Subclinical cardiovascular remodelling in HIV-infection: A multimodal case study of 2 serodiscordant, monozygotic twins.

Cardiovascular abnormalities are increasingly recognised among people newly diagnosed with HIV, but subclinical pathology may be challenging to diagnose. We present a case study of subtle cardiovascular changes in identical twins, one without HIV-infection and the other recently diagnosed with HIV (serodiscordant). We hypothesise that cardiovascular parameters would be similar between the twins, unless non-genetic (environmental) factors are at play. These differences likely represent occult pathology secondary to the effects of early HIV-infection. A 25-year-old female incidentally diagnosed with HIV, and her HIV-uninfected identical twin, living with her since birth, underwent comprehensive cardiovascular assessments. The HIV-positive twin exhibited a globular left ventricle (LV), larger LV volumes, decreased LV strain, peak atrial longitudinal strain (PALS) and higher native T1 and T2 mapping values compared to her sister. Cardiac biomarkers high sensitivity cardiac troponin T and N-terminal proBNP, as well as the novel markers of fibrosis and remodelling, galectin-3 and soluble-ST2, were higher in the HIV-infected twin. Given the twins' shared environment and genetic makeup, these differences likely stem from HIV-infection. Our study supports previous findings and suggests potential screening markers for HIV-associated cardiovascular disease, including PALS. Further research is warranted to explore PALS' utility in this context.

Antiretroviral therapy and HIV-associated cardiovascular disease: a prospective cardiac biomarker and CMR tissue characterization study.

AIMS: Biochemical markers are fundamental in cardiac evaluation, and various novel assays have recently been discovered. We prospectively evaluated the hearts of newly diagnosed people living with human immunodeficiency virus (PLWH) using cardiac biomarkers, compared them with human immunodeficiency virus (HIV)-uninfected controls, and correlated our prospective findings with cardiovascular magnetic resonance imaging (CMR). METHODS AND RESULTS: Newly diagnosed, antiretroviral therapy (ART)-naïve PLWH were recruited along with HIV-uninfected, age-matched, and sex-matched controls. All participants underwent measurement of high-sensitivity cardiac troponin T (hs-cTnT), N-terminal pro-B-type natriuretic peptide (NT-proBNP), soluble ST2 (sST2), and galectin-3, as well as a CMR study with multiparametric mapping. The HIV group started ART and was re-evaluated 9 months later. The cardiac biomarkers and their correlation with CMR parameters were evaluated in and between groups. Compared with controls (n = 22), hs-cTnT (4.0 vs. 5.1 ng/L; P = 0.004), NT-proBNP (23.2 vs. 40.8 ng/L; P = 0.02), and galectin-3 (6.8 vs. 9.0 ng/mL; P = 0.002) were all significantly higher in the ART-naïve group (n = 73). After 9 months of ART, hs-cTnT (5.1 vs. 4.3 ng/L; P = 0.02) and NT-proBNP (40.8 vs. 28.5 ng/L; P = 0.03) both decreased significantly and a trend of decrease was seen in sST2 (16.5 vs. 14.8 ng/L; P = 0.08). Galectin-3 did not demonstrate decrease over time (9.0 vs. 8.8 ng/mL; P = 0.6). The cardiac biomarkers that showed the best correlation with CMR measurements native T1, T2, and extracellular volume were NT-proBNP (rs ≥ 0.4, P < 0.001) and galectin-3 (rs ≥ 0.3, P < 0.01). CONCLUSIONS: Our cardiac biomarker data support the presence of subclinical myocardial injury, remodelling, and fibrosis at HIV diagnosis, and ART had a positive influence on these blood markers. It remains unclear if the underlying pathological processes were fully addressed by ART. The ability of cardiac biomarkers to detect and track tissue abnormalities diagnosed with CMR showed promise. With additional research, this could lead to improvements in screening and monitoring myocardial abnormalities, even in CMR-limited settings.

Clinical Profile of Patients with Hypertensive Emergency Referred to a Tertiary Hospital in the Western Cape Province of South Africa.

BACKGROUND: Despite advances in managing hypertension, hypertensive emergencies remain a common indication for emergency room visits. Our study aimed to determine the clinical profile of patients referred with hypertensive emergencies. METHODS: We conducted an observational study involving patients aged ≥18 years referred with hypertensive crisis. A diagnosis of hypertensive emergencies was based on a systolic blood pressure (BP) ≥180 mmHg and/or a diastolic BP ≥110 mmHg, with acute hypertension-mediated organ damage (aHMOD). Patients without evidence of aHMOD were considered hypertensive urgencies. Hypertensive disorders of pregnancy and unconscious patients were excluded from the study. RESULTS: Eighty-two patients were included, comprising 66 (80.5%) with hypertensive emergencies and 16 (19.5%) with hypertensive urgencies. The mean age of patients with hypertensive emergencies was 47.9 (13.2) years, and 66.7% were males. Age, systolic BP, and duration of hypertension were similar in the hypertensive crisis cohort. Most patients with hypertensive emergencies reported nonadherence to medication (78%) or presented de novo without a prior diagnosis of hypertension (36%). Cardiac aHMOD (acute pulmonary edema and myocardial infarction) occurred in 66%, while neurological emergencies (intracranial hemorrhage, ischemic stroke, and hypertensive encephalopathy) occurred in 33.3%. Lactate dehydrogenase (LDH) (P < 0.001), NT-proBNP (P=0.024), and cardiac troponin (P<0.001) were higher in hypertensive emergencies compared to urgencies. LDH did not differ in the subtypes of hypertensive emergencies. CONCLUSION: Cardiovascular and neurological emergencies are the most common hypertensive emergencies. Most patients reported nonadherence to medication or presented de novo without a prior diagnosis of hypertension.

Myocardial Tissue Characterization in Patients with Hypertensive Crisis, Positive Troponin, and Unobstructed Coronary Arteries: A Cardiovascular Magnetic Resonance-Based Study.

Hypertensive crisis can present with cardiac troponin elevation and unobstructed coronary arteries. We used cardiac magnetic resonance (CMR) imaging to characterize the myocardial tissue in patients with hypertensive crisis, elevated cardiac troponin, and unobstructed coronary arteries. Patients with hypertensive crisis and elevated cardiac troponin with coronary artery stenosis <50% were enrolled. Patients with troponin-negative hypertensive crisis served as controls. All participants underwent CMR imaging at 1.5 Tesla. Imaging biomarkers and tissue characteristics were compared between the groups. There were 19 patients (63% male) with elevated troponin and 24 (33% male) troponin-negative controls. The troponin-positive group was older (57 ± 11 years vs. 47 ± 14 years, p = 0.015). The groups had similar T2-weighted signal intensity ratios and native T1 times. T2 relaxation times were longer in the troponin-positive group, and the difference remained significant after excluding infarct-pattern late gadolinium enhancement (LGE) from the analysis. Extracellular volume (ECV) was higher in the troponin-positive group (25 ± 4 ms vs. 22 ± 3 ms, p = 0.008) and correlated strongly with T2 relaxation time (rs = 0.701, p = 0.022). Late gadolinium enhancement was 32% more prevalent in the troponin-positive group (82% vs. 50%, p = 0.050), with 29% having infarct-pattern LGE. T2 relaxation time was independently associated with troponin positivity (OR 2.1, p = 0.043), and both T2 relaxation time and ECV predicted troponin positivity (C-statistics: 0.71, p = 0.009; and 0.77, p = 0.006). Left ventricular end-diastolic and left atrial volumes were the strongest predictors of troponin positivity (C-statistics: 0.80, p = 0.001; and 0.82, p < 0.001). The increased T2 relaxation time and ECV and their significant correlation in the troponin-positive group suggest myocardial injury with oedema, while the non-ischaemic LGE could be due to myocardial fibrosis or acute necrosis. These CMR imaging biomarkers provide important clinical indices for risk stratification and prognostication in patients with hypertensive crisis.

Cardiac Morphology, Function, and Left Ventricular Geometric Pattern in Patients with Hypertensive Crisis: A Cardiovascular Magnetic Resonance-Based Study.

(1) Background: Altered cardiac morphology and function are associated with increased risks of adverse cardiac events in hypertension. Our study aimed to assess left ventricular (LV) morphology, geometry, and function using cardiovascular magnetic resonance (CMR) imaging in patients with hypertensive crisis. (2) Methods: Patients with hypertensive crisis underwent CMR imaging at 1.5 Tesla to assess cardiac volume, mass, function, and contrasted study. Left ventricular (LV) function and geometry were defined according to the guideline recommendations. Late gadolinium enhancement (LGE) was qualitatively assessed and classified into ischemic and nonischemic patterns. Predictors of LGE was determined using regression analysis. (3) Results: Eighty-two patients with hypertensive crisis (aged 48.5 ± 13.4 years, and 57% males) underwent CMR imaging. Of these patients, seventy-eight percent were hypertensive emergency and twenty-two percent were urgency. Diastolic blood pressure was higher under hypertensive emergency (p = 0.032). Seventy-nine percent (92% of emergency vs. 59% of urgency, respectively; p = 0.003) had left ventricular hypertrophy (LVH). The most prevalent LV geometry was concentric hypertrophy (52%). Asymmetric LVH occurred in 13 (22%) of the participants after excluding ischemic LGE. Impaired systolic function occurred in 46% of patients, and predominantly involved hypertensive emergency. Nonischemic LGE occurred in 75% of contrasted studies (67.2% in emergency versus 44.4% in urgency, respectively; p < 0.001). Creatinine and LV mass were independently associated with nonischemic LGE. (5) Conclusion: LVH, altered geometry, asymmetric LVH, impaired LV systolic function, and LGE are common under hypertensive crisis. LVH and LGE more commonly occurred under hypertensive emergency. Longitudinal studies are required to determine the prognostic implications of asymmetric LVH and LGE in hypertensive crisis.

The Role of Cardiac Biomarkers in the Diagnosis of Hypertensive Emergency.

There is a growing interest in the role of biomarkers in differentiating hypertensive emergency from hypertensive urgency. This study aimed to determine the diagnostic utility of lactate dehydrogenase (LDH), high-sensitivity cardiac troponin T (hscTnT), and N-terminal prohormone of brain-type natriuretic peptide (NT-proBNP) for identifying hypertensive emergency. A diagnosis of hypertensive emergency was made based on a systolic blood pressure of ≥180 mmHg and/or a diastolic blood pressure of ≥110 mmHg with acute hypertension-mediated organ damage. The predictive value of LDH, hscTnT, NT-proBNP, and models of these biomarkers for hypertensive emergency was determined using the area under the receiver operator characteristic curve (AUC). There were 66 patients (66.7% male) with a hypertensive emergency and 16 (31.3% male) with hypertensive urgency. LDH, NT-proBNP, and hscTnT were significantly higher in hypertensive emergency. Serum LDH > 190 U/L and high creatinine were associated with hypertensive emergency. LDH had an AUC ranging from 0.87 to 0.92 for the spectrum of hypertensive emergencies, while hscTnT had an AUC of 0.82 to 0.92, except for neurological emergencies, in which the AUC was 0.72. NT-proBNP was only useful in predicting acute pulmonary edema (AUC of 0.89). A model incorporating LDH with hscTnT had an AUC of 0.92 to 0.97 for the spectrum of hypertensive emergencies. LDH in isolation or combined with hscTnT correctly identified hypertensive emergency in patients presenting with hypertensive crisis. The routine assessment of these biomarkers has the potential to facilitate the timely identification of hypertensive emergencies, especially in patients with subtle and subclinical target organ injury.

Altered cardiac structure and function in newly diagnosed people living with HIV: a prospective cardiovascular magnetic resonance study after the initiation of antiretroviral treatment.

HIV associated cardiomyopathy (HIVAC) is a poorly understood entity that may progress along a continuum. We evaluated a group of persons newly diagnosed with HIV and studied the evolution of cardiac abnormalities after ART initiation. We recruited a group of newly diagnosed, ART naïve persons with HIV and a healthy, HIV uninfected group. Participants underwent comprehensive cardiovascular evaluation, including cardiovascular magnetic resonance imaging. The HIV group was started on ART and re-evaluated 9 months later. The cardiovascular parameters of the study groups were compared at diagnosis and after 9 months. The ART naïve group's (n = 66) left- and right end diastolic volume indexed for height were larger compared with controls (n = 22) (p < 0.03). The left ventricular mass indexed for height was larger in the naïve group compared with controls (p = 0.04). The ART naïve group had decreased left- and right ventricular ejection fraction (p < 0.03) and negative, non-linear associations with high HIV viral load (p = 0.02). The left ventricular size increased after 9 months (p = 0.04), while the systolic function remained unchanged. The HIV group had a high rate of non-resolving pericardial effusions. HIV infected persons demonstrate structurally and functionally altered ventricles at diagnosis. High HIV viral load was associated with left- and right ventricular dysfunction. Cardiac parameters and pericardial effusion prevalence did not show improvement with ART. Conversely, a concerning trend of increase was observed with left ventricular size. These subclinical cardiac abnormalities may represent a stage on the continuum of HIVAC that can progress to symptomatic disease if the causes are not identified and addressed.

Evolution of myocardial oedema and fibrosis in HIV infected persons after the initiation of antiretroviral therapy: a prospective cardiovascular magnetic resonance study.

BACKGROUND: Human immunodeficiency virus (HIV) infected persons on antiretroviral therapy (ART) have been shown to have functionally and structurally altered ventricles and may be related to cardiovascular inflammation. Mounting evidence suggests that the myocardium of HIV infected individuals may be abnormal before ART is initiated and may represent subclinical HIV-associated cardiomyopathy (HIVAC). The influence of ART on subclinical HIVAC is not known. METHODS: Newly diagnosed, ART naïve persons with HIV infection were enrolled along with HIV uninfected, age- and sex-matched controls. All participants underwent comprehensive cardiovascular assessment, including contrasted cardiovascular magnetic resonance (CMR) with multiparametric mapping on a 1.5T CMR system. The HIV group was started on ART (tenofovir/lamivudine/dolutegravir) and prospectively evaluated 9 months later. Cardiac tissue characterisation was compared in, and between groups using the appropriate statistical tests for the cross sectional data and the paired, prospective data respectively. RESULTS: Seventy-three ART naïve HIV infected individuals (32 ± 7 years, 45% female) and 22 healthy non-HIV subjects (33 ± 7 years, 50% female) were enrolled. Compared with non-HIV healthy subjects, the global native T1 (1008 ± 31 ms vs 1032 ± 44 ms, p = 0.02), global T2 (46 ± 2 vs 48 ± 3 ms, p = 0.006), and the prevalence of pericardial effusion (18% vs 67%, p < 0.001) were significantly higher in the HIV infected group at diagnosis. Global native T1 (1032 ± 44 to 1014 ± 34 ms, p < 0.001) and extracellular volume (ECV) (26 ± 4% to 25 ± 3%, p = 0.001) decreased significantly after 9 months on ART and were significantly associated with a decrease in the HIV viral load, decreased high sensitivity C-reactive protein, and improvement in the CD4 count (p < 0.001). Replacement fibrosis was significantly higher in the HIV infected group than controls (49% vs 10%, p = 0.02). The prevalence of late gadolinium enhancement did not change significantly over the 9-month study period (49% vs 55%, p = 0.4). CONCLUSION: Subclinical HIVAC may already be present at the time of HIV diagnosis, as suggested by the combination of subclinical myocardial oedema and fibrosis found to be present before administration of ART. Markers of myocardial oedema on tissue characterization improved on ART in the short term, however, it is unclear if the underlying pathological mechanism is halted, or merely slowed by ART. Mid- to long term prospective studies are needed to evaluate subtle myocardial changes over time and to assess the significance of subclinical myocardial fibrosis.

Pulse wave velocity demonstrates increased aortic stiffness in newly diagnosed, antiretroviral naïve HIV infected adults: A case-control study.

Increased aortic stiffness is an important predictor of cardiovascular disease (CVD). It remains controversial whether HIV infected persons have increased aortic stiffness at the time of HIV diagnosis. An explorative, case-control study was performed using carotid-femoral pulse wave velocity (PWV) in a newly diagnosed, antiretroviral treatment (ART)-naïve cohort with modest baseline cardiovascular risk. We recruited 85 newly diagnosed adults without known CVD from health care facilities in South Africa (43 female; mean age 33). Median CD4 count was 285, IQR 156-393 cells/µL. Twenty two HIV uninfected controls were recruited from the same facilities (8 female; mean age 33). PWV was measured using the Vicorder module (Skidmore Medical, United Kingdom) using a corrective factor of 0.8. The HIV infected group's mean PWV measured 11% higher than controls (5.88 vs 5.28 m/s; P = .02). Median aortic distensibility in HIV infected persons was 18% lower than controls (0.37 vs 0.45 mm Hg-1; P = .009). Multivariate analysis revealed that the difference in PWV between groups remained significant when corrected for age, sex, mean blood pressure and kidney function (mean difference 0.52 m/s; P = .01). Mean blood pressure, estimated glomerular filtration rate, HIV infection per se, age and male sex were important associations with increased PWV. Our study provides evidence for increased aortic stiffness in ART naïve adults already demonstrable at the time of HIV diagnosis. The cohort's young age and recent HIV diagnosis makes atherosclerosis a less likely explanation for the difference. Alternative, potentially reversible, explanations that require further research include vasomotor tone abnormalities and endothelial dysfunction.

Cardiac Complications of Hypertensive Emergency: Classification, Diagnosis and Management Challenges.

While mortality in patients with hypertensive emergency has significantly improved over the past decades, the incidence and complications associated with acute hypertension-mediated organ damage have not followed a similar trend. Hypertensive emergency is characterized by an abrupt surge in blood pressure, mostly occurring in people with pre-existing hypertension to result in acute hypertension-mediated organ damage. Acute hypertension-mediated organ damage commonly affects the cardiovascular system, and present as acute heart failure, myocardial infarction, and less commonly, acute aortic syndrome. Elevated cardiac troponin with or without myocardial infarction is one of the major determinants of outcome in hypertensive emergency. Despite being an established entity distinct from myocardial infarction, myocardial injury has not been systematically studied in hypertensive emergency. The current guidelines on the evaluation and management of hypertensive emergencies limit the cardiac troponin assay to patients presenting with features of myocardial ischemia and acute coronary syndrome, resulting in underdiagnosis, especially of atypical myocardial infarction. In this narrative review, we aimed to give an overview of the epidemiology and pathophysiology of hypertensive emergencies, highlight challenges in the evaluation, classification, and treatment of hypertensive emergency, and propose an algorithm for the evaluation and classification of cardiac acute hypertension-mediated organ damage.

Prevalence of Myocardial Injury and Myocardial Infarction in Patients with a Hypertensive Emergency: A Systematic Review.

Myocardial injury and myocardial infarction can complicate a hypertensive emergency, and both are associated with poor prognosis. However, little is known about the prevalence of myocardial injury and the different subtypes of myocardial infarction in patients with hypertensive emergencies. This systematic review aims to determine the prevalence of myocardial infarction and its subtypes, and the prevalence of myocardial injury in patients with hypertensive emergencies following the PRISMA guideline. A systematic search of PubMed, Web of Science, and EBSCOHost (MEDLINE) databases was carried out from inception to identify relevant articles. A total of 18 studies involving 7545 patients with a hypertensive emergency were included. Fifteen (83.3%) studies reported on the prevalence of myocardial infarction ranging from 3.6% to 59.6%, but only two studies specifically indicated the prevalence of ST-elevation and non-ST-elevation myocardial infarction. The prevalence of myocardial injury was obtained in three studies (16.7%) and ranged from 15% to 63%. Despite being common, very few studies reported myocardial injury and the subtypes of myocardial infarction among patients presenting with a hypertensive emergency, highlighting the need for more research in this area which will provide pertinent data to guide patient management and identify those at increased risk of major adverse cardiovascular events.

The variable spectrum of anterior mitral valve leaflet restriction in rheumatic heart disease screening.

INTRODUCTION: The World Heart Federation (WHF) screening criteria do not incorporate a strict, reproducible definition of anterior mitral valve leaflet (AMVL) restriction. Using a novel definition, we have identified two distinct AMVL restriction configurations. The first, called "distal tip" AMVL restriction is associated with additional morphological features of rheumatic heart disease (RHD), while the second, "gradual bowing" AMVL restriction is not. This "arch-like" leaflet configuration involves the base to tip of the medial MV in isolation. We hypothesize that this configuration is a normal variant. METHODOLOGY: The prevalence and associated leaflet configurations of AMVL restriction were assessed in schoolchildren with an established "very low" (VLP), "high" (HP), and "very high" prevalence (VHP) of RHD. RESULTS: 936 studies were evaluated (HP 577 cases; VLP 359 cases). Sixty-five cases of "gradual bowing" AMVL restriction were identified in the HP cohort (11.3%, 95% CI 8.9-14.1) and 35 cases (9.7%, 95% CI 7-13.2) in the VLP cohort (P = .47). In the second analyses, an enriched cohort of 43 studies with proven definite RHD were evaluated. "Distal tip" AMVL restriction was identified in all 43 VHP cases (100%) and affected the central portion of the AMVL in all cases. CONCLUSION: "Gradual bowing" AMVL restriction appears to be a normal, benign variant of the MV, not associated with RHD risk nor with any other morphological features of RHD. Conversely, "Distal tip" AMVL restriction was present in all cases in the VHP cohort with no cases exhibiting a straight, nonrestricted central portion of the AMVL. This novel finding requires further investigation as a potential RHD rule-out test of the MV.

Screening for subclinical rheumatic heart disease: addressing borderline disease in a real-world setting.

Aims: The World Heart Federation (WHF) criteria identify a large borderline rheumatic heart disease (RHD) category that has hampered the implementation of population-based screening. Inter-scallop separations (ISS) of the posterior mitral valve leaflet, a recently described normal variant of the mitral valve, appears to be an important cause of mild mitral regurgitation (MR) leading to misclassification of cases as WHF 'borderline RHD'. This study aims to report the findings of the Echo in Africa project, a large-scale RHD screening project in South Africa and determine what proportion of borderline cases would be re-classified as normal if there were a systematic identification of ISS-related MR. Methods and results: A prospective cross-sectional study of underserved secondary schools in the Western Cape was conducted. Participants underwent a screening study with a handheld (HH) ultrasound device. Children with an abnormal HH study were re-evaluated with a portable laptop echocardiography machine. A mechanistic evaluation was applied in cases with isolated WHF 'pathological' MR (WHF 'borderline RHD'). A total of 5255 participants (mean age 15± years) were screened. A total of 3439 (65.8%) were female. Forty-nine cases of WHF 'definite RHD' [9.1 cases/1000 (95% confidence interval, CI, 6.8-12.1 cases/1000)] and 104 cases of WHF 'borderline RHD' [19.5 cases/1000 (95% CI, 16.0-23.7 cases/1000)] were identified. Inter-scallop separations-related MR was the underlying mechanism of MR in 48/68 cases classified as WHF 'borderline RHD' with isolated WHF 'pathological' MR (70.5%). Conclusion: In a real-world, large-scale screening project, the adoption of a mechanistic evaluation based on the systematic identification of ISS-related MR markedly reduced the number of WHF 'screen-positive' cases misclassified as WHF 'borderline RHD'. Implementing strategies that reduce this misclassification could reduce the cost- and labour burden on large-scale RHD screening programmes.

The hidden continuum of HIV-associated cardiomyopathy: A focussed review with case reports.

HIV-associated cardiomyopathy (HIVAC) is a poorly understood group of diseases with a poor prognosis once ventricular dysfunction is present. Cardiovascular magnetic resonance has revealed a previously unappreciated burden of asymptomatic myocardial abnormalities in people living with HIV, including abnormalities already present at the time of HIV diagnosis. These abnormalities include thickened, inflamed ventricles that bear resemblance to cases of symptomatic HIVAC that are reported on in this article. Our understanding and the significance of asymptomatic HIV-associated myocardial pathology will be explored as early disease on a continuum towards more advanced cardiomyopathy. The need for prospective research in persons naïve to anti-retroviral therapy is emphasised as it may provide key findings to better understand this elusive disease process.

Screening for rheumatic heart disease: The reliability of anterior mitral valve leaflet thickness measurement.

BACKGROUND: Studies determining the reliability of the World Heart Federation (WHF) anterior mitral valve leaflet (AMVL) measurement are limited by the introduction of bias in their test-retest analyses. This study sought to determine the reliability of the current AMVL measurement while controlling for systematic bias. METHODS: Retrospective analysis of echocardiographic data from 16 patients with previous acute rheumatic fever was performed. Included in this study was an optimized cine loop of the mitral valve (MV) [reader-optimized measurement (ROM]) in the parasternal long-axis view and an optimized still image of the MV obtained from the same cine loop [specialist-optimized image (SOI)]. Each still image and associated cine loop was quadruplicated and randomized to determine intra- and inter-rater agreement and quantify the impact of zoom on AMVL measurement. RESULTS: Specialist-optimized image without zoom reflected the highest degree of agreement in both cohorts with an ICC of 0.29 and 0.46. The agreement in ROM images without zoom was ICC of 0.23 and 0.45. The addition of zoom to SOI decreased agreement further to an ICC of 0.20 and 0.36. The setting associated with the poorest agreement profile was ROI with zoom with an ICC of 0.13 and 0.34, respectively. The intra-rater agreement between readers in both cohorts was moderate across all settings with an ICC ranging between 0.64 and 0.86. CONCLUSIONS: The WHF AMVL measurement is only moderately repeatable within readers and demonstrates poor reproducibility that was not improved by the addition of a zoom-optimized protocol. Given our study findings, we cannot advocate the current WHF AMVL measurement as a reliable assessment for RHD.

Diagnostic disparity and identification of two TNNI3 gene mutations, one novel and one arising de novo, in South African patients with restrictive cardiomyopathy and focal ventricular hypertrophy.

INTRODUCTION: The minimum criterion for the diagnosis of hypertrophic cardiomyopathy (HCM) is thickening of the left ventricular wall, typically in an asymmetrical or focal fashion, and it requires no functional deficit. Using this criterion, we identified a family with four affected individuals and a single unrelated individual essentially with restrictive cardiomyopathy (RCM). Mutations in genes coding for the thin filaments of cardiac muscle have been described in RCM and HCM with 'restrictive features'. One such gene encodes for cardiac troponin I (TNNI3), a sub-unit of the troponin complex involved in the regulation of striated muscle contraction. We hypothesised that mutations in TNNI3 could underlie this particular phenotype, and we therefore screened TNNI3 for mutations in 115 HCM probands. METHODS: Clinical investigation involved examination, echocardiography, chest X-ray and an electrocardiogram of both the index cases and close relatives. The study cohort consisted of 113 South African HCM probands, with and without known founder HCM mutations, and 100 ethnically matched control individuals. Mutation screening of TNNI3 for diseasecausing mutations were performed using high-resolution melt (HRM) analysis. RESULTS: HRM analyses identified three previously described HCM-causing mutations (p.Pro82Ser, p.Arg162Gln, p.Arg170Gln) and a novel exonic variant (p.Leu144His). A previous study involving the same amino acid identified a p.Leu144Gln mutation in a patient presenting with RCM, with clinical features of HCM. We observed the novel p.Leu144His mutation in three siblings with clinical RCM and varying degrees of ventricular hypertrophy. The isolated index case with the de novo p.Arg170Gln mutation presented with a similar phenotype. Both mutations were absent in a healthy control group. CONCLUSION: We have identified a novel disease-causing p.Leu144His mutation and a de novo p.Arg170Gln mutation associated with RCM and focal ventricular hypertrophy, often below the typical diagnostic threshold for HCM. Our study provides information regarding TNNI3 mutations underlying RCM in contrast to other causes of a similar presentation, such as constrictive pericarditis or infiltration of cardiac muscle, all with marked right-sided cardiac manifestations. This study therefore highlights the need for extensive mutation screening of genes encoding for sarcomeric proteins, such as TNNI3 to identify the underlying cause of this particular phenotype.

Non-ST elevation myocardial infarction (NSTEMI) in three hospital settings in South Africa: does geography influence management and outcome? A retrospective cohort study.

BACKGROUND: Guidelines advise early angiography in non-ST elevation myocardial infarction (NSTEMI) to ensure an optimal outcome. Resource limitations in secondary hospitals in the Western Cape dictate a local guideline to treat NSTEMIs medically with out-patient assessment for angiography, unless mandatory indications for early angiography occur. METHODS: A retrospective cohort study assessed NSTEMIs at Tygerberg Hospital (TBH), Karl Bremer Hospital (KBH) and Worcester Hospital (WH) over one year. Two cohorts were analysed, secondary hospitals (KBH and WH; SH) and secondary service within a tertiary hospital (TBH). Where differences were found, sub-analysis compared WH and KBH. RESULTS: TBH and SH were similar at baseline and in clinical presentation. Cases at TBH were more likely to receive in-patient angiography (94 vs 51%, p < 0.0001), and had a lower in-patient mortality rate (6 vs 23%, p = 0.0326). There was no difference between KBH and WH in sub-analysis. CONCLUSION: This study confirmed that the management and mortality of NSTEMIs in the public health sector in the Western Cape, South Africa is not influenced by geography, but rather by the level of service available in the hospital of first presentation.