Israel Medical Association Journal

Background: Unconscious adults with spontaneous circulation after out-of-hospital cardiac arrest should be cooled to 32–34ºC (ILCOR recommendations, 2003) when the initial rhythm is ventricular fibrillation.

Objectives: To assess the technique, safety and efficacy of mild induced hypothermia in patients after OHCA[1] due to VF[2].

Methods: Patients were cooled using the MTRE CritiCoolÔ external cooling system. Cold intravenous fluids were added to achieve faster cooling in 17 patients. Data were collected prospectively and patients were analyzed according to their neurological outcome on discharge, defined by their cerebral performance category.

Results: From February 2002 to September 2006, 51 comatose VF patients with OHCA underwent MIH[3]. Treatment was discontinued early in five because of hemodynamic instability; goal temperature was reached in 98% and maintained for an average of 19.5 hours; 61% had a favorable outcome (CPC[4] 1–2) and 37% died. Improved outcome was observed with longer hypothermia time and possibly when time from collapse to return of spontaneous circulation was < 25 minutes.

Conclusions: MIH, using an external cooling system, is simple and feasible, reduces mortality and protects neurological function. Four major factors seem to influence outcome: age, co-morbidities, duration of hypothermia, and possibly the length of time from collapse to ROSC[5].

Background: The decision to perform primary percutaneous coronary intervention in unconscious patients resuscitated after out-of-hospital cardiac arrest is challenging because of uncertainty regarding the prognosis of recovery of anoxic brain damage and difficulties in interpretation of ST segment deviations. In ST elevation myocardial infarction patients after OHCA[1], primary PCI[2] is generally considered the only option for reperfusion. There are few published studies and no randomized trial has yet been performed in this specific group of patients.

Objectives: To define the demographic, clinical and angiographic characteristics, and the prognosis of STEMI[3] patients undergoing primary PCI after out-of-hospital cardiac arrest.

Methods: We performed a retrospective analysis of medical records and used the prospectively acquired information from the Rambam Primary Angioplasty Registry (PARR) and the Rambam Intensive Cardiac Care (RICCa) databases.

Results: During the period March1998 to June 2006, 25 STEMI patients (21 men and 4 women, mean age 56 ± 11years) after out-of-hospital cardiac arrest were treated with primary PCI. The location of myocardial infarction was anterior in 13 patients (52%) and non-anterior in 12 (48%). Cardiac arrest was witnessed in 23 patients (92%), but bystander resuscitation was performed in only 2 patients (8%). Eighteen patients (72%) were unconscious on admission, and Glasgow Coma Scale > 5 was noted in 2 patients (8%). Cardiogenic shock on admission was diagnosed in 4 patients (16%). PCI procedure was successful in 22 patients (88%). In-hospital, 30 day, 6 month and 1 year survival was 76%, 76%, 76% and 72%, respectively. In-hospital, 30 day, 6 month and 1 year survival without severe neurological disability was 68%, 68%, 68% and 64%, respectively.

Conclusions: In a selected group of STEMI patients after out-of-hospital cardiac arrest, primary PCI can be performed with a high success rate and provides reasonably good results in terms of short and longer term survival.

Background: Radiofrequency ablation has been suggested as first-line therapy in the management of accessory pathways. There are limited data on the results of ablation over years of experience.

Objectives: To assess the results and complications following RFA[1] of APs[2] performed in our institution over a 14 year period.

Methods: RFA was performed using deflectable electrode catheters positioned at the mitral or tricuspid annulus. The site of the AP was localized by electrophysiological study and radiofrequency energy was applied via the tip of the catheter

Results: The study cohort comprised 508 consecutive patients (64.2% males, mean age 33.6 ± 15.1 years) who underwent 572 RFA procedures for ablating 534 APs. A single AP was found in 485 (95.5%) patients while multiple APs were noted in 23 patients (4.5%). The APs were manifest, concealed or intermittent in 46.8%, 44.4% and 8.8% of cases, respectively. AP distribution was as follows: left free wall (56.6%), posteroseptal (23%), right anteroseptal (7.9%), right free wall (6.2%), midseptal (3.4%) and right atriofascicular (3.0%). Acute successful rates for a first or multiple ablation attempts were 93.1% and 95.3%, respectively. At a first ablation attempt, acute success and failure rates were the highest for midseptal (100%) and right atriofascicular (12.5%) APs respectively. Right anteroseptal APs were associated with the highest rate (23.9%) of discontinued or non-attempted procedures. Recurrent conduction in an AP after an initial successful ablation was observed in 9.9% of cases; it was the highest (24.2%) for right free wall APs and the lowest (5.0%) for left free wall APs. During follow-up (85 ± 43 months), definite cure of the AP was achieved in 94.9% of cases following a single or multiple procedures: midseptal (100%), left free wall (98%), right free wall (97%), posteroseptal (92.7%), right atriofascicular (87.5%) and right anteroseptal (78.5%). A non-fatal complication occurred in 18 patients (3.5%), more frequently in females (6.6%) than in males (1.8%) (P < 0.01). The two major complications (pericardial effusion and myocardial ischemic events) mainly occurred during RFA of a left free wall AP using a retrograde aortic approach. Catheter-induced mechanical trauma to APs was observed in 56 cases (10.5%). Mechanical trauma mainly involved right atriofascicular (43.8%) and right anteroseptal (38.1%) APs and contributed to the low success rate of RFA at these AP locations. During the 14 year period, our learning curve was achieved quickly in terms of success rate, although the most significant complications were observed at the beginning of our experience.

Conclusions: The results of this study confirm the efficacy and safety of RFA and suggest that it is a reasonable first-line therapy for the management of APs at any location.

Background: Coronary heart disease and ischemic stroke are among the leading causes of morbidity and mortality in adults, and cerebrovascular disease is associated with the presence of symptomatic and asymptomatic CHD[1]. Several studies noted an association between coronary calcification and thoracic aorta calcification by several imaging techniques, but this association has not yet been examined in stable angina pectoris patients with the use of spiral computed tomography.

Objectives: To examine by spiral CT the association between the presence and severity of CC[2] and thoracic aorta calcification in patients with stable angina pectoris.

Methods: The patients were enrolled in ACTION (A Coronary Disease Trial Investigating Outcome with Nifedipine GITS) in Israel. The 432 patients (371 men and 61 women aged 40–89 years) underwent chest CT and were evaluated for CC and aortic calcification.

Results: CC was documented in 90% of the patients (n=392) and aortic calcification in 70% (n=303). A significant association (P < 0.05) was found between severity of CC and severity of aortic calcification (as measured by area, volume and slices of calcification). We also found an association between the number of coronary vessels calcified and the presence of aortic calcification: 90% of patients with triple-vessel disease (n=157) were also positive for aortic calcification (P < 0.05). Age also had an effect: 87% of patients ≥ 65 years (n=219) were positive for both coronary and aortic calcification (P = 0.005) while only 57% ≤ 65 (n=209) were positive for both (P = 0.081).

Conclusions: Our study demonstrates a strong association between the presence and severity of CC and the presence and severity of calcification of thoracic aorta in patients with stable angina pectoris as detected by spiral CT.

Background: Echocardiographic assessment of left ventricular function includes calculation of ejection fraction and regional wall motion analysis. Recently, speckle imaging was introduced for quantification of left ventricular function.

Objectives: To assess LVEF[1] by speckle imaging and compare it with Simpson’s method, and to assess the regional LV strain obtained by speckle imaging in relation to conventional echocardiographic scores.

Methods: Thirty consecutive patients, 28 with regional LV dysfunction, underwent standard echocardiographic evaluation. LV end-diastolic volume, LV end-systolic volume and EF were calculated independently by speckle imaging and Simpson’s rule. The regional peak systolic strain presented by speckle imaging as a bull's-eye map was compared with the conventional visual estimate of echo score.

Results: Average EDV[2] obtained by speckle imaging and by Simpson’s method were 85.1 vs. 92.7 ml (P = 0.38), average ESV[3] was 49.4 vs. 48.8 ml (P = 0.94), calculated EF was 43.9 vs. 50.5% (P = 0.08). The correlation rate with Simpson’s rule was high: 0.92 for EDV, 0.96 for ESV, and 0.89 for EF. The peak systolic strain in two patients without wall motion abnormality was 17.3 ± 4.7; in normal segments of patients with regional dysfunction, peak systolic strain (13.4 ± 4.9) was significantly higher than in hypokinetic segments  (10.5 ± 4.5) (P < 0.000001). The strain in hypokinetic segments was significantly higher than in akinetic segments (6.2 ± 3.6) (P < 0.000001).

Conclusions: Speckle imaging can be successfully used for the assessment of LV volumes and EF. Bull's-eye strain map, created by speckle imaging, can achieve an accurate real-time segmental wall motion analysis.

Background: Electrocardiography has a very low sensitivity in detecting dobutamine-induced myocardial ischemia.

Objectives: To assess the added diagnostic value of a new cardiac performance index (dP/dt^ejc) measurement, based on brachial artery flow changes, as compared to standard 12-lead ECG, for detecting dobutamine-nduced myocardial ischemia, using Tc99m-Sestamibi single-photon emission computed tomography as the gold standard of comparison to assess the presence or absence of ischemia.

Methods: The study group comprised 40 patients undergoing Sestamibi-SPECT[1]/dobutamine stress test. Simultaneous measurements of ECG and brachial artery dP/dt^ejc were performed at each dobutamine level. In 19 of the 40 patients perfusion defects compatible with ischemia were detected on SPECT. The increase in dP/dt^ejc during infusion of dobutamine in this group was severely impaired as compared to the non-ischemic group. dP/dt^ejc outcome was combined with the ECG results, giving an ECG-enhanced value, and compared to ECG alone.

Results: The sensitivity improved dramatically from 16% to 79%, positive predictive value increased from 60% to 68% and negative predictive value from 54% to 78%, and specificity decreased from 90% to 67%.
Conclusions: If ECG alone is used for specificity, the combination with dP/dt^ejc improved the sensitivity of the test and could be a cost-savings alternative to cardiac imaging or perfusion studies to detect myocardial ischemia, especially in patients unable to exercise

Background: Femoral artery vascular complications are the most common adverse events following cardiac catheterization. Smaller diameter introducer sheaths and catheters are likely to lower the puncture site complication rate but may hinder visualization.

Objectives: To evaluate the safety and angiographic quality of 4 French catheters.

Methods: The study was designed to simulate real-life operator-based experience. Diagnostic angiography was performed with either 4F or 6F diagnostic catheters; the size of the catheter used in each patient was predetermined by the day of the month. Patients undergoing 4F and 6F diagnostic angiography were ambulated after 4 and 6 hours, respectively. The following technical parameters were recorded by the operator: ease of introducer sheath insertion, ease of coronary intubation, ease of injection, coronary opacification, collateral flow demonstration, and overall assessment. Adverse events were recorded in all patients and included minor bleeding, major bleeding (necessitating blood transfusion), minor hematoma, major hematoma, pseudo-aneurysm formation and arteriovenous fistula.

Results: The study group included 177 patients, of whom 91 were in the 4F arm and 86 in the 6F arm. Demographic and procedural data were similar in both groups. Seventy-seven percent of 6F and 50% of 4F procedures were evaluated as excellent (P < 0.05). This difference was attributed to easier intubation of the coronary ostium and contrast material injection, increased opacification of the coronary arteries, and demonstration of collateral flow with 6F catheters. Complications occurred in 22% of patients treated with 6F catheters and 10% of those treated with 4F catheters (P = 0.11). Of the 50 patients who switched from 4F to 6F 12% had complications. In patients undergoing diagnostic angiography, the complication rate was 10% vs. 27% (most of them minor) in the 4F and 6F groups, respectively (P < 0.05).
Conclusions: Patients catheterized with 4F have fewer complications compared with 6F diagnostic catheters even when ambulated earlier. Although 4F had a reduced quality compared to 6F angiographies, they were evaluated as satisfactory or excellent in quality 85% of the time. 4F catheters have a potential for reduced hospitalization stay and are a good option for primary catheterization in patients not anticipated to undergo coronary intervention

Backgound: The use of intraoperative transesophageal echocardiogram in patients with infective endocarditis is usually reserved for cases of inadequate preoperative testing or suspected extension to perivalvular tissue.

Objectives: To explore the impact of routine intraoperative TEE[1] in patients with infective endocarditis.

Methods: The impact of intraoperative TEE on the operative plan, anatomic-physiologic results, and hemodynamic assessment or de-airing was analyzed in 59 patients (38 males, 21 females, mean age 57.7 ± 16.8 years, range 20–82) operated for active infective endocarditis over 56 months.

Results: Immediate pre-pump echocardiography was available in 52 operations (86.7%), and changed the operative plan in 6 of them (11.5%). Immediate post-pump study was available in 59 patients (98.3%) and accounted for second pump-run in 6 (10.2%): perivalvular leak (3 cases), and immobilized leaflet, significant mitral regurgitation following vegetectomy, and failing right ventricle requiring addition of vein graft (1 case each). Prolonged de-airing was necessary in 6 patients (10.2%). In 5 patients (8.5%) the postoperative study aided in the evaluation and treatment of difficult weaning from the cardiopulmonary bypass pump. In 21 patients (35.6%) the application of intraoperative TEE affected at least one of the four pre-specified parameters.
Conclusions: Intraoperative TEE has an important role in surgery for infective endocarditis and should be routinely implemented

Background: During the last decade new surgical techniques for mitral valve repair were developed. We have been using those techniques in order to widen the spectrum of patients eligible for MV[1] repair.

Objectives: To assess the operative and mid-term results a wide variety of surgical techniques.

Methods: From January 2004 through December 2006, 213 patients underwent MV repair in our institution. Valve pathology was degenerative in 123 patients (58%), ischemic in 37 (17%), showed annular dilatation in 25 (12%), endocarditis in 16 (8%), was rheumatic in 13 (6%), and due to other causes in 14 (7%). Preoperative New York Heart Association score was 2.35 ± 0.85 and ejection fraction 53 ± 12%. Isolated MV repair was performed in 90 patients (42%) and 158 concomitant procedures were done in 123 patients (58%). A wide variety of surgical techniques was used in order to increase the number of repairs compared to valve replacement.

Results: There were 7 in-hospital deaths (3.3%). NYHA[2] class improved from 2.19 ± 0.85 to 1.4 ± 0.6, and freedom from reoperation was 100%. Echocardiography follow-up of patients with degenerative MV revealed that 93% of the patients (115/123) were free of mitral regurgitation greater than 2+ grade. In patients operated by a minimal invasive approach there were no conversions to sternotomy, no late deaths, none required reoperation, and 96% were free of MR[3] greater than 2+ grade. The use of multiple surgical techniques enabled the repair of more than 80% of pure MR cases.

Conclusions: MV repair provides good perioperative and mid-term results, and supports the preference for MV repair over replacement, when feasible. Multiple valve repair techniques tailored to different pathologies increases the feasibility of mitral repair.

Background: Previous studies found some factors such as physical exertion, anger and heavy meals to be triggers for acute coronary syndrome.

Objectives: To estimate the relative risk of an ACS[1] episode associated with positive and negative emotional experiences and anger as potential work-related triggers.

Methods: A total of 209 consecutive patients were interviewed a median of 2 days after a cardiac event that occurred at work or up to 2 hours later. The case-crossover design was used. Positive and negative emotional experiences and anger episodes in the hours immediately before the onset of ACS were compared with episodes in the comparable hours during the previous workday. For anger the episodes were compared with the usual frequency at work during the previous year. Positive and negative emotional experiences were assessed by the PANAS questionnaire (Positive and Negative Affect Scale), and anger by the Onset Anger Scale.

Results: The relative risks of an acute coronary event during the first hour after exposure to negative and positive emotional experiences were RR[2] = 14.0 (95% confidence interval 1.8–106.5) and RR = 3.50 (95% CI[3], 0.7–16.8) respectively and RR = 9.0 (95% CI, 1.1–71) for an episode of anger. Using conditional logistic regression analysis, the highest relative risk was associated with negative emotional experiences.

Conclusions: Negative emotional experiences and anger at work can trigger the onset of an ACS episode. This could have implications for recognizing a cardiac event as a work accident. The implementation of stress-reduction programs in the workplace or use of preventive medications in workers at high risk for coronary heart disease should be investigated.

Background: Hyperglycemia is common among patients admitted to intensive care units, and carries the risk for complications and prolonged ICU[1] stay. With intensive insulin control of blood glucose, morbidity and mortality can be reduced.

Objectives: To determine whether intensive or conventional insulin control of blood glucose in hyperglycemic ICU patients correlated with the prognosis.

Methods: Following admission to the ICU, hyperglycemic patients were randomly assigned to a group treated intensively with insulin targeting glucose at 110–140 mg/dl, or to a conventional insulin therapy group, where glucose, upon exceeding 200 mg/dl, was controlled at 140–200 mg/dl. Rates of morbidity and mortality, hypoglycemic episodes, and insulin dosage were compared.

Results: In the 41 patients treated intensively with insulin the glucose level was 142 ± 14 mg/dl, as compared to 174 ± 20 mg/dl in the 48 patients on conventional insulin treatment. Both groups were similar in age, acute physiology and chronic health evaluation score. Morbidity was also similar, except for increased vascular damage in the conventional treatment group and slightly shorter ICU stay in the intensive therapy group. Both groups had similar in-ICU, in-hospital, and 28 day mortalities, and similar rates of hypoglycemic episodes. The daily dosage of insulin was significantly higher with the conventional treatment (P = 0.004).

Conclusions: Intensive insulin treatment did not affect the mortality or morbidity rates in ICU patients. The increased insulin dosage of conventional insulin treatment was attributable to the group's higher prevalence of diabetes. Future studies should address this bias and determine the optimal glucose target.  

Background: Ion Channel Innovations has developed a gene transfer product, ftMaxi-K, and has begun clinical trials to investigate the effect of increased expression of Maxi-K channels in the smooth muscle of the penis or bladder in patients with erectile dysfunction and those with overactive bladder. The primary function of K channels is to modulate Ca⁺⁺ influx through Ca-channels (i.e., L-type, voltage-dependent). The amount of Ca⁺⁺ that enters the cell through these channels is a major determinant of the free intracellular calcium levels inside the smooth muscle cell, which in turn determines the degree of smooth muscle cell contraction. Increased Maxi-K channel activity is associated with smooth muscle cell relaxation, resulting in, for example, penile erection and detrussor muscle relaxation. A phase I clinical trial that used dMaxi-K has been completed and a similar trial to assess safety of the transfer for overactive bladder is about to begin.

Objectives: To assess the safety and tolerability of escalating dMaxi-K doses by clinical evaluations and laboratory tests, and to measure efficacy objectives by means of the International Index of Erectile Function scale.

Methods: In the erectile dysfunction trial 11 patients with moderate to severe erectile dysfunction were given a single-dose corpus cavernosum injection of dMaxi-K, a "naked" DMA plasmid carrying the human cDNA encoding for the gene for the a, or pore-forming, subunit of the human smooth muscle Maxi-K channel, hSIo. Three patients each were given 500,1000, and 5000 pg and two patients were given 7500 pg doses of ftMaxi-K and followed for 24 weeks. Patient responses were validated by partner responses.

Results: There were no serious adverse events and no dose-related adverse events attributed to gene transfer for any patient at any dose or study visit. No clinically significant changes from baseline were seen in physical evaluations (general and genitourinary), hematology, chemistry and hormone analyses, or in cardiac events evaluated by repeated electrocardiograms. Importantly, no plasmid was detected in the semen of patients at any time after the injections. Patients given the two highest doses of dMaxi-K had apparent sustained improvements in erectile function as indicated by improved IIEF-EF domain scores over the length of the study. One patient given 5000 (jg and one given 7500 [jg reported EF category improvements that were highly clinically significant and were also maintained through the 24 weeks of study.
Conclusions: Efficacy conclusions cannot be drawn from results of a phase 1 trial with no control group. However, the promising primary safety outcomes of the study and preliminary indications of effectiveness provide evidence that ftMaxi-K gene transfer is a viable approach to the treatment of erectile dysfunction and other smooth muscle diseases with targeted access