of LVH. In this study 69 patients (34.5%) had echocardiographic LVH, as defined by a LVM index exceeding 125 g/m2 for men and 112 g/m2 for women. Almost all criteria demonstrated high levels of specificity (> or = 89%). In the whole group the Lewis index ((RI - RIII)+(SIII - SI) > or = 17 mm) showed a slight superiority in diagnosing LVH (sensitivity = 43%) in comparison to the remaining criteria; the confidence intervals estimate of sensitivities confirmed such diagnostic superiority only with respect to those criteria with a sensitivity < or = 17%. However, the use of McNemar's test to compare sensitivities of all electrocardiographic criteria at matched specificities (> or = 95%) did not show significant differences (P < .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Abnormal blood pressure response to exercise in borderline hypertension. A two year follow-up study.

Twenty-eight men with borderline hypertension according to the World Health Organization criteria underwent maximal exercise testing, and then were followed for a two year period. The prevalence of abnormal blood pressure behavior during exercise was 53.58% (n = 15). During follow-up established hypertension developed in 63.33% (n = 10) of subjects with an abnormal blood pressure response to exercise, and only in 15% (n = 2) of subjects with normal blood pressure behavior. In predicting established hypertension development in a two year follow-up, maximal exercise testing has the following statistical values: sensitivity = 83.33%, specificity = 68.75%, accuracy = 75%, positive predictive value = 66.66%, negative predictive value = 84.61%.

Prevalence of left ventricular hypertrophy and cardiac arrhythmias in borderline hypertension.

Seventy-eight men with borderline hypertension according to the World Health Organization criteria underwent echocardiographic examination, followed by simultaneous ambulatory blood pressure and electrocardiographic monitorings for 24 h. The prevalence of echocardiographic left ventricular hypertrophy was 16.6% (13/78). Borderline hypertensives with left ventricular hypertrophy had more supraventricular (P less than .001) and ventricular ectopic beats (P less than .001) than normotensive controls and borderline hypertensives without cardiac involvement. Furthermore, ventricular ectopic activity was significantly related to left ventricular mass (r = 0.58, P less than .05) in borderline hypertensives showing echocardiographic evidence of left ventricular hypertrophy. Our findings suggest that noninvasive assessment of target organ status, including echocardiography, should be employed to optimize risk stratification in borderline hypertension.

Target organ status and cardiovascular risk in borderline hypertension.

In order to assess the prevalence of target organ damage 78 men with borderline hypertension, according to the World Health Organization criteria, and 67 normotensive controls underwent echocardiographic, electrocardiographic and fundoscopic examination, followed by ambulatory blood pressure monitoring for 24 hours. Echocardiographic left ventricular hypertrophy was found in 13 borderline hypertensive subjects (16.6%), while no electrocardiographic or fundoscopic abnormalities could be detected. Our data suggest that noninvasive assessment of cardiovascular status, including echocardiography, allows recognition of a subset of borderline subjects with an increased risk for subsequent cardiac morbid events, thereby improving prognostic stratification.

Prevalence of silent ST segment depression during long-term ambulatory electrocardiographic monitoring in asymptomatic diabetic patients with essential hypertension.

Thirty-five asymptomatic diabetic patients with non insulin-dependent diabetes and mild moderate essential hypertension (18 males and 17 females, mean age 60 +/- 6 years) underwent echocardiographic examination, followed by simultaneous ambulatory blood pressure and electrocardiographic monitorings. Three hundred and sixteen significant episodes of asymptomatic ST segment depression (at least 1 mm 80 msec after the J point, lasting more than 1 min) were recorded in 21 patients (60%) with a total duration of 5637 minutes. Patients with asymptomatic episodes of ST segment depression had significantly higher values of total cholesterol (p < 0.05), LDL cholesterol (p < 0.05), Glycosylated hemoglobin (p < 0.001), left ventricular mass index (p < 0.02), mean 24-hour systolic and diastolic ambulatory blood pressure (p < 0.001), systolic (p < 0.02) and diastolic (p < 0.01) ambulatory blood pressure variability and hypertensive peaks (p < 0.05), with respect to the rest of the study population. The number of ST segment depression episodes was significantly related to total cholesterol levels (r = 0.40, p < 0.05), LDL cholesterol levels (r = 0.36, p < 0.05) glycosylated hemoglobin levels (r = 0.50, p < 0.01), left ventricular mass index (r = 0.48, p < 0.01), ambulatory systolic (r = 0.43, p < 0.01) and diastolic (r = 0.51, p < 0.01) blood pressure variability and hypertensive peaks (r = 0.50, p < 0.01). Our data suggest that haemodynamic and metabolic factors could have a relevant role in high prevalence of SMI in asymptomatic diabetic patients with EH. The evidence of SMI in these patients warrants further diagnostic work-up and prognostic assessment.

[Ischemic hepatitis: case reports and a review of the literature]. / L'epatite ischemica: contributo casistico e revisione della letteratura.

Ischemic hepatitis represents a condition in which an acute circulatory failure determines a striking elevation of both serum transaminases and total bilirubin and a prolongation of prothrombin time. Such impairment of liver function tests is due to a haemodynamic hepatocyte injury, showing focal centrilobular necrosis as the specific pathologic correlate. In this paper the authors describe four different cases of ischemic hepatitis, in which an acute derangement of liver function tests occurred as a consequence either of myocardial failure or of systemic venous congestion. Finally, the authors review all current international literature concerning the various clinical, pathologic and therapeutic features of ischemic hepatitis.

Left ventricular hypertrophy and diastolic dysfunction in alcohol-associated hypertension.

In order to assess left ventricular structure and diastolic function, 50 hypertensive male subjects, 25 with and 25 without a history of alcohol abuse, and 20 normotensive male controls underwent Doppler echocardiographic examination followed by ambulatory blood pressure monitoring for 24 hours. Left ventricular mass was significantly higher in alcoholic hypertensives in relation to non-alcoholic hypertensives (p < 0.05) and normotensive controls (p < 0.001). Moreover, Doppler parameters expressing left ventricular filling pattern were significantly worse in alcoholic than in non-alcoholic hypertensives (p < 0.01). Clinic and ambulatory blood pressure were similar in alcoholic and non-alcoholic hypertensives, while mean day-time heart rate was significantly higher in alcoholics (p < 0.01). Collected data suggest that non-hemodynamic factors are probably involved in the development of cardiovascular abnormalities in hypertensive alcoholics, and that echocardiography should be employed for risk-profile definition in alcohol-associated hypertension.

[Sublingually administered captopril versus nifedipine in hypertension emergencies]. / Captopril versus nifedipina somministrati per via sublinguale nelle emergenze ipertensive.

Aim of the study was to assess the effectiveness and tolerability of sublingual captopril (SLC) versus sublingual nifedipine (SLN) in treating hypertensive emergencies. During hypertensive crises (systolic blood pressure exceeding 200 mmHg and diastolic blood pressure exceeding 115 mmHg) forty hypertensive patients received either 25 mg of SLC or 10 mg of SLN in a randomized single blind fashion. Blood pressure and heart rate were then controlled after 5, 10, 15, 20, 30, 45, 60, 120 min. and, in 18 cases, up to the 8th hour from the administration. Our results showed: 1) a satisfactory control of the hypertensive crises in 80% of patients treated with SLC with a significant blood pressure reduction after 10 min. (13/8 mmHg, p less than 0.02), while the maximum hypotensive effect was achieved after 30 min. (52/36 mmHg, p less than 0.001); SLN was able to reduce blood pressure in 90% of all the cases, with a significant reduction after 5 min. (15/11 mmHg, p less than 0.02) and hypotensive peak after 20 min (57/38 mmHg, p greater than 0.001); 2) no significant differences for hypotensive effectiveness between the two groups, but with SLC having a mildly delayed onset of action when compared to SLN; 3) antihypertensive effect lasting for about 6 hours in patients treated with SLC and blood pressure progressively raising after 4 hours in patients who received SLN; 4) a significant correlation between blood pressure reduction and blood pressure before drug administration in both groups; a significant correlation between pretreatment PRA and antihypertensive effect in the SLC group. We conclude that both drugs are effective and useful in treating hypertensive emergencies. Anyway we think that in severe forms SLN should be preferred for the shorter time preceding onset of action.

Prevalence and correlates of syncope-related traumatic injuries in tilt-induced vasovagal syncope.

BACKGROUND: Vasovagal syncope represents the most common form of syncope in the general population and is usually considered as a benign affection. However, syncope-related traumatic injuries may represent a major complication of such a condition in a relevant percentage of cases. The aim of this study was to assess the prevalence and clinical correlates of syncope-related trauma in a cohort of consecutive patients with recurrent vasovagal syncope. METHODS: Three hundred and forty-six consecutive patients were studied in whom a diagnosis of vasovagal syncope was established. All subjects were interviewed with a standard questionnaire in order to collect all possible information about their clinical history and the occurrence of trauma during syncopal spells. RESULTS: Ninety-four of the 346 patients (27.2%) reported at least one syncope-related traumatic injury. In 31/346 cases (8.9%) the severity of trauma had determined hospital admission and surgical treatment. When compared to the rest of the study population, patients with syncope-related trauma showed a higher prevalence of male gender (p < 0.01), a higher absolute number (p < 0.01) and frequency (p < 0.01) of syncopal episodes in their history. Patients with trauma also reported a shorter duration of warning symptoms preceding syncope (p < 0.01), while showing a higher prevalence of positive cardioinhibitory response to tilt table testing (p < 0.01). Moreover, the number of syncope-related injuries was found to correlate significantly with the number of syncopal spells (r = 0.64, p < 0.01). CONCLUSIONS: Most practicing physicians consider vasovagal syncope as simply a benign affection in young people. However, such a clinical view should be partially revised, as recurrent vasovagal syncope is associated with significant trauma-related morbidity.

[Effects of slow-release nicardipine on blood pressure, renal function and the renin-angiotensin-aldosterone system in patients with mild-to-moderate essential arterial hypertension]. / Effetti della nicardipina sr sulla pressione arteriosa, la funzione renale e il sistema renina-angiotensina-aldosterone in pazienti con ipertensione arteriosa essenziale lieve-moderata.

The above study was intended to assess the efficacy of nicardipine in mild to moderate essential arterial hypertension and to check whether there are medium term changes in kidney function and urinary excretion of electrolytes in the course of nicardipine treatment. Twenty patients with mild to moderate essential arterial hypertension were treated daily with 40-80 mg doses of slow-release nicardipine after a wash-out period. Systolic and diastolic blood pressure was measured with traditional sphygmomanometer on entry and after 4, 8, and 12 weeks' treatment. Also, on entry and at conclusion of the study, the following parameters were measured: plasma renin activity, creatinine clearance, 24-hour urinary excretion of Na, K, Ca, and aldosterone. Nicardipine treatment was well tolerated and no significant changes of heart rate, creatinine clearance and urinary excretion of Na, K, Ca and aldosterone were observed after 12 weeks' treatment. The efficacy of nicardipine for the management of mild to moderate hypertension was thus confirmed. The absence of a natriuretic effect after 12 weeks' treatment goes to show that any diuretic action of the drug is irrelevant to its therapeutic effect which appears to be due mainly to its vasodilatory action.