Systolic anterior motion of the mitral valve in hypertrophic cardiomyopathy: a narrative review.

Background and Objective: The prevalence of hypertrophic cardiomyopathy (HCM) is estimated to be 1 in 200 to 500 individuals, with systolic anterior motion (SAM) of the mitral valve (MV) and left ventricular outflow tract (LVOT) obstruction present in 60% to 70%. In this narrative review, we aim to elucidate the pathophysiology of SAM-septal contact and LVOT obstruction in HCM by presenting a detailed review on the anatomy of the MV apparatus in HCM, examining the various existing theories pertaining to the SAM phenomenon as supported by cardiac imaging, and providing a critical assessment of management strategies for SAM in HCM. Methods: A literature review was performed using PubMed, EMBASE, Ovid, and the Cochrane Library, of all scientific articles published through December 2021. A focus was placed on descriptive studies, reports correlating echocardiographic findings with pathologic diagnosis, and outcomes studies. Key Content and Findings: The pathophysiology of SAM involves the complex interplay between HCM morphology, MV apparatus anatomic abnormalities, and labile hemodynamic derangements. Echocardiography and cardiac magnetic resonance (CMR) vector flow mapping have identified drag forces, as opposed to the "Venturi effect", as the main hydraulic forces responsible for SAM. The degree of mitral regurgitation with SAM is variable, and its severity is correlated with degree of LVOT obstruction and outcomes. First line therapy for the amelioration of SAM and LVOT obstruction is medical therapy with beta-blockers, non-dihydropyridine calcium-channel blockers, and disopyramide, in conjunction with lifestyle modifications. In refractory cases septal reduction therapy is performed, which may be combined with a 'resect-plicate-release' procedure, anterior mitral leaflet extension, surgical edge-to-edge MV repair, anterior mitral leaflet retention plasty, or secondary chordal cutting. Conclusions: Recent scientific advances in the field of HCM have allowed for a maturation of our understanding of the SAM phenomenon. Cardiac imaging plays a critical role in its diagnosis, treatment, and surveillance, and in our ability to apply the appropriate therapeutic regimens. The increasing prevalence of HCM places an emphasis on continued basic and clinical research to further improve outcomes for this challenging population.

Cardiac geometry, function and mechanics in left ventricular non-compaction cardiomyopathy with preserved ejection fraction.

BACKGROUND: Left ventricular non-compaction (LVNC) cardiomyopathy in adults has primarily been studied with a phenotypic expression of low ejection fraction (EF) and dilated cardiomyopathy; however, data on LVNC with preserved EF is scarce. The present study aimed to evaluate cardiac geometry and mechanics in LVNC patients with preserved EF. METHODS: A retrospective cohort study of patients diagnosed with LVNC and a preserved EF between 2008 and 2019 was performed. LVNC was defined according to the presence of established transthoracic 2D echocardiographic (TTE) criteria as follows: (1) prominent LV trabeculations with deep recesses; (2) bi-layered myocardial appearance; and, (3) systolic non-compacted:compacted ratio≥ 2. Subjects were matched 1:1 to controls without LVNC referred for routine TTE. Geometric, functional and mechanics parameters were analyzed in the two cohorts using 2D and speckle-tracking TTE. RESULTS: Seventeen patients with LVNC and preserved EF were identified. Compared with controls, patients with LVNC had similar LV systolic function and chamber dimensions, but a larger mass and relative wall thickness, and more abnormal LV geometry (76% vs. 18%, p = 0.002), LA remodeling, and pulmonary hypertension. Global longitudinal strain was significantly decreased (-15.4 ± 3.2 vs. -18.9 ± 2.8%, p = < 0.01) and the prevalence of rigid body rotation was significantly increased (57% vs. 14%, p = 0.05) in the LVNC population. The peak twist values were comparable in both cohorts. CONCLUSIONS: Impaired LV geometry and longitudinal mechanics, as well as increased myocardial stiffness as expressed by rigid body rotation, characterize LVNC with preserved EF when compared with controls.

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.

Relationship between compliance and pulmonary vascular resistance in pulmonary arterial hypertension.

BACKGROUND: Pulmonary arterial compliance (PAC) was previously shown to be an important prognostic factor in pulmonary arterial hypertension (PAH), in addition to the conventional pulmonary vascular resistance (PVR). The product of PAC and PVR, the arterial time (RC) constant, expresses the logarithmic relationship between the hemodynamic parameters. The objective of the study was to test RC constant stability in PAH patients followed beyond 12 months after diagnosis, and to report possible RC variations in different etiologies. METHODS: Fourteen PAH patients followed between 2008 and 2019 were included. Type 1 PAH was defined as a mean pulmonary artery pressure (PAP) ≥25 mmHg at rest and PVR ≥3 Wood units (WU). All patients who fulfilled WHO group I PAH criteria and had undergone two right heart catheterizations at least 1 year apart were included. The recorded hemodynamic data for each patient were used to compute PVR and PAC. RESULTS: PAH etiologies included scleroderma (n=2), liver cirrhosis (n=1), hereditary hemorrhagic telangiectasia (HHT) (n=1), mixed connective tissue disease (MCTD) (n=3), and idiopathic (n=7). The RC constant remained stable for all 14 patients over a follow-up period of 3.9±2 years. Patients with MCTD displayed more favorable hemodynamics, evidenced by higher RC (12.54 vs. 10.01, P<0.01) and PAC values (2.59 vs. 1.62, P=0.02), when compared with non-MCTD PAH patients. For the entire cohort the mean PAP measured 51±14 mmHg at baseline, and 46±13 mmHg at follow-up, respectively. CONCLUSIONS: The relationship between PAC and PVR remains stable in follow-up periods averaging 4 years, making compliance an important disease marker past the early stages. Patients with MCTD displayed more advantageous hemodynamic profiles when compared with patients with other PAH etiologies.

Novel GUCY2D mutation causes phenotypic variability of Leber congenital amaurosis in a large kindred.

BACKGROUND: Leber congenital amaurosis (LCA) is a severe retinal degenerative disease that manifests as blindness or poor vision in infancy. The purpose of this study was to clinically characterize and identify the cause of disease in a large inbred Bedouin Israeli tribe with LCA. METHODS: Thirty individuals of a single kindred, including eight affected with LCA, were recruited for this study. Patients' clinical data and electroretinography (ERG) findings were collected. Molecular analysis included homozygosity mapping with polymorphic markers and Sanger sequencing of candidate genes. RESULTS: Of the eight affected individuals of the kindred, nystagmus was documented in five subjects and keratoconus in three. Cataract was found in 5 of 16 eyes. Photopic and scotopic ERG performed in 5 patients were extinguished. All affected subjects were nearly blind, their visual acuity ranged between finger counting and uncertain light perception. Assuming autosomal recessive heredity of a founder mutation, studies using polymorphic markers excluded homozygosity of affected individuals at the genomic loci of all previously known genes associated with LCA, except GUCY2D. Sequencing of GUCY2D identified a novel missense mutation (c.2129C>T; p.Ala710Val) resulting in substitution of alanine by valine at position 710 within the protein kinase domain of the retina-specific enzyme guanylate cyclase 1 (GC1) encoded by GUCY2D. Molecular modeling implied that the mutation changes the conformation of the regulatory segment within the kinase styk-domain of GC1 and causes loss of its helical structure, likely inhibiting phosphorylation of threonine residue within this segment, which is needed to activate the catalytic domain of the protein. CONCLUSIONS: This is the first documentation of the p.Ala710Val mutation in GC1 and the second ever described mutation in its protein kinase domain. Our findings enlarge the scope of genetic variability of LCA, highlight the phenotypic heterogeneity found amongst individuals harboring an identical LCA mutation, and possibly provide hope for gene therapy in patients with this congenital blinding disease. As the Bedouin kindred studied originates from Saudi Arabia, the mutation found might be an ancient founder mutation in that large community.

A quality improvement project to decrease emergency department and medical intensive care unit transfer times.

OBJECTIVE: To reduce transfer time of critically ill patients from the emergency department (ED) to the medical intensive care unit (MICU). DESIGN: A prospective, observational study assessing preimplementation and postimplementation of quality improvement interventions in a tertiary academic medical center. INTERVENTIONS: A team of frontline health care professional including ED, MICU, and supporting services using the clinical microsystems approach mapped out existing practice patterns, determined causes for delays, and used the Plan-Do-Study-Act to test changes. Measurements and Main Results The team identified multiple issues that contributed to delays. These included poor coordination between transport services, respiratory therapy, and nursing in transferring patients from the ED as well delays in identification and transfer of stable MICU patients. These interventions reduced transfer time from 4.2 (3.4-5.7) hours to 2.2 (1.4-3.1) hours (median [interquartile range]; P<.001). Hospital length of stay decreased from 9.9±9 to 8.3±7 days (P<.03). CONCLUSION: A team made up of frontline health care professionals using a structured quality improvement process and implementing multifaceted, multistage interventions, reduced transfer delays, and length of stay. Added benefits included engagement among members of the 2 microsystems and a more cohesive approach to patient care.

Screening for diabetic retinopathy: review of current methods.

OBJECTIVE: To review the current screening methods for diabetic retinopathy, with a focus on nonmydriatic digital fundus photography. METHODS: Articles from Medline were reviewed from 1976 to November 2011 for different combinations of the words "diabetic retinopathy," "screening," "fundus photography," and "nonmydriasis." RESULTS: Because of its ease of use and cost-effectiveness, digital fundus photography is becoming the preferred method for diagnosing diabetic retinopathy. Current research has proven that pupillary dilation is not a necessary step in the fundus examination, although it reduces the number of unnecessary referrals to ophthalmologists. Automated grading systems, while saving time and reducing human error, still need refinement before they can replace manual grading by trained ophthalmologists. CONCLUSION: Nonmydriatic digital fundus photography with manual grading by a trained technician is an acceptable method of screening for diabetic retinopathy.

Diabetic retinopathy in Africa: advantages of screening.

OBJECTIVE: To review the epidemiology of diabetic retinopathy (DR) in Africa and discuss the various methods of screening for the disease. METHODS: Review of the peer-reviewed articles in PubMed, Google, and Scirus about DR published from 1985 to 2010. Articles in all languages were considered, provided that the non-English articles included English abstracts. RESULTS: Screening for DR can significantly prevent the loss of vision resulting from long-standing diabetes mellitus. Screening is also financially advantageous for both patients and health care systems. Several screening methods can be employed by primary care providers, who over the past 20 years have become responsible for the treatment and follow-up of patients with diabetes rather than hospitals. An additional concern for screening in African countries is the inefficient referral to ophthalmologists, given their scarce distribution in the African population. Finally, education of both the patient population and caregivers should be included as an essential component of screening programs. CONCLUSION: As of now, African health care systems are not prepared to deal with the increasing burden of diabetes and its complications. With inappropriate glycemic or blood pressure control, most patients will only seek care once micro- or macrovascular complications have already developed. Given the current difficulty in providing costly therapeutic interventions, a well-planned, cost-effective prevention strategy is required.