Thomas D. Ryan

Cardiovascular Health of Patients With Cancer and Cancer Survivors : A Roadmap to the Next Level

Many existing and emerging cancer therapies have a significant effect on the cardiovascular health of patients with cancer and cancer survivors. This paper examines current aspects of interdisciplinary cardio-oncology clinical care delivery and education in the United States and outlines how these data provide a platform for future development of the field. We present the results of the nationwide survey on cardio-oncology services, practices, and opinions, conducted among chiefs of cardiology and program directors, which demonstrate ranges of clinical activities and identify significant interest for increased educational opportunities and expert training of cardiovascular physicians in this field. The survey respondents recognized clinical relevance but emphasized lack of national guidelines, lack of funds, and limited awareness and infrastructure as the main challenges for development and growth of cardio-oncology. We discuss potential solutions to unmet needs through interdisciplinary collaboration and the active roles of professional societies and other stakeholders.

Implantation of the HeartMate II and HeartWare left ventricular assist devices in patients with duchenne muscular dystrophy: lessons learned from the first applications.

Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder affecting 1 in 3,500 males, characterized by progressive skeletal muscle weakness and death secondary to cardiac or respiratory failure in the 2nd or 3rd decade. Being a progressive disease, patients are rarely candidates for cardiac transplantation and death from dilated cardiomyopathy (DCM) is common. Implantation of left ventricular assist device (LVAD) offers the potential to alter clinical trajectory by alleviating heart failure symptoms. We report implantation of HeartMate II device in a 29-year-old male patient and HeartWare device in a 23-year-old female patient, each with DMD and end-stage DCM. By improving cardiac output, we were able to achieve resolution of the symptoms of heart failure and improve their quality of life. Preoperative planning and patient selection played a significant role in the postoperative course for these patients. These cases represent the first use for each device in this patient population and the first reported LVAD implantations in patients with DMD in North America.

The evolving role of the total artificial heart in the management of end-stage congenital heart disease and adolescents.

Advances in medical therapies have yielded improvement in morbidity and a decrease in mortality for patients with congenital heart disease, both surgically palliated and uncorrected. An unintended consequence is a cohort of adolescent and adult patients with heart failure who require alternative therapies. One intriguing option is placement of a total artificial heart (TAH) either as a bridge to transplant or as a destination therapy. Of the 1091 Jarvik-7 type TAH (Symbion, CardioWest and SynCardia) placed between 1985 and 2012, only 24 have been performed in patients with congenital heart disease, and a total of 51 were placed in patients younger than 21. At our institution, the SynCardia TAH was implanted in a 19-year-old patient with cardiac allograft failure because of chronic rejection and related multisystem organ failure including need for hemodialysis. Over the next year, she was nutritionally and physically rehabilitated, as were her end organs, allowing her to come off dialysis, achieve normal renal function and eventually be successfully transplanted. Given the continued growth of adolescent and adult congenital heart disease populations with end-stage heart failure, the TAH may offer therapeutic options where previously there were few. In addition, smaller devices such as the SynCardia 50/50 will open the door for applications in smaller children. The Freedom Driver offers the chance for patients to leave the hospital with a TAH, as does the AbioCor, which is a fully implantable TAH option. In this report, we review the history of the TAH and potential applications in adolescent patients and congenital heart disease.

Abnormal Echocardiography 7 Days after Stem Cell Transplantation May Be an Early Indicator of Thrombotic Microangiopathy

Cardiac complications after hematopoietic stem cell transplantation (HSCT) can lead to significant morbidity and mortality. Cardiac evaluation during the first 100 days after HSCT is usually performed only if clinically indicated, and no studies have examined whether routine screening is beneficial in this patient population at high risk for tissue injury. We conducted a single-center prospective clinical study to screen for cardiac complications in pediatric and young adult patients. One hundred consecutive HSCT patients underwent scheduled echocardiographic screening on day +7 after transplantation, independent of their clinical condition. At least 1 abnormality was identified in 30% of cases. Seventeen children had a pericardial effusion, 13 elevated right ventricular pressure, and 3 reduced left ventricular function. Survival was reduced in children with any echocardiographic abnormality at day 7 (67% versus 80% in those with and without, respectively, abnormality, P = .073). Moreover, raised right ventricular pressure at day +7 was significantly associated with transplant-associated thrombotic microangiopathy (TA-TMA; P = .004) and may indicate early vascular injury in the lungs. These data suggest that echocardiography 7 days after HSCT can detect early cardiac complications of HSCT and may identify early vascular injury associated with TA-TMA.

Transplantation in the Highly Sensitized Pediatric Patient

Sensitization against HLA antigens is a growing problem in the field of pediatric cardiac transplantation. Although surgical outcomes for congenital heart disease have improved over the decades, these successes have added to the growing list of sensitized patients who eventually may require transplantation.Cardiac transplantation survival has improved, but morbidity and mortality secondary to HLA antibodies hinder outcome. Aside from acute hemodynamic compromise, there is compelling evidence linking sensitization and AMR with the development of CAV, a major limiting factor affecting long-term graft survival. Clinical advances have improved our understanding of the roles of antibody type, CFAs and non-CFAs, and DSAs and non-DSAs. Therapeutic strategies target both the T- and B-cell lines. Combinations that include plasmapheresis, IVIG, cyclophosphamide, and rituximab have been used in clinical studies with variable success.Two newer agents show promise, targeting both ends of the antibody-mediated spectrum: Bortezomib depletes plasma cell populations, and eculizumab blocks the terminal effects of antibody action, thus preventing myocardial cell dysfunction and death. Despite numerous diagnostic and therapeutic advances, many questions remain about the best approaches.The role of HLA antibodies remains the central target of investigation.

Left ventricular non-compaction cardiomyopathy associated with epidermolysis bullosa simplex with muscular dystrophy and PLEC1 mutation

Plectin mutations have been reported in epidermolysis bullosa simplex with muscular dystrophy. We report the first case of left ventricular non-compaction in an 18-year-old male with epidermolysis bullosa simplex with muscular dystrophy. The patient was diagnosed with epidermolysis bullosa simplex after blistering was noted at birth. Motor function difficulties were first recognized at age 11, however the patient was lost to follow up. He was re-evaluated at age 17 and demonstrated significant ptosis, ophthalmoparesis, and pharyngeal muscle weakness. He had predominant proximal muscle weakness with the inability to raise arms against gravity. He was ambulatory for short distances but lost the ability to rise from the floor at 14 years. He was subsequently diagnosed with epidermyolysis bullosa simplex with muscular dystrophy and a PLEC1 mutation. Screening cardiovascular imaging revealed a diagnosis of isolated left ventricular non-compaction. This case highlights the potential for delayed onset muscular dystrophy in patients with epidermolysis bullosa simplex. Furthermore, this case also underscores the importance of long term, routine cardiac evaluation, including imaging and electrophysiologic evaluation, in patients with epidermolysis bullosa simplex with muscular dystrophy as the cardiac phenotype appears to parallel the variable severity and age of onset that characterize the neuromuscular phenotype.

Left Ventricular Noncompaction Cardiomyopathy and Aortopathy in a Patient With Recessive Dystrophic Epidermolysis Bullosa

Both epidermolysis bullosa (EB) and nonischemic cardiomyopathy (CM) are rare clinical entities. An association between EB and dilated CM (DCM) has been appreciated for at least 25 years, but a common mechanism of disease has not emerged.1 In this report, we present a patient with EB and left ventricular noncompaction (LVNC), a newly recognized type of CM.2 EB is a broad group of diseases characterized by skin fragility and blistering. Dystrophic EB occurs as either a dominantly or recessively inherited (RDEB) type, with scarring and blistering in the sublamina densa layer of the skin. DCM has been described in several patients with RDEB,1 but the relationship between these conditions has not been understood. For this reason, RDEB patients at our EB Center are screened yearly with echocardiograms. Outcomes for patients with RDEB are generally determined by comorbidities, and treatment currently focuses on symptomatic management; however, active areas of research include gene, protein, and stem cell therapies. There …

Cardiotoxicity and cardiomyopathy in children and young adult survivors of hematopoietic stem cell transplant

Cardiomyopathy is common in long‐term survivors of pediatric hematopoietic stem cell transplant (HSCT). Events occurring before and after HSCT when combined with specific insults during HSCT likely contribute to long‐term risk. Strategies for detecting subclinical cardiomyopathy prior to patients developing overt heart failure are under investigation. Changes in HSCT preparative regimens and cardioprotective medications administered during chemotherapy may alter the risk for cardiomyopathy. Interventions in long‐term survivors such as lifestyle modification and cardioactive medications are of increasing importance. Herein we review the causes of cardiac injury, discuss strategies for detection of cardiomyopathy, and evaluate therapeutic options for long‐term HSCT survivors.

Abnormal circumferential strain measured by echocardiography is present in patients with Shwachman–Diamond syndrome despite normal shortening fraction

Shwachman–Diamond Syndrome (SDS) is an autosomal recessive disorder characterized by bone marrow failure and exocrine pancreatic dysfunction. Heart failure has been described in patients with SDS. Circumferential strain (εcc) is a measure of cardiac performance that may identify dysfunction when standard measures are normal.

Pericardial effusion requiring surgical intervention after stem cell transplantation: a case series.

Pericardial effusion requiring surgical intervention after stem cell transplantation: a case series