Israel Medical Association Journal

Background: Left ventricular assist devices (LVAD) are a staple element in contemporary treatment of advanced heart failure. LVAD surgeries are mostly done in heart transplantations centers, as a destination therapy or as a bridge to heart transplantation.

Objectives: To describe our step-by-step experience in establishing and implementing a new LVAD program in a non-heart transplant center. To give insight to our short- and long-term results of our first 25 LVAD patients.

Methods: Preliminary steps included identifying the need for a new program and establishing the leading team. Next is defining protocols for pre-operative evaluation, operating room, post-operative management, and outpatient follow-up. The leading team needs to educate other relevant units in the hospital that will be involved in the care of these patients. It is essential to work in collaboration with a heart transplant center from the very beginning. Patient selection is of major importance especially in the early experience. Initially “low risk” patients should be enrolled.

Results: We describe our first 25 LVAD patients. Our first five patients all survived beyond 2 years, with no major complications. Overall, there was one operative death due to massive GI bleeding. There were four late deaths due to septic events.

Conclusions: Establishing a new LVAD program can be successful also with small- and medium-size programs. With careful and meticulous planning LVAD implantation can be extended to more centers thus offering an excellent solution for advanced heart failure patients.

Phosphoglucomutase 1 (PGM1) deficiency is a rare genetic disorder that affects glycogen metabolism and manifests as a multisystem disease. Most patients present with oropharyngeal malformations, cardiomyopathies, elevated liver enzymes, and hypoglycemia. Treatment with D-galactose has been shown to improve symptoms. Our patient presented with PGM1 deficiency. She conceived spontaneously. Throughout her pregnancies, our patient was monitored by a multidisciplinary team of cardiologists, endocrinologists, and physicians with experience in high-risk pregnancy. She delivered twice by cesarean section. Our case highlights the importance of a multidisciplinary approach and individualized management of prenatal and postpartum care of a patient with a PGM1 deficiency. To the best of our knowledge, there have been no reports about a PGM1-deficient patient who conceived and delivered.

Recognizing myocarditis is a diagnostic and therapeutic challenge due to the heterogeneity of its clinical presentation and the wide range of etiologies. There is a lack of uniformity among position papers and guidelines from various professional societies regarding the definition and diagnostic workout, including recommendations for performing endomyocardial biopsy (EMB) and medical management, especially the use of immunosuppressive regimens [1-3]. Moreover, there is significant variability among medical centers in Israel in the diagnostic and therapeutic approaches to acute myocarditis. The purpose of this position paper is to present ways to standardize the management of acute myocarditis in Israel [4] by providing up-to-date definitions of the clinical categories of myocarditis, diagnostic criteria, and therapeutic approaches that correspond to the realities of our healthcare system.

In the position statement on the definition and diagnosis of acute myocarditis on page XXX of this issue of the Israel Medical Association Journal (IMAJ), we discussed contemporary criteria for definition of acute myocarditis and inflammatory cardiomyopathy [1-6]. We also addressed current diagnostic methods including indications for endomyocardial biopsy (EMB) [7-21]. In this position statement, we discuss the management approaches during hospitalization and following hospital discharge, including specific forms of myocarditis and recommendations for returning to physical activity after myocarditis [21-36].

Background: Peripartum cardiomyopathy (PPCM) is a rare but potentially devastating complication of pregnancy. Although the pathophysiology of PPCM is not fully understood, there are known risk factors for developing PPCM, which are maternal and gestation related. In the first wave of the coronavirus disease 2019 (COVID-19) pandemic, we witnessed an elevated incidence of PPCM among COVID-19 survivors.

Objectives: To present a single-center case series of three patients diagnosed with peripartum cardiomyopathy after recovered from COVID-19 during the index pregnancy.

Methods: In this single center case study, all patients diagnosed with PPCM at our institute during the examined time frame were included. Electronic medical records were studied.

Results: Three patients previously diagnosed with asymptomatic or mildly symptomatic COVID-19 disease during pregnancy presented with PPCM before or shortly after delivery. Patients underwent testing to rule out residual COVID-19 myocarditis, were treated pharmacologically and with wearable defibrillators as needed, and were examined in follow-up 1–9 months after delivery.

Conclusions: Residual endothelial damage due to COVID-19 disease, even if originally mild in presentation, could predispose pregnant patients to PPCM and should be considered as a risk factor when assessing patients with new onset symptoms of heart failure. Further research is needed to confirm this hypothesis and fully determine the underlying pathophysiology. These preliminary findings warrant a high index of suspicion for PPCM in COVID-19 recoverers.

Background: The diagnosis of atrial fibrillation (AFIB) related cardiomyopathy relies on ruling out other causes for heart failure and on recovery of left ventricular (LV) function following return to sinus rhythm (SR). The pathophysiology underlying this pathology is multifactorial and not as completely known as the factors associated with functional recovery following the restoration of SR.

Objectives: To identify clinical and echocardiographic factors associated with LV systolic function improvement following electrical cardioversion (CV) or after catheter ablation in patients with reduced ejection fraction (EF) related to AFIB and normal LV function at baseline.

Methods: The study included patients with preserved EF at baseline while in SR whose LVEF had reduced while in AFIB and improved LVEF following CV. We compared patients who had improved LVEF to normal baseline to those who did not.

Results: Eighty-six patients with AFIB had evidence of reduced LV systolic function and improved EF following return to SR. Fifty-five (64%) returned their EF to baseline. Patients with a history of ischemic heart disease (IHD), worse LV function, and larger LV size during AFIB were less likely to return to normal LV function. Multivariant analysis revealed that younger patients with slower ventricular response, a history of IHD, larger LV size, and more significant deterioration of LVEF during AFIB were less likely to recover their EF to baseline values.

Conclusions: Patients with worse LV function and larger left ventricle during AFIB are less likely to return their baseline LV function following the restoration of sinus rhythm.

Background: Takotsubo syndrome (TTS) is a non-ischemic cardiomyopathy characterized by an acute reversible left ventricular dysfunction with typical apical ballooning, usually with subsequent complete spontaneous recovery. TTS may be triggered by several physical and emotional stressors. The name Covidsubo was recently adopted to describe this emerging entity. TTS during quarantine may be a reasonable outcome of the overwhelming stress and fear of this pandemic. However, according to the current literature, conflicting results have been reported regarding the incidence of this syndrome during the first wave of the pandemic, and further studies are needed. High index of suspicion is needed to identify patients during the next waves of the pandemic, particularly given the need for minimizing imaging modalities and contact with the patients.

Objectives: To describe two cases of TTS triggered by quarantine during the coronavirus disease-2019 (COVID-19) pandemic.

Methods: Two patients (age 81 years and 70 years) were admitted to our medical center with severe chest pain with normal blood pressure and heart rate.

Results: TTS should always be in the differential diagnosis in patients presenting with chest pain suspected to be from coronary origin. Based on the typical clinical, echocardiographic, and angiographic findings, we assumed TTS.

Conclusions: The only prominent stressor in the two cases in this article was the stress accompanying quarantine.

Background: Early identification of patients with a likelihood of cardiac improvement has important implications for management strategies.

Objectives: To evaluate whether tissue Doppler imaging (TDI) and two-dimensional (2D) strain measures may predict left ventricular (LV) improvement in patients with recent onset dilated cardiomyopathy (ROCM).

Methods: Clinical and comprehensive echo were performed at baseline and at 6 months. Patients who achieved an increase of ≥ 10 LV ejection fraction (LVEF) units and LV reverse remodeling (LVRR) (group 1) and those who improved beyond the device threshold achieving LVEF of ≥ 0.40 (group 2) were compared to patients who did not improve to this level.

Results: Among 37 patients with ROCM (mean age 56.3 ± 12.9 years and LVEF 29.1 ± 7.0%), 48% achieved LVEF ≥ 0.40 and 37.8% demonstrated LVRR. Patients with LVEF improvement ≥ 40% presented at diagnosis with higher LVEF (P = 0.006), smaller LV end-diastolic diameter (LVEDd) (P = 0.04), higher E’ septal (P = 0.02), lower E/E’ ratio (P = 0.02), increased circumferential strain (P = 0.04), and apical rotation (P = 0.009). Apical rotation and LVEDd were found to be independent predictors of LVRR. End-systolic LV volume was a significant predictor of LVEF improvement (≥ 40%).

Conclusions: Nearly half of the patients with ROCM demonstrated cardiac function improvement beyond the device threshold by 6 months. Apical rotation was introduced in our study as 2D strain prognostic parameter and found to be an independent predictor of LVRR. LV size and volume were predictors of LV improvement.

Background: Systemic CD11b+ cells have been associated with several cardiac diseases, such as chronic heart failure.

Objectives: To assess the levels of circulating CD11b+ cells and pro-inflammatory cytokines in cardiomyopathy induced by chronic adrenergic stimulation.

Methods: Male Lewis rats were injected with low doses of isoproterenol (isoprel) for 3 months. Cardiac parameters were tested by echocardiography. The percentage of CD11b+ cells was tested by flow cytometry. The levels of inflammatory cytokines in the sera were determined by an inflammation array, and the expression levels of cardiac interleukin-1 (IL-1) receptors were analyzed by real-time polymerase chain reactions. Cardiac fibrosis and inflammation were determined by histological analysis.

Results: Chronic isoprel administration resulted in increased heart rate, cardiac hypertrophy, elevated cardiac peri-vascular fibrosis, reduced fractional shortening, and increased heart weight per body weight ratio compared to control animals. This clinical presentation was associated with accumulation of CD11b+ cells in the spleen with no concomitant cardiac inflammation. Cardiac dysfunction was also associated with elevated sera levels of IL-1 alpha and over expression of cardiac IL-1 receptor type 2.

Conclusions: CD11b+ systemic levels and IL-1 signaling are associated with cardiomyopathy induced by chronic adrenergic stimulation. Further studies are needed to define the role of systemic immunomodulation in this cardiomyopathy.

 

Background: Left ventricular outflow tract (LVOT) arrhythmias are increasingly recognized. Data regarding the distribution of the sites of origin (SOO) of the arrhythmias are sparse.

Objectives: To describe the clinical characteristics of patients with LVOT arrhythmias and the distribution of their SOO. 

Methods: All 42 consecutive patients with LVOT arrhythmias who underwent radiofrequency (RF) ablation during the period 2000–2014 were included. SOO identification was based on mapping activation, pace mapping and a 3D mapping system in eight patients. 

Results: The study group comprised 28 males (66.7%) and 14 females, the mean age was 55 ±15.4 years. Most patients (76%) were symptomatic. All suffered from high grade ventricular arrhythmias. Left ventricular (LV) dysfunction (ejection fraction ≤ 50%) was observed in 15 patients (35.7%), of whom 14 (93.3%) were males. The left coronary cusp (LCC) was the most common arrhythmia SOO (64.3%). Other locations were the right coronary cusp (RCC), the junction of the RCC-LCC commissure, aortic-mitral continuity, endocardial-LVOT, and a coronary sinus branch. Acute successful ablation was achieved in 29 patients (69%) and transient arrhythmia abolition in 40 (95.2%). There was a trend for a higher success rate using cooled tip ablation catheters as compared to standard catheters. The ablation procedure significantly improved LV function in all patients with tachycardiomyopathy. 

Conclusions: LVOT arrhythmias mostly originate from the LCC and are associated with LV dysfunction in 36% of patients. Knowledge regarding the prevalence of the anatomic origin of the LVOT arrhythmias may help achieve successful ablation. The use of cooled tip ablation catheters might have beneficial effects on the success rate of the procedure.

 

Background: Hypertrophic cardiomyopathy (HCM) is a familial disease with autosomal dominant inheritance and age-dependent penetrance, caused primarily by mutations of sarcomere genes. Because the clinical variability of HCM is related to its genetic heterogeneity, genetic studies may improve the diagnosis and prognostic evaluation in HCM.

Objectives: To analyze the impact of genetic diagnosis on the clinical management of HCM.

Methods: Genetic studies were performed for either research or clinical reasons. Once the disease-causing mutation was identified, the management plan was reevaluated. Family members were invited to receive genetic counseling and encouraged to be tested for the mutation.

Results: Ten mutations in sarcomere protein genes were identified in 9 probands: 2 novel and 8 previously described. Advanced heart failure or sudden death in a young person prompted the genetic study in 8 of the 9 families. Of 98 relatives available for genotyping, only 53 (54%) agreed to be tested. The compliance was higher in families with sudden death and lower in what appeared to be sporadic HCM or elderly-onset disease. Among the healthy we identified 9 carriers and 19 non-carriers. In 6 individuals the test result resolved an uncertainty about "possible HCM." In several cases the genetic result was also used for family planning and played a role in decisions on cardioverter-defibrillator implantation.

Conclusions: Recurrence of a same mutation in different families created an opportunity to apply the information from the literature for risk stratification of individual patients. We suggest that the clinical context determine the indication for genetic testing and interpretation of the results.

Background: Contemporary therapies improve prognosis and may restore left ventricular (LV) size and function.

Objectives: To examine the prevalence, clinical features and therapies associated with reverse remodeling (RR) in dilated cardiomyopathy (DCM).

Methods: The study group comprised 188 DCM patients who had undergone two echo examinations at least 6 months apart. RR was defined as increased LV ejection fraction (LVEF) by ≥ 10% concomitant with ≥ 10% decreased LV end-diastolic dimension.

Results: RR occurred in 50 patients (26%) and was associated with significantly reduced end-systolic dimension, left atrial size, grade of mitral regurgitation, and pulmonary artery pressure. NYHA class improved in the RR group. RR was less common in familial DCM and a long-standing disease and was more prevalent in patients with prior exposure to chemotherapy. Recent-onset disease, lower initial LVEF and normal electrocardiogram were identified as independent predictors of RR. Beta-blocker dose was related to improved LVEF but not to RR. Over a mean follow-up of 23 months, 16 patients (12%) from the 'no-RR' group died or underwent heart transplantation compared to none from the RR group (P < 0.01).

Conclusions: Contemporary therapies led to an an improvement in the condition of a considerable number of DCM patients. A period of close observation while optimizing medical therapy should be considered before deciding on invasive procedures.