Israel Medical Association Journal

Background: Apparent treatment-resistant hypertension (aTRH) is a high-risk phenotype associated with increased cardiovascular and renal morbidity. Renal denervation (RDN) has emerged as a promising intervention for patients with refractory blood pressure (BP) despite maximal medical therapy.

Objectives: To present the first Israeli prospective cohort evaluating RDN outcomes in aTRH patients.

Methods: The Tel Aviv Renal Denervation registry is a single-center, prospective cohort of 19 patients with aTRH who underwent RDN between 2021 and 2024. Baseline data included demographics, co-morbidities, medication burden, ambulatory BP monitoring (ABPM), and renal function. Outcomes were assessed at 3 and 12 months post-procedure, with repeated measures analyses used to evaluate longitudinal trends.

Results: The cohort (median age 62 years, 42% female) exhibited a high burden of co-morbidities including ischemic heart disease (37%), diabetes (26%), and chronic kidney disease (21%). Baseline ABPM showed a median 24-hour systolic BP of 152 mmHg. Following RDN, mean systolic BP decreased to 143 mmHg at 3 months and 138 mmHg at 12 months (P = 0.097), with a significant reduction in nighttime systolic BP (P = 0.033). Pill burden decreased from a median of 7 to 4 pills daily (P = 0.037). The number of antihypertensive drug classes declined from 6 to 4 (P = 0.052). Renal function remained stable throughout follow-up.

Conclusions: In this Israeli RDN cohort, patients with aTRH experienced clinically meaningful reductions in BP and medication burden, with preserved renal function and minimal complications. These findings support further expansion of national RDN registries to better guide patient selection and optimize long-term outcomes.

Background: Lung transplantation is an advanced medical therapy reserved for patients with end-stage lung disease. Relative to other solid organ transplants, lung transplantation in children is infrequently performed. The most common etiologies for pediatric lung transplantation worldwide are cystic fibrosis, pulmonary hypertension, and children’s interstitial lung disease.

Objectives: To describe our experience in pediatric lung transplants at Israel's largest transplant center.

Methods: We performed a retrospective review of all pediatric lung transplantations conducted in our center since 1997. We recorded demographic characteristics, indication for transplantation, clinical and laboratory parameters, post-transplant complications, and survival rates.

Results: Of 965 lung transplants, 29 (3.0%) were pediatric patients who underwent lung or heart-lung transplants for end-stage lung disease. Age at transplantation ranged from 2 to 18 years, with a median of 14.0 years (IQR 11–15). Primary etiologies for transplantation were cystic fibrosis (44%), pulmonary hypertension (17%), and children’s interstitial lung disease (10%). Survival at 1, 5, 10, and 15 years post-transplant were 90%, 65%, 55%, and 20%, respectively, which is consistent with data reported by pediatric lung transplantation registries. The primary cause of mortality post-transplant was chronic lung allograft dysfunction. Four patients (13.8%) underwent re-transplant. There was no association between survival and transplant indication, nor between survival and type of procedure (lung vs. heart-lung transplant).

Conclusions: The short- and long-term outcomes from our program are consistent with published registry data. These outcomes may reflect the benefits of a centralized pediatric lung transplant program, supported by a multidisciplinary team trained in high-capacity international centers.

Pheochromocytoma, a rare neuroendocrine tumor, classically manifests symptoms such as hypertension, palpitations, and sweating. In this report, we present an unusual case in which muscle complaints were the primary symptoms, accompanied by elevated interleukin-6 (IL-6) levels. Our findings underscore the importance of considering pheochromocytoma in the differential diagnosis of patients presenting with unexplained muscle weakness and aches, and suggests a potential link between pheochromocytoma, myositis-like symptoms, and IL-6 elevation.

We presented the emergent development of pulmonary hypertension and right ventricular impairment in a 64-year-old woman with metastatic breast cancer undergoing carboplatin–gemcitabine combination therapy. The patient's acute decompensation, characterized by dyspnea and desaturation, occurred 2 days after chemotherapy initiation. Clinical assessments revealed right ventricular dilation and systolic dysfunction, a rare manifestation not previously associated with the administered drugs, but which may be associated with cardiopulmonary toxicity of gemcitabine therapy. Prompt discontinuation of chemotherapy and initiation of diuretic therapy resulted in clinical improvement and resolution of the right ventricular dysfunction within several weeks. While a definitive causal link to gemcitabine remains inconclusive, this report highlights a potential and under-reported side effect, emphasizing the need for increased awareness and further investigation into the cardiopulmonary effects of gemcitabine.

Acute or chronic aortic dissection is considered a rare emergency, with an estimated rate of 2.9 to 5 cases per 100,000 patients each year. This condition is most prevalent in males older than 65 years of age with a history of hypertension, atherosclerosis, and previous cardiac surgery [1,2]. To confirm the diagnosis, imaging is used, often by computed tomography angiography (CTA) of the chest. Although prompt treatment is required, patients often present with non-specific symptoms, such as abdominal pain or neurologic deficits, resulting in the early diagnosis of less than 20% and a high mortality rate [1].

Background: Acquired hepatocerebral degeneration (AHD) is a neurologic complication of severe chronic liver disease (CLD) with portosystemic shunts. The proposed etiology is manganese accumulation in the brain tissue, especially in the basal ganglia. Combination of clinical manifestation, mostly extrapyramidal movement disorders, and hyperintensities on T1-weighted brain magnetic resonance imaging (MRI) is diagnostic. Although liver transplantation controversial, it is suggested for AHD.

Objectives: To depict clinical and neuroimaging characteristics and response to treatments in patients diagnosed with AHD at Sheba Medical Center.

Methods: Review of patients with AHD diagnosis at the Liver Diseases Center at Sheba Medical Center between 2012 and 2017, data of clinical and neuroimaging, follow-up, and response to treatments, including liver transplantation were recorded.

Results: Five patients with diagnosis of AHD were identified, median age at diagnosis 55 years (range 45–64 years). Four patients had cirrhosis at the time of AHD diagnosis. The main risk factor for AHD was the presence of portosystemic shunts. The most prevalent clinical manifestations were movement disorders, specifically a combination of extrapyramidal and cerebellar signs including instability, rigidity, tremor, bradykinesia, and cognitive impairment. Brain MRI revealed hyperintensities on T1-weighted images in the basal ganglia in all patients. Administration of antiparkinsonian drugs showed clinical improvement, whereas liver transplantation performed in two patients was not associated to neurological improvement.

Conclusions: AHD is related to portosystemic shunts. The combination of Parkinsonism and cerebellar signs and MRI pallidal lesions should alert physicians to the diagnosis. The role of liver transplantation in AHD is still controversial.

Background: Gestational hypertensive (GH) disorders remain a major obstetric problem.

Objective: To evaluate the incidence of gestational hypertensive disorders among participants undergoing intrauterine insemination (IUI) after exposure to various levels of sperm from sperm donation (SD).

Methods: A retrospective case-control study was conducted at a single tertiary medical center between 2011 and 2019. Participants conceived via IUI using SD from a single sperm bank and had a successful singleton birth. Group 1 conceived during 1–2 cycles of IUI from the same sperm donor; whereas Group 2 after 3+ cycles.

Results: Overall 171 patients (Group 1 = 81, Group 2 = 90) met inclusion criteria. Participants showed no differences in age, chronic medical conditions, or history of pregnancy complications. The groups differed in gravidity and parity. The factors positively associated with Group 1 included either preeclampsia or GH (11 [13.5%] vs. 1 [1.1%], P = 0.001) and GH alone (8 [9.9%] vs. 1 [1.1%], P = 0.014). Newborns from Group 1 had a statistically significant lower birth weight than those from Group 2 (3003 grams ± 564.21 vs. 3173 grams ± 502.59, P = 0.039). GH was more prevalent in Group 1 (P = 0.008) than a control group of 45,278 participants who conceived spontaneously. No significant differences were observed between Group 2 and the control group.

Conclusions: The incidence of GH and preeclampsia in participants was higher among those exposed to 1–2 cycles than those exposed to 3+ cycles of IUI.

Background: The association between use of renin-angiotensin-aldosterone (RAAS) inhibitors and both SARS-CoV-2 infection and the development of severe COVID-19 has been presented in the recent medical literature with inconsistent results.

Objectives: To assess the association between RAAS inhibitor use and two outcomes: infection with SARS-CoV-2 (Model 1) and severe COVID-19 among those infected (Model 2).

Methods: We accessed used electronic health records of individuals from Israel who were receiving anti-hypertensive medications for this retrospective study. For Model 1 we used a case-control design. For Model 2 we used a cohort design. In both models, inverse probability weighting adjusted for identified confounders as part of doubly robust outcome regression.

Results: We tested 38,554 individuals for SARS-CoV-2 who had hypertension and were being treated with medication; 691 had a positive test result. Among those with a positive test, 119 developed severe illness. There was no association between RAAS inhibitor use and a positive test. Use of RAAS inhibitors was associated with a decreased risk for severe COVID-19 (adjusted odds ratio [OR] 0.47, 95% confidence interval [95%CI] 0.29–0.77) compared with users of non-RAAS anti-hypertensive medication. The association remained significant when use of angiotensin-converting-enzyme inhibitors (adjusted OR 0.46, 95%CI 0.27–0.77) and angiotensin II receptor blockers (adjusted OR 0.39, 95%CI 0.16–0.95) were analyzed separately.

Conclusions: Among individuals with hypertension using RAAS inhibitors, we found a lower risk of severe disease compared to those using non-RAAS anti-hypertensive medications. This finding suggests that RAAS inhibitors may have a protective effect on COVID-19 severity among individuals with medically treated hypertension.

Hypertension and cancer are both common due to the aging of the population and the advances in medical treatment which result in increased survival of cancer patients today. More patients with cancer; therefore, present with hypertension, which is attributed to different factors, including genetics and age as well as the type of tumor and cancer-related treatments. Given the increased cardiovascular and mortality risk related to hypertension, it is important to appropriately identify and treat hypertension, particularly in the population of vulnerable cancer patients. In this article we discuss the epidemiology, different etiologies, and approaches to the management of hypertension in cancer patients.

Background: Idiopathic pulmonary fibrosis (IPF) has poor prognosis. Anti-fibrotic treatment has been shown to slow disease progression. Lung transplantation (LTx) offers a survival benefit. The 5-year survival after LTx in IPF is between 40 and 50%

Objectives: To evaluate which IPF patients have better prognosis following LTx.

Methods: A retrospective study was conducted with all IPF patients who had undergone LTx in the Rabin Medical Center between 2010 and 2018. We collected data on pre-evaluation of pulmonary function tests, echocardiographic and right heart catherization, and anti-fibrotic treatments. The Kaplan-Meier method was used for survival analysis.

Results: Among148 patients who underwent LTx, 58 were double LTx (DLT) and 90 single LTx (SLT). Mean age was 58.07 ± 9.78 years; 104 males and 44 females. DLT patients had significantly lower survival rates than SLT in the short and medium term after LTx. Patients with saturation above 80% after the 6-minute walk test (6MWT) had higher survival rates. Patients over 65 years of age had a lower survival rates. Those with pulmonary hypertension (PHT) above 30 mmHg had a poorer prognosis with lower survival rates.

Conclusions: IPF patients with higher mean PHT, older age (> 65 years), and desaturation following 6MWT had lower survival rates following LTx. DLT may decrease survival rate compared to SLT just for the short and medium period of time after LTx. These results may lead to better selection of IPF patient candidates for LTx. Additional studies are warranted for choosing which patients will have better prognosis after LTx.

Background: Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare, distinct pulmonary vascular disease caused by chronic obstruction of major pulmonary arteries, which can be cured by pulmonary endarterectomy. However, many CTEPH patients are not surgical candidates. Balloon pulmonary angioplasty (BPA) is an emerging technique used to treat inoperable CTEPH.

Objectives: To describe the first Israeli experience with BPA for inoperable CTEPH.

Methods: In 2017 we established a BPA program at our institution. We reviewed the outcomes to date of BPA in our center.

Results: Forty-seven BPA procedures were performed in five patients with inoperable CTEPH (4–17 procedures/patient). Mean pulmonary artery pressure improved in all patients (median decrease 17 mmHg, range 10–26 mmHg). Pulmonary vascular resistance also improved (median decrease 11 Woods Units/m², range 8–16 Woods Units/m²). Cardiac output increased in 4 of 5 patients and decreased in one. Functional capacity improved from New York Heart Association (NYHA) III to II in four patients; one patient was NYHA II at baseline without change after BPA. Six-minute walking distance improved by a median of 97 meters. (range 21–197 meters). Hemodynamic and functional improvements were sustained at follow-up 5–11 months after the last BPA procedure. BPA enabled 2 of 3 patients treated with parenteral prostanoids to be switched to oral therapy. There were no major complications.

Conclusions: We successfully established BPA as a treatment for inoperable CTEPH in our center. BPA resulted in hemodynamic and clinical improvements that were sustained over time.

Background: Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare, distinct pulmonary vascular disease, which is caused by chronic obstruction of major pulmonary arteries. CTEPH can be cured by pulmonary endarterectomy (PEA). PEA for CTEPH is a challenging procedure, and patient selection and the perioperative management are complex, requiring significant experience.

Objectives: To describe the establishment of a national CTEPH–PEA center in Israel and present results of surgery.

Methods: In this study, we reviewed the outcomes of PEA in a national referral, multi-disciplinary center for CTEPH–PEA. The center was established by collaborating with a high-volume center in Europe. A multidisciplinary team from our hospital (pulmonary hypertension specialist, cardiac surgeon, cardiac anesthesiologist and cardiac surgery intensivist was trained under the guidance of an experienced team from the European center.

Results: A total of 38 PEA procedures were performed between 2008 and 2018. We included 28 cases in this analysis for which long-term follow-up data were available. There were two hospital deaths (7%). At follow-up, median New York Heart Association (NYHA) class improved from III to I (P < 0.0001), median systolic pulmonary pressure decreased from 64 mmHg to 26 mmHg (P < 0.0001), and significant improvements were seen in right ventricular function and exercise capacity.

Conclusions: A national center for performance of a rare and complex surgical procedure can be successfully established by collaboration with a high-volume center and by training a dedicated multidisciplinary team.

Background: Idiopathic intracranial hypertension (IIH) is a disorder of unknown etiology. Its occurrence in the general population is 1/100,000, and 20/100,000 among overweight women of childbearing age. Familial occurrence is reportedly uncommon and not well-characterized.

Objectives: To describe a familial association with IIH.

Methods: We conducted a retrospective chart review of all familial cases of IIH examined in the neuro-ophthalmology clinic of our medical center between January 2006 and June 2013.

Results: Of a total of 520 patients with IIH, 15 had other family members with IIH (from seven different families). The family relation was a mother and daughter in two families, a brother and sister in four families, and an aunt and two first-degree cousins in the seventh family. Symptoms, course of disease, and risk factors were similar among the relatives of all seven families, except for the age at diagnosis, which was different in one family. All of the adult patients of six families were obese (body mass index 25–35 kg/m²), and all of the members of the other family were morbidly obese. There was no association between other systemic risk factors and IIH.

Conclusions: IIH occurrence within a family is more common than previously believed, and its incidence in families is more common than in the general population. The clinical course appears to be similar in family members. Our findings suggest a genetic predisposition. Further investigation of familial cases may yield useful information on the pathogenesis and genetic nature of this condition.