Issa Alesh

Effect of Long-Term Exposure to Lower Low-Density Lipoprotein Cholesterol Beginning Early in Life on the Risk of Coronary Heart Disease: A Mendelian Randomization Analysis

OBJECTIVES The purpose of this study was to estimate the effect of long-term exposure to lower plasma low-density lipoprotein cholesterol (LDL-C) on the risk of coronary heart disease (CHD). BACKGROUND LDL-C is causally related to the risk of CHD. However, the association between long-term exposure to lower LDL-C beginning early in life and the risk of CHD has not been reliably quantified. METHODS We conducted a series of meta-analyses to estimate the effect of long-term exposure to lower LDL-C on the risk of CHD mediated by 9 polymorphisms in 6 different genes. We then combined these Mendelian randomization studies in a meta-analysis to obtain a more precise estimate of the effect of long-term exposure to lower LDL-C and compared it with the clinical benefit associated with the same magnitude of LDL-C reduction during treatment with a statin. RESULTS All 9 polymorphisms were associated with a highly consistent reduction in the risk of CHD per unit lower LDL-C, with no evidence of heterogeneity of effect (I(2) = 0.0%). In a meta-analysis combining nonoverlapping data from 312,321 participants, naturally random allocation to long-term exposure to lower LDL-C was associated with a 54.5% (95% confidence interval: 48.8% to 59.5%) reduction in the risk of CHD for each mmol/l (38.7 mg/dl) lower LDL-C. This represents a 3-fold greater reduction in the risk of CHD per unit lower LDL-C than that observed during treatment with a statin started later in life (p = 8.43 × 10(-19)). CONCLUSIONS Prolonged exposure to lower LDL-C beginning early in life is associated with a substantially greater reduction in the risk of CHD than the current practice of lowering LDL-C beginning later in life.

Myocardial fibrosis on cardiac magnetic resonance and cardiac outcomes in hypertrophic cardiomyopathy: a meta-analysis

Objective Late gadolinium enhancement (LGE) on cardiac MRI that indicates the extent of myocardial fibrosis in hypertrophic cardiomyopathy (HCM) is a potential risk factor of sudden cardiac death (SCD) in non-high-risk patients according to conventional clinical markers. Methods The present study was designed to systematically review prospective trials and assess the association between LGE and SCD in HCM. We systematically searched the electronic databases, MEDLINE, PubMed, Embase and Cochrane for prospective cohort studies of the effects of LGE on clinical outcomes (SCD/aborted SCD, all-cause mortality, cardiac and heart failure death) in HCM. Results We identified six clinical studies, examining 1414 patients without LGE and 1653 with LGE and an average follow-up of 3.05 years. The incidence of SCD/aborted SCD in patients with HCM and LGE was significantly increased as compared with patients without LGE (OR 2.52, 95% CI 1.44 to 4.4, p=0.001). The all-cause mortality and cardiac death rates were also significantly increased in patients with LGE. The extent of LGE was not significantly related to the risk of SCD. Conclusions LGE is significantly associated with SCD risk, cardiac mortality and all-cause mortality in patients with non-high-risk HCM according to conventional risk factors.

Catheter-directed thrombolysis (intrathrombus injection) in treatment of deep venous thrombosis: a systematic review.

Methods of delivery of thrombolytic agents for massive or limb threatening deep venous thrombosis (DVT) include a systemic infusion, local–regional administration, and catheter‐directed therapy (tip of catheter placed inside the thrombus). We evaluated the effectiveness of catheter‐directed therapy and compared the results with randomized clinical trials of systemic and local–regional thrombolytic therapy. Many who used catheter‐directed thrombolysis used balloon angioplasty, stents, or thrombectomy in addition. Pooled data showed higher rates of complete early opening of occluded veins with catheter‐directed thrombolysis alone, 90%, or with catheter‐directed thrombolysis often followed by adjunct therapy, 76%, than with a systemic infusion, 28%, or local–regional administration, 20%. The prevalence of postthrombotic syndrome was lower with catheter‐directed combined with adjunct therapy, 26%, compared with 56% and 69%, respectively. Rates of any bleeding were higher with catheter‐directed thrombolytic therapy, but bleeding was usually minor. In conclusion, the data suggest that catheter‐directed thrombolytic therapy may be more beneficial than systemic or local regional administration. An advantage is that it lends itself to adjunct treatment following the administration of thrombolytic agents if the thrombolysis is inadequate.

Mortality From Acute Pulmonary Embolism According to Season

BACKGROUND Varying observations have been made on seasonal differences of mortality from acute pulmonary embolism (PE). METHODS The number of deaths each year from PE, from 1980 through 1998, based on death certificates, was obtained from the US National Center for Health Statistics Multiple Cause-of-Death Files. RESULTS Acute PE as the cause of death ranged from 0.91 to 1.03 PE deaths per quarter per 100,000 population. Small differences were statistically significant due to the large number of patients evaluated. Quarterly mortality rates from PE in the northeast, south, midwest, and west, where seasonal weather varies widely, showed no meaningful seasonal differences. CONCLUSION Mortality rates from PE do not vary to a meaningful extent according to season.

Long (>12 Months) and Short (<6 Months) Versus Standard Duration of Dual Antiplatelet Therapy After Coronary Stenting: A Systematic Review and Meta-Analysis.

Dual antiplatelet therapy (DAPT) is recommended for 6–12 months after drug-eluting stent (DES) implantation to prevent ischemic events and late stent thrombosis. The optimal duration of DAPT has not been established. We performed a meta-analysis of the comparative effects of short and long versus standard duration DAPT duration on adverse cardiovascular and major bleeding. We conducted an EMBASE and MEDLINE search for studies in which patients were randomized to treatment with a different duration of DAPT. We included studies that provided data on DES selection, DAPT regimen and duration, and incidence of the selected endpoints at the end of the follow-up period. We identified 5 prospective randomized studies comparing short versus standard duration DAPT and 3 comparing long versus standard duration DAPT with a total of 28,343 patients. Short-term DAPT has similar incidence of stent thrombosis, MI, and death compared to standard duration DAPT, whereas major bleeding was significantly lower in short duration DAPT. Long-term DAPT was associated with lower rates of stent thrombosis and MI but significantly increased major bleeding and all-cause mortality compared to standard duration DAPT. In this meta-analysis of prospective controlled studies we found that short duration DAPT is safer and as effective as standard duration DAPT in patients with second-generation DES. Extended DAPT is associated with less ischemic events at the expense of high bleeding and mortality rates.

Lipomatous hypertrophy of the right ventricle and interventricular septum associated with ventricular arrhythmia

We report a case of lipomatous hypertrophy of the right ventricle and interventricular septum associated with extensive epicardial and pericardial fat. A 54-year-old morbidly obese Caucasian female without family history of sudden cardiac death (SCD) presented with multiple episodes of pre-syncope, dizziness and palpitations. The electrocardiogram showed normal sinus rhythm without pre-excitation, QT prolongation or Brugada pattern and a subsequent transthoracic echocardiogram showed focal spindle shaped increase in right ventricle (RV) free wall thickness along with prominent anterior epicardial and pericardial fat pad. Cardiac MRI was performed for further evaluation and it showed lipomatous hypertrophy of the entire RV and the mid/apical portion of the inter-ventricular septum with extensive epicardial fat on the RV free wall but with normal RV volumes and function without regional wall motion abnormalities but with at the delayed gadolinium enhancement (Fig. 1a–c). An event monitor showed twelve episodes of non-sustained ventricular tachycardia (VT) (Fig. 1d) associated with symptoms and frequent premature ventricular beats, despite treatment with maximum tolerated doses of metoprolol. Cardiac catheterization did not reveal any obstructive coronary artery disease. An exercise stress test did not reveal any exercised induced arrhythmias. Electrophysiology study was negative for inducible VT. Based on the age of presentation, absence of family history of SCD, unremarkable baseline electrocardiogram and normal RV function,