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.

Incremental Value of Global Longitudinal Strain to Michigan Risk Score and Pulmonary Artery Pulsatility Index in Predicting Right Ventricular Failure Following Left Ventricular Assist Devices.

BACKGROUND: The incremental utility of right ventricular (RV) strain on predicting right ventricular failure (RVF) following left ventricular assist device (LVAD) implantation, beyond clinical and haemodynamic indices, is not clear. METHODS: Two hundred and forty-six (246) patients undergoing LVAD implantation, who had transthoracic echocardiograms pre and post LVAD, pulmonary artery pulsatility index (PAPI) measurements and Michigan risk score, were included. We analysed RV global longitudinal strain (GLS) using speckle tracking echocardiography. RVF following LVAD implantation was defined as the need for medical support for >14 days, or unplanned RV assist device insertion after LVAD implantation. RESULTS: Mean preoperative RV-GLS was -7.8±2.8%. Among all, 27% developed postoperative RVF. A classification and regression tree analysis identified preoperative Michigan risk score, PAPI and RV-GLS as important parameters in predicting postoperative RVF. Eighty per cent (80%) of patients with PAPI <2.1 developed postoperative RVF, while only 4% of patients with PAPI >6.8 developed RVF. For patients with a PAPI of 2.1-3.2, having baseline Michigan risk score >2 points conferred an 81% probability of subsequent RVF. For patients with a PAPI of 3.3-6.8, having baseline RV-GLS of -4.9% or better conferred an 86% probability of no subsequent RVF. The sensitivity and specificity of this algorithm for predicting postoperative RVF were 67% and 93%, respectively, with an area under the curve of 0.87. CONCLUSION: RV-GLS has an incremental role in predicting the development of RVF post-LVAD implantation, even after controlling for clinical and haemodynamic parameters.

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.

Surgical ablation of atrial fibrillation in hypertrophic obstructive cardiomyopathy: Outcomes of a tailored surgical approach.

OBJECTIVE: To assess outcomes of concomitant ablation for atrial fibrillation (AF) in patients with preoperative AF undergoing septal myectomy for hypertrophic obstructive cardiomyopathy. METHODS: From 2005 to 2016, 67 patients underwent concomitant ablation for AF and septal myectomy and had a follow-up beyond a 3-month blanking period. Ablation strategy (pulmonary vein isolation [PVI], modified Cox-maze III [CM-III], or Cox-maze IV [CM-IV]) was tailored to preoperative AF burden, with high AF burden defined as persistent AF or need for cardioversion. AF recurrence was analyzed as a time-related event and predictors of recurrence identified using a random forest methodology. RESULTS: A total of 38 patients (57%) had low AF burden and 29 (43%) high burden. Patients with low AF burden most frequently underwent PVI (68%). Patients with high AF burden more frequently underwent CM-III (62%) or CM-IV (35%). Besides the preoperative AF burden, baseline characteristics were similar between patients receiving CM-III, CM-IV, and PVI. After surgery, the maximum provoked left ventricular outflow tract (LVOT) gradient decreased from 99 ± 34 to 18 ± 11mm Hg (P < .001). Eight patients (12%) required a permanent pacemaker. Cumulative AF recurrence at 1, 2, and 5 years was 11%, 22%, and 48%, respectively. Age, low preoperative resting LVOT gradient, and large left atrial diameter were predictors of AF recurrence. CONCLUSIONS: Surgical outcomes of concomitant ablation for AF and septal myectomy are good, although recurrence of AF by 5 years is frequent.

Extracorporeal Membrane Oxygenation in Pulmonary Endarterectomy Patients.

OBJECTIVES: To investigate short-term outcomes in patients with chronic thromboembolic pulmonary hypertension (CTEPH) presenting for pulmonary endarterectomy (PEA) and requiring extracorporeal membrane oxygenation (ECMO) during the perioperative period. DESIGN: Retrospective observational case series involving patients who underwent PEA for CTEPH, with focus on a subpopulation requiring perioperative ECMO support. SETTING: Single academic tertiary center. PARTICIPANTS: Patients who underwent PEA for CTEPH between January 1997 and December 2015 and required ECMO support. INTERVENTIONS: PEA for CTEPH with ECMO support at any time during the perioperative period. MEASUREMENTS AND MAIN RESULTS: A total of 150 patients underwent PEA for CEPTH during the study period. Of the 150 patients, 14 (9.3%) required ECMO support and (43%) survived, were discharged, and were alive at the time of the review. A total of 8 (57%) ECMO patients died during hospitalization. Although indications and type of support changed in some patients during their hospital course, the majority of patients required venovenous ECMO support for hypoxia (N = 9) versus venoarterial ECMO for hemodynamic support (N = 5) as initial indication. The mean length of stay among survivors was 42.2 ± 22 days. Severe RV dysfunction was present preoperatively among 6 patients in the nonsurvivors group (75%) and 2 in the survivors group (33%). The overall mean duration of ECMO support was 7.3 ± 5.3 days (8.3 ± 7.3 days among survivors and 6.5 ± 3.5 days among nonsurvivors). Four patients died while on ECMO. CONCLUSIONS: Although still associated with high morbidity and mortality, ECMO appears to be an important treatment adjunct providing additional time for healing and recovery of cardiopulmonary function in patients who develop severe hypoxemia or right ventricular failure after PEA.

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.

Mesenchymal precursor cells as adjunctive therapy in recipients of contemporary left ventricular assist devices.

BACKGROUND: Allogeneic mesenchymal precursor cells (MPCs) injected during left ventricular assist device (LVAD) implantation may contribute to myocardial recovery. This trial explores the safety and efficacy of this strategy. METHODS AND RESULTS: In this multicenter, double-blind, sham-procedure controlled trial, 30 patients were randomized (2:1) to intramyocardial injection of 25 million MPCs or medium during LVAD implantation. The primary safety end point was incidence of infectious myocarditis, myocardial rupture, neoplasm, hypersensitivity reaction, and immune sensitization (90 days after randomization). Key efficacy end points were functional status and ventricular function while temporarily weaned from LVAD support (90 days after randomization). Patients were followed up until transplant or 12 months after randomization, whichever came first. Mean age was 57.4 (±13.6) years, mean left ventricular ejection fraction was 18.1%, and 66.7% were destination therapy LVADs. No safety events were observed. Successful temporary LVAD weaning was achieved in 50% of MPC and 20% of control patients at 90 days (P=0.24); the posterior probability that MPCs increased the likelihood of successful weaning was 93%. At 90 days, 3 deaths (30%) occurred in control patients, and none occurred in MPC patients. Mean left ventricular ejection fraction after successful wean was 24.0% (MPC=10) and 22.5% (control=2; P=0.56). At 12 months, 30% of MPC patients and 40% of control patients were successfully temporarily weaned from LVAD support (P=0.69), and 6 deaths (30%) occurred in MPC patients. Donor-specific HLA sensitization developed in 2 MPC and 3 control patients and resolved by 12 months. CONCLUSIONS: In this preliminary trial, administration of MPCs appeared to be safe, and there was a potential signal of efficacy. Future studies will evaluate the potential for higher or additional doses to enhance the ability to wean LVAD recipients off support. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01442129.

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.

Unmasking Severe Systolic Anterior Motion With Left Ventricular Outflow Tract Obstruction Following Mitral Valve Repair.

A 38-year-old male with a history of myxomatous mitral valve disease post-repair presented with recurrent dyspnea during exertion. Initial evaluation showed mild systolic anterior motion and mitral regurgitation, but medical management was unsuccessful. The patient underwent reoperation; intraoperative transesophageal echocardiogram with provocation unmasked severe systolic anterior motion and torrential mitral regurgitation.

Predicting hypertension control using machine learning.

Hypertension is a widely prevalent disease and uncontrolled hypertension predisposes affected individuals to severe adverse effects. Though the importance of controlling hypertension is clear, the multitude of therapeutic regimens and patient factors that affect the success of blood pressure control makes it difficult to predict the likelihood to predict whether a patient's blood pressure will be controlled. This project endeavors to investigate whether machine learning can accurately predict the control of a patient's hypertension within 12 months of a clinical encounter. To build the machine learning model, a retrospective review of the electronic medical records of 350,008 patients 18 years of age and older between January 1, 2015 and June 1, 2022 was performed to form model training and testing cohorts. The data included in the model included medication combinations, patient laboratory values, vital sign measurements, comorbidities, healthcare encounters, and demographic information. The mean age of the patient population was 65.6 years with 161,283 (46.1%) men and 275,001 (78.6%) white. A sliding time window of data was used to both prohibit data leakage from training sets to test sets and to maximize model performance. This sliding window resulted in using the study data to create 287 predictive models each using 2 years of training data and one week of testing data for a total study duration of five and a half years. Model performance was combined across all models. The primary outcome, prediction of blood pressure control within 12 months demonstrated an area under the curve of 0.76 (95% confidence interval; 0.75-0.76), sensitivity of 61.52% (61.0-62.03%), specificity of 75.69% (75.25-76.13%), positive predictive value of 67.75% (67.51-67.99%), and negative predictive value of 70.49% (70.32-70.66%). An AUC of 0.756 is considered to be moderately good for machine learning models. While the accuracy of this model is promising, it is impossible to state with certainty the clinical relevancy of any clinical support ML model without deploying it in a clinical setting and studying its impact on health outcomes. By also incorporating uncertainty analysis for every prediction, the authors believe that this approach offers the best-known solution to predicting hypertension control and that machine learning may be able to improve the accuracy of hypertension control predictions using patient information already available in the electronic health record. This method can serve as a foundation with further research to strengthen the model accuracy and to help determine clinical relevance.

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.