Israel Medical Association Journal

Romidepsin is an intravenously administered antineoplastic agent, which acts by inhibiting histone deacetylases, thus preventing removal of acetyl groups from histones. The accrual of acetyl groups on histones causes cell cycle arrest and apoptotic cell death. It was approved for use in the United States in 2009 for treatment of refractory or relapsed cutaneous and peripheral T cell lymphomas [1-3].

The most common side effects are mild to moderate in severity and include nausea, vomiting, fatigue, fever, myelosuppression (e.g., anemia, neutropenia, thrombocytopenia), elevated liver enzymes, constipation, and rash. More severe adverse events can include marked neutropenia, thrombocytopenia, serious infections such as line sepsis, acute renal failure, tumor lysis syndrome, and cardiac arrhythmias [1].

Background: Patients admitted to the hospital after successful resuscitation from sudden cardiac death (SCD) are treated with therapeutic hypothermia (TH) to facilitate brain preservation. The prognostic significance of J (Osborn) waves (JOW) in the 12 leads electrocardiogram in this setting has not been elucidated as yet.

Objectives: To ascertain retrospectively the prognostic significance of JOW recorded during TH in SCD survivors.

Methods: The study comprised 55 consecutive patients who underwent TH. All patients achieved a core temperature of 33°C at the time of electrocardiogram analysis. We compared 33 patients with JOW to 22 patients without JOW. The endpoints were in-hospital, long-term all-cause mortality, and irreversible anoxic brain injury (IABI).

Results: Patients with JOW compared to patients without JOW were younger (55.1 ± 11.6 vs. 64.5 ± 11.7 years, respectively, P < 0.006), with a lower incidence of hypertension (52% vs. 86%, P < 0.007), diabetes mellitus (15% vs. 50%, P < 0.005), and congestive heart failure (15% vs. 45%, P < 0.013). In-hospital and long-term mortality were significantly higher in patients without JOW (86% vs. 21%, 91% vs. 24%, respectively, P < 0.000001). Among patients without JOW who survived hospitalization, 66.7% presented with IABI versus 7.7% of the patients with JOW (P < 0.0001). In multivariate analysis, the absence of JOW was a significant predictor for poor prognosis.

Conclusions: The absence of J (Osborn) waves on electrocardiograms obtained during TH is associated with poor prognosis among SCD survivors

Background: Since the introduction of the electrocardiogram (ECG) in 1902, the fundamentals of ECG data acquisition, display, and interpretation in the clinical arena have not changed much.

Objectives: To present a new method to enhance and improve acquisition, analysis, and display of the standard ECG.

Methods: We performed ECG enhancement by superimposition and summation of multiple standard ECG cycles of each lead, by temporal alignment to peak R wave and voltage alignment to an improved baseline, at the T-P segment.

Results: We enhanced ECG recordings of 504 patients who underwent coronary angiograms for routine indications. Several new ECG features were noted on the enhanced recordings. Examination of a subgroup of 152 patients with a normal rest 12-lead ECG led to the discovery of a new observation, which may help to distinguish between patients with and without coronary artery disease (CAD): namely, a spontaneous cycle-to-cycle voltage spread (VS) at the S-T interval, normalized to VS at the T-P interval. The mean normalized VS was significantly greater in those with CAD (n=61, 40%) than without (n=91, 60%), 5.61 ± 3.79 vs. 4.01 ± 2.1 (P < 0.05).

Conclusions: Our novel method of multiple ECG-cycle superimposition enhances the ECG display and improves detection of subtle electrical abnormalities, thus facilitating the standard rest ECG diagnostic power. We describe, for the first time, voltage spread at the S-T interval, an observed phenomenon that can help detect CAD among individuals with normal rest 12-lead ECG.

Background: The prognostic value of P-wave duration has been previously evaluated by signal-averaged ECG (SAECG) in patients with various arrhythmias not associated with acute myocardial infarction (AMI).

Objectives: To investigate the clinical correlates and prognostic value of P-wave duration in patients with ST elevation AMI (STEMI).

Methods: The patients (n=89) were evaluated on the first, second and third day after admission, as well as one week and one month post-AMI. Survival was determined 2 years after the index STEMI.

Results: In comparison with the upper normal range of P-wave duration (< 120 msec), the P-wave duration in STEMI patients was significantly increased on the first day (135.31 ¡À 29.29 msec, P < 0.001), up to day 7 (127.17 ¡À 30.02 msec, P = 0.0455). The most prominent differences were observed in patients with left ventricular ejection fraction (LVEF) ¡Ü 40% (155.47 ¡À 33.8 msec), compared to LVEF > 40% (128.79 ¡À 28 msec) (P = 0.001). P-wave duration above 120 msec was significantly correlated with increased complication rate namely, sustained ventricular tachyarrhythmia (36%), congestive heart failure (41%), atrial fibrillation (11%), recurrent angina (14%), and re-infarction (8%) (P = 0.012, odds ratio 4.267, 95% confidence interval 1.37¨C13.32). P-wave duration of 126 msec on the day of admission was found to have the highest predictive value for in-hospital complications including LVEF < 40% (area under the curve 0.741, P < 0.001).  However, we did not find a significant correlation between P-wave duration and mortality after multivariate analysis.

Conclusions: P-wave duration as evaluated by SAECG correlates negatively with LVEF post- STEMI, and P-wave duration above 126 msec can be utilized as a non-invasive predictor of in-hospital complications and low LVEF following STEMI.

Objectives: To investigate the spectrum of findings in 32 consecutive patients with chest pain who underwent CT coronary angiogram in order to determine the clinical situations that will benefit most from this new technique.

Methods: Thirty-two patients with chest pain were studied by MDCT[1] using 4 x 1 mm cross-sections, at 500 msec rotation with pitch 1–1.5, intravenous non-ionic contrast agent and a retrospectively ECG-gated reconstruction algorithm. The heart anatomy was evaluated using multi-planar reconstructions in the axial, long and short heart axes planes. Coronary arteries were evaluated using dedicated coronary software and the results were compared to those of the conventional coronary angiograms in 12 patients. The patients were divided into four groups according to the indication for the study: group A – patients with high probability for coronary disease; group B – patients after CCA[2] with undetermined diagnosis; group C – patients after cardiac surgery with possible anatomic derangement; and group D – symptomatic patients after coronary artery bypass graft, before considering conventional coronary angiography.

Results: Artifacts caused by coronary motion, heavy calcification and a lumen diameter smaller than 2 mm were the most frequent reasons for non-evaluable arteries. Assessment was satisfactory in 83% of all coronary segments. The overall sensitivity of 50% stenosis was 74% (85% for main vessels) with a specificity of 96%. Overall, the CTCA[3] results were critical for management in 18 patients.

Conclusions: Our preliminary experience suggests that CTCA is a reliable and promising technique for the detection of coronary artery stenosis as well as for a variety of additional cardiac and coronary structural abnormalities.

Background: The evaluation of hospitalized patients with chest pain and non-diagnostic electrocardiogram is problematic and the optimal cost-effective strategy for their management controversial.

Objectives: To determine the utility of myocardial perfusion imaging with thallium-201 for predicting outcome of hospitalized patients with chest pain and a normal or non-diagnostic ECG.

Methods: On pain cessation, 109 hospitalized patients, age 61+14 years (mean+SD), with chest pain and non-diagnostic ECG underwent stress myocardial perfusion SPECT imaging with thallium-201. Costs related to their management were calculated. The occurrence of non-fatal myocardial infarction or cardiac death was recorded at 12+5 months follow-up.

Results: A normal SPECT was found in 84 patients (77%). During one year follow-up, only 1 (1.2%) compared to 7 (28%) cardiac events (6 myocardial infarctions, 1 cardiac death) occurred in patients with normal versus abnormal scans respectively (P < 0.0001). Negative predictive value and accuracy of the method were 99% and 83% respectively. Multivariate regression analysis identified an abnormal SPECT as the only independent predictor of adverse cardiac event (P = 0.0016). Total cost from admission until discharge was 11,193 vs. 31,079 shekels (P < 0.0001) for normal and abnormal scan. Considering its high negative predictive value, shortening the hospital stay from admission until scan performance to 2 days would result in considerably reduced management costs (from NIS 11,193 to 7,243) per patient.

Conclusion: Stress SPECT applied to hospitalized patients with chest pain and a normal or non-diagnostic ECG is safe, highly accurate and potentially cost effective in distinguishing between Iow and high risk patients.