Ventricular Outflow Tract Research Articles

Infective endocarditis in an adult with undiagnosed tetralogy of Fallot: a case report of a rare presentation.

Unrepaired tetralogy of Fallot (TOF) is uncommonly diagnosed in adulthood and only 3% of patients survive to reach the age of 40 without surgical repair. If unrepaired, these patients are at risk for infective endocarditis (IE). In this report, we present a case of a middle-aged, previously healthy female whose only complaint was unexplained fever. Echocardiography led to the discovery of undiagnosed TOF complicated with IE with a vegetation on the right ventricular (RV) side of the ventricular septal defect (VSD) which was appropriately managed with antibiotics. In rare cases of acyanotic TOF where there is a lesser degree of right ventricular outflow tract obstruction (RVOTO), patients may survive into adulthood and can be asymptomatic till becoming initially presented with complications such as infective endocarditis.

Abstract 4138268: The Use of Mavacamten for Management of Post TAVR Obstruction: A Novel Approach to Treatment

Background: Treatment of left ventricular outflow tract (LVOT) obstruction involves a combination of negative inotropic agents. However, these therapies have limitations which may result in insufficient control of symptoms, leading to more invasive options such as surgical septal myectomy or septal alcohol ablation. Mavacamten, a cardiac myosin inhibitor, is currently approved for the treatment of patients with symptomatic obstructive hypertrophic cardiomyopathy (HCM). We present a case of a patient treated with mavacamten in addition to β-blockers (BB) for management of post-TAVR LVOT obstruction. Case: A 76 year old female with a past medical history of hypertension, severe aortic stenosis, and coronary artery disease underwent a Medtronic Evolut TAVR in March 2022. Her TTE post TAVR showed LVOT peak gradient greater than 100 mm Hg, LVEF 75% and severe eccentric mitral regurgitation secondary to systolic anterior motion (SAM) of the mitral valve (MV). After multidisciplinary discussion, the patient was discharged on maximally tolerated BB therapy. Follow up TTE showed persistent obstruction and gradients, so diltiazem was added to her regimen. Her subsequent TTE showed a peak LVOT > 100 mmHg at rest, and severe MR. Given persistent findings, she was started on mavacamten, continued on metoprolol, and tapered off of diltiazem. Her TTE two months after initiation of mavacamten revealed resolution of LVOT gradients, reduction of MR to mild and normal LV and TAVR function. She tolerated the therapy well and endorsed ongoing symptomatic improvement on subsequent follow up. Discussion: With the increasing use of TAVR therapy, there has been a corresponding rise in cases of post-TAVR obstruction that must be managed. As demonstrated by this case, management with BB therapy alone may be suboptimal. Although mavacamten is currently approved in patients with HCM, the obstruction in post-TAVR patients is functionally similar. Thus, this medication was trialed as a supplemental treatment in this patient and yielded positive results. This case highlights the potential benefit of extending use of mavacamten alongside β-blocker therapy for this patient population and suggests the need for future studies.

Abstract 4135212: An Overlap Between Takotsubo Cardiomyopathy and Hypertrophic Obstructive Cardiomyopathy Causing Dynamic Left Ventricular Outflow Tract Obstruction: A Unique Case Report

Background: Takotsubo cardiomyopathy (TC) can cause dynamic left ventricular outflow tract (LVOT) obstruction leading to cardiogenic shock. Due to differential wall-motion abnormalities, flow acceleration in the LVOT can lead to systolic anterior motion (SAM) of the mitral valve which worsens LVOT obstruction and leads to hemodynamic compromise. We present a case of overlap between TC and hypertrophic obstructive cardiomyopathy (HOCM) with worsening LVOT obstruction leading to cardiogenic shock. Case: A 76-year-old female presented with typical chest pain, nausea, and worsening shortness of breath. On examination, she was hypotensive and cold to touch. EKG showed T-wave inversions in lateral leads with elevated cardiac troponins. Coronary angiogram showed non-obstructive coronary artery disease, and right heart catheterization revealed elevated filling pressures. Transthoracic echocardiogram (TTE) showed septal hypertrophy and SAM of the mitral valve causing dynamic LVOT obstruction (Figure 1) and ejection fraction (EF) of 20%. TTE with contrast showed apical ballooning consistent with TC (Figure 2). Decision Making: Initially with diuresis, she became hypotensive so it was stopped and she received controlled intravenous fluids along with phenylephrine to reduce LVOT obstruction. Her blood pressure improved and she was started on low-dose metoprolol succinate along with ivabradine to reduce heart rate. She tolerated this therapy and hemodynamics stabilized. Conclusion: Cardiogenic shock can be a severe complication of TC. Early detection of LVOT obstruction in cardiogenic shock is important as traditional management strategies of increased inotropy and reduction of afterload can be fatal in these cases. The treatment strategy focuses on reducing the LVOT gradient and includes fluid administration to increase preload, beta-blockers to increase diastolic filling time, and vasopressors to raise afterload.

Abstract 4123391: CardioMEMS and Mavacamten: A Synergistic Approach in Managing Hypertrophic Obstructive Cardiomyopathy with HFpEF Phenotype

Introduction: Mavacamten is a cardiac myosin inhibitor that has been approved for obstructive hypertrophic cardiomyopathy (oHCM). The CardioMEMS PA (pulmonary artery) sensor allows remote pulmonary artery diastolic (PAD) pressure monitoring to adjust diuresis in heart failure with preserved ejection fraction (HFpEF). We present the case of a patient with oHCM and HFpEF where data extrapolated from CardioMEMS provided valuable insight to the hemodynamic impact of cardiac myosin inhibitors. Case: A 66-year-old female with hypertension, obesity and oHCM presented with worsening dyspnea and was evaluated for septal myectomy. However, surgery was deferred because of decompensated HFpEF, as evidenced by significant leg edema on exam, and severely elevated left and right-side filling pressure, with restrictive physiology on right heart catheterization. A CardioMEMS PA sensor was implanted to guide decongestion, however, escalation of diuresis was limited due to severe left ventricular outflow tract (LVOT) obstruction. PAD remained elevated at 20-30 mmHg. Due to the refractory LVOT obstruction and despite the use of maximally tolerated beta blockers, Mavacamten was initiated and escalated according to protocol. LVOT obstruction resolved on follow up echocardiogram. Without any adjustment in her diuretic regimen, her PAD decreased to 15-20 mmHg. On follow-up visit, the patient reported improvement in dyspnea and reduction in lower extremity edema. Discussion: Managing oHCM is challenging, particularly when complicated by HFpEF. Mavacamten has shown promise in reducing LVOT gradients and improving symptoms in oHCM. However, managing fluid status in these patients can be difficult due to the risk of exacerbating LVOT obstruction while optimizing filling pressures. Our case provides direct evidence that treating LVOT obstruction with a cardiac myosin inhibitor leads to improvement in decompensated heart failure, as evidenced by the reduction in PAD. Conclusion: Addressing LVOT obstruction is key to decongesting and managing heart failure in oHCM patients. In our case, the use of CardioMEMS PA sensor system allowed a novel perspective of assessing hemodynamic impact of cardiac myosin inhibitors.

Abstract 4132223: Mavacamten in adolescent patients with symptomatic obstructive hypertrophic cardiomyopathy: design of the Phase 3 SCOUT-HCM trial

Background: While most current treatments can improve symptoms in patients with obstructive hypertrophic cardiomyopathy (HCM), they may be poorly tolerated and do not target the underlying pathophysiology. Mavacamten is the first and only cardiac myosin inhibitor approved for the treatment of adults with symptomatic New York Heart Association (NYHA) class II-III obstructive HCM but has not been evaluated in a pediatric age group. SCOUT-HCM (Study of MavaCamten in AdOlescents with Symptomatic ObstrUcTive HCM; NCT06253221) will evaluate the efficacy, safety, and pharmacokinetics of mavacamten in adolescents with symptomatic obstructive HCM. Methods: SCOUT-HCM is a randomized, double-blind, placebo-controlled, international phase 3 clinical trial that will enroll 40 adolescents (age 12 to <18 years) with obstructive HCM ( Figure ). Patients will receive mavacamten or placebo during the first 28 weeks, followed by a 28-week double-blind active treatment period. Inclusion criteria include a diagnosis of HCM with presence of symptoms and left ventricular outflow tract (LVOT) obstruction. Patients with HCM phenocopies, LVEF <50% at rest in the past 6 months, planned escalation in HCM therapy or upcoming intervention (eg, major cardiac surgery) will be excluded. The primary endpoint is change in Valsalva LVOT gradient from baseline to week 28. Key secondary endpoints include other echocardiographic parameters, safety, pharmacokinetics, and exercise capacity. Conclusions: SCOUT-HCM is the first randomized controlled trial evaluating a targeted myosin inhibitor in adolescents with symptomatic obstructive HCM. The results will inform the utility of mavacamten in adolescent patients with symptomatic obstructive HCM.

Abstract 4112591: Delayed Migration of a Valve-in-Valve Transcatheter Aortic Valve Replacement

Introduction: Migration of a transcatheter aortic valve replacement (TAVR) is a rare, life-threatening complication that typically occurs during or shortly after the procedure. We present a unique case of an exceptionally rare, delayed migration of a valve-in-valve TAVR three years post-procedure that was subsequently treated with surgical explantation of the TAVR prosthesis and surgical aortic valve replacement (SAVR). Clinical Case: A 64-year-old male presented to an outpatient cardiology visit with one month of exertional dyspnea and near-syncopal episodes with a new diastolic murmur. Notable history included aortic regurgitation due to bicuspid aortic valve resulting in subcoronary implantation of a 27 mm Medtronic Freestyle stentless porcine bioprosthesis 20 years prior to presentation. Following the development of severe bioprosthetic regurgitation, a valve-in-valve TAVR with a 26 mm Edwards SAPIEN 3 Ultra was implanted 3 years prior to presentation with no evidence of stenosis or regurgitation on transthoracic echocardiograms completed 1 month and 1 year after implantation. Transesophageal echocardiogram now demonstrated migration of the TAVR valve into the left ventricular outflow tract 2 cm proximal to the surgical bioprosthesis. Severe eccentric transvalvular regurgitant flow through the surgical bioprosthesis and severe paravalvular regurgitation around the TAVR valve was seen with an unstable “rocking appearance”. No evidence of abscess or endocarditis was appreciated and blood cultures showed no growth. Following a short hospitalization, the patient underwent TAVR explantation and implantation of a 25 mm Edwards Inspiris Resilia stented bovine bioprosthesis with subsequent resolution of his symptoms. Discussion: Recognizing atypical presentations of TAVR complications such as delayed valve migration is facilitated by understanding key risk factors. This case highlights notable risk factors for TAVR migration including a valve-in-valve TAVR over a degenerative regurgitant bioprosthesis, decreased aortic annulus calcification resulting in suboptimal anchoring, the patient’s younger age, and the lack of a radiopaque marker on the stentless bioprosthesis which increases the potential for malpositioning.

Residual pulmonary stenosis and right ventricular contractility in repaired tetralogy of fallot.

The impact of residual pulmonary stenosis (rPS) or right ventricular (RV) outflow tract obstruction on prognosis after surgical pulmonary valve insertion (SPVI) in repaired tetralogy of Fallot (TOF) patients with pulmonary regurgitation (PR) remains controversial. rPS assessment is partially dependent on RV contractility. We investigated the impact of rPS according to RV ejection fraction (RVEF). In this multicentre, retrospective study, 117 repaired TOF patients who underwent SPVI for more than moderate PR between 2003-2021 were examined. Regarding rPS, the threshold for PR with rPS (PSR) and PR was 25 mmHg. For RVEF, the threshold for preserved RVEF (pEF) and reduced RVEF (rEF) was 40%. The patients were divided into four groups: patients with PR and pEF (PR-pEF) (n = 48), those with PR and rEF (PR-rEF) (n = 44), those with PSR and pEF (PSR-pEF) (n = 16), and those with PSR and rEF (PSR-rEF) (n = 9). Clinical parameters, postoperative adverse event rates, and their associations were studied. The 5-year freedom from adverse cardiovascular events was the highest in the PSR-pEF and the lowest in the PSR-rEF groups. The PSR-rEF group had the highest RV end-diastolic pressure (RVEDP) (12 ± 2.2 mmHg) (p = 0.006). From multivariable analysis, RVEDP was associated with postoperative adverse events (p = 0.016). RVEDP > 8mmHg was associated with a lower freedom from adverse events. The freedom from adverse events was the lowest in the PSR-rEF group, with the highest RVEDP, suggesting RV systolic and diastolic dysfunction. Reduced RVEF may mask the intrinsic degree of residual stenosis, delay SPVI timing, and increase adverse events.

Abstract 4138007: Mechanisms of Mitral Regurgitation in Fabry Disease

Introduction: Fabry disease, caused by mutations in the gene encoding alpha-galactosidase A, results in the accumulation of globotriaosylceramide (Gb3), leading to systemic complications including cardiac involvement such as mitral regurgitation (MR). The aim of this study is to investigate the association between MR severity and mitral leaflet morphology in Fabry disease patients. A cohort of 38 symptomatic Fabry disease patients with moderate or significant MR was followed up. Mitral leaflet morphology was categorized as normal, fibrodegenerative changes, or leaflet thickening. MR severity varied, with the primary cause being leaflet restriction. Additionally, left ventricular outflow tract obstruction (LVOTO) and annular dilatation were observed. The study suggests that MR in Fabry disease is primarily due to leaflet restriction, either through degenerative changes or leaflet thickening. This study investigates the association between MR severity and mitral leaflet morphology in Fabry disease patients. Methods: A cohort of 38 symptomatic Fabry disease patients with moderate or significant MR was followed up. Echocardiographic assessments were conducted to determine MR severity and categorize mitral leaflet morphology. Statistical analyses were performed to evaluate associations between MR severity and leaflet morphology. Echocardiographic assessments of the mitral valve were conducted using a Vivid E95 Cardiac Ultrasound and meticulously analyzed using the EchoPAC TM and TOMTEC Imaging Systems. A crucial aspect of the examination involved measuring all components of the mitral valve and determining the requisite angles to evaluate each mechanism thoroughly. Results: Most patients exhibited leaflet restriction as the primary cause of MR, with varying degrees of severity. Mitral leaflet morphology was categorized as normal in 15,8%, fibrodegenerative changes were in 31,5% and leaflet thickening in 52,7%. In addition, outflow tract obstruction (LVOTO) was observed in 15,7% but without systolic anterior motion (SAM) and annular dilatation (dilatation of anteroposterior annulus more than 35 mm in systole) was present in 66%. Conclusion: The study suggests that MR in Fabry disease is primarily attributed to leaflet restriction, either due to degenerative changes or leaflet thickening. An additional, albeit not unexpected, finding not always considered is the presence of anteroposterior annular dilatation in some cases.

Outcomes of Concomitant Mitral Intervention in Hypertrophic Obstructive Cardiomyopathy Surgery?: A Systematic Review and Meta-Analysis of Contemporary Evidence

The 2020 American Heart Association Guidelines advise not to perform mitral valve replacement (MVR) during septal myectomy (SM) to alleviate outflow obstruction. This study aims to review outcomes after concomitant mitral valve (MV) intervention versus SM alone. We conducted a comprehensive literature search across Embase, PubMed, and Scopus. Studies published up to June 15, 2024 were considered. We included studies that compared SM alone to concomitant MV repair or replacement. Subgroup analyses based on MV intervention were performed. Seven studies met our criteria, including 1 randomized and 6 observational studies. The total sample size was 17,565 patients with hypertrophic cardiomyopathy (11,849 SM, 2303 SM + MVR, and 3390 SM + MV repair). Patients who underwent SM + MV intervention had more pronounced preoperative MV regurgitation. SM + MVR was associated with significantly higher early mortality [risk ratio (RR): 2.85, 95% confidence interval (CI): 2.37–3.43, P < 0.00001, I² = 0%]. However, there was no difference in early mortality in patients who underwent SM + MV repair compared with SM alone (RR: 1.14, 95% CI: 0.88–1.49, P = 0.33, I² = 0%). Thirty days systolic anterior motion was significantly lower in patients who underwent SM + MV repair compared with SM alone (RR: 0.15, 95%CI: 0.05–0.45, P = 0.0007). Peak pressure left ventricular outflow tract gradient was significantly lower in the SM + MV repair group compared with SM alone (mean difference: −3.47, 95% CI: −5.55 to −1.39, P = 0.001). Current observational evidence suggests an increased risk of in-patient mortality in patients who underwent SM + MVR. SM + MV repair did not affect early mortality but was linked to improved outcomes. Future comprehensive and matched studies are warranted.

Abstract 4147610: Efficacy and Safety of Selective Cardiac Myosin Inhibitors in Symptomatic Hypertrophic Obstructive Cardiomyopathy: A Meta-Analysis of Randomized Controlled Trials

Background: Hypertrophic Obstructive Cardiomyopathy (HOCM) is an autosomal dominant inherited condition with limited management options, primarily focusing on symptom improvement through beta blockers. A novel selective cardiac myosin inhibitor, Mavacamten has been shown to improve exercise tolerance and NYHA functional class as compared to placebo in multiple randomized controlled trials (RCTs). A recent RCT from 2024 studied another oral cardiac myosin inhibitor, Aficamten which potentially decreases left ventricular outflow tract obstruction (LVOTO) in symptomatic HOCM. One limitation of all these RCTs, for obvious reasons, is the small sample size, which poses a challenge in its actual clinical significance. Aims: To analyze the efficacy and safety of novel selective cardiac myosin inhibitors in symptomatic HOCM patients Methods: We included 4 RCTs, comparing the efficacy and safety of selective cardiac myosin inhibitors and placebo groups. These studies were selected through a detailed search of the MEDLINE, COCHRANE, and PUBMED databases. We compared various common primary and secondary endpoints between both the groups: changes in exercise tolerance, NYHA functional class, and Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score (KCCQ-CSS). The results were reported as Odds Ratios (OR) with 95% confidence intervals (CI), using a random effects model. Results: The outcomes from 704 HOCM patients, which consisted of 361 patients who received a myosin inhibitor and 343 who received a placebo were analyzed. The primary endpoint in all the studies was improvement in exercise tolerance [measured as 1.5 mL/kg per min or greater increase in peak oxygen consumption (pVO2)], which was not statistically significant in our study (OR: 1.75, 95% CI: 0.89-3.43, p:0.1). There was a statistically significant improvement in ≥1 NYHA functional Class (OR: 3.9, 95% CI:2.49-6.12 p<0.05). There was no significant change seen in KCCQ-CSS (OR: 1.26, 95% CI: 0.75-2.12, p:0.3) and1 or more Serious Adverse Events (OR: 0.75, 95% CI: 0.42-1.32, p:0.3). (Figures A-D) Conclusion: Novel cardiac myosin inhibitors have shown statistically significant results in improving NYHA functional class, but not much difference in objective criteria like pVO2 with no significant adverse events. While these results appear promising and 2024 ACC/AHA guidelines have Class 1 Recommendation regarding their use for symptomatic HOCM, further analysis from a large population is needed.

Abstract 4128606: Detailed Measurements of Surgical Mitral Valves: Implications for Transcatheter Mitral Valve-in-Valve Interventions

Background: With the increasing prevalence of transcatheter mitral valve-in-valve interventions (V-in-V), a detailed understanding of the surgical valves (SV) is of paramount importance. Left ventricular outflow tract obstruction (LVOTO) is a feared complication and is typically caused by the anterior displacement of the LVOT-facing surgical leaflet, which, along with the surgical post at that level, forms a fixed obstruction. Traditionally, the risk is estimated using computed tomography software by simulating a valve that extends to the surgical post height of the implanted SV. However, this does not account for the actual leaflet length and post width at the level of the leaflet tip, which could differ significantly from the surgical post height but accurately estimate LVOTO risk. Methods: We conducted detailed measurements of three different sizes of two commonly used surgical mitral valves: the Biocor EPIC ( Abbott ) in sizes 27 mm, 31 mm, and 33 mm, and the Mosaic ( Medtronic ) in sizes 25 mm, 31 mm, and 33 mm. Using a digital caliper and height gauge, we measured several key parameters for each valve, including leaflet height, post height, leaflet width, post width at the level of the leaflet tip, maximal post width, and valve inner diameter. Results: The results, presented in Table 1, show significant differences in leaflet height and post widths across manufacturers and sizes. Leaflet height was consistently shorter than post height in both Abbott and Medtronic valves, with this discrepancy more pronounced in larger valves and Medtronic valves. The post width at the leaflet tip also varied considerably. Conclusions: Given the substantial differences between leaflet and post heights—with the leaflet typically much shorter—an accurate assessment of LVOTO risk should account for both the leaflet height and the width of the post at that level to avoid overestimating the risk of LVOTO.

Abstract 4138350: Candidemia in Patients with Left Ventricular Assist Device-A Case Series

Introduction: Candidemia is rare but associated, have significant morbidity and mortality. Outcomes are not well-characterized in patients with left ventricular assist devices (LVADs). With an increasing number of patients living with LVADs, we sought to characterize risk factors to help optimize outcomes for this high-risk population. Methods: We retrospectively reviewed records of 97 patients who underwent LVAD implant between January 2012 to May 2024 at Indiana University Health, Indianapolis Indiana. Demographic and clinical data were extracted. Candidemia was defined as a positive blood culture with candida species. Result: We identified three patients with candidemia, with an overall attack rate of 3.09%. All patients had a HeartMate III (HM3) at the time of infection. The mean age of patients was 40.3 years (Range 29.0 – 58.0 years) and mean BMI was 35.7 kg/m 2 (Range, 30.0 – 42.0 kg/m 2 ). One patient grew Candida auris and Candida tropicana, the other patient grew Candida auris and the third patient grew Candida globrata. All patients had an automatic implantable cardiac defibrillation, a peripherally inserted central catheter line, and right heart failure. Two patients had driveline infections (one fungal, one bacterial) while one patient developed LVAD endocarditis with a right ventricular outflow tract vegetation. Two patients had persistently positive blood cultures despite treatment with a multi-drug anti-fungal regimen (Flucytosine, Amphotericin B and micafungin) and expired. The third patient initially cleared her blood cultures after treatment with IV micafungin only but was re-admitted with muti-organ failure and expired. Summarily, all patients with candidemia died with a mortality rate of 100%. None of the patients were candidates for heart transplantation. Average survival from the time of diagnosis of candidemia was 5 months (Range 1.0 – 11.0 months). RHF, chronic DL infection and high BMI were associated with candidemia in our series. Conclusion: Candidemia in LVAD patients, while less common than bacterial infections, carry high mortality without cardiac transplantation (100% mortality in our cohort). Its rare occurrence makes it challenging to identify reversible risk factors, leading to poor survival. Multicenter registries are needed to fully elucidate these risk factors and determine effective treatment strategies.

Abstract 4139196: Long-term effectiveness and safety of mavacamten in a real-world, multi-center, global study: Preliminary results of COLLIGO-HCM from a diverse cohort in the United States

Introduction: The mavaCamten ObservationaL evIdence Global cOnsortium in hypertrophic cardiomyopathy (COLLIGO-HCM; ClinicalTrials.gov ID NCT06372457) is a multinational, multicenter observational research initiative aiming to describe the real-world outcomes of mavacamten for the treatment of obstructive HCM. Aims: Describe the real-world effectiveness and safety of mavacamten, measured by echo measurements and NYHA class. Methods: This retrospective study used data from medical records from two participating HCM centers in the US. Patient-level data was extracted to assess the effectiveness and safety of mavacamten post-treatment initiation through 60 weeks. Patient characteristics and outcomes were described, including echocardiogram measurements, New York Heart Association (NYHA) functional class, and safety. Results: A total of 93 patients were treated with mavacamten (mean age 60.6 ± 13.9 years, 23.7% black, 57.0% female, and 77.4% NYHA class III at baseline) with a mean follow-up of 37.0 ± 28.1 weeks ( Table ). From baseline to week 60, 3 (3.2%) patients experienced temporary treatment discontinuation, and 3 (3.2%) discontinued mavacamten due to left ventricular ejection fraction (LVEF) <50%. By week 12, 77.1% of patients had improved by ≥1 NYHA class. The percentage increased to 89.5% by week 24 and remained stable through week 60. Mean changes from baseline in resting and Valsalva left ventricular outflow tract gradients were 31.8 ± 32.8 and 57.3 ± 47.3 mmHg, respectively, at week 24, and remained similar through week 60. Mean change in LVEF from baseline was 4.1 ± 7.1% at week 12 and remained largely unchanged through week 60 (Figure) . Conclusions: This study demonstrated the early and sustained effectiveness of mavacamten with one of the longest follow-ups to date, in a real-world population with a higher racial diversity and disease burden than those in the clinical trials. This data further substantiates the effectiveness and safety profile of mavacamten.

Contemporary Clinical Characteristics, Imaging, Management, and Surgical and Nonsurgical Outcomes of Adult Patients With Subaortic Stenosis.

Subaortic stenosis (SAS) is characterized by a fibromuscular membrane located just below the aortic valve, causing fixed outflow tract obstruction. There is a paucity of studies evaluating this condition. This cohort study reviewed the contemporary characteristics and outcomes of SAS in adult patients in a single large referral center. We retrospectively studied adult patients with SAS evaluated at our center during 2011 to 2022. The primary outcome was all-cause mortality and heart failure hospitalizations during follow-up, with secondary end points including recurrence of SAS and repeat surgery after initial SAS surgery. Among 484 patients with SAS, key characteristics included mean age 55±18 years, 67.5% female, left ventricular outflow tract peak velocity 352±140 cm/s and gradient 57±40 mm Hg, left ventricular ejection fraction 60%±14%, 54.8% had prior SAS surgery, and 45.1% had surgery during follow-up. Over a median follow-up of 5.5 (1.5-12.3) years, 11.5% (n=56) died, 6.8% (n=33) had heart failure hospitalizations, 8.0% (n=39) experienced SAS recurrence, and 14 (5.9%) underwent repeat SAS surgery. Multivariable analyses identified older age per 10-years (hazard ratio [HR], 1.37 [95% CI, 1.12-1.68]) and baseline New York Heart Association class (HR, 2.48 [95% CI, 1.54-3.99]) to be statistically significantly associated with the primary end point; higher body mass index, New York Heart Association class, and peak left ventricular outflow tract gradient were also statistically significantly associated with SAS recurrence and redo surgery. Almost half of patients with SAS had surgery in the past or during follow-up, and a significant minority had mortality or morbidity events during follow-up. Identified prognosticators warrant further research to guide management.

Respiratory variation of velocity time integral and peak velocity of left ventricular outflow tract for predicting hypotension after induction of general anesthesia in elderly patients.

Hypotension after induction of general anesthesia may lead to severe complications in elderly patients. This study investigated whether the respiratory variation of velocity time integral (ΔVTI) and peak velocity (ΔVpeak) of left ventricular outflow tract (LVOT) could predict hypotension after induction of general anesthesia in elderly patients. 120 elderly patients undergoing selective operation under general anesthesia were enrolled in this study. ΔVTI and ΔVpeak of LVOT were measured by transthoracic echocardiography before induction of general anesthesia. After induction, mean arterial pressure (MAP) was recorded every 1 minute for 15 min. Hypotension was defined as a decrease of more than 30% in MAP at baseline or MAP below 65 mmHg from the start of induction. Receiver operating characteristic curves with gray zone and multivariate logistic regression analysis were used to assess the ability of ΔVTI and ΔVpeak of LVOT to predict hypotension after induction of general anesthesia. Hypotension occurred in 64 (53.3%) patients after induction of general anesthesia. The area under receiver operating characteristic curves (AUC) for ΔVpeak of LVOT to predict hypotension after induction of general anesthesia was 0.811, and the optimal cutoff value was 13.1% with a gray zone of 9.9% to 13.8%, including 45.0% of patients. The AUC for ΔVTI of LVOT was 0.890, and the optimal cutoff value was 13.8% with a gray zone of 11.1% to 13.9%, including 25.8% of patients. After adjusting for confounders, ΔVTI (Odds ratio = 2.24) and ΔVpeak (Odds ratio = 2.09) of LVOT were two significant independent predictors of hypotension after induction of general anesthesia. ΔVTI of LVOT was a reliable predictor of hypotension after the induction of general anesthesia in elderly patients. ΔVpeak of LVOT should be used cautiously to predict hypotension after induction of general anesthesia due to nearly half of elderly patients in the gray zone.Trial registrationThis study was registered in the Chinese Clinical Trial Registry (registration number: ChiCTR2300077117).

Relationships Among the EmPHasis-10 Questionnaire, the Simplified Four-Strata Risk Assessment Tool, and Echocardiographic Parameters in Patients with Precapillary Pulmonary Hypertension

Background/Objectives: Pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) are complex diseases that require precise diagnosis and management. The ESC risk score has been used in both conditions. We assessed the relationship between the EmPHasis-10 questionnaire (patient subjective evaluation) and objective assessment using endorsed tools (simplified four-strata risk assessment and right ventricular imaging by transthoracic echocardiography). Methods: The present study retrospectively extracted data from 40 adult patients (27 PAH and 13 CTEPH cases) diagnosed in a single center in Romania. The EmPHasis-10 questionnaire and the four-strata risk assessment (FSRA) tool were applied to each patient. Mean pulmonary artery pressure (mPAP), tricuspid annular plane systolic excursion (TAPSE), TAPSE/systolic pulmonary artery pressure (TAPSE/sPAP) ratio, and right ventricular outflow tract acceleration time (RVOT-AT) were assessed. Results: A significant correlation was observed between the EmPHasis-10 scores and the FSRA tool, the WHO functional class, and the 6 min walking distance. Emphasis-10 score did not correlate with any of the echocardiographic parameters. The FSRA tool showed a moderate positive correlation with mPAP (r = 0.42, p = 0.01) and a negative correlation with TAPSE (r = −0.46, p = 0.003); additionally, across the entire cohort, it was moderately negatively correlated with both RVOT-AT (r = −0.42, p = 0.01) and TAPSE/sPAP ratio (r = −0.43, p = 0.005). Conclusions: Our study evidenced the alignment between EmPHasis-10 scores and prognostic risk score, with poorer health-related quality of life corresponding to higher FSRA. The EmPHasis-10 questionnaire proves to be a valuable, easy-to-use instrument, offering meaningful insights into patients’ health-related quality of life, underscoring its utility in enhancing comprehensive patient assessment and management.

Mavacamten: Real-World Experience from 22 Months of the Risk Evaluation and Mitigation Strategy (REMS) Program.

Background: Mavacamten is the only cardiac myosin inhibitor approved by the US FDA for treatment of symptomatic New York Heart Association class II-III obstructive hypertrophic cardiomyopathy (HCM) patients. Under the risk evaluation and mitigation strategy (REMS) program for mavacamten, patients are required to be monitored for development of systolic heart failure, and reduction of left ventricular ejection fraction (LVEF) to <50%. We report results from the mavacamten REMS database (28-Apr-2022 to 27-Feb-2024). Methods: Data on healthcare providers and pharmacy certification, patient monitoring (from Patient Status Forms, based partly on echocardiograms), and screening for drug interactions prior to each dispense were collected. Results: Of 6,299 patients who received ≥1 dose of mavacamten, 60.0% were women; 64.6% were >60 years of age. Of 5,573 patients with submitted Patient Status Forms, 256 (4.6%) developed LVEF <50% and 71 (1.3%) experienced heart failure requiring hospitalization (HFH). On the 29,111 status forms in these patients, each representing an assessment of an echocardiogram, LVEF <50% was reported on 276 (0.9%) and HFH was reported on 86 (0.3%). Of 1,929 patients with ≥1 year of treatment, 78 (4.0%) had an LVEF reduction to <50% and 4 (0.2%) experienced LVEF <50% + HFH but later resumed treatment. Of 3,228 patients initiated on 5 mg/day mavacamten and were treated for at least 6 months, 2,391 (74.1%) remained at 5 or 10 mg/day. At 3- and 6-months following mavacamten treatment initiation, 57.2% and 70.3%, respectively, demonstrated post-Valsalva LV outflow tract gradient <30 mmHg. Conclusions: We describe the feasibility and experience of the first 22 months of the REMS program for prescribing mavacamten in >6,000 symptomatic obstructive HCM patients. The need for temporary interruption for LVEF <50% was low, including for patients on therapy ≥1 year, with even fewer LVEF reductions associated with HFH.

Clinical assessment of patient outcomes post percutaneous pulmonary valve implantation: Insights from a single tertiary centre

Background: Percutaneous pulmonary valve implantation (PPVI) has emerged as a promising treatment for congenital right ventricular outflow tract (RVOT) dysfunction and restoring conduit graft viability. Methods: This is a single-centre retrospective study of 41 patients (18 men, 23 women; mean age 26.1±10.2 years) who underwent PPVI between December 2007 and November 2014 and were evaluated for right ventricular pressures and exercise tolerance. Results: PPVI significantly reduced mean baseline RVOT gradients across different pathologies: stenosis (45 vs 18.4 mmHg), regurgitation (19.2 vs 7.6 mmHg), and mixed disease (32.5 vs 12 mmHg). Furthermore, mean right ventricular (RV) systolic pressures decreased from 61.6±2.3 to 41.9±2 mmHg (p&lt;0.001), while RV diastolic pressures decreased by about 60% from 14.3±1.1 to 8.6±1.4 mmHg (p&lt;0.001). Echocardiography revealed significant improvements in pulmonary and tricuspid valve velocities (p for trend&lt;0.01). Additionally, there was a consistent reduction in the main pulmonary artery maximum pressure gradient measured pre-procedure. No significant changes were observed in PR, QRS, or QTc interval duration on follow-up electrocardiograms. Similarly, no changes were noted in cardiopulmonary exercise test performance during follow-up. Conclusion: The study highlights the effectiveness of PPVI using Medtronic Melody and Edwards SAPIEN valves in patients with various pulmonary diseases. Immediate improvements in right ventricular pressures and functional outcomes suggest that PPVI is a valuable treatment option for individuals with RVOT dysfunction. Multi-centre collaborations are crucial for further elucidating the long-term effects of PPVI on cardiac function, exercise tolerance, and quality of life in RVOT dysfunction.

Diagnosis and management of hypertrophic cardiomyopathy: European vs. American guidelines.

Hypertrophic cardiomyopathy (HCM) is the most common genetic heart disease, affecting 1:200 to 1:500 individuals worldwide. Guidelines on the diagnosis and management of HCM have been recently published by the European Society of Cardiology (ESC) and American societies. The ESC guidelines cover a broad range of cardiomyopathies, including HCM, with 119 recommendations, whereas the American guidelines focus exclusively on HCM with 141 specific recommendations. Both guidelines emphasize a comprehensive diagnostic approach, including imaging and genetic testing, but differ in some specific aspects. For example, sudden cardiac death (SCD) risk assessment is a primary point of divergence. The ESC guidelines advocate for the use of a validated Risk-SCD calculator, while the American guidelines rely on specific risk markers for individualized risk evaluation. Management strategies also vary: both guidelines prioritize beta-blockers and calcium channel blockers in patients with resting or provocable left ventricular outflow tract (LVOT) obstruction. If beta-blockers (or verapamil/diltiazem) are ineffective, either disopyramide or the myosin inhibitor mavacamten may be an option with slightly different indications among the two guidelines. Septal reduction therapy is recommended in ESC guidelines for symptomatic patients with significant LVOT gradients, while American guidelines suggest earlier myectomy for certain clinical factors and emphasize shared decision-making. The ESC guidelines recommend sequential atrioventricular pacing and dual-chamber defibrillators for reducing LVOT gradients. The American guidelines focus on genetic testing for risk assessment and suggest periodic cardiac magnetic resonance imaging. This paper provides a detailed comparison of these guidelines, highlighting key differences and areas needing further research and expert debate.

Loss of quality of life and increased societal costs in patients with hypertrophic cardiomyopathy: the AFFECT-HCM study.

Hypertrophic cardiomyopathy (HCM) is the most prevalent inherited cardiac disease. The impact of HCM on quality of life (QoL) and societal costs remains poorly understood. This prospective multi-centre burden of disease study estimated QoL and societal costs of genotyped HCM patients and genotype-positive phenotype-negative (G+/P-) subjects. Participants were categorized into three groups based on genotype and phenotype: 1) G+/P- (left ventricular (LV) wall thickness <13 mm), 2) non-obstructive HCM (nHCM, LV outflow tract (LVOT) gradient <30 mmHg), and 3) obstructive HCM (oHCM, LVOT gradient ≥30 mmHg). We assessed QoL with EQ-5D-5L and Kansas City Cardiomyopathy Questionnaires (KCCQ). Societal costs were measured using medical consumption (iMCQ) and productivity cost (iPCQ) questionnaires. We performed subanalyses within three age groups: <40, 40-59, and ≥60 years. From three Dutch hospitals, 506 subjects were enrolled (84 G+/P-, 313 nHCM, 109 oHCM; median age 59 years, 39% female). HCM (both nHCM and oHCM) patients reported reduced QoL vs G+/P- subjects (KCCQ: 88 vs 98, EQ-5D-5L: 0.88 vs 0.96; both p<0.001). oHCM patients reported lower KCCQ scores than nHCM patients (83 vs 89, p=0.036). Societal costs were significantly higher in HCM patients (€19,035/year vs €7,385/year) compared to G+/P- controls, mainly explained by higher healthcare costs and productivity losses. Being symptomatic and of younger age (<60 years) particularly led to decreased QoL and increased costs. HCM is associated with decreased QoL and increased societal costs, especially in younger and symptomatic patients. oHCM patients were more frequently symptomatic than nHCM patients. This study highlights the substantial disease burden of HCM and can aid in assessing new therapy cost-effectiveness for HCM in the future.