Isolated papillary muscle rupture with nonobstructive coronary artery disease, minimal myocardial infarction, and normal wall motion.

Papillary muscle (PM) rupture can usually complicate inferior or posterior myocardial infarctions, but selective PM infarction is extremely rare, and the exact underlying pathophysiological mechanism is not entirely clear. We present a case of PM rupture due to isolated PM infarction in a patient with unobstructed coronary arteries, which could be misdiagnosed as a vegetation or other mass given the absence of regional wall motion abnormalities (RWMAs) on transthoracic echocardiogram. Our case highlights that in patients with severe mitral regurgitation and associated mitral valve mass, the absence of RWMAs should not exclude ischemic PM rupture from differential diagnosis.

Cardiac resynchronization therapy (CRT) device replacement considerations: upgrade or downgrade? A complex decision in the current clinical setting.

There are limited data about the management of patients presenting for elective generator replacements in the setting of previously implanted cardiac resynchronization therapy (CRT) devices that are nearing end-of-life. The individual patient's clinical status and concomitant morbidities may evolve so that considerations may include not only replacement of the pulse generator, but also potentially changing the type of device [e.g. downgrading CRT-defibrillator (CRT-D) to CRT-pacemaker (CRT-P) or ICD or upgrading of CRT-P to CRT-D]. Moreover, the clinical evidence for CRT-D/CRT-P implantation may change over time, with ongoing research and availability of new trial data. In this review we discuss the ethical, clinical and financial implications related to CRT generator replacements and the need for additional clinical trials to better understand which patients should undergo CRT device downgrading or upgrading at the time of battery depletion.

Alterations in the expression of genes related to contractile function and hypertrophy of the left ventricle in chronically paced patients from the right ventricular apex.

AIM: Long-term right ventricular apical (RVA) pacing may lead to left ventricular (LV) remodelling and heart failure. This study assessed changes in the expression of genes regulating LV contractile function and hypertrophy, after permanent RVA pacing and investigated whether such changes proceed or even predict LV remodelling. METHODS AND RESULTS: We enrolled 52 consecutive patients (age 79.1 ± 7.7 years, 34 males) who underwent pacemaker implantation for bradycardic indications: Group A, 24 individuals with atrioventricular conduction disturbances and group B, 28 patients with sinus node disease. In group A, peripheral blood mRNA levels of gene sarcoplasmic reticulum calcium ATPase decreased at 3, 6, and 12 months' follow-up, while α-myosin heavy chain (MHC) decreased and ß-MHC increased until 6 months follow-up. In this group, 25% of patients demonstrated significant LV remodelling. At 4 years, LV end-systolic diameter increased from 29.67 ± 3.39 mm at baseline to 35.38 ± 4.22 mm, LV end-diastolic diameter increased from 50 ± 4.95 to 56.71 ± 5.52 mm, and ejection fraction declined from 63.04 ± 10.22 to 52.83 ± 10.81%. Early alterations in gene expression were associated with a deterioration in LV function and geometry that became apparent months later. In group B, echocardiographic indexes and mRNA levels of the evaluated genes demonstrated no statistically significant changes. CONCLUSIONS: Permanent RVA pacing in patients with preserved ejection fraction is associated with alterations in the expression of genes regulating LV contractile function and hypertrophy, measured in the peripheral blood. These alterations are traceable at an early stage, before echocardiographic changes are apparent and are associated with LV remodelling that becomes evident in the long term.

Short-term effects of angiotensin receptor-neprilysin inhibitors on diastolic strain and tissue doppler parameters in heart failure patients with reduced ejection fraction: A pilot trial.

OBJECTIVE: Although sacubitril/valsartan has recently shown its long-term benefits on morbidity and mortality in symptomatic patients with chronic heart failure with reduced ejection fraction (HFrEF), its short-term effects on diastolic function remain uncertain. We sought to assess 30-day effects of sacubitril/valsartan on left ventricular (LV) diastolic paremeters determined by speckle tracking and tissue Doppler imaging (STI and TDI respectively) as well as their association with functional capacity change evaluated by peak oxygen uptake (VO2max) in stable patients with symptomatic HFrEF. METHODS: A total of 35 patients (aged 61 ± 9 years) eligible for sacubitril/valsartan underwent a complete two-dimension (2D) echocardiographic study and a cardiopulmonary exercise test at baseline and 30 days after the initiation of therapy. RESULTS: Significant improvements in ratio of trans-mitral inflow early diastolic velocity E to mitral annulus early diastolic velocity E' (ΔΕ//Ε' = -35.9%, p = 0.001), peak early diastolic strain rate SRE (ΔSRE = +22.5%, p = 0.024) and ratio E/SRE (ΔE/SRE = -33.2%, p = 0.025) were observed after 1-month therapy. Compared with baseline, VO2max also increased significantly by 16.7 % (p = 0.001). Baseline E/SRE and ΔE/SRE were the strongest independent predictors of VO2max improvement (beta = -0.43, p = 0.004 and beta = 0.45, p = 0.021 respectively) in the multivariate analysis. CONCLUSION: Sacubitril/valsartan was associated with early improvement in LV diastolic function determined by TDI and 2D STI. Baseline E/SRE was stronger than standard echocardiographic parameters in predicting the early benefit of sacubitril/valsartan therapy.

The role of C-reactive protein in atherosclerotic cardiovascular disease: an overview.

C-reactive protein (CRP) is an acute-phase protein, which has been used in clinical practice as a non specific marker of inflammation. Many studies have shown that CRP is associated with atherosclerotic cardiovascular disease. It is currently unknown if CRP plays an active role as an etiologic factor in cardiovascular disease. The mechanisms by which CRP may contribute to the pathogenesis of cardiovascular disease are poorly understood. The effect of CRP on atherogenesis may include interactions with other factors of immunity and inflammation, such as the complement system, as well as a direct effect of CRP on the cells involved in atherosclerotic lesions. We review the literature concerning the mechanisms by which CRP may influence the development of cardiovascular disease and discuss the findings of clinical studies assessing the association between CRP and cardiovascular disease.

Orlistat-associated adverse effects and drug interactions: a critical review.

Orlistat, an anti-obesity drug, is a potent and specific inhibitor of intestinal lipases. In light of the recent US FDA approval of the over-the-counter sale of orlistat (60 mg three times daily), clinicians need to be aware that its use may be associated with less well known, but sometimes clinically relevant, adverse effects. More specifically, the use of orlistat has been associated with several mild-to-moderate gastrointestinal adverse effects, such as oily stools, diarrhoea, abdominal pain and faecal spotting. A few cases of serious hepatic adverse effects (cholelithiasis, cholostatic hepatitis and subacute liver failure) have been reported. However, the effects of orlistat on non-alcoholic fatty liver disease are beneficial. Orlistat-induced weight loss seems to have beneficial effects on blood pressure. No effect has been observed on calcium, phosphorus, magnesium, iron, copper or zinc balance or on bone biomarkers. Interestingly, the use of orlistat has been associated with rare cases of acute kidney injury, possibly due to the increased fat malabsorption resulting from the inhibition of pancreatic and gastric lipase by orlistat, leading to the formation of soaps with calcium and resulting in increased free oxalate absorption and enteric hyperoxaluria. Orlistat has a beneficial effect on carbohydrate metabolism. No significant effect on cancer risk has been reported with orlistat.Orlistat interferes with the absorption of many drugs (such as warfarin, amiodarone, ciclosporin and thyroxine as well as fat-soluble vitamins), affecting their bioavailability and effectiveness. This review considers orlistat-related adverse effects and drug interactions. The clinical relevance and pathogenesis of these effects is also discussed.

Troponin-I levels as a potential prognostic biomarker of sacubitril/valsartan treatment response in heart failure with reduced ejection fraction: Who will benefit most?

BACKGROUND: Despite robust data on the benefits of sacubitril/valsartan (LCZ696) in patients with chronic heart failure with reduced ejection fraction (HFrEF), there is no evidence yet on prespecified predictive markers of its efficacy. Hypothesis The objective of this study was to identify potential prognostic factors of LCZ696 treatment response. METHODS: We included 48 symptomatic patients with chronic HFrEF (left ventricular ejection fraction ≤35%) and New York Heart Association (NYHA) class II/III: Group A (N = 23) received LCZ696 (105 ± 30 mg twice daily), whereas it was not prescribed in group B (N = 25) according to physician's judgment. Analysis of biochemical parameters, cardiopulmonary exercise testing, and echocardiographic evaluation was performed at baseline and 6 months later. RESULTS: The baseline serum troponin-I levels (TnI) and peak oxygen uptake (VO2 max) were positively associated with the increase in VO2 max (ΔVO2 max = +14.11%, P < 0.05 vs group B) after sacubitril/valsartan treatment (r = 0.68, P = 0.001 and r = 0.57, P = 0.004, respectively). Positive correlations were reported between ΔVO2 max and the improvements in the ratio of early diastolic filling to myocardial tissue velocity (ΔE/E') and the tricuspid annular peak systolic velocity (ΔSa) in group A (r = 0.58, P = 0.004 and r = 0.60, P = 0.002, respectively). In multiple regression analysis, ΔVO2 max was correlated significantly with TnI (beta = 0.35, P = 0.048), ΔE/E' (beta = 0.36, P = 0.031) and ΔSa (beta = 0.37, P = 0.035). CONCLUSIONS: TnI levels may be an independent predictive marker of sacubitril/valsartan efficacy in HFrEF.

A 12-week, prospective, open-label analysis of the effect of rosuvastatin on triglyceride-rich lipoprotein metabolism in patients with primary dyslipidemia.

BACKGROUND: Although the effect of statins on lowering low-density lipoprotein cholesterol (LDL-C) has been extensively studied, their hypotriglyceridemic capacity is not fully understood. OBJECTIVE: The present study examined clinical and laboratory factors potentially associated with the triglyceride (TG)-lowering effect of rosuvastatin. METHODS: Eligible patients had primary dyslipidemia and a moderate risk of heart disease. Patients were prescribed rosuvastatin 10 mg/d in an open-label fashion and kept 3-day food diaries. Laboratory measurements, performed at baseline and 12 weeks, included serum lipid parameters (total cholesterol [TC], TGs, LDL-C, high-density lipoprotein cholesterol [HDL-C], and apolipoprotein [apo] levels), non-lipid metabolic variables (including carbohydrate metabolism parameters and renal, liver, and thyroid function tests), and LDL-subfraction profile (by high-resolution 3% polyacrylamide gel electrophoresis). Tolerability was assessed at each visit. RESULTS: Participants were 75 hyperlipidemic patients (39 men and 36 women; mean age, 51.7 years). At 12 weeks, TC levels were reduced by 35.1% (P < 0.001), TGs by 15.2% (P < 0.001), LDL-C by 48.5% (P < 0.001), apoE by 35.4% (P < 0.001), and apoE by 17.3% (P < 0.001) from baseline, whereas HDL-C and apoA1 levels were not significantly changed. Stepwise linear regression analysis showed that baseline TG levels were most significantly correlated (R(2) = 42.0%; P < 0.001) with the TG-lowering effect of rosuvastatin, followed by the reduction in apoCIII levels (R(2) = 13.6%; P < 0.01). Rosuvastatin use was associated with a reduction in cholesterol mass of both large LDL particles (mean [SD], from 150.5 [36.6] to 90.5 [24.3] mg/dL; P < 0.001) and small, dense LDL (sdLDL) particles (from 11.5 [8.4] to 6.6 [4.5] mg/dL; P < 0.001). Rosuvastatin had no effect on cholesterol distribution of the LDL subfractions (mean [SD], large particles, from 90.8% [7.0%] to 91.8% [5.1%]; sdLDL, from 7.1% [4.7%] to 7.5% [4.8%]) or the mean LDL particle size (from 26.5 [4.2] to 26.6 [4.0] rim). A significant increase in mean LDL particle size after rosuvastatin treatment (mean [SD], from 26.4 [0.4] to 26.9 [0.4] rim; P = 0.02) was observed only in patients with baseline TG levels > or =120 mg/dL. No serious adverse events requiring study treatment discontinuation were reported. One patient who presented with headache and 2 patients who presented with fatigue quickly recovered without discontinuing rosuvastatin treatment. A posttreatment elevation in aminotransferase levels <3-fold the upper limit of normal (ULN) was recorded in 5 (6.7%) patients, and 2 (2.7%) patients experienced elevated creatine kinase concentrations <5-fold ULN. CONCLUSION: Baseline TG levels were the most important independent variable associated with the TG-lowering effect of rosuvastatin.

New therapeutic options in heart failure. What's on the horizon? An overview.

Heart failure is a complex clinical syndrome responsible for high morbidity and mortality in the world. Despite advances in the management of heart failure, the prognosis of these patients remains poor and there is a critical need for new treatment strategies improving the clinical outcomes. New approaches in heart failure therapies target cellular mechanisms, as well as mechanical and structural aspects of heart failure that are not addressed by recent therapies. These include abnormalities in molecular mechanisms, electrical conduction and ventricular remodeling. This review presents the pathophysiological basis, mechanisms of action and available clinical efficacy and safety data of drugs and mechanical therapies that are currently under development.

Efficacy and safety of ezetimibe plus orlistat or rimonabant in statin-intolerant nondiabetic overweight/obese patients with dyslipidemia.

AIMS: To compare the effects of ezetimibe plus orlistat or rimonabant on anthropometric and lipid parameters in nondiabetic statin-intolerant overweight/obese patients with dyslipidemia. METHODS AND RESULTS: Thirty participants received a hypocaloric diet and were randomized to open-label combination of ezetimibe (10 mg/day) with orlistat (120 mg, 3 times a day with meals; ezetimibe/orlistat [EO], n = 15) or rimonabant (20 mg/day; ezetimibe/rimonabant [ER], n = 15). Anthropometric and metabolic variables were assessed at baseline and 3 months posttreatment. Similar reductions in body weight, body mass index, and waist circumference were recorded in both groups (-8.3%, -8.6%, and -5.2% in the EO group and -7.3%, -7.2%, and -7.0% in the ER group, P < .01 vs baseline for all). Low-density lipoprotein cholesterol (LDL-C) levels decreased in both treatment groups, but this reduction tended to be more pronounced in the EO group (28.4% vs 15.3%, respectively; P < .01 vs baseline for both). Triglycerides tended to decrease more in the ER compared with the EO group (-20.4% vs -14.1%, P < .01 vs baseline for both). High-density lipoprotein cholesterol (HDL-C) levels tended to decrease in EO group, but remained unaltered with ER treatment. Apolipoprotein B levels were equally reduced in both treatment groups. CONCLUSION: For similar body weight reduction, the combination of ezetimibe with orlistat may be more efficient in LDL-C lowering, whereas the combination of ezetimibe with rimonabant may be more potent in terms of improving HDL-C and triglycerides.