Israel Medical Association Journal

Erectile dysfunction (ED) is a syndrome associated with endothelial dysfunction, which may predict cardiovascular events in men presenting with this syndrome. It has been shown to be associated with a higher rate of acute myocardial infarction and cardiovascular mortality, vascular inflammation, and impaired endothelial function. In this review we present the literature findings and describe the mechanistic pathways that are known to be involved in this syndrome and its related clinical consequences.

Background: Kidney transplantation is associated with early improvement in cardiac function and structure; however, data on cardiac adaptation and its relation to kidney allograft function remain sparse.

Objectives: To investigate the relationship between post-transplant kidney function and echocardiographic measures in patients with normal/preserved pre-transplant cardiac structure and function.

Methods: The study included 113 patients who underwent kidney transplantation at a single tertiary medical center from 2000 to 2012. The patients were evaluated by echocardiography before and after transplantation, and the relation between allograft function and echocardiographic changes was evaluated. Echocardiography was performed at a median of 510 days after transplantation.

Results: The post-transplantation estimated glomerular filtration rate (eGFR) was directly correlated with left ventricular (LV) systolic function and inversely correlated with LV dimensions, LV wall thickness, left atrial diameter, and estimated systolic pulmonary arterial pressure. In patients with significant allograft dysfunction (eGFR ≤ 45 ml/min), LV hypertrophy worsened, with no improvement in LV dimensions. In contrast, in patients with preserved kidney function, there was a significant reduction in both LV diameter and arterial pulmonary systolic pressure.

Conclusions: Our results show that in kidney transplant recipients, allograft function significantly affects cardiac structure and function. Periodic echocardiographic follow-up is advisable, especially in patients with kidney graft dysfunction.

Background: Endothelial progenitor cells may have a role in ongoing endothelial repair. Impaired mobilization or depletion of these cells may contribute to progression of vascular disease. Our hypothesis was that endothelial progenitor cells would be suppressed in patients with acute cerebrovascular event based on our previous study that found severe endothelial dysfunction in those patients.

Objectives: To study the ability of patients with acute stroke to build colonies of endothelial progenitor cells.

Methods: We studied the number of colony-forming units of endothelial progenitor cells (CFU-EPCs) from the peripheral blood of 22 male patients with a first-time acute stroke (age 58.09 ± 9.8 years) and 13 healthy men (34 ± 6.7 years), 8 female patients with a first-time acute stroke (54.6 ± 10.3 years) and 6 healthy women (38.3 ± 11.6 years). Endothelium-dependent function was assessed by high-resolution ultrasonography of the brachial artery that measured the change in diameter of the artery by flow-mediated diameter percent change (FMD%). All patients had strokes demonstrated by a brain computed tomography (CT) scan done on admission. Peripheral blood was drawn soon after admission and was processed for endothelial progenitor cells in culture.

Results: Thirty patients without known cardiovascular risk factors and who did not take any medications were admitted with a first-time acute stroke. All demonstrated a strong correlation between CFU-EPCs grown in culture and endothelial dysfunction (r = 0.827, P < 0.01). Endothelial dysfunction with an FMD% of -2.2 ± 9.7% was noted in male patients vs. 17.5 ± 6.8% in healthy males (P = 0.0001), and -7.2 ± 10.1% in female patients vs. 25.1 ± 7.1% in healthy females (P = 0.0001). CFU-EPCs were 5.5 ± 6.3 in men with stroke vs. 23.75 ± 5.3 in healthy males (P = 0.0001), and 7.6 ± 4.9 in women with stroke vs. 22.25 ± 6.7 in healthy females (P = 0.0004).

Conclusions: Patients with acute stroke had an impaired ability to grow CFU-EPCs in culture and exhibited endothelial dysfunction. The novelty of this study was the discovery of the phenomenon of depressed numbers of EPCs and the poor ability to grow colonies of EPCs in the first 24 hours of the cerebrovascular event.

Background: A cardiac restrictive filling patterns are associated with unfavorable prognoses. Cardiac interventions may change the natural history of patients.

Objectives: To investigate the prevalence of restrictive filling pattern in routine echocardiographic examinations and their association with morbidity and mortality.

Methods: The clinical and echocardiographic data of patients with newly diagnosed restrictive filling pattern were analyzed and summarized.

Results: Among 8000 patients who underwent an echocardiographic examination in our hospital in 2013, a restrictive filling pattern was identified in 256. Of these, 134 showed a restrictive filling pattern that was newly diagnosed. Mean age was 69 years. Hypertension, diabetes, and ischemic heart disease were found in 81%, 60%, and 53%, respectively. Left ventricular ejection fraction was 42% ± 16%. Severe valvular abnormalities were found in 18%. During follow-up (29 ± 15 months), 40% of patients died. The strongest predictor of mortality (73%) was moderate or more advanced aortic stenosis, P = 0.005. Renal failure was an important independent predictor of mortality (53%, P < 0.05). A very high E/E' ratio ≥ 20, was another independent mortality predictor (50%, P < 0.03). Patients who died were less likely to have undergone cardiac interventions than those who survived (26% vs. 45%, P < 0.03).

Conclusions: Prevalence of restrictive filling among echocardiographic studies is 3.2%. In a half of these, the restrictive filling pattern is a new diagnosis. Patients who are diagnosed with a new restrictive filling pattern have higher mortality rates. Patients with restrictive filling should be evaluated thoroughly for possible coronary artery or valvular heart disease.

Background: Mortality and decrease in function after hip fracture are significantly related to patient factors including age, gender, co-morbidities, and mental status. Several studies demonstrated ethnic disparities in incidence, mortality, and functional outcome after hip fractures in the United States.

Objectives: To assess the relationship between ethnicity and hip fracture incidence and outcomes of mortality, functional change, and perioperative complications in the Israeli population.

Methods: We reviewed our institutional hip fracture registry for all patients from 2014–2015. Patients with incomplete data, < 60 years of age, or pathologic and periprosthetic fractures were excluded. Our study comprised 693 patients. Ethnicity was based on country of birth. Specifically, for those born in Israel, the nationality of either Jewish or Arab was further dichotomized. Perioperative complications, mortality, and mobility status at 1 year follow-up were recorded. The ethnicities of 27,130 patients admitted to the medicine and surgical wards during the same time interval served as a control group for the hip fracture cohort.

Results: Immigrants from Europe and America had the highest incidence of hip fractures. Fracture types varied in incidence in groups with 70% of extracapsular hip fractures occurring in Arabs and immigrants from Eastern countries, compared to 60% in immigrants from Western countries and the former Soviet Union. Mortality, perioperative complications, and mobility at 1 year were similar in all ethnic groups.

Conclusion: Our study demonstrated significant differences in incidence and fracture characteristic among ethnicities, but no difference in patient outcome. These findings differed from the available North American studies.

Background: Cardiac damage caused by oncological therapy may manifest early or many years after the exposure.

Objectives: To determine the differences between sub-acute and late-onset cardiotoxicity in left ventricular ejection fraction (LVEF) recovery as well as long-term prognosis.

Methods: We studied 91 patients diagnosed with impaired systolic function and previous exposure to oncological therapy. The study population was divided according to sub-acute (from 2 weeks to ≤ 1 year) and late-onset (> 1 year) presentation cardiotoxicity. Recovery of LVEF of at least 50% was defined as the primary end point and total mortality was the secondary end point.

Results: Fifty-three (58%) patients were classified as sub-acute, while 38 (42%) were defined as late-onset cardiotoxicity. Baseline clinical characteristics were similar in the two groups. The mean LVEF at presentation was significantly lower among patients in the late-onset vs. sub-acute group (28% vs. 37%, respectively, P < 0.001). Independent predictors of LVEF recovery were trastuzumab therapy and a higher baseline LVEF. Although long-term mortality rates were similar in the groups with sub-acute and late-onset cardiotoxicity, improvement of LVEF was independently associated with reduced mortality.

Conclusions: Our findings suggest that early detection and treatment of oncological cardiotoxicity play an important role in LVEF recovery and long-term prognosis.

Background: Laparoscopic salpingectomy is strongly related to successful in vitro fertilization (IVF) treatments.

Objectives: To compare the ovarian reserve, including anti-mullerian hormone (AMH) levels, in patients who underwent salpingectomy before IVF to IVF patients who had not been salpingectomized.

Methods: In this retrospective study, medical records of women who were treated by the IVF unit at our institute were reviewed. We retrieved demographic data, surgical details, and data regarding the ovarian reserve. Details of 35 patients who were treated by IVF after salpingectomy were compared to 70 IVF patients with no history of salpingectomy treatment. Nine women underwent IVF treatment before and after having salpingectomy, and their details were included in both groups.

Results: The levels of AMH, follicular stimulating hormone (FSH), estradiol, and progesterone were not significantly different in the groups. The antral follicular count (AFC), number of oocytes retrieved, amount of gonadotropin administered for ovarian stimulation, and number of embryos transferred (ET) were also not significantly different.

Conclusions: Salpingectomy does not seem to affect ovarian reserve in IVF patients.

Background: About half of all patients with heart failure are diagnosed with heart failure preserved ejection fraction (HFpEF). Until now, studies have failed to show that medical treatment improves the prognosis of patients with HFpEF.

Objectives: To evaluate changes in exercise capacity of patients with HFpEF compared to those with heart failure with reduced ejection fraction (HFrEF) following an exercise training program.

Methods: Patient data was retrieved from a multi-center registry of patients with heart failure who participated in a cardiac rehabilitation program. Patients underwent exercise testing and an echocardiogram prior to entering the program and were retested6  months later.

Results: Of 216 heart failure patients enrolled in the program, 170 were diagnosed with HFrEF and 46 (21%) with HFpEF. Patients with HFpEF had lower baseline exercise capacity compared to those with HFrEF. Participating in a 6 month exercise program resulted in significant and similar improvement in exercise performance of both HFpEF and HFrEF patients: an absolute metabolic equivalent (MET) change (1.45 METs in HFrEF patients vs. 1.1 in the HFpEF group, P = 0.3).

Conclusions: An exercise training program resulted in similar improvement of exercise capacity in both HFpEF and HFrEF patients. An individualized, yet similarly structured, cardiac rehabilitation program may serve both heart failure groups, providing safety and efficacy.

Background: Circulating endothelial progenitor cells have an important role in the process of vascular repair. Impaired recruitment and function of endothelial progenitor cells is related to the pathophysiology of congestive heart failure. Endothelial progenitor cells have been shown to express the mineralocorticoid receptor. 

Objectives: To investigate the effect of mineralocorticoid receptor antagonists on endothelial progenitor cells in patients with heart failure. 

Methods: Twenty-four patients with compensated heart failure, who were not under mineralocorticoid receptor antagonist therapy, were recruited. Either eplerenone (n=8) or spironolactone (n=16) therapy was initiated. Circulating endothelial progenitor cell level, identified as the proportion of mononuclear cells expressing vascular endothelial growth factor receptor 2 (VEGFR-2), CD133, and CD34, was evaluated by flow cytometry at baseline and after 8 weeks. Following 7 days of culture, colonies were counted by microscopy and MTT assay was performed on randomly selected patients (n=12) to estimate viability.

Results: Both median CD34+/VEGFR2+ and median CD133+/VEGFR2+ increased significantly (P = 0.04 and 0.02, respectively). However, the number of colonies and viability of the cells after therapy (as assessed by the MTT assay) was not significantly different compared with the baseline. 

Conclusions: These preliminary results suggest that mineralocorticoid receptor blockade may enhance endothelial progenitor cells recruitment in patients with compensated heart failure.

Background: Weight loss surgery is the most effective treatment for obesity, and it reduces cardiovascular and cancer risk through poorly understood mechanisms. MicroRNAs (miRNAs) are short RNA molecules that regulate the stability and translation of many mRNAs. We hypothesized that levels of specific circulating miRNAs are altered following surgery and may contribute to lower cancer risk.

Objectives: To investigate the change of miRNA following surgery.

Methods: All patients underwent gastric “sleeve operation”. RNA was isolated from sera of 21 patients (14 men, 7 women) before and 3 months after surgery. Sera were combined into two pools, which served for cDNA library construction followed by miSeq sequencing. The levels of candidate miRNAs were validated in the individual samples by QRT-PCR.

Results: Serum miR-122 was significantly up-regulated 3 months post-bariatric surgery in sera of patients, whose endothelial function had greatly improved. In addition, serum miR-122 levels correlated positively with endothelial function as measured by FMD. The changes in miR-122 levels from pre-surgery to 3 months post-surgery also tended to correlate with the respective changes in FMD.

Conclusions: The serum miR-122/miR-451 ratio may serve as a marker for endothelial function in obese patients. miR-122 is the dominant miRNA in the liver and a known tumor suppressor. Our findings suggest a role for circulating miR-122 in the maintenance of vascular endothelial cells (VECs) and in the prevention of cancer. Further studies are required to elucidate the mechanism of its secretion into circulation and its absorption by VECs, as well as its relevant cellular targets.

Background: Both cigarette smoking and chronic kidney disease (CKD) are linked to cardiovascular morbidity and development of atherosclerosis. However, the relationship between cigarette smoking and renal function is not clearly understood. 

Objectives: To investigate the relationship between cigarette smoking and renal function, and determine whether the intensity of cigarette smoking influences renal function.

Methods: We conducted a retrospective analysis of subjects attending the screening center at the Rabin Medical Center. Subjects were classified as smokers, non-smokers and past smokers. Renal function was evaluated by means of the CKD-EPI equation for estimating glomerular filtration rate (eGFR). Multivariate and gender-based analyses were performed.

Results: The study population comprised 24,081 participants, of whom 3958 (17%) were classified current smokers, and 20,123 non-smokers of whom 4523 were classified as past smokers. Current smokers presented a higher eGFR compared to the non-smoking group (100.8 vs. 98.7, P < 0.001) as well as higher rates of proteinuria (15.3% vs. 9.3%, P < 0.001). The difference in eGFR between smokers and non-smokers was more significant in males than in females. Past smokers had the lowest eGFR of all groups, this difference remained significant after age adjustments (P = 0.005). 

Conclusions: Cigarette smoking is associated with higher eGFR compared to non-smoking. This difference was more pronounced in males than females, implying a gender-based difference. The higher prevalence of proteinuria in smokers suggests a mechanism of hyperfiltration, which might result in future progressive renal damage.

 

Background: Androgen deprivation therapy (ADT) added to radiation therapy (RT) in intermediate to high risk prostate cancer negatively impacts quality of life. 

Objectives: To compare health-related quality of life (HR-QOL) in patients receiving combined RT with and without ADT 

Methods: The study population comprised patients treated with definitive RT for prostate cancer who completed the Expanded Prostate Cancer Index Composite-26 form between 3 and 24 months after completing RT. Covariance and a stepwise backward logistic regression model was used. 

Results: Data were available for 143 patients who received RT+ADT and 70 who received RT alone. The sexual function and hormonal vitality scores of patients receiving RT+ADT were significantly lower than those receiving RT alone (P < 0.0001). Patients with only compulsory school education had significantly lower sexual function scores than patients with university level education (P ≤ 0.005). Patients with depression had significantly lower hormonal vitality scores than those without depression (P ≤ 0.0001). 

Conclusions: The addition of ADT to RT is responsible for decrements in quality of life in the sexual and hormonal vitality domains, which is further compounded by lack of education and depression. This underlines the need to improve education, identify and treat depression, and develop strategies to improve the quality of life of patients receiving combination therapy. 

 

Background: Erectile dysfunction (ED), a common problem in males of all ages, can be of organic, psychogenic or combined etiology. Organic ED is mainly caused by vascular and neurological disorders. One of the available tests for differentiating organic from inorganic ED is measuring penile tumescence and rigidity during the REM phase of sleep. However, this test lacks the ability to differentiate between a vascular and non-vascular cause of organic ED. 

Objectives: To compare the results of the EndoPAT test and the nocturnal penile tumescence (NPT) test in patients with erectile dysfunction.

Methods: Twenty patients with ED were recruited for the study. Each participant was evaluated by the SHIM score, RigiScan during polysomnography, and two EndoPAT tests (at the beginning and end of the study).

Results: Seventeen patients had SHIM score ≤ 21; 4 of them had organic ED with a mean EndoPAT score of 1.49, significantly lower than the 1.93 mean EndoPAT score of the 11 patients in the psychogenic ED group (P = 0.047). Two participants had a neurological impairment (spinal trauma and herniated disk). The average SHIM score in the vascular organic group was 6.25 points as compared to 11.69 for the psychogenic group (P = 0.027). The positive predictive value was 43% and the negative predictive value 90%.

Conclusions: EndoPAT could be helpful in excluding organic ED.