Dearani, Joseph A.

Background: Treatment of progressive heart failure, due to left ventricular (LV) outflow tract obstruction has been a major component of hypertrophic cardiomyopathy (HCM) disease management for 50 years. Septal myectomy has been the primary treatment option to abolish gradients and relieve heart failure symptoms. The role of myectomy in HCM management has depended on effectiveness in relieving heart failure symptoms, but also an acceptable operative risk. Methods: Over the most recent 15-year period, we reviewed 3,700 consecutive isolated myectomy operations performed at major North American HCM institutions. Composite operative mortality (first 30 days) was only 0.4%. Seventeen operative deaths were at ages 24 to 82 (≥70 years), and only 6 occurred after 2010. Notably, 2 of the 4 Mayo Clinic deaths were in patients with prior alcohol septal ablation. Septal myectomy, when performed in experienced HCM centers, was much safer when compared to operative mortality with coronary artery bypass grafting (2.3%); valve replacement (3.5%); mitral valve replacement specifically (5.7%) (STS Database), similar to atrial or ventricular septal defect closure and 15-fold less than myectomy in community hospital or low volume surgical settings. Conclusions: Surgical myectomy performed in dedicated HCM centers with experienced surgeons and staff is one of the safest open-heart procedures currently practiced, with a mortality rate as low as 0.4%. The large mortality discrepancy for myectomy between community hospitals and dedicated HCM centers underscores that this operation should be considered a specialized procedure best performed in high volume HCM institutions.

Objectives: CABG and PCI are used for revascularization of multivessel coronary artery disease (MVCAD). However, limited information is available comparing the rates of in-hospital and 30-day major adverse cardiac and cerebrovascular event (early MACCE), including early death, stroke, myocardial infarction (MI), and repeat revascularization, among patients with multiple arterial CABG (MultArt) vs PCI. Methods: We reviewed 12,615 MVCAD patients with isolated primary CABG or PCI from 1993 through 2009. CABG patients (n=6,667) were grouped by number of arterial grafts into left internal mammary artery/saphenous vein (LIMA/SV) (n=5,712) or MultArt (n=955); PCI patients (n=5,948) into balloon angioplasty (BA) (n=1,020), bare metal stent (BMS) (n=3,242), and drug-eluting stent (DES) (n=1,686). Results: Early MACCE rate was significantly greater for PCI than CABG (8.5% vs 4.1% [P<.001]) and lower for MultArt than LIMA/SV or PCI (1.5% vs 4.5% and 8.5%, respectively [P<.001]). Stroke and early death rates were higher in CABG vs PCI (2.2% vs 0.4% [P<.001], and 1.5% vs 1.0% [P=0.01], respectively), whereas MI and repeat revascularization were lower (0.5% vs 6.0% and 0.3% vs 2.2%, respectively [P<.001]). Stroke and early death were similar in MultArt and PCI and lower vs LIMA/SV (0.6% and 0.4% vs 2.6%, and 0.5% and 1.0% vs 1.7%, respectively [P<.001]); MI and repeat revascularization rates were similar in MultArt and LIMA/SV and lower vs PCI (0.4% and 0.6% vs 6.0%, and 0.3% and 0.3% vs 2.3%, respectively [P<.001]). In propensity score-matched analysis, CABG had significantly improved early MACCE rate compared with BA (4.7% vs 13.2% [P<.001]), BMS (4.3% vs 8.3% [P<.001]), and DES (2.9% vs 5.5% [P=.008]), and MultArt compared with PCI (1.8% vs 7.8% [P<.001]) fig. Conclusions: In MVCAD patients undergoing isolated primary revascularization, CABG conferred lower early MACCE rate vs PCI. Early MACCE rate was markedly decreased after MultArt compared with LIMA/SV, BA, BMS, and DES.

Introduction: We compared outcome of repeat CABG (RCABG) and PCI in patients with previous CABG. Hypothesis: RCABG may improve survival versus PCI. Methods: From 1993 through 2009, 3,058 patients underwent revascularization after previous CABG. RCABG patients (n=530) were grouped by the use of arterial grafts (n=396), or saphenous vein grafts (SVG; n=134). At previous CABG, 37% of RCABG patients received IMA graft. PCI patients (n=2,528) were grouped into balloon angioplasty (BA; n=491), bare metal stent (BMS; n=1,267), and drug-eluting stent (DES; n=769). PCI patients were further stratified by the treated target into native coronary artery (n=1,637), bypass grafts (n=674), or both (n=216). Propensity score analysis matched 287 patients. Results: RCABG had increased 30-day mortality compared with PCI (HR=3.92; 95% CI, 2.25-6.84; P <.001) in multivariable analysis, while in propensity matched analysis it did not ( P =.09). Overall survival, however, was greater for RCABG compared with PCI in multivariable analysis (HR=0.70; 95% CI, 0.59-0.83; P <.001), as well as in propensity matched analysis (10-year survival rates were 52% vs 37%, respectively [ P =.005]). Compared with RCABG, PCI involving bypass grafts had increased mortality (HR, 1.39; 95% CI, 1.09-1.78; P =.008), whereas PCI targeting only the native coronaries did not (HR, 1.12; 95% CI, 0.85-1.47; P =.43); BMS patients had increased mortality (HR, 1.34; 95% CI, 1.06-1.68; P =.013), but DES did not (HR, 1.28; 95% CI, 0.77-2.12; P =.35). At RCABG, 318 patients (60%) received an IMA graft and late survival was similar to those receiving SVG; The use of IMA in previous CABG was associated with improved survival (HR=0.82; 95% CI, 0.72-0.92; P <.001]. Conclusions: Long-term survival after previous CABG is improved with RCABG compared to PCI, especially when PCI involves bypass grafts. There is no difference in long-term survival between RCABG using arterial grafts vs SVG only if IMA is used in either previous or RCABG.

Background Little is known about the effects of permanent transvenous device leads on bioprosthetic tricuspid valve (BTV) function. Hypothesis The goal of this study was to test the hypothesis that transvalvular device leads promote clinically significant BTV regurgitation. Methods A retrospective review of 58 patients who underwent BTV implantation and subsequently required endocardial pacemaker (n=52) or defibrillator (n=6) lead implantation through the BTV was conducted. Patient and prosthesis characteristics, lead type, and clinical events were collected. The incidence and severity of prosthetic tricuspid regurgitation (TR), determined by Doppler echocardiography, was compared to 265 patients who underwent BTV implantation without undergoing subsequent transvalvular device lead implantation. Results Over a mean follow up of 25 months, 5 patients (9%) with a transvalvular lead developed ≥ moderate prosthetic TR compared to 12 patients (5%) in the control group (P = 0.20). Kaplan Meier survival analysis revealed no significant difference in the incidence of TR in BTV patients with and without transvalvular leads (p = 0.45). Clinically significant prosthetic TR in patients with and without a transvalvular lead more commonly occurred 2 years or later after lead implantation or BTV implantation (4/5, 80% and 10/12, 83%). Conclusions Compared to BTV controls, there was no significant difference in the incidence of ≥ moderate prosthetic TR in patients with a transvalvular pacemaker or defibrillator lead (p = 0.45). Transvalvular lead implantation appears to be an acceptable approach for patients with a BTV who require permanent pacemaker or defibrillator placement.

Objectives. The use of the left internal mammary artery (IMA) in revascularization of multivessel coronary artery disease has been shown to improve survival following coronary artery bypass graft surgery (CABG), however the incremental survival benefit of multiple arterial grafts is still debated. Methods. We reviewed outcome of 8,622 pt that had isolated primary CABG for multivessel disease from 1993 to 2009.Pt were stratified according to the number of arterial grafts; (1) single IMA plus saphenous vein (SV) IMA/SV group (n=7,435; 83% 3VD) and (2) multiple arterial (MultArt) group (n=1,187; 74% 3VD) Results. Early mortality rate was 0.8% (n=10) in the MultArt group and 2.1% (n=154) in the IMA/SV group (P=0.004). However, the difference was not statistically significant (P=0.996) after adjusting for age, gender, chronic lung disease, renal failure, PVD, MI, EF, and number of diseased vessels. Late survival was significantly greater for the MultArt group compared to IMA/SV group (5-, 10- and 15-year survival rates were 95%, 84% and 71% versus 85%, 61% and 35% p<0.001). MultArt subgroups with the use of bilateral internal mammary artery (BIMA)/SV (n=589) and BIMA only (n=271), had significantly improved 15-years survival (97%, 86%, 76% and 94%, 82%, 75% at 5-, 10- and 15-years, p<0.001), and BIMA/RA (n=147) and LIMA/RA (n=169), had significantly greater 10-years survival (95%, 84% and 93%, 78% at 5- and 10-years, p<0.001) compared to IMA/SV group. In multivariate analysis, use of multiple arterial grafts remained a strong independent predictor of survival (HR=0.78, 95% CI 0.66 - 0.93, p=0.006). Conclusion. Use of the right IMA or radial artery in addition to the left IMA is associated with significantly better overall and late survival compared with single IMA and saphenous vein in patients with two and three-vessel disease undergoing isolated CABG.

AbstractBackgroundRoutine defibrillation threshold testing (DFT) of transvenous implantable defibrillators (ICDs) has largely been in decline. In patients with non‐transvenous ICDs that utilize subcutaneous and pleural ICD leads, serial DFT testing can detect a significant number of failures. Data about the utility of follow‐up defibrillation safety margin testing (DSM) testing in pediatric patients and young adults with an epicardial ICD are lacking.MethodsPatients aged < 25 years old who underwent epicardial ICD placement at Mayo Clinic from 2014 to 2023 with at least one follow‐up DSM test were included. The patients were divided into a “routine” (R) and “clinically indicated” (CI) group based on the index of clinical concern. Inadequate DSM was defined as unsuccessful defibrillation at an output of less than 10 J below the maximum output of the device. The purpose of this study was to assess the utility of follow‐up DSM testing.ResultsAn epicardial ICD system was placed in 122 patients. A total of 26 patients met inclusion criteria and underwent a total of 47 DSM follow up tests. Inadequate DSM occurred in 1/33 (3%) in the R group and 2/14 (14%) DSM tests in the CI group. The median follow‐up period was 54 and 36 months for the R and CI group, respectively.ConclusionsOur data suggest that epicardial ICDs are reliable and routine follow‐up DSM testing may not be necessary for all patients. DSM testing should be performed in individuals with epicardial ICD systems when there is clinical concern about lead or coil performance.

Introduction: Recently, we demonstrated transcriptional down-regulation of hypertrophy pathways in myectomy tissue derived from patients with obstructive hypertrophic cardiomyopathy (HCM) despite translational activation of associated hypertrophy pathways. Previous studies of other forms of cardiac hypertrophy demonstrate hypertrophy pathways are activated via histone acetylation and histone deacetylase (HDAC) inhibitors prevented development of hypertrophy. Whether histone modifications regulate hypertrophy pathways in HCM remains unexplored. Methods: Chromatin immunoprecipitation sequencing (ChIP-seq) was performed on myectomy tissues from 40 patients with HCM and 23 controls to characterize differential histone marks for H3K4me3 (active promoter), H3K9ac (active promoter), H3K9me3 (heterochromatin), H3K27ac (active enhancer), H3K27me3 (repression) across the genome. The differential histone marks were integrated with RNA-sequencing (RNA-seq) data derived from the same patients. Results: Overall, we identified 2,912 (7%) differential H3K4me3 peaks impacting 5 pathways, 23,339 (21%) differential H3K9ac peaks impacting 87 pathways, 33 (0.05%) differential H3K9me3 peaks, and 58,837 (42%) differential H3K27ac peaks impacting 50 pathways. There was increased H3K27ac (q-value = 0.002) and H3K9ac (q-value = 0.009) at RAS-MAPK loci. Univariate analysis of concordance between H3K9ac with RNA-seq data showed activation of cardiac hypertrophy signaling (z-score=4.5; -log [BH p-value] = 3.1), while H3K27me showed down-regulation of cardiac hypertrophy signaling (z-score=-2.4; -log [BH p-value] = 2.4). Multivariate integration of the ChIP-seq data with RNA-seq data identified 3,189 transcripts concordant with all five histone marks impacting 254 pathways, 18 (7%) of which are involved in cardiac hypertrophy. Conclusions: Myectomy tissue from patients with obstructive HCM shows enrichment of histone modifications at cardiac hypertrophy loci with activation via H3K27 and H3K9 acetylation and repression via H3K27 methylation. Further studies are needed to understand the balance and temporal relationship between these competing regulators in HCM pathobiology and the potential for epigenetic therapies.

Background: Robust models exist to predict risk-adjusted mortality following congenital heart surgery. It is known that underlying diagnosis modifies predicted risk of operations, and institution-level outcomes vary based on their unique case mix. We therefore evaluated risk-adjusted outcomes for a subset of diagnosis-procedure (D-P) combinations within the Society of Thoracic Surgeons' (STS) congenital heart surgery database (CHSD). Methods: A clinician panel identified the most frequently encountered D-P combinations in CHSD between 07/2017 and 06/2021. Candidate modeling techniques were compared in a random 80% development cohort. Model performance was assessed using internal and cross-validation calibration, discrimination plots and optimism adjusted C-statistics. The final selected model was evaluated in the 20% validation sample. Results: The chosen subset of D-P combinations represented 45,384 of 87,589 (52%) unique episodes of surgical care in CHSD during this time-period. The development cohort (36,350 episodes) had 1.8% mortality (667 deaths). All candidate models had excellent discrimination with C-statistics ranging from 0.862 to 0.876. The model with the best combination of discrimination, calibration, and clinical face validity was a modified version of the current STS mortality risk model. This version included all current risk model variables with the addition of indicator variables for D-P combinations. In the 20% validation sample (9,034 episodes), this model was well calibrated (Figure) and had excellent discrimination (C = 0.879). Conclusion: We describe a cohort of D-P combinations widely encountered in the STS CHSD. Further, we refined the existing STS CHSD risk model for application to these D-P dyads to derive empirical risk-adjusted benchmark outcomes. This approach will benefit quality improvement efforts at an institutional level and may have implications for publicly reporting congenital heart surgery outcomes.

Hepatocellular carcinoma (HCC), constituting the predominant manifestation of liver cancer, stands as a formidable medical challenge. The prognosis subsequent to surgical intervention, particularly for individuals presenting with a solitary tumor, relies heavily on the degree of invasiveness. The decision-making process surrounding therapeutic modalities in such cases assumes paramount importance. This case report illuminates a rather unusual clinical scenario. Here, we encounter a patient who, following a disease-free interval, manifested an atypical presentation of HCC, specifically, a solitary cardiac metastasis. The temporal interval of remission adds an additional layer of complexity to the case. Through a multidisciplinary planning process, the decision was made for surgical removal of the metastatic tumor.