Israel Medical Association Journal

Background: Despite improved management of heart failure patients, their prognosis remains poor.

Objectives: To characterize hospitalized HF[1] patients and to identify factors that may affect their short and long-term outcome in a national prospective survey.

Methods: We recorded stages B-D according to the American College of Cardiology/American Heart Association definition of HF patients hospitalized in internal medicine and cardiology departments in all 25 public hospitals in Israel.

Results: During March-April 2003, 4102 consecutive patients were recorded. Their mean age was 73 ± 12 years and 57% were males; 75.3% were hypertensive, 50% diabetic and 59% dyslipidemic; 82% had coronary artery disease, 33% atrial fibrillation, 41% renal failure (creatinine ³ 1.5 mg/dl), and 49% anemia (hemoglobin £ 12 g/dl). Mortality rates were 4.7% in-hospital, 7.6% at 30 days, 18.7% at 6 months and 28.1% at 12 months. Multiple logistic regression analysis revealed that increased 1 year mortality rate was associated with New York Heart Association III–IV (odds ratio 2.07, 95% confidence interval 1.78–2.41), age (for 10 year increment) (OR[2] 1.41, 95% CI[3] 1.31–1.52), renal failure (1.79, 1.53–2.09), anemia (1.50, 1.29–1.75), stroke (1.50, 1.21–1.85), chronic obstructive pulmonary disease (1.25, 1.04–1.50) and atrial fibrillation (1.20, 1.02–1.40).

Conclusions: This nationwide heart failure survey indicates a high risk of long-term mortality and the urgent need for the development of more effective management strategies for patients with heart failure discharged from hospitals.

Background: Heart failure with preserved systolic left ventricular function is a major cause of cardiac disability.

Objectives: To examine the prevalence, characteristics and late clinical outcome of patients hospitalized with HF-PSF[1] on a nationwide basis in Israel.

Methods: The Israel nationwide HF survey examined prospectively 4102 consecutive HF patients admitted to 93 internal medicine and 24 cardiology departments in all 25 public hospitals in the country. Echocardiographic LV function measurements were available in 2845 patients (69%). The present report relates to the 1364 patients who had HF-PSF (LV ejection fraction ≥ 40%).

Results: Mortality of HF-PSF patients was high (in-hospital 3.5%, 6 months 14.2%, 12 months 22.0%), but lower than in patients with reduced systolic function (all P < 0.01). Mortality was higher in patients with HF as the primary hospitalization diagnosis (16.0% vs. 12.5% at 6 months, P = 0.07 and 26.2% vs. 18.0% at 12 months, P = 0.0002). Patients with HF-PSF who died were older (78 ± 10 vs. 71 ± 12 years, P < 0.001), more often female (P = 0.05) and had atrial fibrillation more frequently (44% vs. 33%, P < 0.01). There was also a relationship between mortality and pharmacotherapy: after adjustment for age and co-morbid conditions, mortality was lower in patients treated with angiotensin-converting enzyme inhibitors (P = 0.0003) and angiotensin receptor blockers (P = 0.002) and higher in those receiving digoxin (P = 0.003) and diuretic therapy (P = 0.009).

Conclusions: This nationwide survey highlights the very high late mortality rates in patients hospitalized for HF without a decrease in systolic function. The findings mandate a focus on better evidence-based treatment strategies to improve outcome in HF-PSF patients.

Background: Halofuginone is a novel antifibrotic agent that can reserve the fibrotic process by specific inhibition of collagen type I synthesis.

Objectives: To evaluate the effect of Halo on the development of glomerulosclerosis and interstitial fibrosis in the 5/ 6 nephrectomy rat model.

Methods: Male Wistar rats were assigned to undergo 5/6 NX or sham operation, and then divided into three groups: 5/6 NX rats (NX-Halo and NX-Control) and sham. Systolic blood pressure proteinuria and body weight were determined every 2 weeks. At sacrifice (10 weeks) creatinine clearance was evaluated and remnant kidneys removed for histologic examination, Sirius red staining and in situ hybridization.

Results: Systolic blood pressure increased progressively in both 5/6 NX groups. Halo slowed the increase in proteinuria in 5/6 NX rats. As expected, creatinine clearance was lower in 5/6 NX groups when compared to sham rats. Creatinine clearance was significantly higher in the NX-Halo group at the end of the study period. Histologic examination by light microscopy showed significantly less severe interstitial fibrosis and glomerulosclerosis in Halo-treated rats. The increase in collagen α1 (I) gene expression and collagen staining after nephrectomy was almost completely abolished by Halo.

Conclusions: Halofuginone reduced proteinuria as well as the severity of interstitial fibrosis and glomerulosclerosis in 5/6 NX rats. The renal beneficial effect of Halo was also demonstrated by the blunted decrease in creatinine clearance observed in the treated animals.  
 

Background: Despite significant advances in the therapy of heart failure, many patients still do not receive optimal treatment.

Objectives: To document the standard of care that patients hospitalized with HF[1] in Israel received during a 2 month period.

Methods: The Heart Failure Survey in Israel 2003 was a prospective 2 month survey of patients admitted to all 25 public hospitals in Israel with a diagnosis of HF.

Results: The mean age of the 4102 patients was 73 years and 43% were female. The use of angiotensin-converting enzyme/angiotensin receptor blockers and beta blockers both declined from NYHA class I to IV (68.8% to 50.6% for ACE[2]-inhibitor/ARB[3] and 64.1% to 52.9% for beta blockers, P < 0.001 for comparisons). The percentage of patients by NYHA class taking an ACE-inhibitor or ARB and a beta blocker at hospital discharge also declined from NYHA class I to IV (47.5% to 28.8%, P < 0.002 for comparisons). The strongest predictor of being discharged with an ACE-inhibitor or ARB was the use of these medications at hospital admission. Negative predictors for their usage were age, creatinine, disease severity class, and functional status.

Conclusions: Despite the dissemination of guidelines many patients did not receive optimal care for HF. Reasons for this discrepancy need to be identified and modified.

Objective: To evaluate the contribution of the sestamibi-SPECT (MIBI) localization, cervical ultrasonography, and intraoperative rapid turbo intact parathormone assay in minimal invasive parathyroidectomy.

Methods: Between August 1999 and March 2004, 146 consecutive hyperthyroid patients were treated using the MIBI and ultrasound for preoperative localization and iPTH[1] measurements for intraoperative assessment.

Results: Parathyroid adenoma was detected in 106 patients, primary hyperplasia in 16, secondary hyperplasia in 16, tertiary hyperplasia in 5 and parathyroid carcinoma in 1 patient. Minimal invasive exploration of the neck was performed in 84 of the 106 patients (79.2%) with an adenoma, and in 17 of them this procedure was performed under local cervical block anesthesia in awake patients. Adenoma was correctly diagnosed by MIBI scan in 74% of the patients, and by ultrasound in 61%. The addition of ultrasonography to MIBI increased the accuracy of adenoma detection to 83%. In 2 of the 146 patients (1.4%) iPTH could not be significantly reduced during the initial surgical procedure. Minimal invasive surgery with minimal morbidity, and avoiding bilateral neck exploration, was achieved in 79.2% of patients with a primary solitary adenoma.

Objective: To investigate gender differences in the baseline characteristics, clinical presentation, treatment and prognosis of women with unstable angina.

Method: Data were collected prospectively as part of the Acute Coronary Syndromes Israeli Survey in 2000 at Soroka University Medical Center. In-hospital management and 2 year follow-up were monitored for 226 consecutive patients with unstable angina admitted to our medical center during February and March 2000.

Results: Women were older (71 ± 12 vs. 66 ± 12, P = 0.006), more diabetic (41.3% vs. 34.5%, not significant) and hypertensive (76.3% vs. 64.6%, P = 0.07). Women presented more often with atypical chest pain (18.8% vs. 7.5%, P = 0.038). Heparin, aspirin and angiotensin-converting enzyme inhibitor were equally delivered, but more beta-blockers were administered to women (88.5% vs. 75.7%, P = 0.02) and more statins to men (48.1% vs. 35.4%, P = 0.07). Angiography rates were similar (17.7% vs. 19.6%). Similar management was documented during the 2 year follow-up. Re-hospitalization rates were similar (53.3% of women and 63.7% of men, NS). Men had a tendency to develop acute myocardial infarction more often (9.6% vs. 2.7%, P = 0.06) and to develop peripheral vascular disease (3.7% vs. 0%, P = 0.09), and they had a non-significant higher rate of coronary artery bypass graft (6.7% vs. 1.3%, P = 0.08). No gender difference was found in angiography (14.7% of women vs. 16.3% of men) or percutaneous intervention (13% vs. 16.7%). At 2 years there was no gender-related difference in mortality (13.3% of women vs. 16.3% of men, NS). Kaplan-Meier analysis for event-free survival after 2 years showed no gender difference in survival. Multi-regression analysis showed that gender was not a prognostic factor for survival.

Conclusions. We found no major difference in the management of men and women with unstable angina. Although men showed a tendency to suffer more major cardiac events, their 2 year prognosis was the same as for women.

Background: Among the various new technologies in the field of parathyroid surgery are intraoperative quick parathormone measurements.

Objectives: To evaluate the contribution of QPTH[1] measurements during parathyroidectomy to the achievement of higher success rates. 

Methods: QPTH assay using Immulite Turbo Intact PTH[2] was measured in 32 patients undergoing parathyroidectomy: 30 for primary and 2 for secondary hyperparathyroidism.  QPTH levels were measured at time 0 minutes (before incision) and at 10, 20, and 30 minutes after excision of the hyperfunctioning gland.  Only a drop of 60% or more from the 0’ level was considered to be a positive result.

Results: The mean QPTH level at time 0’ for PHPT[3] patients was 38.12 ± 25.15 pmol/L (range 9.1–118 pmol/L).  At 10 minutes post-excision of the hyperfunctioning gland (or glands), QPTH dropped by a mean of 73.80% to 9.89 ± 18.78 pmol/L. 

Conclusions: Intraoperative QPTH level measurement is helpful in parathyroid surgery.  A drop of 60% or more from 0’ level indicates a successful procedure, and further exploration should be avoided.

Background: In the emergency department the physician is often confronted with the decision of where to hospitalize a patient presenting with chest pain and a possible acute myocardial infarction – in the cardiac care unit or in the internal medicine ward.

Objective: To characterize the clinical factors involved in the triage disposition of patients hospitalized with AMI[1] in Israel to either CCUs[2] or IMWs[3] and to determine to what extent the perceived probability of ischemia influenced the disposition decision.

Methods: During a 2 month nationwide prospective survey in the 26 CCUs and 82 of the 94 IMWs in Israel, we reviewed the charts of 1,648 patients with a discharge diagnosis of AMI. The probability of ischemia at admission was determined retrospectively by the Acute Coronary Ischemia Time-Insensitive Predictive Instrument. Co-morbidity was coded using the Index of Coexistent Diseases.

Results: The ACI-TIPI[4] score for patients admitted to CCUs or to IMWs was 76.2% and 57.7% respectively (P < 0.001). Multivariate analysis showed that young patients with a high probability of ischemia and low co-morbidity or functional impairment were more likely to be hospitalized in CCUs than in IMWs.

Conclusion: In Israel, the factors that strongly influence the initial triage disposition of patients with AMI to CCUs or IMWs are age, perceived probability of ischemia, status of co-morbid conditions and functional impairment.

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Background: Lower limb critical ischemia is a major problem in dialysed patients.

Objective: To evaluate the results of revascularization procedures, amputations and prosthetic rehabilitation in dialysed amputees.

Methods: Major amputation was carried out in 48 patients (4.5% of the dialysis population), and 24 patients entered the rehabilitation program. Widespread arterial calcification was common and led to falsely elevated ankle-brachial pressure indices in 9 of 14 limbs. Eight patients underwent revascularization. Subsequent major amputation was carried out 4 ± 4.5 months after the revascularization (above knee in 5 patients and below knee in 3). Of the 16 patients who underwent primary amputation, only 2 were above-knee amputees. Seven patients with toe or metatarsal amputation went on to a major amputation 1.8 ± 1.2 months after the distal amputation.

Results: No differences were found between diabetic and non-diabetic patients regarding the number of revascularization operations performed, the level of major amputation, or overall survival. Prosthetic rehabilitation was considered successful in 12 patients, partially successful in 8, and failed in 4 patients. Patient survival time was shortest in those patients with failed rehabilitation. A younger age confirmed favorable rehabilitation results, while long-standing diabetics and bilateral amputees were poor rehabilitation candidates. Patients who underwent primary amputation had more successful rehabilitation. A comparison between 24 dialysed amputees and 138 non-uremic amputees revealed similar rehabilitation results, although hospitalization time was longer in the dialysed patients.

Conclusions: Early definitive therapy is essential when dealing with critical ischemia. After diagnostic angiography, proximal revascularization should be performed where feasible. Primary amputation is indicated in patients with extensive foot infection or gangrene. Prosthetic rehabilitation is warranted in most dialysed amputees.
 

Background: Technetium-99m sestamibi scintigraphy has become one of the most popular techniques for localization of the parathyroid gland after failure of primary neck exploration.

Objective: To examine the efficacy of sestamibi with the hand-held gamma ray detecting probe for the identification of parathyroid adenomas during revision parathyroidectomy.

Methods: We reviewed six cases of probe-assisted neck exploration for parathyroid lesions following unsuccessful primary exploration.

Results: In all cases, the pathologic glands were successfully detected and removed.

Conclusions: With careful planning, a gamma ray detecting probe can be used optimally at 2–3 hours after technetium-99m sestamibi injection. The probe is efficient, easy and convenient to use.
 

Background: Primary hyperparathyroidism in elderly patients is usually associated with additional co-morbidity that increases operative risk, and thus many geriatric patients are denied the benefit of surgery for a single parathyroid adenoma.

Objectives:  To evaluate the safety and efficacy of accurate single photon emission computed tomography sestamibi scintigraphy, enabling precise localization of a single adenoma, in the geriatric population

Methods: Twenty-two patients aged 70 years and over with biochemically proven PHPT[1] and with a single parathyroid adenoma identified by localization studies (sestamibi SPECT[2] scan and ultrasonography) underwent 23 operations over 29 months (out of a total of 140 patients operated upon during the same period). Immediate preoperative sestamibi scintigraphy and marking of focal adenoma uptake followed by intraoperative hand-held gamma probe were used for the removal of the parathyroid adenoma by unilateral minimal access surgery. Associated major co-morbid conditions and pre- and postoperative calcium, phosphorus and parathormone levels were recorded. Indications for surgery were listed and operative and postoperative complications were noted. The patients were followed for a mean period of 17.7 months using the same parameters.

Results: The 22 patients with PHPT had a mean age of 76.3 ± 5.9 years (range 70–88 years)  and a female to male ratio of 13:9. Associated co-morbidity included ischemic heart disease (n=15), hypertension (n=22), non-insulin-dependent diabetes mellitus (n=9), chronic obstructive pulmonary disease (n=3), and previous neck surgery (n=3). Mean preoperative serum calcium, phosphorous and PTH[3] were 11.7 ± 1.3 mg/dl, 2.5 ± 0.5 mg/dl and 160.9 ± 75.4 pg/ml respectively. In 20 of the 22 patients, surgery was successful in curing PHPT (91%). One patient had persistent hypercalcemia due to a missed adenoma, and repeat operation (by focused minimal access surgery) was successfully performed 2 weeks later. There were no complications and no morbidity postoperatively. Mean postoperative serum calcium, phosphorous and PTH were 9.6 ± 1.2 mg/dl, 3.0 ± 0.5 mg/dl and 35.2 ± 24 pg/ml respectively. In all patients, serum calcium levels remained normal (9.7 ± 1.3 mg/ml) after long-term follow-up (mean 17.7 ± 9.6 months).

Conclusions: Minimally invasive, radio-guided focused parathyroidectomy for a single adenoma is a safe and effective method to cure hyperparathyroidism in the elderly. Success of surgery is directly related to the surgeon's experience and to the precise localization marking provided by sestamibi scintigraphic SPECT localization and concurrent sonographic findings.