Dose-Blinded Myosin Inhibition in Patients With Obstructive Hypertrophic Cardiomyopathy Referred for Septal Reduction Therapy: Outcomes Through 32 Weeks.

BACKGROUND: Septal reduction therapy (SRT) in patients with intractable symptoms from obstructive hypertrophic cardiomyopathy (oHCM) is associated with variable morbidity and mortality. The VALOR-HCM trial (A Study to Evaluate Mavacamten in Adults with Symptomatic Obstructive Hypertrophic Cardiomyopathy Who Are Eligible for Septal Reduction Therapy) examined the effect of mavacamten on the need for SRT through week 32 in oHCM. METHODS: A double-blind randomized placebo-controlled multicenter trial at 19 US sites included patients with oHCM on maximal tolerated medical therapy referred for SRT with left ventricular outflow tract gradient ≥50 mm Hg at rest or provocation (enrollment, July 2020-October 2021). The group initially randomized to mavacamten continued the drug for 32 weeks, and the placebo group crossed over to dose-blinded mavacamten from week 16 to week 32. Dose titrations were based on investigator-blinded echocardiographic assessment of left ventricular outflow tract gradient and left ventricular ejection fraction. The principal end point was the proportion of patients proceeding with SRT or remaining guideline eligible at 32 weeks in both treatment groups. RESULTS: From the 112 randomized patients with oHCM, 108 (mean age, 60.3 years; 50% men; 94% in New York Heart Association class III/IV) qualified for week 32 evaluation (56 in the original mavacamten group and 52 in the placebo cross-over group). After 32 weeks, 6 of 56 patients (10.7%) in the original mavacamten group and 7 of 52 patients (13.5%) in the placebo cross-over group met SRT guideline criteria or elected to undergo SRT. After 32 weeks, a sustained reduction in resting left ventricular outflow tract gradient (-33.0 mm Hg [95% CI, -41.1 to -24.9]) and Valsalva left ventricular outflow tract gradient (-43.0 mm Hg [95% CI, -52.1 to -33.9]) was observed in the original mavacamten group. A similar reduction in resting (-33.7 mm Hg [95% CI, -42.2 to -25.2]) and Valsalva (-52.9 mm Hg [95% CI, -63.2 to -42.6]) gradients was quantified in the cross-over group after 16 weeks of mavacamten. After 32 weeks, improvement by ≥1 New York Heart Association class was observed in 48 of 53 patients (90.6%) in the original mavacamten group and 35 of 50 patients (70%) after 16 weeks in the cross-over group. CONCLUSIONS: In severely symptomatic patients with oHCM, 32 weeks of mavacamten treatment showed sustained reduction in the proportion proceeding to SRT or remaining guideline eligible, with similar effects observed in patients who crossed over from placebo after 16 weeks. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT04349072.

Study design and rationale of VALOR-HCM: evaluation of mavacamten in adults with symptomatic obstructive hypertrophic cardiomyopathy who are eligible for septal reduction therapy.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is a primary myocardial disorder which frequently leads to symptoms such as dyspnea and exercise intolerance, often due to severe dynamic left ventricular outflow tract obstruction (LVOTO). Current guideline-recommended pharmacotherapies have variable therapeutic responses to relieve LVOTO. In recent phases 2 and 3, clinical trials for symptomatic obstructive HCM (oHCM), mavacamten, a small molecule inhibitor of ß-cardiac myosin has been shown to improve symptoms, exercise capacity, health status, reduce LVOTO, along with having a beneficial impact on cardiac structure and function. METHODS: VALOR-HCM is designed as a multicenter (approximately 20 centers in United States) phase 3, double-blind, placebo-controlled, randomized study. The study population consists of approximately 100 patients (≥18 years old) with symptomatic oHCM who meet 2011 American College of Cardiology/American Heart Association and/or 2014 European Society of Cardiology HCM-guideline criteria and are eligible and willing to undergo septal reduction therapy (SRT). The study duration will be up to 138 weeks, including an initial 2-week screening period, followed by16 weeks of placebo-controlled treatment, 16 weeks of active blinded treatment, 96 weeks of long-term extension, and an 8-week posttreatment follow-up visit. The primary endpoint will be a composite of the decision to proceed with SRT prior to or at Week 16 or remain guideline eligible for SRT at Week 16. Secondary efficacy endpoints will include change (from baseline to Week 16 in the mavacamten group vs placebo) in postexercise LVOT gradient, New York Heart Association class, Kansas City Cardiomyopathy Questionnaire clinical summary score, NT-proBNP, and cardiac troponin. Exploratory endpoints aim to characterize the effect of mavacamten on multiple aspects of oHCM pathophysiology. CONCLUSIONS: In severely symptomatic drug-refractory oHCM patients meeting guideline criteria of eligibility for SRT, VALOR-HCM will primarily study if a 16-week course of mavacamten reduces or obviates the need for SRT using clinically driven endpoints.

Robotic trans-mitral septal myectomy and papillary muscle reorientation for HOCM combined with or without mitral valve repair: Technical aspects - How we do it.

Hypertrophic obstructive cardiomyopathy (HOCM) is one of the more common genetic disorders. The pathophysiology and natural history of the disease have been well studied. Left ventricular outflow tract obstruction (LVOTO) and systolic anterior motion (SAM) of the anterior mitral leaflet can result in sudden cardiac death, progressive heart failure and arrythmias. Surgical septal myectomy for HOCM is the standard of care and is routinely performed through a median sternotomy. Septal myectomy has also been performed using the trans-atrial, trans-mitral approach either directly or with robotic assistance. In cases with severe LVOT obstruction in the setting of only mild to moderate proximal septal hypertrophy, intrinsic problems with the mitral valve contribute. Typically, these are hypermobile papillary muscles and or excessive height of the anterior mitral leaflet. Combining septal myectomy with reorientation of hypermobile anteriorly positioned papillary muscles has shown to prevent SAM and thereby additionally decrease the subvalvular aortic outflow obstruction. Our extensive experience in both septal myectomy and robotic mitral valve repair has given us a different perspective in approaching the primary mitral regurgitation in HOCM patients where a combined septal myectomy, papillary muscle reorientation and complex mitral valve repair has been safely performed using the less invasive robotic-assisted approach.Our objective here is to discuss the technical aspects of the procedure.

Unexpected abrupt increase in left ventricular assist device thrombosis.

BACKGROUND: We observed an apparent increase in the rate of device thrombosis among patients who received the HeartMate II left ventricular assist device, as compared with preapproval clinical-trial results and initial experience. We investigated the occurrence of pump thrombosis and elevated lactate dehydrogenase (LDH) levels, LDH levels presaging thrombosis (and associated hemolysis), and outcomes of different management strategies in a multi-institutional study. METHODS: We obtained data from 837 patients at three institutions, where 895 devices were implanted from 2004 through mid-2013; the mean (±SD) age of the patients was 55±14 years. The primary end point was confirmed pump thrombosis. Secondary end points were confirmed and suspected thrombosis, longitudinal LDH levels, and outcomes after pump thrombosis. RESULTS: A total of 72 pump thromboses were confirmed in 66 patients; an additional 36 thromboses in unique devices were suspected. Starting in approximately March 2011, the occurrence of confirmed pump thrombosis at 3 months after implantation increased from 2.2% (95% confidence interval [CI], 1.5 to 3.4) to 8.4% (95% CI, 5.0 to 13.9) by January 1, 2013. Before March 1, 2011, the median time from implantation to thrombosis was 18.6 months (95% CI, 0.5 to 52.7), and from March 2011 onward, it was 2.7 months (95% CI, 0.0 to 18.6). The occurrence of elevated LDH levels within 3 months after implantation mirrored that of thrombosis. Thrombosis was presaged by LDH levels that more than doubled, from 540 IU per liter to 1490 IU per liter, within the weeks before diagnosis. Thrombosis was managed by heart transplantation in 11 patients (1 patient died 31 days after transplantation) and by pump replacement in 21, with mortality equivalent to that among patients without thrombosis; among 40 thromboses in 40 patients who did not undergo transplantation or pump replacement, actuarial mortality was 48.2% (95% CI, 31.6 to 65.2) in the ensuing 6 months after pump thrombosis. CONCLUSIONS: The rate of pump thrombosis related to the use of the HeartMate II has been increasing at our centers and is associated with substantial morbidity and mortality.

Predictors of long-term outcomes in patients with hypertrophic cardiomyopathy undergoing cardiopulmonary stress testing and echocardiography.

BACKGROUND: Patients with hypertrophic cardiomyopathy (HCM) have exercise intolerance due to left ventricular outflow tract (LVOT) obstruction, mitral regurgitation, and left ventricular dysfunction. We sought to study predictors of outcomes in HCM patients undergoing cardiopulmonary stress testing (CPT). METHODS: We studied 1,005 HCM patients (50 ± 14 years, 64% men, 77% on ß-blockers) who underwent CPT with echocardiography. Clinical, echocardiographic, and exercise variables (peak oxygen consumption [VO2] and heart rate recovery [HRR] at first minute postexercise) were recorded. End point was a composite of death, appropriate defibrillator discharges, resuscitated sudden death, stroke, and heart failure admission. RESULTS: Mean left ventricular ejection fraction (LVEF), postexercise LVOT gradient, and peak VO2 were 62% ± 6%, 92 ± 51 mm Hg, and 21 ± 6 mL kg(-1) min(-1), respectively. Despite 789 patients (78%) being in New York Heart Association classes I to II, only 8% achieved >100% age-gender predicted peak VO2, whereas 77% and 15% achieved 50% to 100% and <50%, respectively. Left ventricular outflow tract gradient ≥30 mm Hg was observed in 83% patients, whereas 23% had abnormal HRR. More than 5.5 ± 4 years, there were 94 (9%) events; 511 (50%) patients underwent surgery for LVOT obstruction. Multivariable Cox proportional analysis demonstrated % age-gender predicted peak VO2 (hazard ratio [HR] 0.96 [0.93-0.98]), normal vs abnormal HRR (HR 0.48 [0.32-0.73]), higher LVEF (HR 0.96 [0.93-0.98]), surgery (0.53 [0.33-0.83]), and atrial fibrillation (HR 1.65 [1.04-2.60]) were associated with outcomes (all P < .05). CONCLUSIONS: In HCM patients undergoing CPT, a higher % of achieved age-gender predicted VO2 and surgical relief of LVOT obstruction were associated with better outcomes, whereas abnormal HRR, atrial fibrillation, and lower LVEF were associated with worse outcomes.

Low-dose 3-factor prothrombin complex concentrate for warfarin reversal prior to heart transplant.

BACKGROUND: Anticoagulation with warfarin is common in patients presenting for heart transplant. Prior to surgery, anticoagulation reversal is necessary to avoid significant intraoperative and perioperative bleeding complications. Commonly, warfarin reversal is achieved with vitamin K and fresh frozen plasma (FFP); however, these therapies have significant limitations. An alternative to FFP for reversal exists with prothrombin complex concentrate (PCC). A warfarin reversal protocol prior to heart transplant was implemented using low-dose PCC at our institution. OBJECTIVE: To assess blood product use, effectiveness, and safety post-low-dose PCC administration in patients needing warfarin reversal prior to heart transplant compared with historical controls. METHODS: This was a single-center, retrospective cohort study. The PCC cohort included patients undergoing heart transplant presenting with an international normalized ratio ≥1.5 on warfarin therapy and who received at least 1 dose of PCC. Blood product use was measured from postoperative day 0 to 2. RESULTS: The PCC and historical control cohorts included 16 and 50 patients, respectively. There was a significant reduction in the use of FFP (4 vs 8 units, P = 0.0239) in the PCC cohort compared with the historical control cohort. No differences were identified in the use of other blood products as well as other secondary efficacy or safety end points. CONCLUSIONS: Use of PCC, per the reversal protocol, prior to heart transplant reduced FFP use and showed a non-statistically significant trend toward reductions in the use of other blood products in the intraoperative and perioperative setting, with no difference identified in thrombotic or embolic complications compared with historical controls.

Ventricular septal rupture complicating acute myocardial infarction: a contemporary review.

Ventricular septal rupture (VSR) after acute myocardial infarction is increasingly rare in the percutaneous coronary intervention era but mortality remains high. Prompt diagnosis is key and definitive surgery, though challenging and associated with high mortality, remains the treatment of choice. Alternatively, delaying surgery in stable patients may provide better results. Prolonged medical management is usually futile, but includes afterload reduction and intra-aortic balloon pump placement. Using full mechanical support to delay surgery is an attractive option, but data on success is limited to case reports. Finally, percutaneous VSR closure may be used as a temporizing measure to reduce shunt, or for patients in the sub-acute to chronic period whose comorbidities preclude surgical repair.

Long-term survival of patients with radiation heart disease undergoing cardiac surgery: a cohort study.

BACKGROUND: Thoracic radiation results in radiation-associated heart disease (RAHD), often requiring cardiothoracic surgery (CTS). We sought to measure long-term survival in RAHD patients undergoing CTS, to compare them with a matched control population undergoing similar surgical procedures, and to identify potential predictors of long-term survival. METHODS AND RESULTS: In this retrospective observational cohort study of patients undergoing CTS, matched on the basis of age, sex, and type/time of CTS, 173 RAHD patients (75% women; age, 63±14 years) and 305 comparison patients (74% women; age, 63±4 years) were included. The vast majority of RAHD patients had prior breast cancer (53%) and Hodgkin lymphoma (27%), and the mean time from radiation was 18±12 years. Clinical and surgical parameters were recorded. The preoperative EuroSCORE and all-cause mortality were recorded. The mean EuroSCOREs were similar in the RAHD and comparison groups (7.8±3 versus 7.4±3, respectively; P=0.1). Proximal coronary artery disease was higher in patients with RAHD versus the comparison patients (45% versus 38%; P=0.09), whereas redo CTS was lower in the RACD versus the comparison group (20% versus 29%; P=0.02). About two thirds of patients in either group had combination surgical procedures. During a mean follow-up of 7.6±3 years, a significantly higher proportion of patients died in the RAHD group than in the comparison group (55% versus 28%; P<0.001). On multivariable Cox proportional hazard analysis, RAHD (2.47; 95% confidence interval, 1.82-3.36), increasing EuroSCORE (1.22; 95% confidence interval, 1.16-1.29), and lack of ß-blockers (0.66; 95% confidence interval, 0.47-0.93) were associated with increased mortality (all P<0.01). CONCLUSIONS: In patients undergoing CTS, RAHD portends increased long-term mortality. Alternative treatment strategies may be required in RAHD to improve long-term survival.

Predictors of long-term outcomes in symptomatic hypertrophic obstructive cardiomyopathy patients undergoing surgical relief of left ventricular outflow tract obstruction.

BACKGROUND: We report the predictors of long-term outcomes of symptomatic hypertrophic cardiomyopathy patients undergoing surgical relief of left ventricular outflow tract obstruction. METHODS AND RESULTS: We studied 699 consecutive patients who have hypertrophic cardiomyopathy with severe symptomatic left ventricular outflow tract obstruction (47±11 years, 63% male) intractable to maximal medical therapy, who were referred to a tertiary hospital between January 1997 and December 2007 for the surgical relief of left ventricular outflow tract obstruction. We excluded patients <18 years of age, those with an ejection fraction <50%, those with hypertensive heart disease of the elderly, and those with more than mild aortic or mitral stenosis. Clinical, echocardiographic, and Holter data were recorded. A composite end point of death, appropriate internal cardioverter defibrillator discharges, resuscitated from sudden death, documented stroke, and admission for congestive heart failure was recorded. During a mean follow-up of 6.2±3 years, 86 patients (12%) met the composite end point with 30-day, 1-year, and 2-year event rates of 0.7%, 2.8%, and 4.7%, respectively. The hard event rate (death, defibrillator discharge, and resuscitated from sudden death) at 30 days, 1 year, and 2 years was 0%, 1.5%, and 3%, respectively. Stepwise multivariable analysis identified residual postoperative atrial fibrillation (hazard ratio, 2.12; confidence interval, 1.37-3.34; P=0.001) and increasing age (hazard ratio, 1.49; confidence interval, 1.22-1.82; P=0.001) as independent predictors of long-term composite outcomes. CONCLUSIONS: Symptomatic adult hypertrophic cardiomyopathy patients undergoing surgery for the relief of left ventricular outflow tract obstruction have low event rates during long-term follow-up; worse outcomes are predicted by increasing age and the presence of residual atrial fibrillation during follow-up.

Efficacy and safety of a transaortic approach to midventricular and apical septal myectomy.

OBJECTIVE: The study objective was to evaluate the safety and efficacy of a transaortic approach to midventricular and apical septal myectomy in patients with hypertrophic cardiomyopathy with left ventricular outflow tract or midventricular obstruction. METHODS: From January 2018 to August 2023, 940 patients underwent transaortic septal myectomy at the Cleveland Clinic, of whom 682 (73%) had midventricular or apical resection. Patients who underwent isolated basal myectomies were excluded. Templated operative reports designated septal regions resected as basal (opposition to mitral valve up to the leaflet tips), midventricular (leaflet tips to just beyond the papillary muscle heads), and apical (apical third of the ventricle). Myocardial resection specimen weights, intraventricular gradients, and clinical outcomes were assessed. RESULTS: Of the 682 patients, 582 (85%) had basal plus midventricular resection and 78 (11%) had basal, midventricular, and apical resection. Mean preoperative intraventricular gradient was 102 ± 41 mm Hg. Median resection weight was 10 g (15th, 85th percentiles: 7, 15), and mean postoperative intraventricular gradient was 16 ± 10 mm Hg, with 625 (96%) patients achieving gradients 36 mm Hg or less. There were no iatrogenic mitral or aortic valve injuries. Permanent pacemaker placement was required in 38 patients (5.6%), of whom 8 (1.2%) had normal preoperative conduction. Operative mortality occurred in 1 patient (0.1%) after an intraoperative ventricular septal defect. CONCLUSIONS: Most patients undergoing septal myectomy for relief of obstruction required resection beyond the basal septum. With specialized instrumentation, detailed imaging and knowledge of variable septal anatomy, resecting midventricular and apical septal muscle can be safely and effectively achieved through a transaortic approach.

Association between septal strain rate and histopathology in symptomatic hypertrophic cardiomyopathy patients undergoing septal myectomy.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is histopathologically characterized by myocyte hypertrophy, disarray, interstitial fibrosis, and small intramural coronary arteriole dysplasia, which contribute to disease progression. Longitudinal systolic and early diastolic strain rate (SR) measurements by speckle tracking echocardiography are sensitive markers of regional myocardial function. We sought to determine the association between septal SR and histopathologic findings in symptomatic HCM patients who underwent surgical myectomy. METHODS: We studied 171 HCM patients (documented on histopathology) who underwent surgical myectomy to relieve left ventricular outflow tract obstruction. Various clinical and echocardiographic parameters were recorded. Segmental longitudinal systolic and early diastolic SRs (of the septal segment removed at myectomy) were measured from apical 4- and 2-chamber views (VVI 2.0; Siemens, Erlangen, Germany). Histopathologic myocyte hypertrophy, disarray, small intramural coronary arteriole dysplasia, and interstitial fibrosis were classified as none, mild (1%-25%), moderate (26%-50%), and severe (>50%). RESULTS: The mean age was 53 ± 14 years (52% men, ejection fraction 62% ± 5%, mean left ventricular outflow tract gradient 102 ± 39 mm Hg, and basal septal thickness of 2.2 ± 0.5 cm). Mean longitudinal systolic and early diastolic SRs were -0.91 ± 0.5 and 0.82 ± 0.5 (1/s), respectively. There was an inverse association between systolic and early diastolic septal SR and degree of myocyte hypertrophy, disarray, and interstitial fibrosis (all P < .05). There was no association between histopathologic characteristics and other echocardiography parameters. On multivariable regression analysis, myocyte disarray and echocardiographic septal hypertrophy were associated with systolic and early diastolic septal SR (P < .05). CONCLUSION: In HCM patients, there is inverse association between various histopathologic findings and septal SR. Strain rate might potentially provide further insight into HCM pathophysiology.

Survival After Septal Reduction in Patients >65 Years Old With Obstructive Hypertrophic Cardiomyopathy.

BACKGROUND: Obstructive hypertrophic cardiomyopathy (oHCM) is increasingly being diagnosed in elderly patients. OBJECTIVES: The authors sought to study long-term outcomes of septal reduction therapies (SRT) in Medicare patients with oHCM, and hospital volume-outcome relation. METHODS: Medicare beneficiaries aged >65 years who underwent SRT, septal myectomy (SM) or alcohol septal ablation (ASA), from 2013 through 2019 were identified. Primary outcome was all-cause mortality, and secondary outcomes included heart failure (HF) readmission and need for redo SRT in follow-up. Overlap propensity score weighting was used to adjust for differences between both groups. Relation between hospital SRT volume and short-term and long-term mortality was studied. RESULTS: The study included 5,679 oHCM patients (SM = 3,680 and ASA = 1,999, mean age 72.9 vs 74.8 years, women 67.2% vs 71.1%; P < 0.01). SM patients had fewer comorbidities, but after adjustment, both groups were well balanced. At 4 years (IQR: 2-6 years), although there was no difference in long-term mortality between SM and ASA (HR: 0.87; 95% CI: 0.74-1.03; P = 0.1), on landmark analysis, SM was associated with lower mortality after 2 years of follow-up (HR: 0.72; 95% CI: 0.60-0.87; P < 0.001) and had lower need for redo SRT. Both reduced HF readmissions in follow-up vs 1 year pre-SRT. Higher-volume centers had better outcomes vs lower-volume centers, but 70% of SRT were performed in low-volume centers. CONCLUSIONS: SRT reduced HF readmission in Medicare patients with oHCM. SM is associated with lower redo and better long-term survival compared with ASA. Despite better outcomes in high-volume centers, 70% of SRT are performed in low-volume U.S. centers.

Patient reported outcomes in obstructive hypertrophic cardiomyopathy undergoing myectomy: Results from SPIRIT-HCM study.

BACKGROUND: Patient reported outcomes (PRO) can assess quality of life (QOL) in obstructive hypertrophic cardiomyopathy (oHCM). In symptomatic oHCM patients, we sought to study the correlation between various PROs, their association with physician reported New York Heart Association (NYHA) class and changes after surgical myectomy. METHODS: We prospectively studied 173 symptomatic oHCM patients undergoing myectomy (age 51 years, 62% men) between 3/17-6/20. PROs, including a) Kansas City Cardiomyopathy Questionnaire (KCCQ) summary score b) Patient-Reported Outcomes Measurement Information System [PROMIS] c) Duke Activity Status Index [DASI] & d) European QOL score [EQ-5D], along with NYHA class, 6-min walk test (6MWT) distance and peak left ventricular outflow tract gradient (PLVOTG) were recorded at baseline and 12 month follow-up. RESULTS: The median baseline PRO scores (KCCQ summary, PROMIS physical, PROMIS mental, DASI, EQ-5D) were 50, 67, 63, 25, 50, 37, 44, 25 and 0.61, respectively; 6MWT distance was 366 m. There were significant correlations between various PROs (r-values between 0.66 and 0.92, p < 0.001), but only modest correlations with 6MWT and provokable LVOTG (r-values between 0.2 and 0.5, p < 0.01). At baseline, 35-49% patients in NYHA class II had PROs worse than median, while 30-39% patients in NYHA Class III/IV had PROs better than median. At follow-up, a 20 point improvement in KCCQ summary score was observed in 80%, 4 point improvement in DASI score in 83%, 4 point improvement in PROMIS physical score 86% and a 0.04 point improvement in EQ-5D in 85%); along with improvements in NYHA class (67% in Class I) and peak LVOTG (median 13 mmHg) and 6MWT (median distance 438 m). CONCLUSIONS: In a prospective study of symptomatic oHCM patients, surgical myectomy significantly improved PROs, LVOT obstruction, and functional capacity, with a high correlation between various PROs. However, there was high rate of discordance between PROs and NYHA class. STUDY REGISTRATION: ClinicalTrials.gov: NCT03092843.

Increasing surgeon experience and cumulative institutional experience drive decreasing hospital mortality after reoperative cardiac surgery.

OBJECTIVE: The study objective was to identify the effects of surgeon experience and age, in the context of cumulative institutional experience, on risk-adjusted hospital mortality after cardiac reoperations. METHODS: From 1951 to 2020, 36 surgeons performed 160,338 cardiac operations, including 32,871 reoperations. Hospital death was modeled using a novel tree-bagged, generalized varying-coefficient method with 6 variables reflecting cumulative surgeon and institutional experience up to each cardiac operation: (1) number of total and (2) reoperative cardiac operations performed by a surgeon, (3) cumulative institutional number of total and (4) reoperative cardiac operations, (5) year of surgery, and (6) surgeon age at each operation. These were adjusted for 46 patient characteristics and surgical components. RESULTS: There were 1470 hospital deaths after cardiac reoperations (4.5%). At the institutional level, hospital death decreased exponentially and became less variable, leveling at 1.2% after approximately 14,000 cardiac reoperations. For all surgeons as a group, hospital death decreased rapidly over the first 750 reoperations and then gradually decreased with increasing experience to less than 1% after approximately 4000 reoperations. Surgeon age up to 75 years was associated with ever-decreasing hospital death. CONCLUSIONS: Surgeon age and experience have been implicated in adverse surgical outcomes, particularly after complex cardiac operations, with young surgeons being novices and older surgeons having declining ability. However, at Cleveland Clinic, outcomes of cardiac reoperations improved with increasing primary surgeon experience, without any suggestion to mid-70s of an age cutoff. Patients were protected by the cumulative background of institutional experience that created a culture of safety and teamwork that mitigated adverse events after cardiac surgery.

Public reporting for coronary artery bypass graft surgery: The quest for the optimal scorecard.

OBJECTIVE: A number of publicly available rating algorithms are used to assess hospital performance in coronary artery bypass grafting (CABG). However, concerns remain that these algorithms fail to correlate with each other and inadequately capture the case complexity of individual center practices. METHODS: Composite star ratings for isolated CABG from the Society of Thoracic Surgeons public reporting database were extracted for 2018-2019. U.S. News & World Report Best Hospitals was used to extract CABG ratings as well as overall cardiology and heart surgery ranking, and the Centers for Medicare & Medicaid Services Hospital Compare was used to extract CABG volume and 30-day mortality. Spearman correlation coefficients were used to assess possible relationships. Expert opinion on risk adjustment and program evaluation was incorporated. RESULTS: Correlations between Society of Thoracic Surgeons star rating and U.S. News & World Report overall ranking in cardiology and heart surgery (r = 0.15) and Centers for Medicare & Medicaid Services 30-day mortality (r = -0.27) were poor. Society of Thoracic Surgeons star rating correlated weakly with U.S. News & World Report CABG ratings (r = 0.33) and with Centers for Medicare & Medicaid Services CABG volume (r = 0.32), whereas the latter 2 correlated moderately (r = 0.52) with each other. Of the 75 centers with accredited cardiac surgery training programs, 13 (17%) did not participate in Society of Thoracic Surgeons public reporting. Important gaps were identified in risk assessment, and potential solutions are proposed. CONCLUSIONS: Correlations between current CABG public reporting systems are weak. Further work is needed to refine and standardize CABG rating systems to more adequately capture the scope and complexity of an individual center's clinical practice and to better inform patients.

Mavacamten in Patients With Hypertrophic Cardiomyopathy Referred for Septal Reduction: Week 56 Results From the VALOR-HCM Randomized Clinical Trial.

Importance: There is an unmet need for novel medical therapies before recommending invasive therapies for patients with severely symptomatic obstructive hypertrophic cardiomyopathy (HCM). Mavacamten has been shown to improve left ventricular outflow tract (LVOT) gradient and symptoms and may thus reduce the short-term need for septal reduction therapy (SRT). Objective: To examine the cumulative longer-term effect of mavacamten on the need for SRT through week 56. Design, Setting, and Participants: This was a double-blind, placebo-controlled, multicenter, randomized clinical trial with placebo crossover at 16 weeks, conducted from July 2020 to November 2022. Participants were recruited from 19 US HCM centers. Included in the trial were patients with obstructive HCM (New York Heart Association class III/IV) referred for SRT. Study data were analyzed April to August 2023. Interventions: Patients initially assigned to mavacamten at baseline continued the drug for 56 weeks, and patients taking placebo crossed over to mavacamten from week 16 to week 56 (40-week exposure). Dose titrations were performed using echocardiographic LVOT gradient and LV ejection fraction (LVEF) measurements. Main Outcome and Measure: Proportion of patients undergoing SRT, remaining guideline eligible or unevaluable SRT status at week 56. Results: Of 112 patients with highly symptomatic obstructive HCM, 108 (mean [SD] age, 60.3 [12.5] years; 54 male [50.0%]) qualified for the week 56 evaluation. At week 56, 5 of 56 patients (8.9%) in the original mavacamten group (3 underwent SRT, 1 was SRT eligible, and 1 was not SRT evaluable) and 10 of 52 patients (19.2%) in the placebo crossover group (3 underwent SRT, 4 were SRT eligible, and 3 were not SRT evaluable) met the composite end point. A total of 96 of 108 patients (89%) continued mavacamten long term. Between the mavacamten and placebo-to-mavacamten groups, respectively, after 56 weeks, there was a sustained reduction in resting (mean difference, -34.0 mm Hg; 95% CI, -43.5 to -24.5 mm Hg and -33.2 mm Hg; 95% CI, -41.9 to -24.5 mm Hg) and Valsalva (mean difference, -45.6 mm Hg; 95% CI, -56.5 to -34.6 mm Hg and -54.6 mm Hg; 95% CI, -66.0 to -43.3 mm Hg) LVOT gradients. Similarly, there was an improvement in NYHA class of 1 or higher in 51 of 55 patients (93%) in the original mavacamten group and in 37 of 51 patients (73%) in the placebo crossover group. Overall, 12 of 108 patients (11.1%; 95% CI, 5.87%-18.60%), which represents 7 of 56 patients (12.5%) in the original mavacamten group and 5 of 52 patients (9.6%) in the placebo crossover group, had an LVEF less than 50% (2 with LVEF ≤30%, one of whom died), and 9 of 12 patients (75%) continued treatment. Conclusions and Relevance: Results of this randomized clinical trial showed that in patients with symptomatic obstructive HCM, mavacamten reduced the need for SRT at week 56, with sustained improvements in LVOT gradients and symptoms. Although this represents a useful therapeutic option, given the potential risk of LV systolic dysfunction, there is a continued need for close monitoring. Trial Registration: ClinicalTrials.gov Identifier: NCT04349072.

What determines outcomes in multivalve reoperations? Effect of patient and surgical complexity.

OBJECTIVE: Patient characteristics, risks, and outcomes associated with reoperative multivalve cardiac surgery are poorly characterized. Effect of patient variables and surgical components of each reoperation were evaluated with regard to operative mortality. METHODS: From January 2008 to January 2022, 2324 patients with previous cardiac surgery underwent 2352 reoperations involving repair or replacement of multiple cardiac valves at Cleveland Clinic. Mean age was 66 ± 14 years. Number of surgical components representing surgical complexity (valve procedures, aortic surgery, coronary artery bypass grafting, and atrial fibrillation procedures) ranged from 2 to 6. Random forest for imbalanced data was used to identify risk factors for operative mortality. RESULTS: Surgery was elective in 1327 (56%), urgent in 1006 (43%), and emergency in 19 (0.8%). First-time reoperations were performed in 1796 (76%) and 556 (24%) had 2 or more previous operations. Isolated multivalve operations comprised 54% (1265) of cases; 1087 incorporated additional surgical components. Two valves were operated on in 80% (1889) of cases, 3 in 20% (461), and 4 in 0.09% (2). Operative mortality was 4.2% (98 out of 2352), with 1.7% (12 out of 704) for elective, isolated multivalve reoperations. For each added surgical component, operative mortality incrementally increased, from 2.4% for 2 components (24 out of 1009) to 17% for ≥5 (5 out of 30). Predictors of operative mortality included coronary artery bypass grafting, surgical urgency, cardiac, renal dysfunction, peripheral artery disease, New York Heart Association functional class, and anemia. CONCLUSIONS: Elective, isolated reoperative multivalve surgery can be performed with low mortality. Surgical complexity coupled with key physiologic factors can be used to inform surgical risk and decision making.

Surgical management of right aortic arch with tailored surgical approach.

BACKGROUND AND AIM OF STUDY: Right-sided aortic arch is a rare congenital anomaly for which different surgical approaches have been reported. This study reviewed our experience with several techniques. METHODS: We retrospectively reviewed 17 patients undergoing right-sided arch repair at the Cleveland Clinic from 2001 to 2010. Computed tomographic angiograms of the aorta and its branches were reviewed and correlated with patient presentation and surgical approach. RESULTS: Fourteen patients had type II right aortic arch with aberrant left subclavian artery. Fifteen patients presented with obstructive symptoms. Surgical approach included right thoracotomy (11 patients), left thoracotomy (two patients), full sternotomy (one patient), and hybrid repair (three patients). Cardiopulmonary bypass (CPB) with deep hypothermic circulatory arrest was used in 11 patients, and two patients had partial CPB. Left subclavian artery bypass was performed in seven patients. Median duration of intubation was 1.9 days. Average length of intensive care unit stay was three days and average hospital stay 11 days. Postoperative outcomes included respiratory failure (one patient), renal failure (one patient), bloodstream infection (two patients), and death (one patient). No patient had stroke or paraplegia. In-hospital death occurred in one patient, and all survivors were alive and asymptomatic for a mean of 38 months. CONCLUSION: The surgical treatment for right-sided aortic arch can be performed with excellent perioperative outcomes when tailored to patient presentation and anatomic configuration. Patients with obstructive symptoms benefit from open or hybrid surgical treatment, with immediate relief of compression. Patients with aneurysmal dilatation without compression symptoms can be managed with open, endovascular, or hybrid surgical intervention.