Lower Left Ventricular Outflow Tract Research Articles

Low left ventricular outflow tract velocity time integral predicts normotensive shock in patients with acute pulmonary embolism

Abstract Funding Acknowledgements None. Introduction In patients with intermediate-risk acute pulmonary embolism (PE) outcomes vary widely, with mortality rates ranging from 3-15% and rates of normotensive shock up to 30%.1-3 Current risk models don't fully capture those at higher risk and identify patients who may benefit from advanced therapies. The left ventricular outflow tract (LVOT) velocity time integral (VTI), a surrogate marker of cardiac output, has been associated with increased mortality in acute PE.4 Our objective was to determine the association between LVOT VTI and its predictive value in identifying normotensive shock in this patient population. Methods Patients who underwent percutaneous mechanical thrombectomy (MT) between August 2020 and March 2023 at a large academic public hospital were considered for the study. Inclusion criteria comprised of normotensive patients (SBP ≥ 90 mmHg) with invasive measures of cardiac index (CI). VTI was obtained by pulsed wave doppler at the LVOT in either the apical 3 or apical 5 chamber view. The primary outcome was the association between LVOT VTI and normotensive shock and a cut off of 15 cm was used to examine this association based on prior studies.4 Results A total of 49 patients with intermediate-risk PE underwent MT, 16 patients had incomplete data, resulting in a final cohort of 33 patients (mean age: 57 ± 13yrs; 38% female). Patients with LVOT VTI of <15 cm were younger (53 vs 62 years p=0.02), had lower systolic blood pressure at presentation (122 vs 134 mmHg, p=0.047), higher heart rate (112.6 vs 96.2 beats/min, p=0.008), a higher composite shock score (CPES) (5 vs 3, p=0.012), lower cardiac index (1.9 vs 3.1 L/min/m2, p<0.001), a higher PASP (61.4 vs 48.9 mmHg, p=0.018), and higher rates of elevated lactate (90% vs 42%, p=0.027). LVOT VTI threshold of <15cm effectively identified patients with normotensive shock (90% vs 8% p<0.001). There was no statistically significant difference in the rates of saddle emboli, left ventricular ejection fraction, sPESI and BOVA scores in patients with VTI above or below 15cm. In patients with normotensive shock, 19/20 (95%) had LVOT VTI ≤ 15cm with a median of 13 cm (IQR 12, 14) (Figure). In patients without normotensive shock, 11/13 (84%) had LVOT VTI >15 with a median of 18 (IQR 17, 21). The area under the curve for LVOT VTI ≤ 15 cm in predicting normotensive shock was 0.89. The sensitivity and specificity of LVOT VTI ≤ 15 cm in predicting normotensive shock was 91.6% and 90.4% respectively. Conclusion Our study suggests that LVOT VTI is a reliable surrogate for cardiac output in patients with acute PE and can effectively identify those in the intermediate-risk group who are at risk for normotensive shock. A LVOT VTI <15cm may identify intermediate-risk patients at higher risk for hemodynamic decompensation and further studies are needed to evaluate whether these patients would benefit from upfront catheter-based therapies.

Low left ventricular outflow tract velocity time integral predicts normotensive shock in patients with acute pulmonary embolism

In this study, we found that a low LVOT VTI (<15 cm), a simple bedside point-of-care measurement, predicts normotensive shock in patients with acute intermediate-risk PE.

Aficamten: A Breakthrough Therapy for Symptomatic Obstructive Hypertrophic Cardiomyopathy.

Aficamten is a novel cardiac myosin inhibitor that has demonstrated its ability to safely lower left ventricular outflow tract (LVOT) gradients and improve heart failure symptoms in patients with obstructive hypertrophic cardiomyopathy (HCM). Based on the REDWOOD-HCMopen label extension (OLE) study, participants receiving aficamten had significantly reduced resting and Valsalva LVOT gradient within 2 weeks after initiating treatment, with ongoing improvements over 24 weeks, and recent evidence suggests effects can sustain up to 48 weeks. While beta-blockers, calcium channel blockers, and disopyramide have shown some benefits in managing HCM, they have limited direct impact on the underlying disease process in patients with obstructive HCM. Aficamten achieves its therapeutic effect by reducing hypercontractility and improving diastolic function in obstructive HCM. Mavacamten was the first cardiac myosin inhibitor approved for symptomatic obstructive HCM. However, aficamten has a shorter human half-life (t1/2) and fewer drug-drug interactions, making it a preferable treatment option. This review evaluates the long-term clinical value and safety of aficamten in patients with obstructive HCM based on available data from completed and ongoing clinical trials. Additionally, the molecular basis of sarcomere-targeted therapy in reducing LVOT gradients is explored, and its potential in managing obstructive HCM is discussed.

HCM-AF South Italy score for prediction of new-onset atrial fibrillation in patients with hypertrophic cardiomyopathy: data from a derivation and validation italian cohorts

Abstract Background Only one score for prediction of new-onset atrial fibrillation (AF) in patients with hypertrophic cardiomyopathy (HCM) has been developed in North America (HCM-AF North America score). Purpose To develop a new score (HCM-AF South Italy score) in an Italian derivation cohort and to test the new score with that from North America, in an Italian validation cohort. Methods A cohort of 228 patients with HCM and without history of AF, followed at referral center 1 for HCM, was used for model development. A cohort of 226 patients without history of AF, followed at referral center 2, was used for external validation. During follow-up (IQR 3–13 years, median 8 years), 59 (26%) patients developed new-onset AF. Data in the development cohort generated the HCM-AF South Italy score, a point score to predict AF probability: left atrial dimension &amp;gt;49 mm (+5 points), age at clinical evaluation &amp;lt;55 years (+2 points), the use of angiotensin-converting enzyme (ACE) or inhibitor or angiotensin receptor blocker (ARB) at initial evaluation (+2 points), low left ventricular (LV) ejection fraction (&amp;lt;50%) (+2 points), LV outflow tract obstruction (LVOTO) &amp;gt;25 mmHg (+2 points), NYHA class &amp;gt;1 (+1 point). Results Patients from the validation cohort were older, had lower prevalence of HCM family history, lower systolic and diastolic blood pressure, taken fewer drugs like beta-blockers, ACE or ARB, calcium-channel blockers, and antiarrhythmic drugs and had lower LVOTO than patients from the derivation cohort, (overall p&amp;lt;0.05). During follow-up (IQR 1–10 years, median 5 years), 25 (11%) patients developed AF. ROC curve analysis demonstrated that HCM-AF South Italy score was superior to HCM-AF North America score (Figure). A HCM- AF South Italy score &amp;gt;4 identified patients at risk of AF with a sensitivity of 48%, specificity of 76%, PPV of 20% and NPV of 92%. Conclusion Although derived and tested in little and quite different populations, the performance of the HCM-AF South Italy score was superior to that of the score developed in North America. Funding Acknowledgement Type of funding sources: None.

Paediatric subaortic stenosis: long-term outcome and risk factors for reoperation.

Surgical repair of subaortic stenosis (SAS) is associated with a substantial reoperation risk. We aimed to identify risk factors for reintervention in relation to discrete and tunnel-type SAS morphology. Single-centre retrospective study of paediatric SAS diagnosed between 1992 and 2017. Multivariable Cox regression analysis was performed to identify reintervention risk factors. Eighty-five children [median age 2.5 (0.7-6.5) years at diagnosis] with a median follow-up of 10.1 (5.5-16.4) years were included. Surgery was executed in 83% (n = 71). Freedom from reoperation was 88 ± 5% at 5 years and 82 ± 6% at 10 years for discrete SAS, compared to, respectively, 33 ± 16% and 17 ± 14% for tunnel-type SAS (log-rank P < 0.001). Independent risk factors for reintervention were a postoperative gradient >20 mmHg [hazard ratio (HR) 6.56, 95% confidence interval (CI) 1.41-24.1; P = 0.005], tunnel-type SAS (HR 7.46, 95% CI 2.48-22.49; P < 0.001), aortic annulus z-score <-2 (HR 11.07, 95% CI 3.03-40.47; P < 0.001) and age at intervention <2 years (HR 3.24, 95% CI 1.09-9.86; P = 0.035). Addition of septal myectomy at initial intervention was not associated with lesser reintervention. Fourteen children with a lower left ventricular outflow tract (LVOT) gradient (P < 0.001) and older age at diagnosis (P = 0.024) were followed expectatively. Children with SAS remain at risk for reintervention, despite initially effective LVOT relief. Regardless of SAS morphology, age <2 years at first intervention, a postoperative gradient >20 mmHg and presence of a hypoplastic aortic annulus are independent risk factors for reintervention. More extensive LVOT surgery might be considered at an earlier stage in these children. SAS presenting in older children with a low LVOT gradient at diagnosis shows little progression, justifying an expectative approach.

Clinical and molecular characterization of seven patients with Danon disease.

Danon disease is an X-linked glycogen storage disease characterized by skeletal myopathy, cardiomyopathy and intellectual impairment. It is caused by a loss-of-function mutation in the lysosome-associated membrane protein-2 (LAMP2) gene. In the present study, exon and boarding intron analysis of 96 cardio disease-associated genes was performed in 770 patients with hypertrophic cardiomyopathy (HCM) using second-generation sequencing. Next, the identified mutations were confirmed in family members of the patients and 300 healthy controls. Detailed clinical, electrocardiographic (ECG) and echocardiographic findings were recorded. A pathogenic mutation in LAMP2 was identified in 7 patients who phenotypically presented with HCM. A total of four patients had a fragmented QRS complex (fQRS) on surface ECG. In addition, two patients presented with ventricular preexcitation with a short PR interval. Compared with the patients with protein kinase AMP-activated non-catalytic subunit γ2 syndrome and Fabry disease, the 7 patients with Danon disease presented at an earlier age, had a smaller left atrial size, a thinner maximal left ventricular wall thickness and a lower probability of pacemaker implantation. Compared with 12 sex- and age-matched patients with sarcomere-protein mutations, the 4 patients with Danon disease had a lower left ventricular outflow tract gradient and worse diastolic function. The present study provided a comprehensive comparison of different pathologies presenting with HCM and reported on features of early-onset Danon disease, including the characteristic preexcitation and fQRS on ECG. This may provide valuable information that may be utilized for the early diagnosis and treatment of patients with Danon disease. The present study was registered as a clinical trial with ClinicalTrials.gov (Sep. 2, 2016; registry no. NCT02888132).

A new calcium score to predict paravalvular leak in transcatheter aortic valve implantation.

The present study sought to develop a reliable calcium score (Ca-score) to predict paravalvular leak (PVL) in patients undergoing transcatheter aortic valve (AV) implantation. A total of 965 patients were prospectively included from 2012 to 2019. Preprocedural contrast-media-enhanced computed tomography scans were analysed regarding the amount of AV cusp calcification and the presence of upper and lower left ventricular outflow tract calcification. The calcium volume threshold of each AV cusp [non-coronary cusp (NCC); left coronary cusp (LCC); right coronary cusp (RCC)] with optimal PVL prediction was defined using the Youden index value derived from receiver operating characteristic analysis. The final score was developed based on the multivariable regression analysis, while individual variables were weighted based on their corresponding odds ratio. The AV calcium volume threshold with optimal PVL prediction was 733.6, 296.0 and 131.2 mm3 for the NCC, RCC and LCC respectively. Overall, calcification of the upper left ventricular outflow tract was present in 233 (23%), 111 (12%) and 304 (32%) of patients below the NCC, RCC and LCC respectively, while 260 (27%), 44 (5%) and 217 (23%) patients suffered from calcification under the NCC, RCC and LCC, respectively. A total Ca-score of ≥4 was present in 356 (37%) of patients and was independently associated with ≥ mild PVL [odds ratio 3.662; 95% confidence interval (2.740-4.911); P < 0.001]. The area under the curve of the Ca-score was 0.713 [95% confidence interval (0.678-0.748); P < 0.001]. The provided Ca-score independently correlates with the development of PVL and improves risk stratification in patients undergoing transcatheter AV implantation.

Long-Term Aortic Valve Function in Patients With or Without Surgical Treatment for Discrete Subaortic Stenosis.

The purpose of this study was to evaluate the long-term function of the aortic valve in patients with discrete subaortic stenosis (DSS), and its prognostic implications. 34 patients with the diagnosis of isolated DSS were treated at our pediatric heart center between 1992 and 2019. Demographic, echocardiographic and surgical data were analyzed. 26 patients had surgery to remove the subaortic membrane. The primary endpoint of this study was a change in the aortic valve function, secondary outcomes included functional class, aortic valve replacement, and reoperation due to recurrence of DSS. The mean post-operative follow-up time was 7.07years (1-22.5). At the time of the most recent follow up, in the surgical group 11 patients (46%) had echocardiographic evidence of deterioration in their aortic valve insufficiency (AI) (p < 0.002). The deterioration was associated with a pre-operative left ventricular outflow tract (LVOT) gradient greater than 49mmHg (p < 0.022). 8 patients with DSS were followed for a mean of 12.9years (6.8-21.3), without meeting the criteria for surgical intervention, none showed any change in the aortic valve function during follow-up time. DSS resection may not prevent worsening of aortic valve insufficiency over time. Patients with stable AI and low LVOT gradient may not require surgery. Given these findings, it may be appropriate to carefully follow patients with new onset AI and low LVOT gradient, delaying surgical intervention.

Abstract P177: Treatment Of Resistant Hypertension In Hypertrophic Cardiomyopathy And Left Ventricular Outflow Tract Obstruction

Background: Lowering blood pressure (BP) in patients with resistant hypertension (RH) is challenging. When RH co-exists with hypertrophic cardiomyopathy (HCM) and left ventricular outflow tract (LVOT) obstruction, nuanced management is required. Diuretics and medications with vasodilating effects are commonly used for the treatment of hypertension; however they can worsen LVOT obstruction, leading to harm in patients with HCM. There is limited data for the treatment of RH in this patient population. Methods: Seven patients were referred to a RH clinic with uncontrolled BP and HCM with LVOT obstruction. Antihypertensive medications and BP were assessed at initial (T 0 ) and follow up (T 1 ) visits. Change in LVOT gradients - both at rest and provoked - were reviewed from echocardiographic data before and after adjustment of medications. Results: Medication regimens were personalized to eliminate dihydropyridine calcium-channel antagonists and renin-angiotensin system antagonists. When required, they were dosed once nightly. Beta blocker and non-dihydropyridine calcium channel antagonist dosages were optimized. Thiazides were prescribed at lowest dose possible and spironolactone was used in the majority of patients (Table 1). Patients experienced an average reduction of 21 mmHg in office systolic BP (4 - 57 mmHg) and 15 mmHg reduction in diastolic BP (3- 39 mmHg). LVOT gradient at rest decreased by an average of 23.8 mmHg, while provoked gradient decreased by 23 mmHg. Conclusions: Improved BP control and lower LVOT gradients were observed among HCM patients with RH through personalized adjustment of their medication regimen.

Low left ventricular outflow tract velocity time integral is associated with poor outcomes in acute pulmonary embolism.

The left ventricular outflow tract (LVOT) velocity time integral (VTI) is an easily measured echocardiographic stroke volume index analog. Low values predict adverse outcomes in left ventricular failure. We postulate the left ventricular VTI may be a signal of right ventricular dysfunction in acute pulmonary embolism, and therefore a predictor of poor outcomes. We retrospectively reviewed echocardiograms on all Pulmonary Embolism Response Team activations at our institution at the time of pulmonary embolism diagnosis. Low LVOT VTI was defined as ⩽ 15 cm. We examined two composite outcomes: (1) in-hospital death or cardiac arrest; and (2) shock or need for primary reperfusion therapies. Sixty-one of 188 patients (32%) had a LVOT VTI of ⩽ 15 cm. Low VTI was associated with in-hospital death or cardiac arrest (odds ratio (OR) 6, 95% CI 2, 17.9; p = 0.0014) and shock or need for reperfusion (OR 23.3, 95% CI 6.6, 82.1; p < 0.0001). In a multivariable model, LVOT VTI ⩽ 15 remained significant for death or cardiac arrest (OR 3.48, 95% CI 1.02, 11.9; p = 0.047) and for shock or need for reperfusion (OR 8.12, 95% CI 1.62, 40.66; p = 0.011). Among intermediate-high-risk patients, low VTI was the only variable associated with the composite outcome of death, cardiac arrest, shock, or need for reperfusion (OR 14, 95% CI 1.7, 118.4; p = 0.015). LVOT VTI is associated with adverse short-term outcomes in acute pulmonary embolism. The VTI may help risk stratify patients with intermediate-high-risk pulmonary embolism.

Clinical features of the systolic anterior motion of the mitral valve among patients without hypertrophic cardiomyopathy

BackgroundThe prevalence and clinical features of the systolic anterior motion of the mitral valve (SAM) without hypertrophic cardiomyopathy (HCM) have not been studied well. MethodsRecords of 9180 sequential patients who underwent echocardiography at Tokyo Women's Medical University Hospital were reviewed. SAM patients were divided into those with HCM (HCM; n=60, 68%) and those without HCM (non-HCM; n=28, 32%). To assess SAM morphology, non-HCM patients were divided into the valvular and chordal groups. ResultsThe prevalence of non-HCM SAM was 0.3%. Non-HCM patients showed older age (65.7±15.0 years vs. 56.9±16.8 years, p=0.02), higher prevalence of sigmoid septum (75% vs. 50%, p=0.03), and lower left ventricular outflow tract pressure gradient (LVOT-PG) (27±31mmHg vs. 43±41mmHg, p=0.03) than HCM patients. However, 8 of 28 non-HCM patients showed a LVOT-PG >30mmHg. Valvular SAM showed higher dyspnea prevalence (29% vs. 0%, p=0.04), higher LVOT-PG (39±36mmHg vs. 6±2mmHg, p<0.001), longer anterior mitral leaflet (28±2mm vs. 26±3mm, p=0.04) and more pronounced mitral regurgitation than chordal SAM. ConclusionNon-HCM SAM prevalence was 0.3% in the Japanese population. Non-HCM SAM correlated with older age, sigmoid septum, and a lower LVOT-PG compared with HCM SAM. Among non-HCM SAM, valvular SAM showed a significant symptom, higher LVOT-PG, and more pronounced mitral regurgitation than chordal SAM.

Comparison of Clinical Features in Blacks Versus Whites With Hypertrophic Cardiomyopathy

To date, there has not been a large systematic examination of the hypertrophic cardiomyopathy (HC) phenotype in blacks versus whites. In this study, we investigate differences in presentation of HC between blacks and whites. We included 441 consecutive patients with HC seen at the Johns Hopkins HC clinic in the period from February 2005 to June 2012. We compared 76 blacks for clinical presentation, electrocardiogram, exercise capacity, left ventricular morphology, and hemodynamics by echocardiography to 365 whites. Black patients with HC more often presented with abnormal electrocardiogram (93% vs 80%, p= 0.009), driven by a significant difference in repolarization abnormalities (79% vs 56%, p <0.001). Apical hypertrophy was more common in blacks (26% vs 9%, p <0.001); however, blacks had less severe systolic anterior movement of the mitral valve and had significantly lower left ventricular outflow tract gradients at rest (9mm Hg; interquartile range [IQR] 7 to 19 vs 16mm Hg; IQR 8 to 40, p <0.001) and during provocation (36mm Hg; IQR 16 to 77 vs 59mm Hg; IQR 26 to 110, p= 0.002). Despite the nonobstructive pathophysiology, blacks had lower exercise capacity (adjusted difference 1.45 metabolic equivalents [0.45 to 2.45], p=0.005). In conclusion, blacks have an HC phenotype characterized by lower prevalence of the well-recognized echocardiographic features of HC such as systolic anterior movement of the mitral valve and left ventricular outflow tract obstruction and display worse exercise capacity.

Extremely Low Velocity Time Integral of the Left Ventricular Outflow Tract Predictive of Death and LVAD Placement

Velocity time integral (VTI) of the Left ventricular outflow tract (LVOT) is a standard echocardiographic measurement that correlates with stroke volume. We hypothesized that an extremely low LVOT VTI (<10 cm) would be a useful predictive marker for mortality, left-ventricular assist device (LVAD) placement or cardiac transplantation.

Left Ventricular Outflow Obstruction

Left ventricular outflow tract obstructions (LVOTOs) encompass a series of stenotic lesions starting in the anatomic left ventricular outflow tract (LVOT) and stretching to the descending portion of the aortic arch (Figure 1). Obstruction may be subvalvar, valvar, or supravalvar. These obstructions to forward flow may present alone or in concert, as in the frequent association of a bicuspid aortic valve with coarctation of the aorta. All of these lesions impose increased afterload on the left ventricle and, if severe and untreated, result in hypertrophy and eventual dilatation and failure of the left ventricle. LVOTOs are congenital in the vast majority of individuals younger than 50 years in the United States; some variants of subaortic obstruction are the exception. It is imperative to consider all patients with LVOTO at a high risk for developing infective endocarditis, and one should always institute appropriate measures for prophylaxis. The present article is intended as a contemporary review of the causes, manifestations, treatments, and outcomes of LVOTO; it will not address LVOTO in the pediatric population or genetic hypertrophic cardiomyopathy but will focus strictly on congenital malformations in the adult. Figure 1. Artist’s rendering of the LVOTO lesions in sequence as viewed from a superolateral orientation. A, Gradient echo cardiac MR image as viewed from the frontal projection demonstrating flow acceleration at a site of supravalvar aortic stenosis (white arrow) in a patient with Williams syndrome. The black arrow identifies the level of the unrestricted aortic valve. B, Classic radiological signs of coarctation of the aorta: rib notching (white arrows) as seen on a posteroanterior chest x-ray in a patient with coarctation of the aorta. The rib notching is caused by erosion of the inferior rib margins by dilated pulsatile posterior intercostals collateral arteries. The black arrow points to the Figure 3 silhouette that …

Systolic anterior motion begins at low left ventricular outflow tract velocity in obstructive hypertrophic cardiomyopathy

OBJECTIVESThe purpose of this study was to determine whether the dynamic cause for mitral systolic anterior motion (SAM) is a Venturi or a flow drag (pushing) mechanism.BACKGROUNDIn obstructive hypertrophic cardiomyopathy (HCM), if SAM were caused by the Venturi mechanism, high flow velocity in the left ventricular outflow tract (LVOT) should be found at the time of SAM onset. However, if the velocity was found to be normal, this would support an alternative mechanism.METHODSWe studied with echocardiography 25 patients with obstructive HCM who had a mean outflow tract gradient of 82 ± 6 mm Hg. We compared mitral valve M-mode echocardiogram tracings with continuous wave (CW) and pulsed wave (PW) Doppler tracings recorded on the same study. A total of 98 M-mode, 159 CW, and 151 PW Doppler tracings were digitized and analyzed. For each patient we determined the LVOT CW velocity at the time of SAM onset. This was done by first determining the mean time interval from Q-wave to SAM onset from multiple M-mode tracings. Then, CW velocity in the outflow tract was measured at that same time interval following the Q wave.RESULTSSystolic anterior motion began mean 71 ± 5 ms after Q-wave onset. Mean CW Doppler velocity in the LVOT at SAM onset was 89 ± 8 cm/s. In 68% of cases SAM began before onset of CW and PW Doppler LV ejection.CONCLUSIONSSystolic anterior motion begins at normal LVOT velocity. At SAM onset, though Venturi forces are present in the outflow tract, their magnitude is much smaller than previously assumed; the Venturi mechanism cannot explain SAM. These velocity data, along with shape, orientation and temporal observations in patients, indicate that drag, the pushing force of flow, is the dominant hydrodynamic force that causes SAM.