Emergence of the natural history of Myhre syndrome: 47 patients evaluated in the Massachusetts General Hospital Myhre Syndrome Clinic (2016-2023).

Myhre syndrome is an increasingly diagnosed ultrarare condition caused by recurrent germline autosomal dominant de novo variants in SMAD4. Detailed multispecialty evaluations performed at the Massachusetts General Hospital (MGH) Myhre Syndrome Clinic (2016-2023) and by collaborating specialists have facilitated deep phenotyping, genotyping and natural history analysis. Of 47 patients (four previously reported), most (81%) patients returned to MGH at least once. For patients followed for at least 5 years, symptom progression was observed in all. 55% were female and 9% were older than 18 years at diagnosis. Pathogenic variants in SMAD4 involved protein residues p.Ile500Val (49%), p.Ile500Thr (11%), p.Ile500Leu (2%), and p.Arg496Cys (38%). Individuals with the SMAD4 variant p.Arg496Cys were less likely to have hearing loss, growth restriction, and aortic hypoplasia than the other variant groups. Those with the p.Ile500Thr variant had moderate/severe aortic hypoplasia in three patients (60%), however, the small number (n = 5) prevented statistical comparison with the other variants. Two deaths reported in this cohort involved complex cardiovascular disease and airway stenosis, respectively. We provide a foundation for ongoing natural history studies and emphasize the need for evidence-based guidelines in anticipation of disease-specific therapies.

Amyloidosis and Considerations for the Hand Surgeon.

Amyloidosis can lead to cardiac, renal, and other multiorgan failure. New treatments have become available that can prolong survival but rely on early diagnosis. Manifestations of amyloidosis in hand surgery include carpal tunnel syndrome, trigger finger, peripheral neuropathy, and spontaneous distal biceps rupture. Often, these can predate systemic amyloidosis, offering hand surgeons an opportunity to diagnose patients with amyloidosis before systemic disease, refer them for treatment, and potentially alter disease course and prolong survival. In this review, we describe the pathophysiology and two most common subtypes of amyloidosis seen by hand surgeons. We provide guidance on biopsy practices and referral for patients with amyloidosis. Lastly, we provide a brief overview of the treatments for amyloidosis and their effect on disease course.

6-Minute walk test predicts prolonged hospitalization in patients undergoing transcatheter mitral valve repair by MitraClip.

BACKGROUND: The 6-minute walk test (6MWT) is a simple functional test that can predict exercise capacity and is widely employed to assess treatment outcomes. Although mortality with transcatheter mitral valve repair (TMVr) using the MitraClip (Abbott Vascular, Menlo Park, CA) is significantly less than for open mitral valve surgery in high-risk patients, identifying which patient will benefit the most from TMVr remains a concern. There are limited prognostic metrics guiding patient selection and, no studies have reported relationship between prolonged hospitalization and 6MWT. This study aimed to determine if the 6MWT can predict prolonged hospitalization in patients undergoing TMVr by MitraClip. METHODS: We retrospectively reviewed 162 patients undergoing 6MWT before TMVr. Patients were divided into three groups according to the 6MWT distance (6MWTD) using the median (6MWTD ≥219 m, 6MWTD <219 m, and Unable to Walk). Multivariate logistic regression model was applied to select the demographic characteristics that were associated with the prolonged hospitalization defined as total length of stay ≥4 days in the study. RESULTS: We found that 6MWT (odds ratio 3.64, 95% confidence interval 2.03-6.52, P < 0.001) was independently associated with prolonged hospitalization after adjustment in multivariate analysis. Area under the curve of 6MWT for predicting prolonged hospitalization was 0.79 (95% confidence interval 0.72-0.85). CONCLUSIONS: Our study demonstrates that 6MWT was independently associated with prolonged hospitalization in patients with TMVr, and has a good discriminatory performance for predicting prolonged hospitalization.

Ventricular assist devices and increased blood product utilization for cardiac transplantation.

BACKGROUND AND AIM OF STUDY: The purpose of this study was to examine whether blood product utilization, one-year cell-mediated rejection rates, and mid-term survival significantly differ for ventricular assist device (VAD patients compared to non-VAD (NVAD) patients following cardiac transplantation. METHODS: From July 2004 to August 2011, 79 patients underwent cardiac transplantation at a single institution. Following exclusion of patients bridged to transplantation with VADs other than the HeartMate II® LVAD (n = 10), patients were stratified by VAD presence at transplantation: VAD patients (n = 35, age: 54.0 [48.0-59.0] years) vs. NVAD patients (n = 34, age: 52.5 [42.8-59.3] years). The primary outcomes of interest were blood product transfusion requirements, one-year cell-mediated rejection rates, and mid-term survival post-transplantation. RESULTS: Preoperative patient characteristics were similar for VAD and NVAD patients. NVAD patients presented with higher median preoperative creatinine levels compared to VAD patients (1.3 [1.1-1.6] vs. 1.1 [0.9-1.4], p = 0.004). VAD patients accrued higher intraoperative transfusion of all blood products (all p ≤ 0.001) compared to NVAD patients. The incidence of clinically significant cell-mediated rejection within the first posttransplant year was higher in VAD compared to NVAD patients (66.7% vs. 33.3%, p = 0.02). During a median follow-up period of 3.2 (2.0, 6.3) years, VAD patients demonstrated an increased postoperative mortality that did not reach statistical significance (20.0% vs. 8.8%, p = 0.20). CONCLUSIONS: During the initial era as a bridge to transplantation, the HeartMate II® LVAD significantly increased blood product utilization and one-year cell-mediated rejection rates for cardiac transplantation. Further study is warranted to optimize anticoagulation strategies and to define causal relationships between these factors for the current era of cardiac transplantation.

Significantly higher rates of gastrointestinal bleeding and thromboembolic events with left ventricular assist devices.

BACKGROUND & AIMS: The risk of gastrointestinal (GI) bleeding (GIB) and thromboembolic events may increase with continuous-flow left ventricular assist devices (CF-LVADs). We aimed to characterize GIB and thromboembolic events that occurred in patients with CF-LVADs and compare them with patients receiving anticoagulation therapy. METHODS: We performed a retrospective analysis of 159 patients who underwent CF-LVAD placement at 2 large academic medical centers (mean age, 55 ± 13 y). We identified and characterized episodes of GIB and thromboembolic events through chart review; data were collected from a time period of 292 ± 281 days. We compared the rates of GIB and thromboembolic events between patients who underwent CF-LVAD placement and a control group of 159 patients (mean age, 64 ± 15 y) who received a cardiac valve replacement and were discharged with anticoagulation therapy. RESULTS: Bleeding events occurred in 29 patients on CF-LVAD support (18%; 45 events total). Sixteen rebleeding events were identified among 10 patients (range, 1-3 rebleeding episodes/patient). There were 34 thrombotic events among 27 patients (17%). The most common source of bleeding was GI angiodysplastic lesions (n = 20; 44%). GIB and thromboembolic events were more common in patients on CF-LVAD support than controls; these included initial GIB (18% vs 4%, P < .001), rebleeding (6% vs none, P = .001), and thromboembolic events (17% vs 8%, P = .01). CONCLUSIONS: Patients with CF-LVADS receiving anticoagulants have a significantly higher risk of GIB and thromboembolic events than patients receiving anticoagulants after cardiac valve replacement surgery. GI angiodysplastic lesions are the most common source of bleeding.

The Cohn felt plug: an effective HeartMate II® reimplantation technique.

We report the first documented case of HeartMate II® left ventricular assist device (LVAD) reimplantation following Cohn Teflon felt plug repair of the initial left ventricular apical cannulation site. This case highlights the current limitations of the predictability of myocardial recovery while describing an effective technique for possible future LVAD reimplantation.

Progression to Transplant Under the New Heart Allocation System: The Society of Thoracic Surgeons Intermacs Database.

BACKGROUND: Under the new heart allocation policy patients needing durable left ventricular assist devices receive lower priority on the transplant list. We sought to identify predictors of successful heart transplant after durable device implant as a means to inform patient care in the current era. METHODS: All patients (N = 25,164) undergoing primary durable left ventricular device implant in The Society of Thoracic Surgeons Intermacs database (2010-2019) were evaluated. Patients identified as bridge to transplant (BTT; n = 5242) or bridge to candidacy (n = 6248) were analyzed with the endpoint of transplant before (n = 10,588) and after (n = 902) the change in the heart allocation system on October 18, 2018. Multivariable hazard modeling was used to assess risk-adjusted time to event associations. RESULTS: Of 11,490 patients, 45.5% progressed to transplant (BTT, 53.0%; bridge to candidacy, 36.6%), most by 14 months after left ventricular assist device implant. Under the new allocation system progression to transplant was significantly lower at 14 months (18.6% vs 34.8%, P < .001). Factors associated with successful BTT before the allocation change included BTT status, white race, and married. Under the new allocation system BTT status (hazard ratio, 1.79; 95% confidence interval, 1.19-2.69; P < .0054) remained a positive predictor, whereas blood type O (hazard ratio, 0.43; 95% confidence interval, 0.28-0.65; P < .0001) remained a negative predictor. CONCLUSIONS: Despite having priority in the previous allocation system, less than half of BTT and bridge to candidacy patients progressed to transplant. Under the current system these numbers are further reduced. Heart teams should consider the implications of longer wait times for a durable left ventricular assist device when determining the optimal bridging strategy.

Sonication of explanted cardiac rhythm management devices for the diagnosis of pocket infections and asymptomatic bacterial colonization.

BACKGROUND: Correct diagnosis of the causative organism is critical for the treatment of pacemaker and defibrillator pocket infections. No gold standard for this exists, although swab and tissue cultures are frequently used. The purpose of this study was to determine the value of ultrasonication of explanted generators in the diagnosis of pocket infections and asymptomatic bacterial colonization. METHODS: Samples were prospectively collected during pacemaker and defibrillator generator extractions for elective replacements, upgrades, or pocket infections. The devices were placed in an ultrasonicator for 5 minutes and the fluid sent for culture, along with swab and tissue cultures. RESULTS: Eighty-two patients with pacemakers (n = 46) or defibrillators (n = 36) underwent generator explantation, 66 of these for elective reasons and 16 for pocket infection. In patients with pocket infection, 15 (94%) received a definitive bacterial diagnosis using a combination of all three-culture modalities. Cultures were positive in 15 sonicated fluid, 13 tissue, and 11 swab samples, with Staphylococcus aureus and other skin flora commonly seen. In asymptomatic patients, 14 (21%) had positive cultures. Cultures were positive in 11 sonicated fluid, eight tissue, and two swab samples. Skin flora was commonly seen, but three of the sonicated fluid cultures grew gram-negative rods. No patients with asymptomatic colonization developed clinical infection during the follow-up period. CONCLUSIONS: Ultrasonication is an inexpensive and simple technique that improves the bacteriologic diagnosis of device pocket infections. It also identifies a significant proportion of patients with asymptomatic colonization, although this is not a marker of future pocket infection.

Use of a left ventricular assist device in hypertrophic cardiomyopathy.

Late stages of hypertrophic cardiomyopathy (HCM) result in medically refractory heart failure. Current treatments include septal myomectomy or alcohol ablation; however, not all patients are eligible for these procedures. We describe the technical aspects of implantation of a HeartMate II left ventricular assist device as a bridge to transplant therapy for a patient with HCM and end-stage heart failure. Pre- and post-operative imaging demonstrates the importance of establishing a functional inflow tract for the device.

Electrocardiographic ST-segment elevation: Takotsubo cardiomyopathy versus ST-segment elevation myocardial infarction--a case series.

Takotsubo cardiomyopathy, or left ventricular apical ballooning syndrome, is a newly described disorder in which patients develop anginal symptoms, often times with acute congestive heart failure, during periods of stress. The electrocardiogram demonstrates ST-segment and/or T-wave abnormalities similar to those findings seen in acute coronary events; on occasion, serum markers can be abnormal. As an extreme, acute pulmonary edema with or without cardiogenic shock can also be encountered. At cardiac catheterization, these patients are found to have abnormal left ventricular function yet normal coronary arteries. We compared 2 populations encountered in the emergency department (ED) population--Takotsubo cardiomyopathy and ST-segment elevation myocardial infarction. In the ED, features of the presentation and management were similar between the 2 groups with the exception of the presence of female sex and abnormal QT interval occurring more often in Takotsubo cardiomyopathy subgroup. These 2 cardiovascular maladies present in very similar fashion in the ED; distinction in the ED may not be possible.

Improving Heart Failure Readmission Costs and Outcomes With a Hospital-to-Home Readmission Intervention Program.

A retrospective cohort study was performed of the Hospital-to-Home (H2H) program, a rapid clinic follow-up program for patients with recent heart failure (HF) admissions at the University of Virginia Health System. There were 6761 hospitalizations among 4685 patients (age 67.5 ± 14.2 years, 43.9% female), and 759 had H2H follow-up. Thirty day mortality after the initial HF hospitalization was lower in H2H patients (1.84% vs 3.13%; P = .049), and this difference remained significant after adjustment in a multivariable logistic regression model (odds ratio = 0.56 [95% CI = 0.31-099]; P = .046). There also was a 24% reduction in readmission days within the first 30 days after the index admission ( P < .0001), and readmission cost savings were found to be greater than the costs of staffing the H2H clinic. In summary, the H2H program is cost-effective, with significant improvements in survival, readmission days, and readmission costs over 30 days.

Acute pulmonary embolism: an update on diagnosis and management.

Pulmonary embolism (PE) is a common problem. Given the significant overlap of symptoms and signs between the presentation of PE and acute coronary syndromes, it becomes clear that cardiologists must be familiar with the diagnosis and treatment of PE. The critical issue is always to consider PE in the diagnosis of chest pain. It is then important to determine the likelihood of the diagnosis. For patients at moderate-to-high risk, helical CT provides a rapid and noninvasive diagnostic tool. Several other imaging studies are also available including ventilation/perfusion (V/Q) scan, magnetic resonance imaging, and pulmonary arteriography. Echocardiography can also provide valuable prognostic information. Several biomarkers including the d-dimers, troponins, and natriuretic peptides may provide additional information. The cornerstone of treatment includes anticoagulation. For patients with massive or submassive PE, thrombolysis and embolectomy should be considered. Finally, both primary and secondary prevention are critical to the long-term health of the patient.

Extent of myocardial viability predicts response to biventricular pacing in ischemic cardiomyopathy.

BACKGROUND: The clinical response to biventricular pacing is unpredictable, especially in patients with ischemic cardiomyopathy. OBJECTIVES: The purpose of this study was to prospectively examine the relationship between the extent of myocardial viability and the response to cardiac resynchronization therapy. METHODS: Twenty-one patients with ischemic left ventricular (LV) dysfunction (left ventricular ejection fraction [LVEF] 21 +/- 5%), New York Heart Association (NYHA) functional class III-IV, and QRS >120 ms received biventricular devices. Myocardial viability was assessed by myocardial contrast echocardiography, and a perfusion score index (PSI) was calculated from summed segmental perfusion scores. LV performance was assessed by echocardiography on the day after implantation and at 6 months. RESULTS: PSI was closely correlated with acute improvement in LVEF (P = .003, r = 0.65), stroke volume (P = .02, r = 0.54), and end-systolic volume (P = .05, r = -0.49). PSI also correlated with early diastolic LV relaxation (E', P < .05, r = 0.50) and global myocardial performance or Tei index (P = .003, r = 0.63). By multiple linear regression analysis, PSI provided incremental predictive value to the degree of dyssynchrony, measured by tissue Doppler imaging, for predicting improvement in LVEF. At 6 months, PSI remained positively correlated with improvement in ventricular performance and with reduction in LV end-diastolic dimension (P = .003, r = -0.68). PSI also influenced the clinical variables of NYHA class, 6-minute walk distance, quality-of-life score, and number of hospitalizations for heart failure. CONCLUSION: In patients with ischemic cardiomyopathy, the extent of myocardial viability predicts acute and long-term improvement in LV performance, exercise tolerance, and reduction in LV end-diastolic dimension with biventricular pacing.

Management of patients with preformed reactive antibodies who are awaiting cardiac transplantation.

Patients with elevated levels of preformed reactive antibodies to HLA antigens have higher rates of organ rejection than do patients without such antibodies. Consequently, before proceeding with transplantation, many medical centers do prospective cross-matching, that is, mix lymphocytes from the organ donor with sera from the prospective organ recipient, to determine whether a higher rejection rate or an immediate episode of rejection will occur. The problem has been compounded by the increased frequency of preformed reactive antibodies in patients with ventricular assist devices who are awaiting cardiac transplantation. Performing a prospective cross-match can be time-consuming and often is impossible because of the unstable condition of the organ donor or travel logistics, leading to increased costs for transplantation and longer waiting times for recipients. A variety of treatments are used in cardiac transplantation programs in attempts to reduce the concentration of preformed reactive antibodies. Each of these treatments has accompanying complications and considerations for the transplant team. Each treatment must also be assessed for therapeutic response. Options for managing patients with preformed antibodies and a case report are presented.

Recurrent candida prosthetic endocarditis over fifteen years managed with medical therapy and four valvular surgeries: a case report and review of literature.

BACKGROUND: Candida prosthetic endocarditis (CPE) is an uncommon disease involving less than 1 % of infective endocarditis patients and associated with high recurrence rate. Immunosuppresion, intravenous drug abuse, cardiac surgery and indwelling foreign bodies are the major risk factors for CPE. There are very few reported cases of CPE where more than one surgery was performed and there has generally been limited follow up on these cases. CASE PRESENTATION: We report a case of a 35 year old woman who had mitral valve annuloplasty complicated by recurrent episodes of CPE leading to multiple mitral valve replacements (MVR). She underwent MVR surgeries a total of four times over an eighteen year period and had good functionality during most of this time while being on antifungal suppressive treatment. This is a unique case in terms of numbers of surgeries performed, the length of the follow up and the involvement of three different Candida species. CONCLUSION: Current guidelines for the treatment of candida endocarditis recommend surgical treatment followed by long term antifungal therapy although the cure rate by all treatments is low. However we feel that based on this one case it is reasonable to consider multiple redo valve replacement surgeries in conjunction with antifungal treatment for selected patients stable enough to tolerate the surgery.

Coronary risk stratification in patients with end-stage lung disease.

BACKGROUND: Significant coronary artery disease (CAD) has been a contraindication for listing patients for lung transplantation. We hypothesize that coronary risk stratification can help identify a sub-set of patients who need additional diagnostic tools and intervention. METHODS: We performed a retrospective review of 72 consecutive patients who underwent lung transplantation at our institution from 1995 to 2000. Further, a review of patients who are currently listed for transplantation yielded 48 patients. We then identified the various risk factors for CAD, the diagnostic tools used, and pre-operative intervention. Risk factors identified included smoking history, diabetes, hypertension, hypercholesterolemia, CAD, congestive heart failure, age >50, and arrhythmias. Based on these risk factors, the patients were then classified into 2 groups: low risk (< or =1 risk factors) and high risk (> or =2 risk factors). We identified the patients in each group who underwent coronary angiography (CA), those with angiographic evidence of CAD, and those who received pre-operative intervention. RESULTS: Of the 72 patients who underwent lung transplantation, 48 were identified as at high risk for CAD. Of these, 5 patients had CAD diagnosed before surgery using CA, and 1 patient received pre-operative intervention. Of the 48 patients currently on the lung transplant list, we identified 28 patients as high risk for CAD, 12 of whom were noted to have CA, and 2 of whom received pre-operative intervention. CONCLUSIONS: Although CAD was once a contraindication for lung transplantation, pre-operative risk stratification allows identification of CAD with CA in a high-risk group. We believe that by using appropriate pre-operative cardiac intervention, patients with severe CAD could successfully undergo lung transplantation.

Technique for minimizing and treating driveline infections.

Left ventricular assist devices (LVADs) are increasingly utilized in the management of advanced heart failure. A transcutaneous driveline is necessary to power the LVAD, and although this technology has improved over the years in terms of smaller size and increased durability, driveline complications continue to develop in up to 20% of all devices implanted. Driveline infections are associated with significant morbidity and mortality. As more patients live longer with ventricular assist devices, minimizing driveline infections is paramount. A systematic, multidisciplinary approach can be used to develop a strategy to prevent, recognize and treat driveline infections. In this paper, we describe our approach to driveline management which has resulted in zero driveline infections between January 2012 and March 2014.