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Danon disease (DD) is a rare X-linked dominant cardioskeletal myopathy caused by mutations in the lysosome-associated membrane protein-2 (LAMP-2) gene that is usually lethal without cardiac transplantation. The purpose of this study was to characterize post-transplant outcomes in a large cohort of patients with DD who underwent cardiac transplantation.The clinical phenotype and outcome data of patients with DD who underwent cardiac transplantation (n = 38; 19 males and 19 females) were obtained from 8 centers. Study outcomes included graft survival, defined as death or retransplantation, and episodes of acute cellular and antibody-mediated rejection and cardiac allograft vasculopathy at 1 year.Median follow-up time after transplantation for the entire cohort was 4.4 years (IQR: 1.5-12.8 years). The median age at transplant for the cohort was 20.2 years (15.8-27.9 years), with no difference in age between sexes. Median pretransplant left-ventricular ejection fraction for the entire cohort was 30% (range 11%-84%). Males had higher pretransplant aspartate aminotransferase, alanine aminotransferase and creatine phosphokinase levels than females (P0.001). There were 2 deaths in the entire cohort and 2 retransplants. There was no difference in actuarial graft survival between males and females (P = 0.8965); the estimated graft survival was 87.1% (95%CI: 63.6%-95.9%) at 5 years. One episode (2.7%) of antibody-mediated rejection, grade 2, and 7 episodes (19%) of acute cellular rejection, grade 2 or 3, were reported in patients who survived to discharge (6 females and 1 male; P = 0.172).Heart transplantation outcomes are acceptable in DD with high probabilities of 5-year graft survival for males and females suggesting that cardiac transplantation is an effective treatment option for DD patients.

A 40-year-old man with history of prior coronavirus disease 2019 (COVID-19) infection developed pleuritic chest pain 3 days after receiving the first dose of the BNT162b2 mRNA vaccine. Echocardiography results were significant for mild dysfunction and left ventricular hypertrophy. Cardiac magnetic resonance imaging showed myocardial edema as well as delayed enhancement in the inferior wall of the basal left ventricular myocardium, suggestive of acute myocarditis. This case describes the work-up, diagnosis, risk-stratification, and management of acute myocarditis post BNT162b2 mRNA vaccine.

Introduction: Danon disease (DD) is a rare X-linked dominant cardioskeletal myopathy where phenotypic expression varies by sex. It is characterized by severe cardiomyopathy, skeletal myopathy, and ...

Background Myocardial strain can identify subclinical left ventricular dysfunction in various cardiac diseases, but its association with clinical outcomes in genetic cardiomyopathies remains unknown. Herein, we assessed myocardial strain in patients with Danon disease (DD), a rare X‐linked autophagic disorder that causes severe cardiac manifestations. Methods and Results Echocardiographic images were reviewed and used to calculate myocardial strain from a retrospective, international registry of patients with DD. Regression analyses were performed to evaluate for an association of global longitudinal strain (GLS) and ejection fraction with the composite outcome (death, ventricular assist device, heart transplantation, and implantable cardioverter defibrillator for secondary prevention). A total of 22 patients with DD (male 14 [63.6%], median age 16.5 years) had sufficient echocardiograms for analysis. Absolute GLS was reduced with a mean of 12.2% with an apical‐sparing pattern observed. Univariable regression for GLS and composite outcome showed an odds ratio of 1.32 (95% CI, 1.02–1.71) with P =0.03. For receiver operating characteristic analysis, the areas under the curve for GLS and ejection fraction were 0.810 ( P =0.02) and 0.605 ( P =0.44), respectively. An absolute GLS cutoff of 10.0% yielded a true positive rate of 85.7% and false positive rate of 13.3%. Conclusions In this cohort of patients with DD, GLS may be a useful assessment of myocardial function and may predict clinical outcomes. This study highlights the potential use of myocardial strain phenotyping to monitor disease progression and potentially to predict clinical outcomes in DD and other genetic cardiomyopathies.

Danon disease (DD) is a rare X-linked autophagic vacuolar myopathy that affects the lysosome-associated membrane protein ( LAMP ) 2 gene and causes severe cardiac manifestations, frequently progressing to end-stage heart failure ([1][1]). The differential diagnosis includes many different diseases

BACKGROUND Fulminant myocarditis (FM) is a form of acute myocarditis characterized by severe left ventricular systolic dysfunction requiring inotropes and/or mechanical circulatory support. A single-center study found that a patient with FM had better outcomes than those with acute nonfulminant myocarditis (NFM) presenting with left ventricular systolic dysfunction, but otherwise hemodynamically stable. This was recently challenged, so disagreement still exists. OBJECTIVES This study sought to provide additional evidence on the outcome of FM and to ascertain whether patient stratification based on the main histologic subtypes can provide additional prognostic information. METHODS A total of 220 patients (median age 42 years, 46.3% female) with histologically proven acute myocarditis (onset of symptoms

Background Given conflicting findings of previous studies, much remains to be understood regarding a volume-outcomes relationship (VOR) in transcatheter aortic valve replacement (TAVR). Objectives The purpose of this study was: 1) to determine if, after the initial learning curve (LC), a VOR for balloon-expandable (BE) TAVR persisted; and 2) to determine if LCs and VORs differed across different device generations. Methods Data collected by the TVT registry for BE valve implants from November 2011 through January 2017 were included in this analysis (n = 61,949). Primary outcomes included 30-day all-cause mortality, stroke, and major vascular complications. For each center, all implants were ordered chronologically according to case sequence number (CS#). To determine where the learning curve terminated (LCT), a grid search analysis was applied across a range of CS# from 10 to 300 by increments of 1. After LCT, the VOR was assessed by examining case volume/month by center. This analysis was performed separately for: 1) all BE valve types; 2) Sapien 3 (S3) only; and 3) S3 in BE valve naive sites. Results In experience with all commercially available BE valve types, there was an initial LC that terminates around case #201. After the initial LC, a volume–outcomes relationship was no longer evident. In analysis limited to S3, there was no demonstrable LC or VOR. Likewise, there was no demonstrable LC or VOR with S3 for BE valve naive sites. Conclusions After a case experience of 200 cases, there was LCT; subsequent to initial learning, a VOR was no longer evident. In the S3-only analysis, there was no LC or no demonstrable VOR. With current-generation BE-TAVR, centers should expect to achieve consistently excellent outcomes even during early case experience.

BACKGROUND: There is conflicting observational data on the survival benefit cardiac implantable electronic devices (CIED) in patients with LVADs. METHODS: Patients in whom an LVAD was implanted between January 2008 and April 2017 in the multinational Trans-Atlantic Registry on VAD and Transplant (TRAViATA) registry were separated into four groups based on the presence of CIED prior to LVAD implantation: none (n = 146), implantable cardiac defibrillator (ICD) (n = 239), cardiac resynchronization without defibrillator (CRT-P) (n = 28), and CRT with defibrillator (CRT-D) (n = 111). RESULTS: A total of 524 patients (age 52 years ±12, 84.4% male) were followed for 354 (interquartile range: 166-701) days. After multivariable adjustment, there were no differences in survival across the groups. In comparison to no device, only CRT-D was associated with late right ventricular failure (RVF) (hazard ratio 2.85, 95% confidence interval [CI] 1.42-5.72, p = 0.003). There was no difference in risk of early RVF across the groups or risk of ICD shocks between those with ICD and CRT-D. CONCLUSION: In a multinational registry of patients with LVADs, there were no differences in survival with respect to CIED subtype. However, patients with a pre-existing CRT-D had a higher likelihood of late RVF suggesting significant long-term morbidity in those with devices capable of LV‑lead pacing post LVAD implantation. ispartof: INTERNATIONAL JOURNAL OF CARDIOLOGY vol:340 pages:26-33 ispartof: location:Netherlands status: published

BACKGROUND: Geographic variations in management and outcomes of individuals supported by continuous-flow left ventricular assist devices (CF-LVAD) between the United States (US) and Europe (EU) is largely unknown. METHODS: We created a retrospective, multinational registry of 524 patients who received a CF-LVAD (either HVAD or Heartmate II) between January 2008 and April 2017. Follow up spanned from date of CF-LVAD implant to post-HTx period with a median follow up of 44.8 months. RESULTS: The cohort included 299 (57.1%) EU and 225 (42.9%) US patients. Although the US cohort was significantly older with a higher prevalence of comorbidities, survival was similar between the cohorts (US 63.1%, EU 68.4% at 5 years, unadjusted log-rank test p = 0.43).Multivariate analyses suggested that older age, higher body mass index, elevated creatinine, use of temporary mechanical circulatory support prior CF-LVAD, and implantation of HVAD were associated with increased mortality. Among CF-LVAD patients undergoing HTx, the median time on CF-LVAD support was shorter in the US, meanwhile US donors were younger. Finally, the pattern of adverse events (stroke, gastrointestinal bleedings, late right ventricular failure, and driveline infection) during support differed significantly between US and EU. CONCLUSIONS: Although waitlisted patients in the US on CF-LVAD have higher risk comorbid conditions, the overall outcome is similar in US and EU. Geographic variations with regards to donor characteristics, duration of CF-LVAD support prior to transplant, and adverse events on support can explain the disparity in the utilization of mechanical bridge to transplant strategy between US and EU. ispartof: INTERNATIONAL JOURNAL OF CARDIOLOGY vol:324 pages:122-130 ispartof: location:Netherlands status: published

A 32-year-old female with World Health Organization (WHO) group 1 pulmonary arterial hypertension (PAH), presented to the hospital with right lower lobe pneumonia. Her echocardiogram demonstrated severe PAH with a pulmonary artery (PA) systolic pressure of 110 mmHg, an enlarged right ventricle with reduced function, a patent foramen ovale (PFO) with left to right shunt, and mild mitral regurgitation.

Background Danon Disease (DD) is a rare X-linked autophagic disorder due to mutations in the Lysosomal Associated Membrane Protein 2 (LAMP-2) gene and causes severe cardiac manifestations. Measurement of longitudinal strain (LS) has been shown to provide diagnostic insights into different etiologies of hypertrophic cardiomyopathies compared to conventional echocardiographic parameters. Purpose The aim of this study was to describe the pattern of global and regional LS in DD. Methods A retrospective, international registry, using medical records provided by patients, was formed to describe the natural history of DD. Complete echocardiogram images were available for review and LS was analyzed globally and regionally (basal, mid, apex). Results A total of eighteen DD patients (male 72%, mean age 17.2±10 years) had sufficient quality echocardiographic images for both traditional and myocardial strain evaluation. Notable traditional echocardiographic parameters included a mean EF of 60±11%, LV mass index 200±159 g/m2, intraventricular septal diameter 17.7±10.3 mm, LV posterior wall diameter 16.1±7.7 mm, LA volume index 21.9±13 mL/m2. Global longitudinal strain was reduced with a mean of −12.1±4.9% with an observed regional strain gradient: apex (−16.6±6.6%), mid (−10.9±4.7%) and basal (−9.2±4.5%). Bull's eye plot patterns reflected an apical sparing pattern that was similar to that described in cardiac amyloidosis. Conclusion In this DD cohort, we describe for the first time a strain pattern characterized by reduction in global longitudinal strain with apical sparing, which was originally pathognomonic for cardiac amyloidosis. This strain pattern in conjunction with a paradoxically normal LA volume may discriminate patients with DD from other hypertrophic conditions. Funding Acknowledgement Type of funding source: None

Author(s): Contreras, Johanna P; Hong, Kimberly N; Castillo, Javier; Marzec, Lucas N; Hsu, Jonathan C; Cannon, Christopher P; Yang, Song; Maddox, Thomas M | Abstract: BackgroundIn non-valvular atrial fibrillation (NVAF) patients, congestive heart failure (CHF) confers an increased risk of stroke or systemic thromboembolism. This risk is present in both heart failure (HF) with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF). It is unclear if clinicians account for both types of CHF in their NVAF anticoagulation practices. Accordingly, we characterized current outpatient anticoagulation trends in NVAF patients with HFpEF compared to patients with HFrEF.MethodsThe outpatient NCDR PINNACLE-AF registry was analyzed to identify patients with NVAF and CHF. The study population was subdivided into HFpEF (ie, LVEF ≥ 40%) and HFrEF (LVEF l 40%). Anticoagulation rates by CHF group were compared and stratified by CHA2 DS2 -VASc score.ResultsA total of 340 127 patients with NVAF and CHF were identified, of whom 248 136 (73.0%) were classified as HFpEF and 91 991 (27.0%) as HFrEF. Patients with HFpEF had higher mean CHA2 DS2 -VASc scores and were more likely to be female, older, and have hypertension (P l 0.001). Unadjusted anticoagulation rates were significantly lower in patients with HFpEF compared to those with HFrEF (60.6% vs 64.2%, respectively). Lower rates of anticoagulation in the HFpEF group persisted after risk adjustment (RR: 0.93 [95% CI: 0.91, 0.94]). Stratification by CHA2 DS2 -VASc score demonstrated that lower rates of anticoagulation in patients with HFpEF persisted until a score of ≥5.ConclusionsPatients with NVAF and HFpEF have significantly lower anticoagulation rates when compared to their HFrEF counterparts. These findings suggest a potential underappreciation of HFpEF as a risk factor in patients with NVAF.

Diabetes, hyperlipidemia, and hypertension are modifiable risk factors that predict cardiovascular disease events. The effect of these risk factors on incident cardiovascular disease increases with progressively higher levels of glucose, low-density lipoprotein cholesterol, and blood pressure. The thresholds for initiating treatment of these modifiable risk factors and the optimal goals of risk factor modification are a focus of primary prevention research. Although an aggressive approach is appealing, adverse events may occur, and potential physiological barriers may exist. This paper discusses primary prevention of coronary heart disease that may be achieved through modification of diabetes, hyperlipidemia, and hypertension by summarizing current guidelines and pertinent clinical trial data from intervention trials that included a primary prevention cohort.

Purpose Danon Disease is a rare X-linked myopathy caused by defects in the lysosome-associated membrane 2 (LAMP2) gene. It is strongly associated with hypertrophic cardiomyopathy as well as Wolff-Parkinson-White (WPW) syndrome, but the prevalence of WPW in Danon is unclear. This study examined the prevalence of WPW and associated outcomes in a cohort of patients with Danon Disease. Methods Records were reviewed for 41 patients with confirmed Danon Disease enrolled in a previously described retrospective registry, 31 of which had at least one electrocardiogram (EKG) on file. EKGs were assessed for the presence of WPW, as well as left and right ventricular hypertrophy (LVH, RVH), or both. WPW was defined as a PR interval ≤ 120 milliseconds, QRS interval ≥120 milliseconds, and delta wave. Charts were reviewed for internal cardiac defibrillator (ICD) placement, heart transplantation, and death. These outcomes were evaluated between patients with and without WPW on EKG using chi-square analysis, with p Results EKG criteria for LVH, RVH or both was met in 10 of the 11 WPW patients, compared to 9 of the 20 without WPW (p=0.012). ICD devices were present in 9 of the 11 WPW patients, 3 of which were placed for secondary prevention, compared to 9 of the 20 patients without WPW (p=0.119). Six of the 11 WPW patients eventually underwent heart transplant, compared to 4 of the 20 without WPW (p=0.058). Only one death was noted in this cohort, and was determined to not be cardiac related. Conclusion In a cohort of patients with Danon Disease, approximately one-third had WPW syndrome on EKG. Those with WPW on EKG had higher rates of EKG criteria for LVH, RVH or both and were more likely to require advanced therapies such as ICD placement and cardiac transplant. Larger studies involving WPW in Danon Disease should seek to better characterize these outcomes.

Nearly half of all individuals with heart failure with reduced ejection fraction have biventricular dysfunction. By unloading the left ventricle and decreasing left atrial pressures, there is a reasonable chance for right ventricular recovery after left ventricular assist device. Unfortunately, the opposite is also true where right ventricular failure can be unmasked, develop, or worsen. This chapter will focus on the patient selection and management of individuals with pre-existing biventricular failure either from chronic left ventricular failure or dilated cardiomyopathies, as well as those who develop right ventricular failure after left ventricular assist devices have been placed. We will discuss methods for risk stratifying individuals with biventricular dysfunction and pre-, peri-, and postoperative management strategies for improving right ventricular recovery and survival to transplant in these patients.

[No abstract available]

Risk factors for post-operative conduction disturbances after cardiac valve surgery requiring a permanent pacemaker (PPM) are poorly characterized.The aim of this study was to investigate the timing and risk factors for PPM implantation after mitral or aortic valve surgery.All patients who underwent open aortic or mitral valve surgery between January 1996 and December 2014 were reviewed using New York State's mandatory hospital discharge database. Patients with prior cardiac surgery or pre-existing PPM were excluded. The primary endpoint was PPM implantation within 1 year.Among 77,882 patients, 63.8% (n = 49,706) underwent aortic valve replacement (AVR), 18.9% (n = 14,686) underwent mitral valve replacement (MVR), 10.5% (n = 8,219) underwent mitral valve repair (MVr), 5.4% (n = 4,202) underwent AVR plus MVR, and 1.4% (n = 1,069) underwent AVR plus MVr. The 1-year PPM implantation rate was 4.5% after MVr, 6.6% after AVR, 9.3% after AVR plus MVr, 10.5% after MVR, and 13.3% after AVR plus MVR (p 0.001). Across all groups, the majority of PPMs were implanted during the index hospitalization (79.9%). MVr was associated with the lowest risk for PPM and AVR plus MVR with the highest risk. Older age, history of arrhythmias, pre-operative conduction disturbances, and concomitant index procedures were associated with increased risk for PPM during the index hospitalization. Conversely, beyond 30 days, chronic comorbidities were associated with increased risk for PPM.Conduction disturbances requiring PPM remain a common adverse event after valve surgery. Identifying patients at risk for PPM will help facilitate perioperative planning and inform clinical decision making regarding post-operative rhythm surveillance.

PURPOSE: There are conflicting data related to the use of implantable cardioverter-defibrillators (ICDs) in patients supported with continuous-flow ventricular assist devices (LVADs). Several US studies have shown a neutral effect on mortality, whereas a recent European study suggested better outcomes in LVAD patients who have an ICD. We aimed to investigate the benefit of ICDs in patients bridged to transplant with a LVAD in the TRans-Atlantic registry on VAd and TrAnsplant (TRAViATA). METHODS: Data from consecutive patients that received a LVAD as a bridge to transplantation between January 2008 and April 2017 were collected in 7 EU (n=299) and 3 US centers (n=225). Survival analysis was performed using Kaplan-Meier and Cox proportion hazard regression analysis. Patients were censored at time of transplantation. RESULTS: Patients with an ICD at the time of LVAD (n=350) implantation were older (56 vs. 53 years, p

Danon Disease is a rare X-linked myopathy associated with hypertrophic cardiomyopathy and Wolff-Parkinson-White (WPW) syndrome. The prevalence of WPW in Danon Disease is unclear. This study examined the prevalence of WPW and associated outcomes in a cohort of Danon Disease patients. EKGs of 28

Danon Disease (DD) is a rare X-linked disorder due to mutations in the Lysosomal Associated Membrane Protein 2 (LAMP-2) gene and causes severe cardiac manifestations. Longitudinal strain (LS) has emerged as a diagnostic and prognostic tool in various cardiomyopathies. A retrospective, international

Given conflicting findings of previous studies, much remains to be understood regarding a volume-outcomes relationship (VOR) in transcatheter aortic valve replacement (TAVR).The purpose of this study was: 1) to determine if, after the initial learning curve (LC), a VOR for balloon-expandable (BE) TAVR persisted; and 2) to determine if LCs and VORs differed across different device generations.Data collected by the TVT registry for BE valve implants from November 2011 through January 2017 were included in this analysis (n = 61,949). Primary outcomes included 30-day all-cause mortality, stroke, and major vascular complications. For each center, all implants were ordered chronologically according to case sequence number (CS#). To determine where the learning curve terminated (LCT), a grid search analysis was applied across a range of CS# from 10 to 300 by increments of 1. After LCT, the VOR was assessed by examining case volume/month by center. This analysis was performed separately for: 1) all BE valve types; 2) Sapien 3 (S3) only; and 3) S3 in BE valve naïve sites.In experience with all commercially available BE valve types, there was an initial LC that terminates around case #201. After the initial LC, a volume-outcomes relationship was no longer evident. In analysis limited to S3, there was no demonstrable LC or VOR. Likewise, there was no demonstrable LC or VOR with S3 for BE valve naïve sites.After a case experience of 200 cases, there was LCT; subsequent to initial learning, a VOR was no longer evident. In the S3-only analysis, there was no LC or no demonstrable VOR. With current-generation BE-TAVR, centers should expect to achieve consistently excellent outcomes even during early case experience.

Background Strokes are a devastating complication following left ventricular assist device (LVAD). The purpose of this study was to determine if a cerebral vascular accident (CVA) prior to LVAD placement in a bridge-to-transplant population is associated with worse outcomes compared to those without a history of prior CVA. Methods De-identified data were obtained from TRAVIATA (TransAtlantic Registry on VAD and Transplant) a retrospective, observational, multinational registry that included candidates for heart or heart and kidney transplant in whom an LVAD was implanted between January 2008 and April 2017. Only individuals greater than 15 years old who were implanted with either an HVAD (HeartWare, Minnesota, MN, USA) or a Heartmate II (HM2, Abbott, Pleasanton) were included (N=524). Patients were stratified into those with a CVA prior to LVAD ((+)CVA, n=55) and those without a CVA prior to LVAD ((-)CVA, n=469). The primary outcome was survival to transplant. Other outcomes of interest included death on support and post-LVAD CVA. Multivariable regression was performed in order to assess the simultaneous effect of multiple risk factors on transplant. Results The only difference between the preoperative characteristics studied between the study groups was a higher frequency of non-whites in those who had a CVA pre-LVAD (Table1). There were no differences in rates of transplant, death on support, or post-LVAD CVA between the study groups (Table2). In multivariable analysis, older age, higher BMI and preoperative DM were associated with decreased likelihood of transplant. Of interest, in those who were transplanted, time to transplant was longer in the (+)CVA group compared to the (-)CVA group (Table 2). Conclusions Stroke prior to LVAD was not associated with worse outcomes after LVAD, including decreased survival to transplant, death or stroke post-LVAD.

The risk factors for post-operative conduction disturbances after heart valve surgery requiring cardiac implantable electronic devices (CIED) remains poorly characterized. We conducted a retrospective cohort study using a mandatory statewide discharge database, New York's Statewide Planning and

Background The purpose of this study is (1) to define the proportion of patients undergoing emergent open repair of thoracic aortic dissection admitted directly through the emergency room versus those transferred from outside hospitals and (2) to determine if a volume-outcomes relationship exists for those patients across admission types. Methods De-identified patient-level data was obtained from the Nationwide Inpatient Sample (2004–2008). Patients undergoing emergent aortic surgery for thoracic aortic dissection (n = 1,507) were identified by ICD-9 codes and stratified by annual center volume into low volume (≤5 cases/year) (n = 963; 63.9 %), intermediate volume (6–10 cases/year) (n = 370; 24.5 %), and high volume (≥11 cases/year) (n = 174; 11.6 %) groups. The analysis was further stratified by admission type: direct admission (DA), transfer admission (TA), and other. The primary outcome was in-hospital mortality. Multivariate logistic regression analysis was performed comparing outcomes between high vs low and high vs intermediate volume centers. Results Overall in-hospital mortality was 21.8 % (n = 328/1,507). Absolute percent mortality at high volume centers was significantly lower (12.6 %) than at medium (20.6 %) and low volume (23.9 %) centers. For DA patients, mortality was 10.6, 21.4, and 24.0 % for high, medium, and low volume centers respectively. For TA patients, mortality was 10.2, 12.7, and 23.5 % for high, medium, and low volume centers, respectively. Multivariate analysis suggested that patients in low volume center were more likely to die compared to high volume center (Odds Ratio 2.06, 95 % CI 1.25 – 3.38, p = 0.004). Admission source was not associated with increased mortality. Conclusions Direct admissions comprise the largest proportion of dissections regardless of volume strata, and they comprise the largest proportion in the low and intermediate volume cohorts. Admission to low volume center is an independent risk factor for increased mortality. Patients transferred to high volume centers from low volume centers have similar outcome as direct admits in terms of mortality.

ObjectiveThe goal of this study was to quantify the net increase in resource use associated with complications after isolated mitral valve surgery.MethodsDeidentified patient-level claims data on a random sample of mitral valve operations performed in the United States from January 1, 2006, to December 31, 2007, were obtained from the National Inpatient Sample (n = 16,788). Patients with major concomitant cardiac procedures were excluded from the analysis for a net sample size of 6297 patients. Risk-adjusted median total hospital costs and length of stay were analyzed by major complications, including pneumonia, sepsis, stroke, renal failure requiring hemodialysis, cardiac tamponade, myocardial infarction, gastrointestinal bleed, and venous thromboembolism.ResultsThere were a total of 1323 complication events that occurred in 1089 patients. The most common complication was pneumonia (n = 346, 5.5%), which was associated with a $29,692 increase in hospital costs and a 10.2-day increase in median length of stay (P

Over the past decade, minimally invasive (MI) mitral valve surgery has grown in popularity. The purpose of this study was to compare both short- and long-term outcomes of mitral valve repair and replacement performed through a MI versus traditional sternotomy (ST) incision using a propensity analysis approach to account for differences in baseline risk.From January 2000 to December 2008, a total of 1,121 isolated mitral valve operations were performed at our institution (548 ST, 573 MI). Data were retrospectively collected on all patients, and a logistic regression model was created to predict selection to a MI versus ST approach. Propensity scores were then generated based on the regression model and matched pairs created using 1:1 nearest neighbor matching. There were 382 matched pairs in the analysis for a total sample size of 764, or 68.2% of the original cohort. Major outcomes of interest included cardiopulmonary bypass time, cross-clamp time, hospital length of stay, major in-hospital complications, and both short- and long-term survival.Cardiopulmonary bypass time was 117.1 ± 2.0 minutes in the ST group and 139.7 ± 2.6 minutes in the MI group (p0.0001), and cross-clamp time was 79.6 ± 1.5 minutes in the ST group and 83.7 ± 1.9 in the MI group (p = 0.106). The average hospital length of stay was 9.81 ± 0.61 days among ST patients and 7.76 ± 0.37 days among MI patients (p = 0.0043). There was no significant difference in the frequency of major in-hospital complications between groups. The mean duration of survival follow-up was 4.2 ± 2.4 years. There was no significant difference in mortality at 30 days (p = 0.622) or 1 year (p = 0.599). In addition, there was no significant difference in long-term survival between groups (p = 0.569).Although minimally invasive mitral valve surgery required a slightly longer cardiopulmonary bypass time, there was no difference in cross-clamp time, morbidity, or mortality, and hospital length of stay was significantly shorter when compared with matched sternotomy control patients.

Background Primary graft failure (PGF) is the most common cause of short-term mortality after cardiac transplantation. The low prevalence of PGF has limited efforts at identifying risk factors for its development. The purpose of this study was to evaluate risk factors associated with PGF after heart transplantation. Methods Deidentified data were obtained from United Network for Organ Sharing. Analysis included heart transplant recipients more than or equal to 18 years transplanted between January 1, 1999, and December 31, 2007 (n=16,716). PGF was studied from the perspective of "hard outcomes" including death or retransplantation within 90 days of transplant due to graft failure, not related to rejection or infection. Multivariate regression analysis was performed (backward, remove P>0.15) to assess the simultaneous effect of multiple variables on PGF. The odds ratio and 95% confidence interval were reported for each factor. Results Among the 414 heart transplants complicated by PGF, 354 (85.5%) recipients died and 60 (14.5%) were retransplanted. PGF accounted for 23.4% (n=364) of all deaths (n=1555) in the first 90 days posttransplant. Categories of pretransplant variables associated with PGF included: ischemic time, donor gender, donor age, multiorgan donation, center volume, extracorporeal membrane oxygenation, mechanical circulatory support, etiology of heart failure, and reoperative heart transplant. The area under the receiver operative characteristic curve for the multivariate model was 0.764 (0.733-0.796). Conclusions Pretransplant recipient and donor characteristics are associated with PGF. Identification of risk factors may aid in understanding the mechanisms underlying PGF and in matching recipients with donors in efforts to diminish the high mortality associated with this complication.

The lung allocation score (LAS) was initiated in May 2005 to allocate lungs based on medical urgency and posttransplant survival. The purpose of this study was to determine if there is an association between an elevated LAS at the time of transplantation and increased postoperative morbidity and mortality.The United Network for Organ Sharing provided de-identified patient-level data. Analysis included lung transplant recipients agedor= 12 years who received transplants between April 5, 2006, and December 31, 2007 (n = 3,836). Recipients were stratified into three groups: LAS50 (n = 3,161, 83.87%), LAS 50 to 75 (n = 411, 10.9%), and LASor= 75 (n = 197, 5.23%), referred to as low LAS (LLAS), intermediate LAS (ILAS), and high LAS (HLAS), respectively. The primary outcome was posttransplant graft survival at 1 year. Secondary outcomes included length of stay and in-hospital complications.HLAS recipients had significantly worse actuarial survival at 90 days and 1 year compared with LLAS recipients. When transplant recipients were stratified by disease etiology, a trend of decreased survival with elevated LAS was observed across all major causes of lung transplant. HLAS recipients were more likely to require dialysis or to have infections compared with LLAS recipients (P.001). In addition, length of stay was higher in the HLAS group when compared with the LLAS group (P.001).HLAS is associated with decreased survival and increased complications during the transplant hospitalization. Whereas the LAS has improved organ allocation through decreased waiting list deaths and waiting list times, lower survival and higher morbidity among HLAS recipients suggests that continued review of LAS scoring is needed to ensure optimal long-term transplant survival.

To determine the relationship between body mass index (BMI) at the time of transplant and posttransplant survival and morbidity.The recent International Society for Heart and Lung Transplantation listing criteria for heart transplantation stated that candidates should achieve a BMI30 kg/m-or percent ideal body weight140%-before listing for cardiac transplantation. However, data to support these recommendations are limited and often conflicting.United Network of Organ Sharing provided de-identified patient-level data. Analysis included 19,593 orthotopic heart transplant recipients agedor=18 years and transplanted January 1 1995-December 31 2005. Follow-up data were provided through February 8, 2008. Recipients were stratified by BMI at the time of transplantation: BMI18.5 (underweight), 18.5 to 24.99 (normal weight), 25 to 29.99 (overweight), 30 to 34.99 (obesity class I), andor=35 (obesity class II/III). The primary outcome measure was post-transplant survival.Risk-adjusted median survival in the underweight, normal weight, overweight, obesity I, and obesity II/III groups was 8.31, 10.20, 10.03, 9.51, and 9.05 years, respectively. In multivariate Cox proportional hazards regression, BMI in the overweight (HR = 1.08, 0.99-1.17; P = 0.055) and obesity I (HR = 1.05, 0.99-1.12; P = 0.091) ranges were not associated with significantly diminished survival. However, BMI in the underweight (HR = 1.26, 1.11-1.43; P0.001) and obesity II/III (HR = 1.18, 1.01-1.38; P = 0.030) ranges were associated with diminished posttransplant survival.Findings from this analysis do not suggest that obesity I (BMI of 30-34.99) is associated with significantly higher morbidity and mortality. However, underweight and obesity II/III recipients have significantly higher morbidity and mortality compared with other groups.

In May 2005, the lung allocation score (LAS) was introduced as a means of allocating donor lungs in order to decrease wait-list mortality and prioritize candidates based on medical urgency and posttransplant survival. The purpose of this study was to assess changes in recipient wait-list times and mean LAS since the introduction of the LAS model.The United Network for Organ Sharing provided de-identified patient-level data. The study population consisted of all patients in the United States with a reported LAS (n = 3529) undergoing lung transplantation between May 7, 2005 and November 7, 2007. The study period was divided into 6-month intervals. The Kruskal-Wallis test was used to assess differences in variables with nonparametric distributions. The nonparametric trends test was used to determine significance of trends over time.There was a significant decrease in wait-list time during the study period, while LAS among transplant recipients increased (p0.001). There was no significant change in FVC (49.3 +/- 17.5%, p = 0.48) or pulmonary capillary wedge pressure (11.1 +/- 5.8 mm Hg, p = 0.23); however, there was a significant increase in age (51.5 +/- 13.9 years, p0.001) during the study period. When stratified by etiology, the LAS increased for both interstitial pulmonary fibrosis and COPD patients (p0.001). Moreover, the overall number of patients listed for transplantation as well as the LAS among transplant candidates increased (p0.001).Two years after initiation of the LAS model, wait-list times continue to decrease while mean LAS continued to increase. This increase in LAS among transplant recipients was observed most notably in patients with interstitial pulmonary fibrosis and COPD, and reflected in an increased mean LAS at the time of listing.

Left ventricular assist devices (LVADs) have emerged as an important treatment for advanced heart failure (AHF). While LVAD support results in left ventricular reverse remodeling with evidence of improvement on cellular, molecular, and genetic levels, the recovery is partial and generally inadequate for device explant. This has prompted recent interest in the evaluation of adjunctive regenerative therapies, such as stem cells and gene therapy, with LVADs to explore the potential for synergistic effects of myocardial regeneration. This chapter discusses the opportunities and challenges of designing and conducting clinical trials evaluating biological therapies in AHF patients undergoing LVAD implantation. In particular, LVADs as a platform for evaluating adjunctive therapies, and the methodological and technical issues arising from this approach of combining biological treatments with LVADs will be explored.

“Disruptive technology,” a phrase coined by economist Clayton M. Christensen approximately 10 years ago, describes a new technology that unexpectedly displaces an established technology. Whereas sustained technology applies incremental improvements to an established approach, disruptive technology, often lacking in refinement, has the ability to transform common practice. Such has been the case with ventricular assist devices (VADs), which have rapidly transformed the management of end stage heart failure from sole pharmacologic therapy to enhancement with mechanical circulatory support.

Surgical atrial fibrillation ablation (SAFA) has not achieved the efficacy of Cox's original maze procedure, although technical improvements continue to be made. It is possible that biologic factors determine SAFA success. Therefore we examined how patient-specific characteristics affected SAFA success in 353 atrial fibrillation (AF) patients who underwent SAFA at a single institution. Among these, 257 (72.8%) had continuous AF and 96 (27.2%) had intermittent AF. For 297 patients (84.1%) postoperative follow-up was > 3 months. We compared SAFA success in patients whose procedure involved only pulmonary vein isolation with those whose procedure involved extensive lesion sets. Multivariate analysis included AF duration, left atrial size, preoperative atrial flutter, concomitant procedures, lesion sets, and energy source. Early SAFA success was classified as freedom from AF between postoperative months 3 and 6, and intermediate success between postoperative months 6 and 12. Receiver-operating characteristic (ROC) curves and stratum-specific likelihood ratios (SSLR) were generated to compare intermediate failure by left atrial size (LAS) thresholds. SAFA was more successful in the intermittent than the continuous AF group (n = 66, 86% vs n = 165, 71%; P = .014). When pulmonary vein isolation was compared only to more extensive lesion sets, there was no difference in success in the intermittent (34, 91% vs 32, 81%; P = .24) or continuous groups (67, 73% vs. 98, 69%; P = .603). Success for intermittent AF patients was not correlated with variables considered; in continuous AF patients, predictors included presence of concomitant mitral valve repair/replacement (P = .075), decreasing LAS (P = .025) and absence of preoperative atrial flutter (P = .001). In the continuous AF group, ROC curves and corresponding areas under the curve (AUC) were 0.60 (0.50-0.71) for failure at 6 months to 1 year. SSLR analysis generated 2 strata for LAS: < 8 cm with SSLR = 0.87 (0.74-1.0) and < or = 8 cm SSLR = 2.98 (1.07-8.3). In patients with intermittent AF, SAFA achieved acceptable results regardless of tested preoperative and intraoperative variables. In continuous AF, patient-specific characteristics affected success more than intraoperative variables. Failure was more than 3-fold greater in continuous AF patients with an LAS < or = 8 cm. In both patient types, more extensive lesion sets were not shown to improve outcomes. Future improvements in SAFA may depend on pharmacologic and/or surgical substrate modification.

Background. Minimally invasive cardiac surgical procedures have become ubiquitous over the past decade. In many cases, these techniques have been associated with decreased morbidity, shorter length of stay, decreased pain, faster recovery, and superior cosmetic results. The purpose of this study was to compare outcomes using a minimally invasive (mini-thoracotomy) versus standard (sternotomy) approach to the surgical resection of atrial masses.Methods. Analysis was based on 34 consecutive patients who underwent atrial mass resection at the New York-Presbyterian Hospital/Columbia Presbyterian Medical Center in New York, NY. The reference (REF) group included 18 patients who underwent excision of an atrial mass via a standard approach (sternotomy). The minimally invasive (MI) group included 16 patients who underwent excision of an atrial mass via a mini-thoracotomy.Results. There were no statistically significant differences between the REF and MI groups based on demographic or preoperative characteristics. Tissue diagnosis of the masses resected included myxoma (n = 24), fibroblas-toma (n = 3), B-cell lymphoma (n = 1), and other benign masses (n = 6). Cardiopulmonary bypass (70.5 versus 76.5 minutes; P = .57) and aortic cross-clamp times (32.7 versus 47.3 minutes; P = .14) did not differ significantly between the REF and MI groups, nor did intraoperative transfusion of packed red blood cells (0.35 versus 0.38 units; P = .93). As assessed by intraoperative trans-esophageal echocardiogram, there were no moderate to severe valvular abnormalities observed following chest closure. Intensive care unit length of stay (46.1 versus 26.2 hours; P = .15), overall hospital length of stay (6.39 versus 5.06 days; P= .18), and time to extubation (0.78 versus 0.44 days; P = .44) all trended toward shorter duration in the MI group compared with the REF group—although none of these differences achieved statistical significance. Postoperative transthoracic echocardiograms were obtained in 14 of 34 (41.2%) patients; none revealed any new or significant abnormalities. All patients survived to hospital discharge; one patient in the REF group expired during the follow-up period. Among the 34 patients, 26 patients (76.4%) were at least 2 years postoperative from their resection; 25 of the 26 (96.1%) were alive at 2-year follow-up, and the remaining 8 were alive at 1-year follow-up. All patients were free of recurrence at last follow-up.Conclusions. Minimally invasive atrial mass excisions can be accomplished reliably without compromising complete tumor resection and without significant increases in operative times or serious adverse events. In addition, measures of recovery time in this study suggest faster recovery among the MI group, which is consistent with the proposed advantages by proponents of minimally invasive surgery.

Background: In recent years, there has been growing interest in evaluating the health and economic impact of medical devices. Payers increasingly rely on cost-effectiveness analyses in making their coverage decisions, and are adopting value-based purchasing initiatives. These analytic approaches, however, have been shaped heavily by their use in the pharmaceutical realm, and are ill-adapted to the medical device context.Methods: This study focuses on the development and evaluation of left ventricular assist devices (LVADs) to highlight the unique challenges involved in the design and conduct of device trials compared with pharmaceuticals.Results: Devices are moving targets characterized by a much higher degree of post-introduction innovation and “learning by using” than pharmaceuticals. The cost effectiveness ratio of left ventricular assist devices for destination therapy, for example, decreased from around $600,000 per life year saved based on results from the pivotal trial to around $100,000 within a relatively short time period.Conclusions: These dynamics pose fundamental challenges to the evaluation enterprise as well as the policy-making world, which this paper addresses.