Consideration For Heart Transplantation Research Articles

Abstract 167: A Case of Consequential Stroke and Heart Failure in Ebstein's Anomaly

Introduction Ebstein's anomaly (EA) is a rare congenital heart condition, accounting for less than 1% of congenital heart defects. Though uncommon, individuals with EA have a significantly increased risk of stroke, through poorly understood mechanisms. We present a case of a large vessel stroke in a patient with EA, coexisting patent foramen ovale (PFO), and conduction abnormalities, which ultimately required a heart transplant. Materials/Methods N/A Case A 22‐year‐old male with a history of Ebstein's anomaly and Wolff‐Parkinson‐White Syndrome presented with left middle cerebral artery (MCA) syndrome and atrial fibrillation with rapid ventricular response (AFib‐RVR). CT angiography confirmed a left MCA M1 occlusion. He received intravenous tissue plasminogen activator (tPA) followed by emergent mechanical thrombectomy, achieving modified treatment in cerebral ischemia (mTICI) grade 2B (67‐89%). MRI showed a left MCA stroke with hemorrhagic conversion, along with distal embolic strokes in the left MCA M3/M4 segments. Cardioembolic workup revealed a PFO, EA with extreme apical displacement of the tricuspid valve, and severe tricuspid regurgitation. The patient was discharged on full‐dose aspirin with plans for anticoagulation after three weeks. Despite ablation of his AFib during hospitalization, he returned with severe right heart failure, necessitating heart transplant. He currently has no neurological deficits and is followed at our institution. Discussion Ebstein's anomaly (EA) is a rare congenital heart condition occurring in 1 to 5 per 100,000 births. Characterized by tricuspid valve abnormalities, EA often presents with tricuspid regurgitation, atrialization of the right ventricle, and reduced right ventricular ejection fraction. Up to 50% of patients have associated cardiac defects, such as PFO or secundum atrial septal defect (ASD), leading to an increased risk of paradoxical embolic stroke. The risk of stroke in EA increases with age, with an incidence of 1.4% at 10 years, 15.9% at 50 years, and 23.5% at 70 years. This risk is further compounded by comorbid arrhythmias, such as AFib (20%) and accessory pathways, including Wolff‐Parkinson‐White Syndrome (10‐20%). This case highlights the importance of early identification and comprehensive management of cardiac risk factors in EA, including consideration for heart transplantation, to prevent stroke and other complications.

Integrating risks and benefits: pretransplant assessment and patient selection for heart transplantation in adult congenital heart disease.

The number of adult congenital heart disease (ACHD) patients presenting for consideration of heart transplantation continues to grow. Comprehensive pretransplant assessment and thoughtful patient selection are of critical importance to mitigate perioperative and posttransplant morbidity and mortality in this population. There is increasing evidence that patient outcomes after the onset of heart failure in the ACHD population are poor while overall transplant outcomes for ACHD patients have improved over time. Delineation of factors associated with better versus worse posttransplant outcomes is an area of ongoing research. Several studies have found that delayed patient referral, anatomic complexity and the presence of noncardiac organ dysfunction may increase peri-transplant and posttransplant risk. Pretransplant assessment and patient selection in ACHD patients should focus on mitigating perioperative and early posttransplant risk. Anatomic complexity, noncardiac organ dysfunction, and referral timing after the onset of heart failure can contribute to poor posttransplant outcomes and should inform patient selection.

Heart Transplantation in Children With Down Syndrome.

BackgroundChildren with Down syndrome (DS) have a high risk of cardiac disease that may prompt consideration for heart transplantation (HTx). However, transplantation in patients with DS is rarely reported. This project aimed to collect and describe waitlist and post– HTx outcomes in children with DS.Methods and ResultsThis is a retrospective case series of children with DS listed for HTx. Pediatric HTx centers were identified by their participation in 2 international registries with centers reporting HTx in a patient with DS providing detailed demographic, medical, surgical, and posttransplant outcome data for analysis. A total of 26 patients with DS were listed for HTx from 1992 to 2020 (median age, 8.5 years; 46% male). High‐risk or failed repair of congenital heart disease was the most common indication for transplant (N=18, 69%). A total of 23 (88%) patients survived to transplant. All transplanted patients survived to hospital discharge with a median posttransplant length of stay of 22 days. At a median posttransplant follow‐up of 2.8 years, 20 (87%) patients were alive, 2 (9%) developed posttransplant lymphoproliferative disorder, and 8 (35%) were hospitalized for infection within the first year. Waitlist and posttransplant outcomes were similar in patients with and without DS (P=non‐significant for all).ConclusionsWaitlist and post‐HTx outcomes in children with DS selected for transplant listing are comparable to pediatric HTx recipients overall. Given acceptable outcomes, the presence of DS alone should not be considered an absolute contraindication to HTx.

Clinical features of Neonatal Cardiomyopathy

Background: Neonatal cardiomyopathy is a rare disease that ranges from being asymptomatic to abruptly lethal and is not well characterized [1]. We investigated the clinical features of five neonates with cardiomyopathy in our hospital to determine key clinical characteristics. Methods: We retrospectively reviewed the records of five newborns who were diagnosed with cardiomyopathy between January 2000 and December 2018. The primary evaluation included reasons for diagnosis, underlying diseases, therapy, and turning point. Results: Patients with hypertrophic cardiomyopathy (HCM) or left ventricular noncompaction (LVNC) were diagnosed on the basis of cardiac murmur, while the patient with dilated cardiomyopathy (DCM) was diagnosed on the basis of sucking failure. Underlying diseases included Noonan syndrome and LEOPARD syndrome. All patients had received β-blockers, and those with DCM and LVNC were also administered diuretics and angiotensin-converting enzyme inhibitors. The two patients with HCM underwent follow-up as out-patients. One patient with HCM died at 3 years old because of arrhythmia. The patient with DCM died due to heart failure 38 days after birth. The patient with LVNC exhibited severe heart failure after birth, requiring follow-up while considering heart transplantation. Conclusion: Noonan syndrome and LEOPARD syndrome, which is RAS/MAPK-related diseases, should be considered in patients diagnosed HCM. Because heart failure progresses rapidly in patients with neonatal DCM and those with LVNC, planned therapy should include consideration of heart transplantation.

Heart transplantation in survivors of childhood cancer.

There are approximately 450,000 survivors of childhood cancer due, in large part, to successes of therapeutic regimens. With this success comes an increase in the number of patients developing cardiotoxicity as a result of cancer therapies. In certain cases, this includes heart failure recalcitrant to medical therapy, and consideration for heart transplantation may be necessary. However, this group of patients has unique comorbidities that may affect outcomes. Despite this, available data show that complications and overall survival are similar for patients transplanted for anthracycline-induced cardiomyopathy compared to those with other cardiomyopathies, demonstrating that this is a viable treatment option for this population. As other cancer therapies become more common, new cardiovascular toxicities are recognized. Whether heart transplantation will be appropriate for all patients with cancer-therapy related cardiotoxicity (CTRC) will require demonstration of similarly good outcomes to ensure proper allocation of organs.

Characteristics and Outcomes of Heart Transplantation in DiGeorge Syndrome.

DiGeorge syndrome (DGS) is commonly associated with both congenital heart disease (CHD) and immunologic abnormalities. While CHD may prompt consideration for heart transplantation (HTx), little is known about HTx management or outcomes in this group. The aim of this study was to describe the spectrum of patients with DGS who undergo HTx and report post-HTx outcomes. All pediatric HTx recipients (2002-2016) with DGS were identified using ICD codes from a linked billing and clinical registry database. Patient characteristics and outcomes were described and compared to non-DGS HTx recipients with CHD. Kaplan-Meier methods were used to assess overall survival, freedom from infection, and freedom from rejection. A total of 17 patients with DGS who underwent HTx at 12 different centers were included. Median age at HTx was 5years (IQR 0-13years). Steroids were used for induction in all patients in addition to thymoglobulin in 13/17 (76%) and IL2R antagonists in 3/17 (18%). Maintenance immunosuppression was a combination of tacrolimus or cyclosporine and mycophenolate or azathioprine in 16/17 (94%). Half received steroids at the time of discharge. There were six deaths (35%). The median post-HTx survival was 5.4years with no difference in freedom from rejection, infection, or overall survival between patients with and without DGS. Patients with DGS undergoing HTx received standard immunosuppression. We found no difference in freedom from infection, rejection, or overall post-HTx survival compared to non-DGS patients, although the small size of our study resulted in limited statistical power. Given the potential for favorable outcomes, patients with DGS may be considered for HTx in the appropriate clinical setting.

Diagnosing and grading heart failure with tomographic perfusion lung scintigraphy: validation with right heart catheterization.

AimsPulmonary congestion remains a diagnostic challenge in patients with heart failure (HF). The recommended method, chest X‐ray (CXR), lacks in accuracy, whereas quantitative tomographic lung scintigraphy [ventilation/perfusion single‐photon emission computed tomography (V/P SPECT)] has shown promising results but needs independent validation. The aim of this study is to evaluate V/P SPECT as a non‐invasive method to assess and quantify pulmonary congestion in HF patients, using right heart catheterization as reference method. The secondary objective was to investigate the performance of V/P SPECT in the clinical setting compared with CXR.Methods and resultsForty‐six consecutive patients with HF that were under consideration for heart transplantation were studied prospectively. All participants were examined with V/P SPECT, CXR, and right heart catheterization. Pulmonary artery wedge pressure served as reference method. Quantitative perfusion gradients were derived from V/P SPECT images. Ventilation/perfusion single‐photon emission computed tomography images were also assessed both by expert readers and clinical nuclear medicine physicians. Expert readers correctly identified 87% of all patients with an elevated pulmonary artery wedge pressure > 15 mmHg. The average sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for V/P SPECT assessed by the expert readers were 87%, 72%, 85%, and 75%, respectively. In the clinical nuclear medicine setting, V/P SPECT had 87% sensitivity, 63% specificity, 81% PPV, and 71% NPV. Clinically, V/P SPECT outperformed CXR, which had 27% sensitivity, 75% specificity, 67% PPV, and 35% NPV.ConclusionsVentilation/perfusion single‐photon emission computed tomography can be used as a non‐invasive method to diagnose and quantify pulmonary congestion in patients with HF and is more accurate than CXR in diagnosing pulmonary congestion in the clinical setting.

The Peripartum Anesthesiologist

The association between pregnancy and cardiomyopathy has been evident since 1870. Moreover, the incidence of peripartum cardiomyopathy (PPCM) is thought to range from 1 in 2,400 to 1 in 15,000 pregnancies; however, a more recent review suggests an incidence of one in 3,000 to 4,000 pregnancies in western countries. Peripartum cardiomyopathy is more prevalent in older multiparous patients of African descent who have multiple gestations, chronic hypertension or preeclampsia, and have received prolonged tocolytic therapy. There are four principal diagnostic features of PPCM: the development of heart failure in the last month of pregnancy or within five months of delivery; absence of an identifiable cause; absence of underlying heart disease prior to the last month of pregnancy; and evidence of left ventricular systolic dysfunction. Recently, echocardiographic criteria were established, including an ejection fraction 45% and an end-diastolic dimension [ 2.72 cm m. Basic principal treatment of PPCM includes a reduction of both preload and afterload along with the administration of inotropic therapy. Severe cases may require mechanical support and consideration for heart transplantation. Delivery of the fetus is usually indicated when the cardiac failure is intractable. In this month’s edition of the Journal, Ituk et al. report on the peripartum anesthetic management and outcomes of 25 women with dilated cardiomyopathy four of whom were designated as having PPCM. With an average age of 32 and a history of hypertension and diabetes, these patients represent a higher risk group than the overall obstetrical population, which is in keeping with previous reports of PPCM risk factors. This challenging group of patients was optimally managed by a multidisciplinary team with a distinct knowledge of peripartum care a team that followed their patients’ clinical progress at regular multidisciplinary case conferences. Fetal delivery in PPCM is dictated by the obstetric indications and occurs in consultation with the anesthesia team. Vaginal delivery offers minimal blood loss, hemodynamic stability, and avoidance of additional Cesarean delivery-related surgical stresses with an overall reduced chance of postoperative complications. Regional anesthesia is advantageous for reducing preload and afterload and minimizing the fluctuations in cardiac output associated with labour. Cesarean delivery is best reserved for indications such as breech presentation, fetal distress, or failure to progress. Prognostic information of PPCM is limited and often confounded by the inclusion of patients with heart failure of differing etiologies. The reported mortality ranges from 18-50% and it increases as a function of age, ejection fraction 25%, multiparity, African American ethnicity, and delayed diagnosis. The recurrence rate of 50-100% is influenced by the severity of PPCM during the index pregnancy and by left ventricular systolic function at the beginning of pregnancy. Echocardiography may be helpful in delineating future risk in patients considering future pregnancies. Long-term prognosis is related to recovery of left ventricular function with 80% of women recovering partially or completely, and the remaining 20% either dying or undergo cardiac transplantation. In our view, the obstetric anesthesiologist functions as a vital member of the interdisciplinary team caring for women with complicated obstetric issues and, as such, A. Munro, MD R. B. George, MD (&) Department of Women’s & Obstetric Anesthesia, IWK Health Centre, Dalhousie University, 5850/5980 University Avenue, P.O. Box 9700, Halifax, NS B3K 6R8, Canada e-mail: rbgeorge@dal.ca

(139) - Outcomes in Adult Congenital Heart Failure Patients Undergoing Heart Transplantation: A Systematic Review and Meta-Analysis

Advances in the treatment of congenital heart disease (CHD) have led to a growing population of adult CHD patients, many of whom will develop late onset complications prompting consideration for heart transplantation. Studies comparing mortality and morbidity in CHD and non-CHD transplant recipients are limited in number and scope. Our aim was to conduct a systematic review and meta-analysis comparing post-transplant outcomes in adult CHD versus non-CHD patients.

The kidney-heart connection during electrical storm: from bedside back to bench.

One of the most challenging clinical pre-sentations for cardiologists is the ‘electrical storm’ of incessant ventricular tachycardia (VT). This often occurs in patients with previous myocardial infarctions or non-ischaemic cardiomyopathies, who are already on the maximally tolerated doses of cardiac medications (including β-blockers). Such patients may have already been implanted with a cardiac defibrillator (ICD) and are therefore likely to receive multiple therapies from their device. The cardiologist corrects plasma electrolytes, administers additional antiarrhythmic drugs (such as amiodarone and lidocaine) and reprograms the ICD in an attempt to suppress the storm, but ultimately many patients will require general anaesthesia and emergency ablation of their VT. This is a perilous ‘last-ditch’ procedure with limited long-term success. It may, however, stabilize the patient long enough for consideration of heart transplantation. Case reports and small case series have highlighted novel procedures aimed at reducing cardiac sympathetic drive as possible adjunct therapies in such patients. This builds on over 50 years of intense research linking cardiac sympathetic drive to arrhythmogenicity (Shen & Zipes, 2014). Even sedation or general anaesthesia in itself can be antiarrhythmic, because sympathetic hyperactivity during the electrical storm can be reinforced by chest pain from VT and ICD shocks received whilst still conscious. Recent publications have advocated stellatectomy (Schwartz, 2014), thoracic epidural anaesthesia and renal sympathetic nerve denervation (Bradfield et al. 2014) as potential approaches. In this context, the paper by Huang et al. (2014) in this issue of Experimental Physiology is of particular interest. In anaesthetized dogs following renal sympathetic denervation or a sham procedure, Huang et al. (2014) performed catheter-based measurements of ventricular refractory period and action potential duration (APD) restitution at multiple epicardial sites. This is the first publication to my knowledge to characterize ventricular electrophysiological changes in response to renal denervation. Interestingly, the flattening in the slope of the APD restitution curve, prolongation of the refractory period and reduced ability to induce APD alternans mirrors previous reports of the action of selective cardiac sympathetic stimulation on these parameters. Moreover, renal denervation reduced the incidence of ventricular arrhythmias in the hour following ligation of the left anterior descending coronary artery. The paper by Huang et al. (2014) also follows the recently published failure of renal sympathetic nerve denervation to produce a significant reduction in blood pressure in patients with resistant hypertension when compared with a sham procedure in the Symplicity HTN-3 trial (Bhatt et al. 2014). There are a number of interesting methodological differences in the approach to renal denervation taken by Huang et al. (2014) compared with that used in Symplicity HTN-3. In human subjects, renal denervation is usually undertaken via an endovascular approach using a radiofrequency ablation catheter introduced via the femoral artery. Discrete lesions are made circumferentially in a spiral pattern along both renal arteries, but unfortunately there is no way of determining that successful denervation has been achieved during the procedure. Huang et al. (2014) performed epivascular ablation via small bilateral retroperitoneal flank incisions. Furthermore, they demonstrated as evidence of successful denervation that high-frequency electrical stimulation of the adventitia no longer caused hypertension following ablation. This is a useful and novel approach, and a similar clinical end-point of success in patients is clearly needed. The fact that afferent and efferent nerves innervate the kidney through a plexus surrounding the renal arteries has long been appreciated. Renal afferent nerves are able to stimulate the hypothalamus in response to renal hypoxia and ischaemia and thereby increase global sympathetic activity. Likewise, sympathetic efferent nerves cause renin release, sodium and water retention, and through angiotensin II, reinforce sympathetic drive both centrally and by increasing catecholamine release peripherally (Singh et al. 2014). Renal denervation as a method to reduce cardiac sympathetic drive therefore appears logical, although many questions regarding this approach remain unanswered. Can a reduction in cardiac sympathetic activity following renal denervation be measured directly? Do the electrophysiological changes in APD and refractory period observed in the normal canine heart also occur in ischaemic and non-ischaemic cardiomyopathy? How long do these electrophysiological changes persist for and what are the underlying mechanisms by which they occur? In the clinical case reports of renal denervation for electrical storm, patients were already maximally β-blocked. Is the antiarrhythmic action of this procedure therefore independent of β-receptors, and if so, which other receptors or sympathetic cotransmitters play a role? This promises to be an active area of research, which may help us to identify new antiarrhythmic targets as well as refine our approach to renal denervation in patients. Readers are invited to give their opinion on this article. To submit a comment, go to: http://ep.physoc.org/letters/submit/expphysiol;99/11/1451 None declared. N.H. is a British Heart Foundation CRE Intermediate Fellow at the University of Oxford.

Cost-effectiveness of heart failure therapies

Heart failure (HF) is a leading cause of morbidity and mortality worldwide. Management of HF involves accurate diagnosis and implementation of evidence-based treatment strategies. Costs related to the care of patients with HF have increased substantially over the past 2 decades, partly owing to new medications and diagnostic tests, increased rates of hospitalization, implantation of costly novel devices and, as the disease progresses, consideration for heart transplantation, mechanical circulatory support, and end-of-life care. Not surprisingly, HF places a huge burden on health-care systems, and widespread implementation of all potentially beneficial therapies for HF could prove unrealistic for many, if not all, nations. Cost-effectiveness analyses can help to quantify the relationship between clinical outcomes and the economic implications of available therapies. This Review is a critical overview of cost-effectiveness studies on key areas of HF management, involving pharmacological and nonpharmacological clinical therapies, including device-based and surgical therapeutic strategies.

Recommendations for the Use of Mechanical Circulatory Support: Device Strategies and Patient Selection

The era of mechanical circulatory support (MCS) began in 1953 with the development of cardiopulmonary bypass to facilitate open heart surgery.1 In 1964, the National Heart Institute (now the National Heart, Lung, and Blood Institute) funded the Artificial Heart Program and became actively involved in MCS development. This led to requests for Proposals issued in 1977 and 1980, which laid the foundation for the development of implantable MCS for long-term use, including devices capable of hospital discharge, in the 1990s. Although heart transplantation is now commonplace at many hospitals, the inadequate supply of donor hearts and patient contraindications to transplantation continue to severely restrict its application. As the demand for long-term replacement of diseased hearts increases, there is a clear need for innovative, safe, and durable MCS to treat the growing population of patients with advanced heart failure (HF). Many exciting changes in the field of MCS have occurred in the past few years, including the development of smaller portable pumps and the concept of destination therapy (DT), or permanent pump placement as an alternative to heart transplantation. Currently, there are no published guidelines for the use of MCS. Thus, it is our intent that this statement will provide the contemporary cardiologist and other HF providers with an understanding of general considerations when determining the appropriateness of MCS. There is little hope that complete consensus will ever be reached on the definition of advanced HF, but most physicians caring for such patients on a regular basis readily identify the characteristics of these patients. Advanced HF patients are those with clinically significant circulatory compromise who require special care, including consideration for heart transplantation, continuous intravenous inotropic therapy, MCS, or hospice.2,3 Typically, such patients have symptoms at rest or with minimal exertion and cannot perform many activities of …

Who needs a transplant and when?

Heart transplantation remains the treatment of choice for patients with advanced heart failure. We review the current definition of optimal therapy, prediction of prognosis and revisit contraindications for transplant. Clinical trials of eplerenone and ivabradine were associated with improved prognosis, whereas others (nesiritide) were disappointing. Advances in cardiac resynchronization therapy and ventricular assist devices (VAD) have resulted in an expansion of their indications. Advances in catheter ablation for ventricular tachycardia have made this an uncommon indication for heart transplantation. Surgical ventricular reconstruction and mitral valve intervention have not resulted in survival benefit. Bypass surgery was associated with a lower mortality from cardiovascular causes. Prognostic risk scores have been developed in heart failure patients; however, ongoing refinements are needed. Selected patients with diabetes, HIV and pretransplant malignancy, now have favourable outcomes after heart transplantation. VAD as bridge to candidacy is an option in heart failure patients with 'fixed' pulmonary hypertension. Alternate listing strategies have also been studied to provide high-risk patients with an opportunity for heart transplantation. Heart failure patients should be on current optimal medical and device therapy with a poor prognosis before consideration for heart transplantation. An individualized approach to heart transplantation assessment is recommended.

Die isolierte Noncompaction-Kardiomyopathie unter besonderer Berücksichtigung ihrer rhythmologischen Komplikationen

Isolated noncompaction cardiomyopathy (NCCM) is a rare genetically determined myocardial disease caused by abnormal fetal development of the myocardium resulting in a thin compacted and a thicker noncompacted layer of the affected left ventricular (LV) wall. The genetic basis of NCCM is heterogenous. Diagnosis can be made using echocardiography or magnetic resonance imaging. The diagnostic criteria for NCCM are still under discussion. Afflicted patients may present with various symptoms caused by arrhythmias, heart failure and cardioembolic events. Severely reduced LV function as well as left bundle branch block and atrial fibrillation were shown to be linked to worse outcomes. Treatment in patients with NCCM should be targeted at individual symptoms and clinical findings. Therapy includes pharmacological treatment, and in individual cases ablation or device therapy, as well as consideration for heart transplantation in selected cases. Aside from regular clinical follow-up of patients with NCCM screening of first degree family members with assessment of medical history, physical examination, ECG recording, and echocardiography are recommended.

438 Cardiac Transplantation for Chemotherapy Induced Cardiomyopathy: Demographics and Long Term Follow-Up

Purpose: Chemotherapy-induced cardiomyopathy (CIC) is increasing in prevalence due to increased cancer survival. Late onset severe cardiac functional impairment after cure of cancer allows consideration for heart transplantation (HT). Methods and Materials: A retrospective analysis of 980 patients from our heart failure clinic was performed. Patient demographics were collated and patients with CIC were evaluated in relation to their subsequent need for HT and long term follow up. Results: 16/980 (1.6%) patients were diagnosed with CIC and HT required in 6 (38%). Mean age at presentation with CIC was 32.3 years (range 8 – 63). Mean age of CIC presentation for HT recipients was 22.3 (range 8 – 25). Overall cancer diagnosis: Ewing’s sarcoma (5), Osteosarcoma (2), lymphoma (5), Wilm’s tumour (2), breast cancer (1) and 1 patient lymphoma followed 8 years later by sarcoma with subsequent cardiomyopathy. All CIC patients had been treated with Anthracyclines. Cyclophophamide was used in 3 and Cisplatin in 2. Rate of HT by diagnosis: Ewing’ Sarcoma (60%), osteosarcoma (50%) and lymphoma (20%), no other malignancy diagnoses were transplanted. 44% of overall CIC but no HT recipient received chest radiotherapy. Mean interval cancer treatment to cardiomyopathy was 12.8 years. Mean time CIC diagnosis to transplant 6 years (range 0 – 11). Overall mortality was 19%. One death occurred 9 months post HT from rejection. At a mean of 6 years post HT (range 0 – 10) there have been no cases of recurrent malignancy. Conclusions: Chemotherapy-induced cardiomyopathy typically presents late and predominantly affects young patients post lymphoma or sarcoma treated with anthracyclines. The rate of need for HT in CIC is high although this may be reflective of referral bias. Patients who subsequently undergo HT are younger but with judicious selection have a low risk of recurrence.

Hypertrophic Cardiomyopathy in a Neonate Associated with Nemaline Myopathy

Nemaline myopathy is a congenital nonprogressive skeletal muscle disorder with a characteristic rod body formation in the skeletal muscle fibers. Cardiac involvement in nemaline myopathy is rare, although both dilated and hypertrophic cardiomyopathy have been reported. We describe an infant diagnosed with hypertrophic cardiomyopathy and hypotonia on the first day of life. Muscle biopsy confirmed nemaline myopathy at 3 weeks of age. The diagnosis of nemaline myopathy precluded consideration of heart transplantation, thus shifting the focus to comfort care. This is the earliest presentation of hypertrophic cardiomyopathy reported in the literature in the setting of nemaline myopathy. The approach to determining an etiology for hypertrophic cardiomyopathy in an infant is reviewed.

Clinical Outcome and Phenotypic Expression in <emph type="ital">LAMP2</emph> Cardiomyopathy

Mutations in X-linked lysosome-associated membrane protein gene (LAMP2; Danon disease) produce a cardiomyopathy in young patients that clinically mimics severe hypertrophic cardiomyopathy (HCM) due to sarcomere protein mutations. However, the natural history and phenotypic expression of this newly recognized disease is incompletely resolved and its identification may have important clinical implications. To determine the clinical consequences, outcome, and phenotypic expression of LAMP2 cardiomyopathy associated with diagnostic and management strategies. Clinical course and outcome were assessed prospectively in 7 young patients (6 boys) with defined LAMP2 mutations from the time of diagnosis (age 7-17 years; median, 14 years) to October 2008. Phenotypic expression of this disease was assessed both clinically and at autopsy. Progressive heart failure, cardiac death, and transplant. Over a mean (SD) follow-up of 8.6 (2.6) years, and by age 14 to 24 years, the study patients developed left ventricular systolic dysfunction (mean [SD] ejection fraction, 25% [7%]) and cavity enlargement, as well as particularly adverse clinical consequences, including progressive refractory heart failure and death (n = 4), sudden death (n = 1), aborted cardiac arrest (n = 1), or heart transplantation (n = 1). Left ventricular hypertrophy was particularly marked (maximum thickness, 29-65 mm; mean [SD], 44 [15] mm), including 2 patients with massive ventricular septal thickness of 60 mm and 65 mm at ages 23 and 14 years, respectively. In 6 patients, a ventricular pre-excitation pattern at study entry was associated with markedly increased voltages of R-wave or S-wave (15-145 mm; mean [SD], 69 [39] mm), and deeply inverted T-waves. Autopsy findings included a combination of histopathologic features that were consistent with a lysosomal storage disease (ie, clusters of vacuolated myocytes) but also typical of HCM due to sarcomere protein mutations (ie, myocyte disarray, small vessel disease, myocardial scarring). LAMP2 cardiomyopathy is a profound disease process characterized by progressive clinical deterioration leading rapidly to cardiac death in young patients (<25 years). These observations underscore the importance of timely molecular diagnosis for predicting prognosis and early consideration of heart transplantation.

Cardiomyopathy induced by pulmonary vein tachycardia cured by catheter ablation

A 51-year-old male was referred for consideration for heart transplantation because of recently diagnosed congestive heart failure refractory to medical therapy. Previous echocardiography demonstrated a left ventricular ejection fraction of approximately 15% with global hypokinesia. Coronary angiography did not reveal any clinically significant obstructive coronary artery disease and an electrocardiogram documented atrial fibrillation with a rapid ventricular rate of 130 beats/min. Other laboratory tests including thyroid function test were unremarkable. The patient's main complaints were dyspnea on exertion, and orthopnea with minimal palpitations. Physical examination, laboratory testing, electrocardiography, Holter monitoring, chest radiography, transthoracic echocardiography, transesophageal echocardiography, coronary angiogram, and electrophysiologic study with catheter ablation. Cardiomyopathy resulting from pulmonary vein tachycardia. Catheter-based radiofrequency ablation of the focus of pulmonary vein tachycardia.

Prognostic Stratification of Women With Chronic Heart Failure Referred for Heart Transplantation: Relevance of Gender as Compared With Gender-related Characteristics

Few studies are available regarding prognostic stratification of women with severe chronic heart failure (CHF). Although women seem to have a better outcome than men, this may be due to favorable baseline characteristics. We analyzed a cohort of CHF patients referred for heart transplantation (HT) who underwent clinical/laboratory/instrumental evaluation. Women and men were frequency matched for baseline age (53 +/- 14 vs 53 +/- 9 years, p = 0.92), left ventricular ejection fraction (33 +/- 10 vs 31 +/- 8%, p = 0.90) and ischemic etiology (17 vs 22%, p = 0.50). A total of 198 patients were analyzed (109 women matched to 89 men). In addition to matching parameters, prevalence of severe symptoms, diabetes and hypertension were also comparable (p > or = 0.25). After 3 years, cardiovascular death or need for HT (CD/HT) event-free survival was 78 +/- 4% in women and 50 +/- 6% in men (p = 0.005). On multivariate analysis, female gender was associated with a lower risk of CD/HT (relative risk [RR] 0.52; 95% confidence interval [CI] 0.30 to 0.89; p = 0.017), independently of symptoms, blood pressure (BP), left ventricular end-diastolic diameter (LVEDD) and mitral regurgitation (MR). Nevertheless, CD/HT event-free survival at 3 years was 49 +/- 9% for women with New York Heart Association (NYHA) Class III or IV status, who presented with either severe MR, mean BP < or =60 mm Hg or LVEDD > or =35 mm/m2. In advanced CHF, women patients seem to have a better prognosis irrespective of baseline characteristics, supporting the hypothesis that female gender is protective against myocardial injury. However, women with severe symptoms accompanied by either hypotension, severe left ventricular enlargement or MR are at high risk and deserve cautious follow-up and consideration for HT.

Section 10: Surgical Approaches to the Treatment of Heart Failure

Section 10: Surgical Approaches to the Treatment of Heart Failure