Presence of Apical Aneurysm and Its Impact on Left Ventricular Mechanics and Mechano-Energetic Coupling in Patients With Apical Hypertrophic Cardiomyopathy.

BACKGROUND: Left ventricular (LV) apical aneurysms (ApAn+) occur in 10%-15% of apical hypertrophic cardiomyopathy (ApHCM) patients and confer considerable morbidity. We hypothesized that ApAn+ adversely impact ventricular mechanics and mechano-energetic coupling in ApHCM. METHODS: Ninety-eight ApHCM patients were identified, of which nine (9%) had ApAn+ and were compared with 89 (91%) who did not (ApAn-). 2D speckle-tracking echocardiography assessed ventricular mechanics using LV global longitudinal strain (GLS) and torsion, and mechano-energetic coupling as myocardial work indices. Clinical events over follow-up were adjudicated. RESULTS: Mean age was 64 ± 15 years, 46% were female, and 3% had an HCM family history, with similar clinical risk factors between groups. Of the nine ApAn+ patients, there were six small (<2 cm) and three moderate-sized (2-4 cm) aneurysms. There was no difference in LV ejection fraction (65 ± 15 vs. 67 ± 11%, p = 0.51) or GLS (-9.6 ± 3.3 vs. -11.9 ± 3.9%, p = 0.09) between ApAn+ versus ApAn-. ApAn+ patients had greater myocardial global wasted work (347 ± 112 vs. 221 ± 165 mmHg%, p = 0.03) and lower global work efficiency (GWE, 75 ± 5 vs. 82 ± 8%, p = 0.006). LV GLS (ß = -0.67, p < 0.001), ApAn+ (ß = -0.15, p = 0.04), and twist rate (ß = -0.14, p = 0.04) were independently associated with GWE. At 3.9-year follow-up, cardiovascular mortality (4%) and heart failure hospitalization (14%) events were similar between groups. CONCLUSION: ApHCM patients with ApAn+ are characterized by more impaired LV mechano-energetic coupling when compared with ApAn-. ApAn+ is independently associated with worse GWE.

Right ventricular hypertrophy in apical hypertrophic cardiomyopathy.

BACKGROUND: Right ventricular hypertrophy (RVH+) in hypertrophic cardiomyopathy occurs in one third of patients, however, outcomes in apical hypertrophic cardiomyopathy (ApHCM) have not been described. We hypothesized that RVH+ in ApHCM is associated with more ventricular remodeling and dysfunction, and increased adverse events when compared with those without RVH (RVH-). METHODS: Ninety-one ApHCM patients were retrospectively analyzed using 2D and speckle-tracking echocardiography (64 ± 16 years old, 43% female). RVH+ was defined as wall thickness >5 mm and was present in 23 (25%). Ventricular mechanics were characterized by global longitudinal strain (GLS), RV free wall strain, and myocardial work. RESULTS: New York Heart Association functional class > II, atrial fibrillation, and prior stroke were more prevalent in RVH+. Left ventricular (LV) size and ejection fraction were similar between groups, with greater septal (17 vs. 14 mm, p = .001) and apical (20 vs. 18 mm, p = .04) wall thickness in RVH+. When compared with RVH- patients, RVH+ had worse LV GLS (-8.6 vs. -12.8%), global work index (820 vs. 1172 mmHg%) (both p < .001), and work efficiency (76 vs. 83%, p = .001), as well as RV GLS (-14 vs. -17.5%) and free wall strain (-17.3 vs. -21.3%) (both p = .02). At 3-year follow-up RVH+ had greater incidence of heart failure hospitalization compared with RVH- (35 vs. 7%, p = .003). RVH+ was associated with RV GLS (ß = .2, p = .03), independent of clinical and echocardiographic variables. CONCLUSIONS: RVH+ patients with ApHCM have worse biventricular mechanics and myocardial work, and more heart failure hospitalization, as RVH- at mid-term follow-up.

A systematic review and pooled analysis of septal myectomy and edge-to-edge mitral valve repair in obstructive hypertrophic cardiomyopathy.

Left ventricular outflow tract (LVOT) obstruction and systolic anterior motion (SAM) of the mitral valve (MV) occurs in 70% of hypertrophic cardiomyopathy (HCM) patients. In individuals undergoing septal myectomy, concomitant MV surgery is considered for SAM with residual LVOT obstruction or mitral regurgitation (MR); however, the optimal approach remains debated. A literature search was performed in Pubmed, EMBASE, Ovid, and the Cochrane library of published articles through June 2021 reporting on combined septal myectomy and edge-to-edge MV repair for obstructive HCM. Continuous variables were weighted and compared using a student's t-test, and categorical variables using a chi-square test with Yates correction. Six studies with 158 total patients were included. The mean follow-up was 2.8 ± 2.7 years. Compared with pre-operative values, there were significant reductions in the LV ejection fraction (69 ± 10 vs 59 ± 8%), peak LVOT gradient (82 ± 34 vs 16 ± 13 mmHg), prevalence of moderate or greater MR (84 vs 5 %), and presence of SAM (96% vs 0) (p < 0.001 for all). There was no change in LV internal diastolic diameter (4.2 ± 1.3 vs 4.4 ± 1.5 cm, p = 0.32). There were 2 (1%) operative mortalities. At follow-up, the survival rate was 97%, there were 3 (2%) re-operative MV replacements, 4 (3%) patients remained in New York Heart Association functional class III/IV, and 8 (6%) required permanent pacemaker implantation. In conclusion, combined septal myectomy and edge-to-edge MV repair is a safe and effective treatment strategy in carefully selected patients requiring surgical HCM management.

Echocardiographic and clinical outcomes of patients undergoing septal myectomy plus anterior mitral leaflet extension for hypertrophic cardiomyopathy.

Septal myectomy is indicated in patients with obstructive hypertrophic cardiomyopathy (HCM) and intractable symptoms. Concomitant mitral valve (MV) surgery is performed for abnormalities contributing to systolic anterior motion (SAM), or for SAM-mediated mitral regurgitation (MR) with or without left ventricular outflow tract (LVOT) obstruction. One MV repair technique is anterior mitral leaflet extension (AMLE) utilizing bovine pericardium, stiffening the leaflet and enhancing coaptation posteriorly. Fifteen HCM patients who underwent combined myectomy-AMLE for LVOT obstruction or moderate-to-severe MR between 2009 and 2020 were analyzed using detailed echocardiography. The mean age was 56.6 years and 67% were female. The average peak systolic LVOT gradient and MR grade measured 73.4 mmHg and 2.3, respectively. Indications for myectomy-AMLE were LVOT obstruction and moderate-to-severe MR in 67%, MR only in 20%, and LVOT obstruction only in 13%. There was no mortality observed, and median follow-up was 1.2 years. Two patients had follow-up grade 1 mitral SAM, one of whom also had mild LVOT obstruction. No recurrent MR was observed in 93%, and mild MR in 7%. Compared with preoperative measures, there was a decrease in follow-up LV ejection fraction (68.2 vs 56.3%, p = 0.02) and maximal septal wall thickness (25.5 vs 21.3 mm, p < 0.001), and an increase in the end-diastolic diameter (21.9 vs 24.8 mm/m2, p = 0.04). There was no change in global longitudinal strain (-12.1 vs -11.6%, p = 0.73) and peak LV twist (7.4 vs 7.3°, p = 0.97). In conclusion, myectomy-AMLE is a viable treatment option for carefully selected symptomatic HCM patients with LVOT obstruction or moderate-to-severe MR.

Interventricular Septal Involvement Is Associated with More Impaired Ventricular Function and Mechanics in Apical Hypertrophic Cardiomyopathy.

BACKGROUND: The interventricular septum has an important role in bi-ventricular performance. We hypothesized that septal involvement in apical hypertrophic cardiomyopathy (ApHCM-Mixed) adversely impacts ventricular structure and function when compared with isolated apical hypertrophy (ApHCM-Pure). METHODS: A total of 72 patients (ApHCM-Mixed = 36, ApHCM-Pure = 36) with serial 2D and speckle-tracking echocardiographic analyses were identified. Ventricular function and mechanics were characterized by left (LV) and right (RV) ventricular global longitudinal strain (GLS), RV free wall strain, and LV myocardial work indices, and clinical events were adjudicated. RESULTS: Clinical characteristics were similar between groups (mean age, 66 ± 15 years; 49% female; LV ejection fraction, 68 ± 11%). The ApHCM-Mixed group had larger LV mass indexes (141 ± 39 vs. 111 ± 30 g/m2, p < 0.001), worse LV (-9.6 ± 3.1 vs. -14.4 ± 3.4%, p < 0.001) and RV GLS (-14.3 ± 6.7 vs. -19.2 ± 5.2%, p = 0.001), impaired RV free wall strain (-18.5 ± 7.4 vs. -22.4 ± 6.3%, p = 0.02), and lower LV myocardial work indices including global work index (938 ± 306 vs. 1272 ± 339 mmHg%, p < 0.001), when compared with the ApHCM-Pure group. At a mean follow-up of 3.9 years, these differences all persisted. Five deaths were observed, all occurring in the ApHCM-Mixed group (14% vs. 0, p = 0.05), and with four being cardiac-related. This subgroup had a mean LV ejection fraction of 63%, LV GLS of -8.7%, an LV global work index of 875 mmHg%, and RV free wall strain of -15.9%, indicating significant subclinical bi-ventricular dysfunction. CONCLUSIONS: ApHCM-Mixed represents a distinct morphology in hypertrophic cardiomyopathy associated with more impaired ventricular function and mechanics when compared with ApHCM-Pure.

Left ventricular strain and myocardial work in apical hypertrophic cardiomyopathy.

Background: Apical hypertrophic cardiomyopathy (ApHCM) is recognized for its associated cardiovascular morbidity. Herein we describe left ventricular (LV) function and mechanics over long-term follow-up in ApHCM. Methods: A retrospective study of 98 consecutive ApHCM patients was performed (mean age: 64±15 years, 46% female) using 2D and speckle-tracking echocardiography. LV function and mechanics were characterized by global longitudinal strain (GLS), segmental strain, and myocardial work indices. Myocardial work was calculated by integrating longitudinal strain and blood pressure as estimated by the brachial artery cuff pressure, to generate an LV pressure-strain loop with adjusted ejection and isovolumetric periods. Composite complications were defined as all-cause mortality, sudden death, myocardial infarction, and/or stroke. Results: Mean LV ejection fraction measured 67%±11% and GLS was -11.7%±3.9%. Global work index (GWI) was 1,073±349 mmHg%, constructive work was 1,379±449 mmHg%, wasted work was 233±164 mmHg%, and work efficiency was 82%±8%. In 72 patients with follow-up echocardiography, at a median of 3.9 years there was progressive impairment in GLS (-11.9% vs. -10.7%; P=0.006), GWI (1,105 vs. 989 mmHg%; P=0.02), and global constructive work (1,432 vs. 1,312 mmHg%; P=0.03), without change in wasted work or work efficiency. Atrial fibrillation (ß=0.37; P<0.001), mitral annular e' velocity (ß=-0.32; P=0.001), and glomerular filtration rate (ß=-0.2; P=0.03) were independently associated with follow-up GLS; atrial fibrillation (ß=-0.27; P=0.01) and glomerular filtration rate (ß=0.23; P=0.04) were also associated with follow-up GWI. Global wasted work >186 mmHg% was predictive of composite complications (AUC =0.7, 95% CI: 0.53-0.82, sensitivity 93%, specificity 41%). Conclusions: ApHCM is associated with preserved LV ejection fraction but abnormal LV GLS and work indices, with progressive impairment. Important clinical and echocardiographic measures are independently predictive of long-term follow-up LV GLS, GWI and adverse events.

Positive Regadenoson Stress Test in a Patient on Phentermine With Normal Coronaries.

Obesity is a well-established cardiovascular (CV) risk factor with greater mortality and morbidity rates than the general population. Phentermine is a weight loss medication that is approved for short-term obesity treatment in conjunction with lifestyle modifications to decrease CV risk. A 51-year-old female with Raynaud's phenomenon who was started on phentermine one week prior presented with a one-day history of palpitations. Subsequent workup revealed non-ST elevation myocardial infarction (NSTEMI) on presentation and worsening ST segment depressions following regadenoson injection during pharmacological stress testing. Although current evidence suggests that the use of phentermine is safe and may even reduce the risk of CV disease in obese patients, it still may pose adverse CV effects. A detailed medical history, including medications used and predisposing conditions, is crucial to help identify and possibly prevent exacerbation of such CV side effects.

Echocardiographic Features of Longevity: A Cross-Sectional Study of Centenarians.

BACKGROUND: Centenarians represent an under-studied population within cardiovascular medicine. This study aimed to describe the echocardiographic characteristics of a cohort of centenarians at a tertiary referral center. MATERIALS AND METHODS: The institutional Echocardiography database was retrospectively reviewed and identified 100 consecutive centenarians referred for transthoracic echocardiography between January 2009 and December 2020. Cardiac chamber quantification, diastology, and valvular heart disease were assessed according to the American Society of Echocardiography guidelines. Independent t-tests and Mann-Whitney U-tests compared data between males and females. RESULTS: The mean age was 101.5 ± 1.7 years, 78% were female, and the most common co-morbidities were hypertension (77%), coronary artery disease (46%), and congestive heart failure (42%). The mean left ventricular (LV) ejection fraction measured 56.9 ± 11.3% (females vs males, 58.4 ± 9.8 vs 51.6 ± 14.6%, p = 0.01). Males had larger LV end-diastolic (2.8 ± 0.6 vs 2.5 ± 0.5, p = 0.03) and end-systolic diameter (1.9 ± 0.6 vs 1.6 ± 0.4, p = 0.001) indices; a smaller relative wall thickness (0.54 ± 0.18 vs 0.69 ± 0.36, p = 0.06); and a lower E/e' ratio (13.3 [10.3-19.6] vs 17.3 [13.2-23], p = 0.05), when compared with females. The prevalence of severe valvular lesions was 13.5%, and similar between genders. However, in patients with aortic stenosis, the transaortic pressure gradients were significantly higher in females (mean gradient: 32.0 ± 17.7 vs 18.7 ± 9.2 mmHg, p = 0.04). CONCLUSIONS: The present study on centenarians affords a cross-sectional evaluation of cardiac structure and function in a growing population, and highlights important differences between male and female patients.

Left ventricular remodeling after mitral valve repair and papillary muscle approximation.

BACKGROUND: Mitral valve repair with papillary muscle approximation (MVr-PMA) for severe secondary mitral regurgitation (MR) decreases MR recurrence compared with MVr alone. This study assessed the effects of MVr-PMA on left ventricular (LV) remodeling and shape, systolic function and strain mechanics. METHODS: Forty-eight patients who underwent MVr-PMA for severe secondary MR and had follow-up echocardiograms available for review were identified. Student's t-test, linear regression modeling, and receiver-operating characteristic curves were used in the statistical analyses. RESULTS: Median follow-up time was 14.9 months. MVr-PMA was associated with significant LV reverse remodeling with a smaller LV end-diastolic diameter, Systolic Sphericity Index, and interpapillary muscle distance at follow-up. Nine patients (18.8%) experienced moderate recurrent MR. When compared to recurrent MR patients at follow-up, those with durable MVr-PMA had a greater LV ejection fraction (32.8 vs. 22.0%, P=0.03), a smaller end-diastolic diameter (59.6 vs. 67.3 mm, P=0.03), Systolic Sphericity Index (0.35 vs. 0.47, P=0.03), and end-systolic interpapillary muscle distance (16.3 vs. 21.1 mm, P=0.03). A durable MVr-PMA also resulted in stable global longitudinal strain when compared with pre-operative values, while the recurrent MR group experienced a further decline (no recurrent MR: -8.4 vs. -7.5%; recurrent MR: -8.2 vs. -5.4%; P<0.05). A pre-operative LV end-diastolic diameter ≥ 64 mm was a discriminative predictor of MR recurrence (sensitivity=100%, specificity=51%, AUC=0.756, P=0.02). CONCLUSIONS: A durable MVr-PMA confers improved LV geometry and function, and stable LV mechanics. The extent of baseline LV remodeling identifies patients at risk for recurrent MR.

The genes and the environment in nasal allergy.

PURPOSE OF REVIEW: In this review, we summarize the latest publications on the genetic and environmental determinants of allergic rhinitis. RECENT FINDINGS: Recent advances in genetic technology and bioinformatics have enabled simultaneous unbiased analysis of the entire genome regarding DNA sequence variants, epigenetic modifications and gene expression, providing functional correlates for DNA variants and phenotypes. As a result, new genes of mitochondrial and B-lymphocyte metabolism have been associated with allergic rhinitis phenotypes. Epidemiological studies recently showed an increased risk to develop allergic rhinitis in all age groups with reduction in farm exposure and in children with few older siblings. Climate changes seem to have also influenced pollen exposure and pollen-induced allergic disease. Lastly, occupational rhinitis has been increasingly recognized as a large burden to society. SUMMARY: In summary, new high throughput genetics research technologies have pointed to new previously unsuspected pathways that may modulate the risk of developing allergic rhinitis such as mitochondrial metabolism. In addition, recent environmental factors found to influence the risk of developing allergic rhinitis include exposure to farm, pollution, occupational agents, and changes in climate.