Simcha R. Meisel

Usefulness of implantable cardioverter-defibrillators in refractory variant angina pectoris complicated by ventricular fibrillation in patients with angiographically normal coronary arteries

V angina pectoris is characterized by anginal symptoms at rest and transient ST elevation on the electrocardiogram due to coronary artery spasm. Ventricular arrhythmia is a well-recognized complication of this type of angina. Although calcium antagonists have been shown to be effective in preventing coronary spasm–induced ventricular arrhythmia in most patients with variant angina pectoris and normal coronary arteries, some may remain refractory. Implantable cardioverter-defibrillators (ICDs) have become a proven modality for patients at high risk of life-threatening ventricular arrhythmias. In the present study we analyzed the clinical course of 8 patients with refractory variant angina pectoris complicated by ventricular fibrillation (VF) who had normal coronary arteries on angiography. We evaluated the efficacy of the ICD in preventing sudden death in this group. • • • The study group consisted of 8 patients encountered in our own clinical practice and at additional hospitals solicited through a multicenter survey. Their medical records were reviewed. All patients fulfilled the following predefined criteria: (1) typical chest pain at rest associated with transient ST-segment elevations not present on the baseline electrocardiogram and disappearing with relief of pain; (2) documented VF immediately after the ischemic episode; (3) survival of the index episode of VF; (4) angiographically normal coronary arteries defined as patent arteries with no irregularities; (5) angiographic evidence of coronary spasm defined as transient narrowing of arterial lumen or recurrent episodes of electrocardiographically documented ischemia especially if occurring in different coronary territories; and (6) recurrent angina despite medical therapy. All patients were followed at the cardiology outpatient clinic. Patients who underwent ICD implantation were also followed at the arrhythmia clinic. Demographic and clinical data of the studied patients are outlined in Table 1. No patient had organic heart disease or any other condition known to be associated with sudden cardiac death. Seven patients were men. All patients initially presented with ischemic chest pain and transient ST elevation on the electrocardiogram. The electrocardiogram normalized in all patients after myocardial ischemia, without evidence of myocardial infarction on serial electrocardiograms. After the ischemic event, creatine kinase elevation (range 520 to 5,000 U/L [upper normal limit, 200]) was observed in 4 patients. Creatine kinase-MB fraction was within normal range. All patients had good left ventricular function, although 2 patients had reversible left ventricular dysfunction documented on serial echocardiograms. In all patients, VF followed the ischemic episode and required direct-current shock as treatment. Three patients required prolonged cardiopulmonary resuscitation. Coronary angiography demonstrated normal coronary arteries in all patients. Spontaneous coronary spasm was documented in 5 patients (Table 1). Four patients had a history of angina preceding the index event. During a mean follow up of 3.5 3.2 years (range 0.5 to 10, median 2.8), all but 1 patient had recurrent episodes of angina. All patients were discharged from the hospital on calcium antagonists at maximum tolerated doses (Table 1). Although treatment with calcium antagonists seemed to reduce the frequency and intensity of recurrent angina in most patients, it did not prevent its occurrence. Ventricular arrhythmia reoccurred after discharge from the hospital in all patients. Median time to the first arrhythmia recurrence was 15 months (range 2 to 112). An ICD was subsequently implanted in 7 patients. All devices were capable of storing electrograms. Before ICD implantation, 4 patients had another episode of VF, 1 patient had an episode of complete atrioventricular block, and 1 patient had multiple long runs of nonsustained ventricular tachycardia after the ischemic events. After ICD implantation, 4 patients received appropriate ICD shocks for ventricular tachycardia/VF as judged on the basis of stored electrographic analysis (Figure 1). Of these 4, 2 patients experienced 2 episodes of VF each. One patient died 19 months after ICD From the Heart Institute, Hillel Yaffe Medical Center, Hadera; Department of Cardiology, Rabin Medical Center, Petah Tikva; Department of Cardiology, Meir General Hospital, Kfar Saba; Department of Cardiology, Kaplan Medical Center, Rehovot; Golda Medical Center, Petah Tikva; and Soroka Medical Center, Beer Sheba, Israel. Dr. Meisel’s address is: Heart Institute, Hillel Yaffe Medical Center, Hadera 38100, Israel. E-mail: meisel@netvision.net.il. Manuscript received October 18, 2001; revised manuscript received and accepted January 24, 2002.

Serum Leptin Levels Increase following Acute Myocardial Infarction

Leptin is secreted into the circulation and communicates the peripheral nutritional status to specific hypothalamic centers. Recent studies suggest that leptin may be involved in the acute response to stress, and that its interaction with the hypothalamo-pituitary-adrenal axis and the inflammatory cytokine system may be of clinical importance. Since these systems are activated during acute myocardial infarction (AMI), we studied leptin and cortisol levels during hospitalization in 30 consecutive patients admitted for AMI. The results show that leptin reached its peak on the second day of hospitalization, with a 2-fold increase from its baseline level on admission (p < 0.02). On day 3, leptin levels declined, and were 46%, 9%, and 6% above baseline on days 3, 4 and 5, respectively. The mean cortisol level was elevated on day 1 and decreased toward normal levels thereafter (p < 0.001). The cortisol level did not correlate with leptin concentration throughout the study. These findings suggest that leptin may have a role in the metabolic changes taking place during the first days after an AMI.

Atrial fibrillation and long-term prognosis in patients hospitalized for heart failure: results from heart failure survey in Israel (HFSIS).

AIMS Atrial fibrillation (AF) and heart failure (HF) commonly coexist, and each adversely affects the other. The aim of the study was to prospectively evaluate the impact of AF and its subtypes on management, and early and long-term outcome of hospitalized HF patients. METHODS AND RESULTS Data were prospectively collected on HF patients hospitalized in all public hospitals in Israel as part of a national survey (HFSIS). Atrial fibrillation patients were subdivided into intermittent and chronic AF subgroups. During March-April 2003, we enrolled 4102 HF patients, of whom 1360 (33.2%) had AF [600 (44.1%) intermittent, 562 (41.3%) chronic]. Patients with AF were older (76.9 +/- 10.5 vs. 71.7 +/- 12.6 years, P = 0.0001), males, with preserved LV systolic function. Crude mortality rates for AF patients were progressively and consistently higher during hospitalization and during the 4-year follow-up period, especially in the chronic AF group (P = 0.0001). After covariate adjustment, AF was associated with increased 1-year mortality [HR 1.19, 95% CI (1.03-1.36)]. CONCLUSION AF was present in a third of hospitalized HF patients, and identified a population with increased mortality risk, largely due to co-morbidities.

Non-Invasive Lung IMPEDANCE-Guided Preemptive Treatment in Chronic Heart Failure Patients: A Randomized Controlled Trial (IMPEDANCE-HF Trial)

BACKGROUND Previous investigations have suggested that lung impedance (LI)-guided treatment reduces hospitalizations for acute heart failure (AHF). A single-blind 2-center trial was performed to evaluate this hypothesis (ClinicalTrials.gov-NCT01315223). METHODS The study population included 256 patients from 2 medical centers with chronic heart failure and left ventricular ejection fraction ≤35% in New York Heart Association class II-IV, who were admitted for AHF within 12 months before recruitment. Patients were randomized to a control group treated by clinical assessment and a monitored group whose therapy was also assisted by LI, and followed for at least 12 months. Noninvasive LI measurements were performed with a new high-sensitivity device. Patients, blinded to their assignment group, were scheduled for monthly visits in the outpatient clinics. The primary efficacy endpoint was AHF hospitalizations; the secondary endpoints were all-cause hospitalizations and mortality. RESULTS There were 67 vs 158 AHF hospitalizations during the first year (P < .001) and 211 vs 386 AHF hospitalizations (P < .001) during the entire follow-up among the monitored patients (48 ± 32 months) and control patients (39 ± 26 months, P = .01), respectively. During the follow-up, there were 42 and 59 deaths (hazard ratio 0.52, 95% confidence interval 0.35-0.78, P = .002) with 13 and 31 of them resulting from heart failure (hazard ratio 0.30, 95% confidence interval 0.15-0.58 P < .001) in the monitored and control groups, respectively. The incidence of noncardiovascular death was similar. CONCLUSION Our results seem to validate the concept that LI-guided preemptive treatment of chronic heart failure patients reduces hospitalizations for AHF as well as the incidence of heart failure, cardiovascular, and all-cause mortality.

Transient ST-elevation myocardial infarction: clinical course with intense medical therapy and early invasive approach, and comparison with persistent ST-elevation myocardial infarction.

Patients presenting with ST-elevation myocardial infarction (STEMI), whose symptoms and electrocardiographic changes completely resolve upon admission and before the administration of reperfusion therapy, pose a therapeutic dilemma. The optimal management of this syndrome, termed here as transient STEMI (TSTEMI), has not yet been fully determined. We describe 69 prospectively recorded patients with TSTEMI, of which 63 patients (56.7 +/- 11 years, 48 men) were available for long-term follow-up out of 1244 consecutive patients with acute myocardial infarction (5%). Patients with TSTEMI treated with intravenous isosorbide dinitrate, aspirin, and clopidogrel, and/or with glycoprotein IIb/IIIa inhibitors were compared with a control group of matched patients with STEMI without resolution, who were treated conventionally. The time interval from symptom onset to presentation at the emergency department of patients with TSTEMI was 1.7 +/- 1.3 hours, and to first recording of ST elevations, 1.5 +/- 1.4 hours. Symptoms and electrocardiographic changes fully resolved 1.2 +/- 0.8 hours later, 1 hour after aspirin and nitrate administration. Coronary angiography, performed 36 +/- 39 hours (median, 24 hours) from admission, demonstrated no obstructive lesion or single-vessel obstructive disease in 43 patients (70%). Primary coronary intervention was performed in 48 patients (77%), and 8 patients (13%) were referred to surgery. Left ventricular ejection fraction was within normal limits, and peak creatine kinase was mildly elevated. Patients with TSTEMI had less extensive coronary artery disease (P < .038), better thrombolysis in myocardial infarction flow on angiography (P < .01), lower peak creatine kinase level (P < .001), higher left ventricular ejection fraction (P < .0001), and lower likelihood to sustain a second additional coronary event after index admission (P = .024) than patients with STEMI. Transient STEMI was associated with less myocardial damage, less extensive coronary artery disease, higher thrombolysis in myocardial infarction flow grade in culprit artery, and better cardiac function. These data suggest that immediate intense medical therapy with an early invasive approach is an appropriate therapy in patients with TSTEMI.

Prediction of cardiogenic pulmonary edema onset by monitoring right lung impedance.

ObjectiveTo evaluate the ability of internal thoracic impedance (ITI) monitors to predict cardiogenic pulmonary edema in patients at risk.Design and SettingProspective, controlled multicenter study.PatientsWe examined 328 consecutive patients admitted for cardiac conditions. Of these 265 patients aged 27–83 years with no clinical signs of pulmonary edema, extracardiac respiratory failure or pacemakers comprised the study cohort.InterventionMonitoring of the lungs electrical impedance was used for predicting cardiogenic pulmonary edema since accumulation of blood and fluid decreases impedance values.Measurements and resultsImpedance of the lung is the main feature of ITI measured by the RS-207 monitor: decreased ITI prior to the clinical signs of cardiogenic pulmonary edema was used as the prediction criterion. The clinical signs used for confirmation of its prediction were dyspnea, cyanosis, pulmonary rales, crepitations, arterial hypoxemia, and radiographic evidence of pulmonary congestion in chest radiographs. Clinicians were blinded to the results of ITI measurements and radiologists were blinded to both ITI and clinical data. Thirty-seven patients developed cardiogenic pulmonary edema while being monitored. ITI decreased by more than 12% of baseline in all of them; this occurred at 30 min or longer (26 patients) and at 60 min or longer (11 patients) before the appearance of clinical signs. ITI fell by less then 10.1% of baseline in all 228 patients who did not develop the edema.ConclusionMonitoring ITI is suitable for early prediction of cardiogenic pulmonary edema, before the appearance of the clinical signs.

Collateral pressure and flow in acute myocardial infarction with total coronary occlusion correlate with angiographic collateral grade and creatine kinase levels

BACKGROUND The validity of angiographic collateral grade according to the Rentrop classification during acute myocardial infarction (AMI) and its relation to flow in occluded coronary arteries before angioplasty have never been evaluated. METHODS We assessed the validity of the angiographic collateral grade according to Rentrop classification in relation to collateral pressure and flow beyond occluded coronary arteries during AMI. Pressure distal to coronary artery occlusions before balloon dilatation was measured in 111 patients undergoing angioplasty for AMI. We calculated the collateral flow index (CFI) and compared it to observed Rentrop grade and measured creatine kinase sum. RESULTS The values of pressure distal to coronary artery occlusions with respect to collateral grades 0 to 3 were 33 +/- 12, 37 +/- 13, 42 +/- 10, and 60 +/- 14 mm Hg (P < .0001). Overall CFI was 0.35 +/- 0.13 (median 0.33), with CFI values of 0.3 +/- 0.13, 0.33 +/- 0.13, 0.39 +/- 0.1, and 0.57 +/- 0.2 for collateral grades 0 to 3, respectively (P < .0001). Larger creatine kinase elevation (P < .016) and higher white blood cell count (P < .022) were recorded in the lowest tertile CFI compared with highest tertile CFI group; but no difference in the global, regional, or infarct-related regional left ventricular contraction was found. CONCLUSIONS These observations demonstrate that the Rentrop classification is valid in AMI patients with occluded coronary arteries and that collaterals are recruited acutely. These collaterals, whose pressure-derived CFI during AMI was shown for the first time to be higher than its value reported in chronic conditions, may limit the immediate myocardial damage or the systemic inflammatory response. No impact on global or regional cardiac contraction was detected in a population where most patients were treated early.

Usefulness of Lung Impedance-Guided Pre-Emptive Therapy to Prevent Pulmonary Edema During ST-Elevation Myocardial Infarction and to Improve Long-Term Outcomes

Patients sustaining an ST-segment elevation myocardial infarction (STEMI) frequently develop pulmonary congestion or pulmonary edema (PED). We previously showed that lung impedance (LI) threshold decrease of 12% to 14% from baseline during admission for STEMI marks the onset of the transition zone from interstitial to alveolar edema and predicts evolution to PED with 98% probability. The aim of this study was to prove that pre-emptive LI-guided treatment may prevent PED and improve clinical outcomes. Five hundred sixty patients with STEMI and no signs of heart failure underwent LI monitoring for 84 ± 36 hours. Maximal LI decrease throughout monitoring did not exceed 12% in 347 patients who did not develop PED (group 1). In 213 patients LI reached the threshold level and, although still asymptomatic (Killip class I), these patients were then randomized to conventional (group 2, n = 142) or LI-guided (group 3, n = 71) pre-emptive therapy. In group 3, treatment was initiated at randomization (LI = -13.8 ± 0.6%). In contrast, conventionally treated patients (group 2) were treated only at onset of dyspnea occurring 4.1 ± 3.1 hours after randomization (LI = -25.8 ± 4.3%, p <0.001). All patients in group 2 but only 8 patients in group 3 (11%) developed Killip class II to IV PED (p <0.001). Unadjusted hospital mortality, length of stay, 1-year readmission rate, 6-year mortality, and new-onset heart failure occurred less in group 3 (p <0.001). Multivariate analysis adjusted for age, left ventricular ejection fraction, risk factors, peak creatine kinase, and admission creatinine and hemoglobin levels showed improved clinical outcome in group 3 (p <0.001). In conclusion, LI-guided pre-emptive therapy in patients with STEMI decreases the incidence of in-hospital PED and results in better short- and long-term outcomes.

Comparison of Outcome of Recurrent Versus First ST-Segment Elevation Myocardial Infarction (from National Israel Surveys 1998 to 2006)

Patients with recurrent acute myocardial infarction (AMI), who represent ≤35% of hospitalized patients with AMI, are at an increased risk of complications and death. Our study purpose was to compare the treatment and outcome of patients hospitalized with recurrent acute ST-segment elevation myocardial infarction (STEMI) from 1998 to 2006 with those of patients with a first STEMI. We performed 5 biennial nationwide 2-month surveys during 1998 to 2006, collecting data prospectively from all patients hospitalized for AMI or acute coronary syndrome in all 25 coronary care units in Israel. The present cohort included 4,543 patients with STEMI, 3,679 (76%) with first and 864 (24%) with recurrent STEMI. The patients with recurrent STEMI were older (66 ± 13 vs 62 ± 13 years), had greater rates of diabetes, hypertension, and previous angina, had a worse Killip class on admission, and experienced more in-hospital complications. The all-cause hospital crude mortality rate was 8.1% in patients with recurrent STEMI versus 5.5% in those with a first STEMI (adjusted odds ratio 1.71 95% confidence interval 1.19 to 2.44), and the 1-year mortality rate was 18.9% versus 10.9%, respectively (hazard ratio 1.85, 95% confidence interval 1.41 to 2.43). From 1998 to 2006, an insignificant trend toward a 1-year mortality reduction among patients with recurrent STEMI was seen and those with a first STEMI had a significant mortality decrease. In conclusion, patients admitted for recurrent STEMI have worse in-hospital and 1-year outcomes that did not improve during the study period. An improved therapeutic approach is needed for these high-risk patients.

A novel radiological score to assess lung fluid content during evolving acute heart failure in the course of acute myocardial infarction

Background: Monitoring of lung fluid content (LFC) in order to predict acute heart failure (AHF) during acute myocardial infarction (AMI) is an unmet challenge. Aim: To evaluate in AMI patients the ability of proposed radiological score (RS), which is the sum of selected radiological signs of congestion, to reflect correctly LFC, as assessed with repeat physical examinations and lung impedance (LI) measurements. Methods: Chest X-rays were taken at baseline, when rales were detected, whenever indicated, and at conclusion of monitoring. RS grading for LFC assessment was: RS = 0–1 for normal X-ray, RS = 2–4 for interstitial congestion, and RS values of 5–6, 7–8 and 9–10 signified mild, moderate and severe alveolar edema, respectively. Results: 624 AMI patients without AHF at baseline were monitored (94 ± 42 h). 476 patients (76%) with baseline RS of 0.3 ± 0.5 did not develop AHF. Overt AHF developed in 148 patients (24%) during monitoring; baseline RS (0.6 ± 0.8) reached 5.4 ± 0.7, 7.0 ± 0.8, and 9.8 ± 0.5 at the stages of mild, moderate, and severe alveolar edema, respectively. AHF resolved with treatment. RS decreased to 1.5 ± 1.3 (P < 0.01) and correlated with physical examination (r = 0.6, P < 0.01) and LI (r = −0.9, P < 0.01). Conclusion: RS correlated well with findings on physical examination during AHF and closely correlated with LI.