Israel Medical Association Journal

Cardiac amyloidosis is a form of restrictive cardiomyopathy resulting from the accumulation of misfolded protein aggregates in the myocardial extracellular space. Cardiac amyloidosis stems primarily from the misfolding of monoclonal immunoglobulin light chains (AL) originating from abnormal clonal plasma cell proliferation or transthyretin amyloidosis (ATTR).

Diagnosis of amyloidosis demands a high index of suspicion and requires histological confirmation of pathognomonic green birefringence under polarized light when an infiltrated tissue specimen is stained with Congo-red staining [1,2].

Pleural involvement of systemic amyloidosis has rarely been reported and is considered a serious complication [3]. Pleural amyloidosis is diagnosed with the identification of amyloid deposits in pleural biopsy specimens. However, pleural biopsies are rarely performed for this indication.

We describe the case of a patient with AL cardiac amyloidosis presenting as intractable pleural effusion and diagnosed via pleural biopsy.

Background: The use of proprotein convertase subtilisin/kexin type 9 monoclonal antibodies (PCSK9 mAbs) is emerging for lowering low-density lipoprotein cholesterol (LDL-C). However, real-world data is lacking for their use among elderly patients.

Objective: To define the characteristics of elderly patients treated with PCSK9 mAbs and to evaluate the efficacy and tolerability compared with younger patients.

Methods: We conducted a retrospective cohort study of elderly patients (≥ 75 years at enrollment) treated with PCSK9 mAbs for primary and secondary cardiovascular prevention. Data were retrieved for demographic and clinical characteristics; indications for treatment; agents and dosages; concomitant lipid lowering treatment; LDL-C levels at baseline, 6, 12 months, and at the end of follow up. Data also included achieving LDL-C target levels and adverse effects.

Results: The cohort included 91 elderly patients and 92 younger patients, mean age 75.2 ± 3.76 and 58.9 ± 7.4 years (P < 0.0001). Most patients (82%, 80%) were in high/very high-risk categories. For almost all (98%, 99%), the indication was statin intolerance, with PCSK9 mAb monotherapy the most prevalent regimen. The average follow-up was 38.1 ± 20.5 and 30.9 ± 15.8 months (P = 0.0258). Within 6 months the LDL-C levels were reduced by 57% in the elderly group and by 59% in the control group (P = 0.2371). Only 53% and 57% reached their LDL-C target levels. No clinically significant side effects were documented.

Conclusion: PCSK9 mAbs have similar effects and are well tolerated among elderly patients as in younger patients.

Background: Direct oral anticoagulants (DOACs) are the treatment of choice for patients with non-valvular atrial fibrillation; however, bleeding risk remains significant. We reported a single-center experience with 11 patients who presented with hemorrhagic cardiac tamponade while treated with DOACs.

Objectives: To evaluate the characteristics and clinical outcomes of patients under DOACs with cardiac tamponade.

Methods: We retrospectively identified 11 patients treated with DOACs admitted with pericardial tamponade in our cardiology unit during 2018–2021.

Results: The mean age was 84 ± 4 years; 7 males. Atrial fibrillation was the indication for anticoagulation in all cases. DOACs included apixaban (8 patients), dabigatran (2 patients), and rivaroxaban (1 patient). Urgent pericardiocentesis via a subxiphoid approach under echocardiography guidance was successfully performed in 10 patients. One patient was treated with urgent surgical drainage with a pericardial window. Reversal of anticoagulation using prothrombin complex concentrate and idarucizumab was given before the procedure to 6 patients treated with apixaban and one patient treated with dabigatran. One patient, initially treated with urgent pericardiocentesis, underwent pericardial window surgery due to re-accumulation of blood in the pericardium. The pericardial fluid analysis demonstrated hemopericardium. Cytology tests were negative for malignant cells in all cases. Discharge diagnoses regarding the cause of hemopericardium included pericarditis (3 patients) and idiopathic (8 patients). Medical therapy included non-steroidal anti-inflammatory drugs (1 patient), colchicine (3 patients), and steroids (3 patients). No patient died during hospitalization.

Conclusions: Hemorrhagic cardiac tamponade is a rare complication of DOACs. We found good short-term prognosis following pericardiocentesis.

Background: Current guidelines for choosing between revascularization modalities may not be appropriate for young patients.

Objectives: To compare outcomes and guide treatment options for patients < 40 years of age, who underwent percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) between 2008 and 2018.

Methods: Outcomes were compared for 183 consecutive patients aged < 40 years who underwent PCI or CABG between 2008 and 2018, Outcomes were compared as time to first event and as cumulative events for non-fatal outcomes.

Results: Mean patient age was 36.3 years and 96% were male. Risk factors were similar for both groups. Drug eluting stents were implemented in 71% of PCI patients and total arterial revascularization in 74% of CABG patients. During a median follow-up of 6.5 years, 16 patients (8.6%) died. First cardiovascular events occurred in 35 (38.8%) of the PCI group vs. 29 (31.1%) of the CABG group (log rank P = 0.022), repeat events occurred in 96 vs. 51 (P < 0.01), respectively. After multivariate adjustment, CABG was associated with a significantly reduced risk for first adverse event (hazard ratio [HR] 0.305, P < 0.01) caused by a reduction in repeat revascularization. CABG was also associated with a reduction in overall repeat events (HR 0.293, P < 0.01). There was no difference in overall mortality between CABG and PCI.

Conclusions: Young patients with coronary disease treated by CABG showed a reduction in the risk for non-fatal cardiac events. Mortality was similar with CABG and PCI.

Background: The MitraClip procedure is becoming an acceptable alternative for high-risk patients with mitral regurgitation (MR) due to functional (FMR) or degenerative (DMR) disease and suitable mitral anatomy.

Objectives: To evaluate the results of MitraClip at our institute in carefully selected patients.

Methods: We conducted a retrospective analysis of medical records and echocardiography data from January 2012 to December 2017.

Results: A total of 39 MitraClip procedures in 37 patients (aged 75 ± 12 years, 9 women) was performed. Twenty-four patients presented with FMR, 12 with DMR, and 1 with combined pathology. One-day post-procedure MR was moderate to low in 86.1% of patients, with immediate device success in 88.8%. MR at 1 year was moderate to low in 79% at 1 year. Survival at 1 year was 86% and at 2 years 69.4%. Peri-procedural (< 1 week) death and MitraClip failure occurred in one and three patients, respectively. New York Heart Association score improved to class 1 or 2 in 37% of patients at 1 year vs. one patient at baseline. Post-procedural systolic pulmonary pressure was reduced from 53 (range 48–65) to 43 (range 36–52) mmHg at 1 month with a subsequent plateau at follow-up, to 41 (34–57) mmHg at 6 months, and to 47 (38–50) at 12 months.

Conclusions: MitraClip in severe MR resulted in modest improvement in functional status and pulmonary pressure with a small risk of immediate procedural complications. Outcomes are encouraging considering the natural course of MR and the risks of surgical intervention.

Background: Bioresorbable vascular scaffold (BVS) is a promising technology that potentially offers several advantages over contemporary coronary drug-eluting stents (DES). Crucial to BVS implantation is the correct choice of scaffold size (diameter and length) in order to avoid "geographic miss" in length, provide the maximal support to the vessel wall, and avoid leaving “free-floating” foreign material in the coronary vasculature. 

Objectives: To assess the optimal method for measuring coronary stenosis prior to BVS implantation.

Methods: We compared the performance of two quantitative coronary angiography assessment (QCA) techniques: two dimensional real-time QCA (2D-QCA) and offline 3D QCA (3D-QCA) for the evaluation of coronary lesions in patients enrolled in a multicenter randomized controlled trial of BVS vs. metallic stents, by calculating the weighted kappa value for agreement regarding optimal BVS size with the reference method – CoreLab offline 2D-QCA measurements..In addition, we collected 2 year clinical outcomes (death/myocardial infarction/repeat revascularization/scaffold thrombosis) in BVS-implanted patients.

Results: In 17 patients with available CoreLab data, the weighted kappa for agreement for 3D-QCA was significantly better than for 2D-QCA (0.90, 95%CI 0.72–1.00 vs. 0.439, 95%CI 0.16–0.77). The rate of clinical events at 2 years was low (9.5%).

Conclusions: Initial experience in a small group of carefully selected patients at our institution, suggests that the use of BVS for coronary revascularization is associated with a low rate of adverse events in suitable patients. 3D-QCA may be superior to 2D-QCA analysis in terms of reproducibility, and results in more patients receiving optimal size BVS. 

 

Background: Several trials support the trans-radial route of percutaneous coronary intervention (PCI) since it reduces access site vascular complications and bleeding. 

Objectives: To examine the effects of trans-radial interventions (TRI) on clinical outcomes in a 'real world' cohort of patients undergoing PCI.

Methods: We analyzed 4873 consecutive patients who underwent PCI at a tertiary center and identified 373 patients who underwent TRI. Patients (radial vs. femoral) were compared using a propensity score analysis to best match between groups. Outcome parameters included total mortality, myocardial infarction (MI), repeat target vessel revascularization (TVR) rates, length of hospitalization and ∆Ht/Hb/creatinine values during hospitalization. These were evaluated at 6 months and 1 to 3 years after PCI.

Results: The rates of major adverse cardiovascular event (MACE) and its constituents were similar in the trans-radial vs. trans-femoral groups at all time intervals: 6.7% vs. 5.5% at 6 months, 10.3% vs. 10% at 1 year, 15.7% vs. 15% at 2 years, 15.7% vs. 16% at 3 years, respectively (P = 0.6). The length of hospitalization was shorter in the TRI group (2.87 days ± 2.04 vs. 3.3 days ± 3.12, P = 0.023). We did not find significant differences between the groups in the mean ∆Ht/Hb/creatinine values during the hospitalization course.

Conclusions: In a 'real-world' setting of PCI, the TRI route of PCI is as safe and efficient as the femoral approach. TRI is associated with shorter duration of hospitalization.

 

Objectives: To assess the preliminary results of transcatheter mitral valve leaflet repair (TMLR) in a single academic center.

Methods: Data were collected prospectively in the cardiology department of Rabin Medical Center in 2012. Ten consecutive patients (age 69.3 ± 15.9 years, ejection fraction 36.5 ± 9.4) who were poor surgical candidates with severe functional MR underwent general anesthesia, followed by trans-septal puncture and a TMLR procedure using the MitraClip device.

Results: All 10 patients were considered to have severe functional MR prior to TMLR treatment and were all symptomatic; the mean New York Heart Association (NYHA) class was 3.4 ± 0.5. The MR severity was 4 ± 0. There were no immediate complications or failures of the procedure. One patient died on day 5 due to massive gastrointestinal bleeding. Immediately following TMLR all 10 patients showed a profound MR reduction to a mean severity grade of 1.6 ± 0.6. At one month after the procedure, NYHA had decreased to an average of 1.7 ± 1.0 and was at least grade 2 in all but one patient. After 6 months the MR remained ≤ 2 in six of eight patients, with a NYHA average of 1.4 ± 0.5.

Conclusions: The MitraClip procedure was shown to be relatively safe, providing significant clinical benefits to a relatively sick population with severe MR. It is therefore an important alternative to surgery in these high risk patients.

Background: The best therapeutic alternative for patients suffering from in-stent restenosis after drug-eluting stent implantation remains to be elucidated.

Objective: To characterize the pattern, treatment and outcomes of DES[1]-related in-stent restenosis in patients treated at our institution.

Methods: We determined the incidence and major adverse clinical events in 71 consecutive patients with DES failure among 2473 patients who were treated with 2548 drug-eluting stents between 2004 and 2007. We analyzed the clinical data, procedural parameters and clinical outcomes.

Results: The type and number of stents implanted were as follows: Cypher (n=1808), Endeavor (421) and Taxus (319) of these, 53 (2.9%), 10 (2.4%), and 8 (2.5%) patients respectively presented with restenosis. The mean time to restenosis was 11.3 ± 9.9 months. Patients’ mean age was 65 ± 11 years 75% were male, and 68% had diabetes mellitus. Unstable angina was the clinical presentation in 52 (73%). At 6 months, 3 patients had developed myocardial infarction (4.2%), repeat restenosis at follow-up was diagnosed in 8 patients (11.3%), the overall major adverse clinical events rate was 18.3% (13 patients), and 2 patients died (2.8%).

Conclusions: Drug-eluting stent-related restenosis is relatively infrequent but remains a clinical challenge. It occurs more frequently in complex lesion subsets, but the overall intermediate-term prognosis is tolerable.  

[1] DES = drug-eluting stent

Background: Myocardial blush grade is a useful marker of microvascular reperfusion that may influence left ventricular dilatation.

Objectives: To assess the impact of myocardial blush grade on LV[1] remodeling in patients undergoing successful primary  PCI³ for first anterior ST elevation myocardial infarction.

Methods: In 26 consecutive patients MB[2] grade was evaluated immediately after primary PCI[3]. Each patient underwent transthoracic echocardiography at 24 hours and 6 months after PCI for evaluation of LV volumes. LV remodeling was defined as an increase in end-diastolic volume by ≥ 20%.

Results: The presence of myocardial reperfusion (MB 2-3) after primary PCI was associated with a significantly lower rate of remodeling than the absence of myocardial reperfusion (MB 0-1) (17.6% vs. 66.6%, P = 0.012). Accordingly, at 6 months, patients with MB 2-3 had significantly smaller LV end-diastolic volume (94 ± 21.5 ml vs. 115.2 ± 26) compared with patients with MB 0-1. In univariate analysis, only MB (0-1 versus 2-3) was associated with increased risk of LV remodeling (odds ratio 9.3, 95% confidence interval 1.45–60.21, P = 0.019).

Conclusions: Impaired microvascular reperfusion, as assessed by MB 0-1, may be associated with LV remodeling in patients with STEMI[4] treated successfully with primary PCI.

The incidence of aortic valve stenosis is growing rapidly in the elderly. Nonetheless, many symptomatic patients are not referred for surgery usually because of high surgical risk. Unfortunately, percutaneous balloon valvuloplasty is unsatisfactory due to high recurrence rates. In 2002, Cribier and colleagues were the first to describe percutaneous aortic valve implantation, opening a new era of aortic stenosis management. In the present review we report a patient treated by this novel method, discuss and assess how it is implanated, report the findings of studies conducted to date, and suggest future directions for percutaneous treatment of aortic valve disease.
 

Background: Although unprotected left main coronary artery disease is considered by contemporary guidelines to be an indication for surgery, percutaneous coronary intervention may be necessary in patients at high surgical risk.

Objectives: To assess the outcome of angioplasty in the treatment of unprotected LMCA[1] disease.

Methods: Angiographic and clinical data were collected prospectively for all patients who underwent emergent or non-emergent (planned) therapeutic PCI[2] for unprotected LMCA disease at our center from 2003 to 2007. Baseline values were compared with findings at 1, 6 and 12 months after the procedure.

Results: The study group comprised 71 consecutive patients with a mean age of 74 ± 12 years; 63% were men, and 31% had diabetes. Forty-three patients had a planned procedure and 28 an emergent procedure. Mean EuroScore was 7.3 ± 3.6 (range 5–12). Forty-nine percent of the procedures were performed with bare metal stents and 51% with drug-eluting stents. Procedural success was achieved in 100% of cases. The overall mortality rate was 11.3% at 1 month, 18.3% at 6 months and 19.7% at 12 months. Elective PCI was associated with significantly lower mortality (2.3% vs. 25% at 1 month, 4.6% vs. 39% at 6 months and 6.9% vs. 39% at 12 months), and the use of drug-eluting stents was associated with lower rates of target vessel revascularization and major adverse cardiac events than use of bare metal stents (2.8% vs. 14% at 1 month, 8.3% vs. 43% at 6 and 12 months). Variables that correlated with increased mortality or MACE[3] at 6 and 12 months were cardiogenic shock, emergent PCI, ejection fraction < 35%, renal failure, distal left main stenosis location, and reference diameter < 3 mm.

Conclusions: PCI is a feasible and relatively safe therapeutic option for unprotected LMCA. The less favorable outcome of emergent compared to planned PCI is probably attributable to the overwhelming acute myocardial ischemic injury in emergent cases. The use of drug-eluting stents may improve the intermediate-term restenosis rate.

[1] LMCA = left main coronary artery

[2] PCI = percutaneous coronary intervention

Background: The degree of left ventricular dysfunction determines the prognostic outcome of patients with acute myocardial infarction.

Objectives: To define the clinical, angiographic and procedural variables related to LV[1][1] dysfunction in patients with  with anterior wall AMI[1][2] referred for primary percutaneous coronary intervention.

Methods: The sample included 168 patients treated by primary PCI[1][3] for first anterior wall AMI. Clinical, demographic and medical data were collected prospectively into a computerized registry, and clinical outcome (death, reinfarction, major cardiovascular event) were evaluated during hospitalization and 30 days after discharge. Patients were divided into three groups by degree of LV dysfunction (mild, moderate, severe) and compared for clinical, angiographic and procedural variables.

Results: LV dysfunction was associated with pre-PCI renal failure (serum creatinine > 1.4 mg/dl), peripheral vascular disease, high peak creatine kinase level, longer door to balloon time, low TIMI flow grade before and after PCI, and use of an intraaortic balloon pump. On multivariate analysis adjusted for baseline differences, peak creatine kinase level (r = 0.3, P = 0.0001) and door to needle time (r = 0.2, P = 0.008) were the most significant independent predictors of moderate or severe LV dysfunction after anterior AMI.

Conclusion: Abnormal LV function after first anterior AMI can be predicted by door to balloon time and the size of the infarction as assessed by creatine kinase levels. Major efforts should be made to decrease the time to myocardial reperfusion.

[1][1] LV = left ventricular

[1][2] AMI = acute myocardial infarction

[1][3] PCI = percutaneous coronary intervention