Israel Medical Association Journal

Twenty years after being closed due to unfavorable results, a new lung transplant program was started at the Sheba Medical Center. The new team included an experienced lung transplant surgeon, an anesthesiologist, an intensive care specialist, and a pulmonologist with extensive experience in the field.

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: Unicuspid and bicuspid aortic valve (BAV) are congenital cardiac anomalies associated with valvular dysfunction and aortopathies occurring at a young age.

Objectives: To evaluate our experience with aortic valve repair (AVr) in patients with bicuspid or unicuspid aortic valves.

Methods: Eighty patients with BAV or unicuspid aortic valve (UAV) underwent AVr. Mean patient age was 42 ± 14 years and 94% were male. Surgical technique included: aortic root replacement with or without cusp repair in 43 patients (53%), replacement of the ascending aorta at the height of the sino-tubular junction with or without cusp repair in 15 patients (19%), and isolated cusp repair in 22 patients (28%).

Results: The anatomical structure of the aortic valve was bicuspid in 68 (85%) and unicuspid in 12 patients (15%). Survival rate was 100% at 5 years of follow-up. Eleven patients (13.7%) underwent reoperation, 8 of whom presented with recurrent symptomatic aortic insufficiency (AI). Late echocardiography in the remaining 69 patients revealed mild AI in 63 patients, moderate recurrent AI in 4, and severe recurrent AI in 2. Relief from recurrent severe AI or reoperations was significantly lower in patients who underwent cusp repair compared with those who did not (P = 0.05). Furthermore, the use of pericardial patch augmentation for the repair was a predictor for recurrence (P = 0.05).

Conclusions: AVr in patients with BAV or UAV is a safe procedure with low morbidity and mortality rates. The use of a pericardial patch augmentation was associated with higher repair failure.

Background: During the past decades, beta thalassemia major (TM) and beta thalassemia intermedia (TI) have transformed from a universally fatal disease at a young age into a chronic disease. This advancement is attributed to improved chelation therapy as well as enhanced management strategies, with focused attention on disease and treatment-related complications.

Objectives: To describe characteristics of adults with thalassemia as well as treatment modalities, disease and treatment-related complications, and socioeconomic information of the patients.

Methods: We preformed a retrospective analysis of 14 adult patients > 35 years of age with TM and TI who were treated at our institute, a single center specializing in the care of adult thalassemia patients living in Israel, between the years 2006 and 2016.

Results: The median age of patients was 37 years and most patients were transfusion-dependent. The median number of chelation therapeutic lines was three, and 85.7% of patients were treated at one point by combination chelation therapy. Most patients suffered from at least some form of endocrine dysfunction (n=12), and four patients developed overt heart failure. Of the patients, 85% had completed at least a high school education, 78% were employed, and 64.2% were married.

Conclusions: Prolonged survival of thalassemia patients in recent years has been accompanied by a new set of challenges for both the patients and the treating staff. Further research is warranted to improve both medical management and the socioeconomic well-being of this unique group of adult thalassemia patients.

Background: Postpericardiotomy syndrome (PPS) is characterized by pleuro-pericardial inflammation, which occurs in patients undergoing surgical procedures involving the pleura, pericardium, or both. The syndrome is considered to be immune mediated. However, its pathogenesis is not fully understood. It has previously been demonstrated that the Mediterranean Fever (MEFV) gene, which is associated with familial Mediterranean fever (FMF), has a role in the activation and expression of several inflammatory diseases.

Objectives: To investigate whether carriage of the MEFV mutation may precipitate PPS or affect its phenotype.

Methods: The study population included 45 patients who underwent cardiac surgery and developed PPS. The control group was comprised of 41 patients who did not develop PPS. Clinical and demographic data was collected. The severity of PPS was evaluated. Genetic analysis to determine the carriage of one the three most common MEFV gene mutations (M694V, V726A, E148Q) was performed. The carriage rate of MEFV mutations in patients with and without PPS was compared. Association between MEFV mutation carriage and severity of PPS was evaluated. 

Results: The rate of mutation carriage in the MEFV gene was similar in patients with and without PPS (15.6% in the study groups vs. 29.3% in the control group, P = 0.1937). The rate of mutation carriage in the MEFV gene was significantly lower among patients with severe PPS as compared to patients with mild-moderate PPS (4.8% vs. 25%, P < 0.05).

Conclusions: Carriage of mutations in the MEFV gene is not associated with development of PPS; however, it may affect PPS severity.

 

Background: Pulmonary infiltrates (PIs) detected in patients with non-Hodgkin lymphoma (NHL) may present a diagnostic challenge due to their wide differential diagnosis, including infection, pulmonary lymphoma and immunochemotherapy-associated pulmonary toxicity.

Objectives: To characterize therapy-associated PIs by positron emission tomography/computed tomography (PET/CT) imaging.

Methods: We conducted a historical analysis of fluorodeoxyglucose-PET/CT (¹⁸F-FDG-PET/CT) PIs in NHL patients treated with combined immunochemotherapy including rituximab. Incidence of PIs, radiological features, patients’ characteristics, underlying NHL type, rituximab/chemotherapy dosing schedules, and symptoms were recorded. Therapy-associated PIs were defined as new or worsening PIs appearing after treatment onset, without evidence of active pulmonary lymphoma or infection.

Results: Among 80 patients who met the pre-specified criteria, therapy-associated PIs were identified in 17 (21%), 6 of whom had accompanying symptoms. Increased FDG uptake was observed in nine, and PI resolution in six. The incidence of PIs was higher in females and in patients with aggressive lymphoma, at advanced stages, and in those who had received treatment consisting of a combination of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone every 14 days (R-CHOP-14).

Conclusions: This characterization of therapy-associated PIs may support the clinician managing NHL patients. Further prospective studies are needed to establish the role of each therapeutic component and the natural history of this phenomenon.

Background: Prolonged life expectancy has increased the number of elderly high risk patients referred for surgical aortic valve replacement (AVR). These referred high risk patients may benefit from sutureless bioprosthesis procedures which reduce mortality and morbidity.

Objectives: To present our initial experience with sutureless aortic bioprotheses, including clinical and echocardiographic results, in elderly high risk patients referred for AVR. 

Methods: Forty patients (15 males, mean age 78 ± 7 years) with symptomatic severe aortic stenosis underwent AVR with the 3F Enable™ or Perceval™ sutureless bioprosthesis during the period December 2012 to May 2014. Mean logistic EuroScore was 10 ± 3%. Echocardiography was performed preoperatively, intraoperatively, at discharge and at follow-up.

Results: There was no in-hospital mortality. Nine patients (22%) underwent minimally invasive AVR via a right anterior mini-thoracotomy and one patient via a J-incision. Four patients underwent concomitant coronary aortic bypass graft, two needed intraoperative repositioning of the valve, one underwent valve exchange due to inappropriate sizing, three (7.5%) had a perioperative stroke with complete resolution of neurologic symptoms, and one patient (2.5%) required permanent pacemaker implantation due to complete atrioventricular block. Mean preoperative and postoperative gradients were 44 ± 14 and 13 ± 5 mmHg, respectively. At follow-up, 82% of patients were in New York Heart Association functional class I and II.

Conclusions: Sutureless AVR can be used safely in elderly high risk patients with relatively low morbidity and mortality. The device can be safely implanted via a minimally invasive incision. Mid-term hemodynamic results are satisfactory, demonstrating significant clinical improvement.

 

Background: The rate of mitral bioprosthesis implantation in clinical practice is increasing. Transcatheter valve-in-valve implantation has been described for high risk patients requiring redo valve surgery. 

Objectives: To report our experience with transapical valve-in-valve implantation for failed mitral bioprosthesis.

Methods: Since 2010, 10 patients have undergone transapical valve-in-valve implantation for failed bioprosthesis in our center. Aortic valve-in-valve implantation was performed in one of them and mitral valve-in-valve implantation in nine. Mean age was 82 ± 4 years and 6 were female (67%). Mean time from original mitral valve (MV) replacement to valve-in-valve procedure was 10.5 ± 3.7 years. Follow-up was completed by all patients with a mean duration of 13 ± 12 months. 

Results: Preoperatively, all patients presented with significant mitral regurgitation; two with mitral stenosis due to structural valve failure. All nine patients underwent successful transapical valve-in-valve implantation with an Edwards Sapien™ balloon expandable valve. There was no in-hospital mortality. Mean and median hospital duration was 15 ± 18 and 7 days respectively. Valve implantation was successful in all patients and there were no major complications, except for major femoral access bleeding in one patient. At last follow-up, all patients were alive and in NYHA functional class I or II. Echocardiography follow-up demonstrated that mitral regurgitation was absent or trivial in seven patients and mild in two. At follow-up, peak and mean gradients changed from 26 ± 4 and 8 ± 2 at baseline to 16.7 ± 3 and 7.3 ± 1.5, respectively.

Conclusions: Transcatheter transapical mitral valve-in-valve implantation for failed bioprosthesis is feasible in selected high risk patients. Our early experience with this strategy is encouraging. Larger randomized trials with long-term clinical and echocardiographic follow-up are recommended.

 

Background: Trans-catheter valve implantation (TAVI) is a non-surgical alternative for patients with severe aortic stenosis (AS). Pre-procedural computed tomography angiography (CTA) allows accurate “road mapping,” aortic annulus sizing and the detection of incidental findings.

Objectives: To document the prevalence of non-valvular extra-cardiac findings on CTA prior to TAVI and the impact of these findings on the procedure.  

Methods: Ninety AS patients underwent CTA as part of pre-TAVI planning. Scans extended from the clavicles to the groin. Non-vascular non-valvular findings were documented and graded as follows: (A) significant findings causing TAVI cancellation or postponement, (B) significant findings leading to a change in the TAVI procedure approach, (C) non-significant findings not affecting the TAVI procedure. 

Results: TAVI was planned for 90 patients; their average age was 80.2 ± 7.5 years, 53% were females. Overall, non-valvular cardiac, extra-cardiac and extra-vascular significant and non-significant incidental findings were documented in 97% of scans (87/90). Significant pathologies causing TAVI cancellation or postponement (category A) were documented in 8%. Significant findings affecting the TAVI procedure (category B) were found in 16% of patients. 

Conclusions: Pre-TAVI CTA detected non-valvular extra-vascular pathologies leading to procedure cancellation/postponement or procedure modification in 8% and 16%, respectively. Comprehensive CTA evaluation that acknowledges the importance of such findings is of major importance since it might alter the TAVI procedure or even render it inappropriate. 

 

Background: The Syntax score (SS) is a helpful tool for determining the optimal revascularization strategy regarding coronary artery bypass surgery (CABG) vs. percutaneous coronary intervention (PCI) in patients with complex coronary disease. While an association between higher SS and mortality was found for PCI patients, no such association was found for CABG patients.

Objectives: To assess whether the SS predicts late mortality in patients undergoing CABG in a real-world setting.

Methods: The study included 406 consecutive patients referred for CABG over a 2 year period. Baseline and clinical characteristics were collected. Angiographic data SS were interpreted by an experienced angiographer. Patients were divided into three groups based on SS tertiles: low ≤ 21 (n=205), intermediate 22–31 (n=138), and high ≥ 32 (n=63). Five year mortality was derived from the National Mortality Database.

Results: Compared with low SS, patients with intermediate and high scores were significantly older (P = 0.02), had lower left ventricular ejection fraction (64% vs. 52% and 48%, P < 0.001) and greater incidence of acute coronary syndrome, left main disease, presence of chronic total occlusion of the left anterior descending and/or right coronary artery, and a higher EuroSCORE (5% vs. 5% and 8%, P < 0.01). Patients with intermediate and high SS had higher 5 year mortality rates (18.1% and 19%, respectively) compared to patients with low score (9.8%, P = 0.04). On multivariate analysis, SS was not an independent predictor of late mortality.

Conclusion: Patients with lower SS had lower mortality after CABG, which is attributable to lower baseline risk. SS is not independently predictive of late mortality in patients with multi-vessel coronary artery disease undergoing CABG.

Background: Non-mobilized peripheral blood contains mostly committed cells with limited numbers of early progenitors. Objectives: To enrich functional progenitor cells from healthy donors and ischemic heart disease patients by short-term culture of mononuclear cells with defined culture conditions.

Methods: Mononuclear cells obtained from healthy donors and ischemic heart disease patients were cultured for 7 days in a cytokine cocktail. We tested the multilineage differentiation capacities and phenotype of cultured cells.

Results: The short-term culture (7 days) of all study groups with a defined cytokine cocktail resulted in two distinct cell populations (adherent and non-adherent) that differed in their differentiation capacities as well as their cell surface markers. Cultured adherent cells showed higher differentiation potential and expressed endothelial and mesenchymal fibroblast-like surface markers as compared to fresh non-cultured mononuclear cells. The non-adherent cell fraction demonstrated high numbers of colony-forming units, indicating a higher differentiation potential of hematopoietic lineage.

Conclusions: This study proved the feasibility of increasing limited numbers of multipotent progenitor cells obtained from the non-mobilized peripheral blood of healthy donors and ischemic patients. Moreover, we found that each of the two enriched subpopulations (adherent and non-adherent) has a different differentiation potential (mesenchymal, endothelial and hematopoietic).

Background: Trans-catheter aortic valve implantation (TAVI) has emerged as a novel therapeutic approach for patients with severe tricuspid aortic stenosis (AS) not suitable for aortic valve replacement.

Objectives: To describe our initial single-center experience with TAVI in patients with "off-label" indications.

Methods: Between August 2008 and December 2011 we performed TAVI in 186 patients using trans-femoral, trans-axillary, trans-apical and trans-aortic approaches. In 11 patients (5.9%) TAVI was undertaken due to: a) pure severe aortic regurgitation (AR) (n=2), b) prosthetic aortic valve (AV) failure (n=5), c) bicuspid AV stenosis (n=2), and d) prosthetic valve severe mitral regurgitation (MR) (n=2).

Results: Implantation was successful in all: six patients received a CoreValve and five patients an Edwards-Sapien valve. In-hospital mortality was 0%. Valve hemodynamics and function were excellent in all patients except for one who received an Edwards-Sapien that was inside a Mitroflow prosthetic AV and led to consistently high trans-aortic gradients. No significant residual regurgitation in AR and MR cases was observed.
Conclusions: TAVI is a good alternative to surgical AV replacement in high risk or inoperable patients with severe AS. TAVI for non-classical indications such as pure AR, bicuspid AV, and failed prosthetic aortic and mitral valves is feasible and safe and may be considered in selected patients. 

Methods:  Between February 2004 and June 2012, 100 patients in our department suffering from aortic aneurysm with aortic valve regurgitation underwent elective aortic valve-sparing surgery. Of them, 30 had Marfan syndrome, were significantly younger (30 ± 13 vs. 53 ± 16 years), and had a higher percentage of root aneurysm, compared with ascending aorta aneurysm in their non-Marfan counterparts. We evaluated the safety, durability, clinical and echocardiographic mid-term results of these patients.

Results: While no early deaths were reported in either group, there were a few major early complications in both groups. At follow-up (ranging up to 8 years with a mean of 34 ± 26 months) there were no late deaths, and few major late complications in the Marfan group. Altogether, 96% and 78% of the patients were in New York Heart Association functional class I-II in the Marfan and non-Marfan groups respectively. None of the Marfan patients needed reoperation on the aortic valve. Freedom from recurrent aortic valve regurgitation > 3+ was 94% in the Marfan patients.

Conclusions: Aortic valve-sparing surgery in Marfan symdrome patients is safe and yields good mid-term clinical outcomes.