Betty Raman

Early use of N-acetylcysteine with nitrate therapy in patients undergoing primary percutaneous coronary intervention for ST-segment-elevation myocardial infarction reduces myocardial infarct size (the NACIAM trial [N-acetylcysteine in acute myocardial infarction])

Background: Contemporary ST-segment–elevation myocardial infarction management involves primary percutaneous coronary intervention, with ongoing studies focusing on infarct size reduction using ancillary therapies. N-acetylcysteine (NAC) is an antioxidant with reactive oxygen species scavenging properties that also potentiates the effects of nitroglycerin and thus represents a potentially beneficial ancillary therapy in primary percutaneous coronary intervention. The NACIAM trial (N-acetylcysteine in Acute Myocardial Infarction) examined the effects of NAC on infarct size in patients with ST-segment–elevation myocardial infarction undergoing percutaneous coronary intervention. Methods: This randomized, double-blind, placebo-controlled, multicenter study evaluated the effects of intravenous high-dose NAC (29 g over 2 days) with background low-dose nitroglycerin (7.2 mg over 2 days) on early cardiac magnetic resonance imaging–assessed infarct size. Secondary end points included cardiac magnetic resonance–determined myocardial salvage and creatine kinase kinetics. Results: Of 112 randomized patients with ST-segment–elevation myocardial infarction, 75 (37 in NAC group, 38 in placebo group) underwent early cardiac magnetic resonance imaging. Median duration of ischemia pretreatment was 2.4 hours. With background nitroglycerin infusion administered to all patients, those randomized to NAC exhibited an absolute 5.5% reduction in cardiac magnetic resonance–assessed infarct size relative to placebo (median, 11.0%; [interquartile range 4.1, 16.3] versus 16.5%; [interquartile range 10.7, 24.2]; P=0.02). Myocardial salvage was approximately doubled in the NAC group (60%; interquartile range, 37–79) compared with placebo (27%; interquartile range, 14–42; P<0.01) and median creatine kinase areas under the curve were 22 000 and 38 000 IU·h in the NAC and placebo groups, respectively (P=0.08). Conclusions: High-dose intravenous NAC administered with low-dose intravenous nitroglycerin is associated with reduced infarct size in patients with ST-segment–elevation myocardial infarction undergoing percutaneous coronary intervention. A larger study is required to assess the impact of this therapy on clinical cardiac outcomes. Clinical Trial Registration: Australian New Zealand Clinical Trials Registry. URL: http://www.anzctr.org.au/. Unique identifier: 12610000280000.

Relation of Delayed Recovery of Myocardial Function After Takotsubo Cardiomyopathy to Subsequent Quality of Life

Takotsubo cardiomyopathy (TTC) has generally been regarded as a relatively transient disorder, characterized by reversible regional left ventricular systolic dysfunction. However, most patients with TTC experience prolonged lassitude or dyspnea after acute attacks. Although this might reflect continued emotional stress, myocardial inflammation and accentuated brain-type natriuretic peptide (BNP) release persist for at least 3 months. We therefore tested the hypotheses that this continued inflammation is associated with (1) persistent contractile dysfunction and (2) consequent impairment of quality of life. Echocardiographic parameters (global longitudinal strain [GLS], longitudinal strain rate [LSR], and peak apical twist [AT]) were compared acutely and after 3 months in 36 female patients with TTC and 19 age-matched female controls. Furthermore, correlations were sought between putative functional anomalies, inflammatory markers (T2 score on cardiovascular magnetic resonance, plasma NT-proBNP, and high-sensitivity C-reactive protein levels), and the physical composite component of SF36 score (SF36-PCS). In TTC cases, left ventricular ejection fraction returned to normal within 3 months. GLS, LSR, and AT improved significantly over 3-month recovery, but GLS remained reduced compared to controls even at follow-up (-17.9 ± 3.1% vs -20.0 ± 1.8%, p = 0.003). Impaired GLS at 3 months was associated with both persistent NT-proBNP elevation (p = 0.03) and reduced SF36-PCS at ≥3 months (p = 0.04). In conclusion, despite normalization of left ventricular ejection fraction, GLS remains impaired for at least 3 months, possibly as a result of residual myocardial inflammation. Furthermore, perception of impaired physical exercise capacity ≥3 months after TTC may be explained by persistent myocardial dysfunction.

Takotsubo cardiomyopathy presenting as S–T elevation myocardial infarction: Not gone but forgotten?

myocardial edema on cMRI, together with the presence of characteristic (usually peri-apical or mid ventricular) hypokinesis. Elevation of NT-Pro BNP levels and characteristic ECG changes were utilized in screening. Plasma concentrations of normetanephrine and metanephrine were measured on admission. We also examined potential differences in demographics and biomarkers between TTC patients presenting with and without initial S–T elevation. Comparisons between the subsets of TTC patients were made utilizing Students non-paired t tests.

Can Perhexiline Be Utilized Without Long-Term Toxicity? A Clinical Practice Audit.

Background: Perhexiline, originally used as a first-line prophylactic antianginal agent, is now regarded primarily as a treatment for otherwise refractory myocardial ischemia. Recent studies have also demonstrated its short-term utility in heart failure, hypertrophic cardiomyopathy, and inoperable aortic stenosis. Its benefits on myocardial energetics state are potentially counter-balanced by risk of hepatotoxicity and peripheral neuropathy during long-term treatment if drug accumulation occurs. Since perhexiline exhibits complex pharmacokinetics with wide inter-individual variability, its long-term use requires regular plasma concentration monitoring. In this study, the risk of neuro- and hepato-toxicity during long-term perhexiline therapy in relation to the intensity of therapeutic drug monitoring was investigated. Furthermore, determinants of mortality during perhexiline treatment were evaluated. Methods: In 170 patients treated with perhexiline for a median of 50 months (interquartile range: 31–94 months), outcomes and relationship to plasma drug concentrations were documented. Results: Rationale for treatment with perhexiline included myocardial ischemia in 88% and severe systolic heart failure in 38%. Plasma concentrations were within the therapeutic range of 150–600 ng/mL on 65% of assay occasions and toxic levels accounted for 8.8% of measurements. No patient developed hepatotoxicity attributable to perhexiline while 3 developed peripheral neuropathy possibly induced by treatment. Actuarial 5-year survival rate was 83% overall, and 76.3% in patients with associated systolic heart failure. Conclusions: This first audit of a large population treated long-term perhexiline demonstrates the following: (1) Although the frequency of monitoring is less than ideal, therapeutic drug monitoring effectively limits occurrence of toxic drug concentrations and virtually eliminates long-term hepato- and neuro-toxicity and (2) Mortality rates during long-term therapy, notably for patients with concomitant heart failure, are surprisingly low.

Nitrosative Stress as a Modulator of Inflammatory Change in a Model of Takotsubo Syndrome

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