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.

Comparative Analysis of Established Risk Scores and Novel Hemodynamic Metrics in Predicting Right Ventricular Failure in Left Ventricular Assist Device Patients.

BACKGROUND: Right ventricular failure (RVF) portends poor outcomes after left ventricular assist device (LVAD) implantation. Although numerous RVF predictive models have been developed, there are few independent comparative analyses of these risk models. METHODS AND RESULTS: RVF was defined as use of inotropes for >14 days, inhaled pulmonary vasodilators for >48 hours or unplanned right ventricular mechanical support postoperatively during the index hospitalization. Risk models were evaluated for the primary outcome of RVF by means of logistic regression and receiver operating characteristic curves. Among 93 LVAD patients with complete data from 2011 to 2016, the Michigan RVF score (C = 0.74 [95% CI 0.61-0.87]; P = .0004) was the only risk model to demonstrate significant discrimination for RVF, compared with newer risk scores (Utah, Pitt, EuroMACS). Among individual hemodynamic/echocardiographic metrics, preoperative right ventricular dysfunction (C = 0.72 [95% CI 0.58-0.85]; P = .0022) also demonstrated significant discrimination of RVF. The Michigan RVF score was also the best predictor of in-hospital mortality (C = 0.67 [95% CI 0.52-0.83]; P = .0319) and 3-year survival (Kaplan-Meier log-rank 0.0135). CONCLUSIONS: In external validation analysis, the more established Michigan RVF score-which emphasizes preoperative hemodynamic instability and target end-organ dysfunction-performed best, albeit modestly, in predicting RVF and demonstrated association with in-hospital and long-term mortality.

Clinical Impact of Changes in Hemodynamic Indices of Contractile Function During Treatment of Acute Decompensated Heart Failure.

BACKGROUND: The objective of this work was to determine the impact of improving right ventricular versus left ventricular stroke work indexes (RVSWI vs LVSWI) during therapy for acute decompensated heart failure (ADHF). METHODS AND RESULTS: Cox proportional hazards regression and logistic regression were used to analyze key factors associated with outcomes in 175 patients (mean age 56.7 ± 13.6 years, 29.1% female) with hemodynamic data from the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness trial. In this cohort, 28.6% and 69.7%, respectively, experienced the outcomes of death, transplantation, or ventricular assist device implantatation (DVADTX) and DVADTX or HF rehospitalization (DVADTXHF) during 6 months of follow-up. Increasing RVSWI (ΔRVSWI) from baseline to discharge was associated with a decrease in DVADTXHF (hazard ratio [HR] 0.923, 95% confidence interval [CI] 0.871-0.979) per 0.1 mm Hg⋅L⋅m-2 increase); however, increasing LVSWI (ΔLVSWI) had only a nonsignificant association with decreased DVADTXHF (P = .11) In a multivariable model, patients with ΔRVSWI ≤1.07 mm Hg⋅L⋅m-2 and ΔLVSWI ≤4.57 mm Hg⋅L⋅m-2 had a >2-fold risk of DVADTXHF (HR 2.05, 95% CI 1.23-3.41; P = .006). CONCLUSION: Compared with left ventricular stroke work, increasing right ventricular stroke work during treatment of ADHF was associated with better outcomes. The results promise to inform optimal hemodynamic targets for ADHF.

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 device in the emergency department: Evaluation and management considerations.

Ventricular assist devices (VAD) are being used at increasing rates in patients with severe, end-stage heart failure. Specific indications include VAD placement as a bridge to cardiac function recovery, a bridge to cardiac transplantation, or destination therapy (long-term support for patients ineligible for transplant). The assessment and management of the VAD patient is rather complex, requiring a basic knowledge of device structure and function. This article reviews the basic structure and function, discusses the approach to the VAD patient in the ED, and reviews the more common presentations and complications encountered in these technology-complex patients who are critically ill at baseline.

Decreased Pulmonary Arterial Proportional Pulse Pressure After Pulmonary Artery Catheter Optimization for Advanced Heart Failure Is Associated With Adverse Clinical Outcomes.

BACKGROUND: This study evaluated the novel index pulmonary arterial proportional pulse pressure (PAPP) in the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) trial. METHODS AND RESULTS: Multivariable Cox proportional hazards and logistical regression were used to model 6-month death; death, transplantation, or left ventricular assist device (DTLVAD); and DTLVAD or heart failure rehospitalization (DTLVADHF) with respect to PAPP. Among 175 patients with final hemodynamic data, 15.5% and 33.9%, respectively, died in optimal PAPP (PAPP >0.50) and nonoptimal PAPP (PAPP ≤0.50) groups (P = .008), and PAPP was independently associated with death, DTLVAD, and DTLVADHF (P < .01 for all outcomes). The hypothesized logistic regression model with pulmonary capillary wedge pressure, creatinine, and nonoptimal PAPP had an area under the curve of 0.818 (P < .0001) for death. Furthermore, PAPP as a continuous variable was the most powerful predictor of DTLVADHF (hazard ratio 0.793 per 0.1 increase in PAPP [95% confidence interval 0.659-0.955], chi square 8.80; P = .01) in the Cox model, with no other clinical, laboratory, or hemodynamic parameters significant after adjustment for PAPP. CONCLUSIONS: PAPP, a novel parameter for right-sided proportional pulse pressure, is an independent and powerful predictor of adverse clinical outcomes in advanced HF. Increased PAPP promises to be a useful therapeutic target in patients with pulmonary arterial pressure assessment.

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.

Echocardiographic derived pulmonary artery wedge pressure is associated with mortality, heart hospitalizations, and functional capacity in chronic systolic heart failure: insights from the HF-ACTION trial.

BACKGROUND: Heart Failure (HF) is associated with increased morbidity and mortality. Identification of patients at risk for adverse events could lead to improved outcomes. Few studies address the association of echocardiographic-derived PAWP with exercise capacity, readmissions, and mortality in HF. METHODS: HF-ACTION enrolled 2331 outpatients with HF with reduced ejection fraction (HFrEF) who were randomized to aerobic exercise training versus usual care. All patients underwent baseline echocardiography. Echocardiographic-derived PAWP (ePAWP) was assessed using the Nagueh formula. We evaluated the relationship between ePAWP to clinical outcomes. RESULTS: Among the 2331 patients in the HF-ACTION trial, 2125 patients consented and completed follow-up with available data. 807 of these patients had complete echocardiographic data that allowed the calculation of ePAWP. Of this cohort, mean age (SD) was 58 years (12.7), and 255 (31.6%) were female. The median ePAWP was 14.06 mmHg. ePAWP was significantly associated with cardiovascular death or HF hospitalization (Hazard ratio [HR] 1.02, coefficient 0.016, CI 1.002-1.030, p = 0.022) and all-cause death or HF hospitalization (HR 1.01, coefficient 0.010, CI 1.001-1.020, p = 0.04). Increased ePAWP was also associated with decreased exercise capacity leading to lower peak VO2 (p = < 0.001), high Ve/VCO2 slope (p = < 0.001), lower exercise duration (p = < 0.001), oxygen uptake efficiency (p = < 0.001), and shorter 6-MWT distance (p = < 0.001). CONCLUSIONS: Among HFrEF patients, echocardiographic-derived PAWP was associated with increased mortality, reduced functional capacity and heart failure hospitalization. ePAWP may be a viable noninvasive marker to risk stratify HFrEF patients.

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.

Diastolic pulmonary gradient predicts outcomes in group 1 pulmonary hypertension (analysis of the NIH primary pulmonary hypertension registry).

BACKGROUND: Diastolic pulmonary gradient (DPG), calculated as the difference between pulmonary artery diastolic pressure and mean pulmonary capillary wedge pressure ≥ 7 mmHg is associated with pulmonary vascular disease and portends poor prognosis in heart failure (HF). The prognostic relevance of DPG in group 1 pulmonary hypertension (PH) is uncertain. METHODS: Using the Pulmonary Hypertension Connection (PHC) risk equation for 225 patients in the NIH-PPH, the 5-year probability of death was calculated, which was then compared with DPG using a Cox proportional hazards model. Kaplan-Meier survival curves were determined for two cohorts using the median DPG of 30 mmHg as cutoff, and significance was tested using the log-rank test. RESULTS: The mean age was 38.1 ± 16.0 years old, 63% female, and 72% were "white". The mean DPG was 31.6 mmHg ± 13.8 mm Hg and only 1.8% had a DPG <7 mm Hg. Increasing DPG was significantly associated with increased 5-year mortality even after adjustment for the PHC risk equation (HR 1.29 per 10 mm Hg increase). When DPG was dichotomized based on the median of 30 mm Hg, the HR for DPG >30 mm Hg with respect to 5-year mortality was 2.03. After adjustment for pulmonary artery systolic pressure (PASP), increasing DPG remained significantly associated with decreased 5 years survival (HR 1.99 for DPG > 30 mm Hg). CONCLUSIONS: DPG is independently associated with survival in group 1 PH patients even after adjustment for the PHC risk equation or PASP. Patients with increased DPG had a 2-fold increased risk of mortality. The use of DPG for guiding treatment and prognosis in group 1 PH should be further investigated.

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.