Anthracycline-induced cardiotoxicity and the cardiac-sparing effect of liposomal formulation.

The anthracyclines are a group of antibiotics that are among the most potent chemotherapeutic agents. They are highly effective against a broad spectrum of malignancies, including lymphoma, gastric cancer, small cell lung cancer, sarcoma, and breast cancer. Unfortunately, these agents also exhibit a well-recognized cumulative-dose related cardiotoxic profile that limits the extent to which they can be used safely. In clinical practice, most clinicians limit the cumulative dose of doxorubicin (the most widely used agent in this group) to 400-450 mg/m2, but considerable cardiac damage is now known to occur at cumulative dosages considerably below this level. Regimens using newer combinations of agents, the most widely studied of which is the monoclonal antibody trastuzumab, are known to augment the cardiotoxicity of anthracyclines. The application of nanotechnology to medicine involves the use of devices that will interact with the body at the molecular level. These methods can lead to target and tissue specific clinical application, often with minimal or reduced side effects. Liposomal preparations incorporate such technology, thereby altering some important characteristics of the parent compound and facilitating concentration at the tumor site. In the case of liposomal doxorubicin, cardiotoxicity is reduced significantly. This review summarizes the important information on the liposomal preparation of anthracyclines.

Reversible right ventricular dysfunction in patients with HIV infection.

Human immunodeficiency virus-related cardiomyopathy is characterized by global left ventricular (LV) dysfunction commonly associated with biventricular dilation. Human immunodeficiency virus (HIV) cardiomyopathy carries a poor prognosis, and the role of antiretroviral therapy in the reversal of heart failure is not very clear. We report two patients with HIV infection who presented with severe right ventricular (RV) dysfunction in the absence of pulmonary parenchymal, pulmonary arterial and left ventricular myocardial involvement. During the period of intensive antiretroviral therapy, the symptoms of right heart failure progressively and remarkably improved. This was accompanied by normalization of right ventricular size and RV function documented by repeat echocardiograms. Given that the serologic tests for opportunistic infections were negative, and the RV function improvement correlated with a decrement in the viral load, it is likely that the cardiomyopathy was due to direct infection by HIV. These cases illustrate that there can be isolated involvement of the right heart in the absence of lung, significant pulmonary vascular and left ventricular disease, and also that the antiretroviral therapy might reverse the cardiomyopathy.

Assessment of left atrial appendage by live three-dimensional echocardiography: early experience and comparison with transesophageal echocardiography.

BACKGROUND: Live Three-Dimensional Echocardiography (L3D, Sonos 7500, Philips) has the potential to visualize all cardiac structures including left atrial appendage (LAA). We tested the feasibility of evaluating LAA by L3D and compared the findings to transthoracic echocardiography (2D) and in a subset of patients with transesophageal echocardiography (TEE). METHODS: L3D images were obtained in 204 consecutive patients referred for routine 2D or TEE. We performed wide-angled acquisitions from parasternal and apical views. TomTec system (4D Cardio-view, RT 1.2) was used to visualize LAA from multiple vantage points. RESULTS: LAA was adequately visualized by L3D in 139 of 204 (68.1%) patients. L3D visualization was dependent on image quality, suboptimal in 100 and diagnostic in 104 patients. Overall, LAA was visualized in 93 (45.5%) patients by 2D compared to 139 (68.1%) by L3D (P < 0.0001). In 100 patients with suboptimal image quality by L3D, LAA visualization was 16% by 2D and 35% by L3D, whereas in 104 patients with diagnostic images, LAA was visualized in 77 (74%) by 2D and in all 104 (100%) patients by L3D (P < 0.0001). In 37 patients referred for transesophageal echocardiography (TEE), live three-dimensional echocardiography (L3D) visualized left atrial appendage (LAA) in 34 patients with diagnostic image quality. Eight patients with LAA thrombi on TEE had thrombi detected by L3D as well. All patients with LAA thrombus had enlarged LA by both 2D and TEE. CONCLUSIONS: L3D is a promising technique in evaluation of LAA with and without thrombi. In patients with good quality transthoracic images L3D may be used as a screening tool in assessment of LAA.

Enhanced cardioprotection against ischemia-reperfusion injury with combining sildenafil with low-dose atorvastatin.

PURPOSE: Both ATV and SL reduce myocardial infarct size (IS) by enhancing expression and activity of NOS isoforms. We investigated whether atorvastatin (ATV) and sildenafil (SL) have synergistic effects on myocardial infarct size (IS) reduction and enhancing nitric oxide synthase (NOS) expression. METHOD: Rats were randomized to nine groups: ATV-1 (1 mg/kg/d); ATV-10 (10 mg/kg/d); SL-0.7 (0.7 mg/kg); SL-1 (1 mg/kg); ATV-1 + SL-0.7; water alone (controls); 1400W (iNOS inhibitor; 1 mg/kg); ATV-10 + 1400W; and ATV-1 + SL-0.7 + 1400W. ATV was administered orally for 3 days. SL was administered intraperitoneally 18 h before surgery and 1400W intravenously 15 min before surgery. Rats either underwent 30 min ischemia-4 h reperfusion or the hearts were explanted for immunoblotting and enzyme activity tests without being exposed to ischemia. RESULTS: IS (% risk area, mean +/- SEM) was smaller in the ATV-10 (13 +/- 1%), SL-1 (11 +/- 2%), SL-0.7 (18 +/- 2%) and ATV-1 + SL-0.7 (9 +/- 1%) groups as compared with controls (34 +/- 3%; P < 0.001), whereas ATV-1 had no effect (29 +/- 2%). ATV-1 + SL-0.7 (9 +/- 1%) reduced IS more than SL-0.7 alone (p = 0.012). 1400W abrogated the protective effect of ATV-10 (35 +/- 3%) and ATV-1 + SL-0.7 (34 +/- 1%). SL-0.7 and ATV-10 increased phosphorylated endothelial (P-eNOS; 210 +/- 2.5% and 220 +/- 8%) and inducible (iNOS; 151 +/- 1% and 154 +/- 1%) NOS expression, whereas ATV-1 did not. These changes were significantly enhanced by ATV-1 + SL-0.7 (P-eNOS, 256 +/- 2%, iNOS 195 +/- 1%). SL-1 increased P-eNOS (311 +/- 22%) and iNOS (185 +/- 1%) concentrations. CONCLUSIONS: Combining low-dose ATV with SL augments the IS limiting effects through enhanced P-eNOS and iNOS expression.

Arsenic exposure from drinking-water and carotid artery intima-medial thickness in healthy young adults in Bangladesh.

Epidemiological studies have linked high levels (>200 microg/L) of chronic exposure to arsenic in drinking-water with elevated risks of several vascular diseases. In this pilot study, the association between low-level arsenic exposure and carotid artery intimal-medial thickness (IMT) was evaluated among 66 healthy, normotensive, relatively young individuals (mean age 35 years) participating in the ongoing Health Effects of Arsenic Longitudinal Study in Bangladesh. Participants with a higher carotid IMT (>0.75 mm) in general had higher levels of past chronic exposure of arsenic than those with a lower carotid IMT (< or = 0.75 mm). Although the differences in average arsenic exposure between the two groups were not statistically significant, the findings suggest a possible association between low-level arsenic exposure from drinking-water and carotid atherosclerosis, warranting the need for larger studies.

Stress-induced right ventricular ischemia in recurrent pulmonary outflow stenosis in repaired tetralogy of fallot.

Radionuclide uptake by the right ventricle during myocardial perfusion imaging is minimal compared with the left ventricular myocardium and is not given much importance. However, right ventricular hypertrophy from pressure or volume overload may increase right ventricular radiotracer uptake and demonstrate reversible stress-induced perfusion abnormalities in the presence of normal coronary arteries. We report a case of right ventricular ischemia secondary to right ventricular hypertrophy from recurrent right ventricular outflow tract stenosis in a patient with repaired tetralogy of Fallot. Advances in the management of congenital heart disease have led to more patients surviving to adulthood. These patients subsequently present to cardiologists in adulthood with sequelae or complications arising from previous surgery undertaken during childhood.

Acute coronary syndrome induced by intravenous ephedrine in pregnant woman with normal coronaries.

Intravenous ephedrine administered during a C-section was observed to cause an acute coronary syndrome in a pregnant woman with normal coronaries. The patient developed sub-sternal chest pain, was noted to have 10 beats of non-sustained ventricular tachycardia, ST abnormalities were observed on her ECG and cardiac enzymes were elevated. The patient had normal coronary arteries by angiogram and during a one-year period of follow up no further cardiac events occurred.

Abciximab treatment for obstructive prosthetic aortic and mitral valve thrombosis in the presence of large thrombi, cardiogenic shock, and acute evolving embolic stroke.

Obstructive thrombosis of left-sided mechanical prosthetic valves is a life-threatening complication. Intravenous thrombolytic therapy is contraindicated due to risk of clot embolization and surgical treatment is often required for hemodynamically unstable patients. We report for the first time the successful use of abciximab in the management of a patient in cardiogenic shock with multiple prosthetic valve obstructive thrombosis and evolving embolic stroke. Serial Doppler echocardiography and cinefluoroscopy demonstrated resolution of thrombi, improvements in transvalvular gradients and improvement in leaflet motion. This observation suggests abciximab should be considered as a therapeutic option in the treatment of obstructed prosthetic heart valves.