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Subclinical hypertrophic cardiomyopathy (HCM) is a phenotypic entity that has emerged from the increased use of cardiovascular magnetic resonance imaging in the evaluation and family screening of patients with HCM. We describe the case of a competitive athlete with a sarcomere gene mutation and family history of HCM who was found to exhibit the subclinical HCM phenotype on cardiovascular magnetic resonance imaging in the absence of left ventricular hypertrophy. We discuss the clinical uncertainties in her management. (Level of Difficulty: Advanced.), Central Illustration

A 40-year-old man with Marfan syndrome presented with chest pain and troponin elevation. Urgent echocardiography was suggestive of hypertrophic cardiomyopathy, but cardiovascular magnetic resonance identified features of acute myocarditis. Repeated imaging 4 months later showed resolution of septal thickness, confirming acute myocarditis. (Level of Difficulty: Intermediate.), Central Illustration

We report the unusual case of a 68-year-old man with coral reef aorta complicated with severe calcified valvular heart disease who has been undergoing dialysis for 21 years. This report highlights the etiology and the unusual manifestations of coral reef aorta in a long-term dialysis patient. (Level of Difficulty: Intermediate.), Central Illustration

Routine electrocardiogram in a middle-aged man with left ventricular hypertrophy showed sinus rhythm, a short PR interval, and delta wave, confirming ventricular pre-excitation. Pre-excitation was fixed after a premature atrial complex and in atrial fibrillation, features diagnostic of a fasciculo-ventricular pathway. Genetic testing confirmed a diagnosis of hypertrophic cardiomyopathy. (Level of Difficulty: Intermediate.), Central Illustration

Chronic use of hydroxychloroquine can result in cardiomyopathy and conduction disturbances. Here, we describe a case of hydroxychloroquine cardiotoxicity in a patient with heart failure with preserved ejection fraction and severe chronotropic incompetence. (Level of Difficulty: Intermediate.), Central Illustration

This report describes a young adult man presenting with subarachnoid hemorrhage secondary to an intracranial aneurysm who was found to have a short-segment type B interrupted aortic arch. We describe the clinical presentation, evaluation, and management of this patient and highlight imaging findings and percutaneous repair of the aneurysm and interrupted aortic arch. (Level of Difficulty: Intermediate.), Central Illustration

An 86-year-old man with paroxysmal atrial fibrillation on flecainide, a class IC antiarrhythmic, presented with cardiac arrest. The patient had extremely wide QRS complexes with inconsistent pacemaker capture on electrocardiography. Due to cardiac failure and renal failure, the patient developed progressive flecainide toxicity, which led to pacemaker failure, and ultimately, death. (Level of Difficulty: Beginner.), Central Illustration

ST-segment elevation is a dreadful finding in the emergency department because it is often associated with myocardial infarction and demands a prompt and definitive treatment. However, the clinical and echocardiographic assessment of a patient with electrocardiographic changes trumps any electrocardiology expert and should always lead to a clinical decision. (Level of Difficulty: Intermediate.), Central Illustration

A 39-year-old man, painter by profession, presented with symptoms of heart failure. His work up was unrevealing except for elevated blood lead levels (BLL). He was started on guideline-directed medical therapy and was referred to occupational therapy. No improvement in his ejection fraction was noted until his BLL decreased. (Level of Difficulty: Intermediate.), Graphical abstract, A 42-year-old man, painter by profession, presented with symptoms of heart failure. His work up was unrevealing except for elevated blood lead levels (B…

Background Coronary microvascular dysfunction is prevalent in chronic kidney disease (CKD), and may contribute to the development of myocardial dysfunction in CKD. Coronary flow velocity reserve (CFVR) is a marker of coronary microvascular function and falls with increasing CKD stage. Living kidney donors have renal function consistent with early stage CKD and concern has been raised about their cardiovascular risk. No studies to date have investigated the presence of coronary microvascular dysfunction in living kidney donors. Methods 25 healthy controls and 23 living kidney donors were recruited and underwent assessment with transthoracic echocardiography, Doppler CFVR, myocardial contrast echocardiography and serum multiplex immunoassay panels. Results Doppler CFVR was significantly reduced in living kidney donors compared to controls (mean CFVR 3.4 ± 0.7 vs 3.8 ± 0.6, mean difference 0.4 95% confidence interval 0.03–0.8, p =.036). Quantitative myocardial contrast echocardiography showed a trend towards reduced coronary flow reserve in living kidney donors. Compared to controls, living kidney donors had higher serum high sensitivity C reactive peptide (hsCRP) and lower levels of uromodulin. Conclusions This is the first study of CFVR in living kidney donors. We have shown that the modest drop in estimated glomerular filtration rate in living kidney donors is associated with lower values of Doppler CFVR compared to controls, suggesting that isolated reductions in renal function may lead to altered microvascular function. The increase in hsCRP and reduction in uromodulin suggests that chronic subclinical inflammation may contribute to altered microvascular function in this population., Highlights • Coronary flow velocity reserve is reduced in living kidney donors compared to controls. • Markers of inflammation are elevated in living kidney donors. • Inflammation may cause coronary microvascular dysfunction in living kidney donors. • Living kidney donors need aggressive cardiovascular risk factor management.

Objectives Electrocardiographic (ECG) changes have been associated with COVID-19 severity. However, the progression of ECG findings in COVID-19 patients has not been studied. The purpose of this study was to describe ECG features at different stages of COVID-19 cardiovascular (CV) events and to examine the effects of specific ECG parameters and cardiac-related biomarkers on clinical outcomes in COVID-19. Design Retrospective, cohort study Setting Major tertiary care medical centers and community hospitals in Louisville, KY, USA Participants 124 COVID-19 patients who suffered cardiovascular events during hospitalization. Interventions None Measurements and Main Results 12 lead ECG parameters, biomarkers of cardiac injuries, and clinical outcomes were analyzed with Spearman's correlation coefficients and Kruskal–Wallis one-way ANOVA. Atrial fibrillation/atrial flutter was more frequent in ECG obtained at the time of CV event when compared to admission ECG (9.5% vs. 26.9%; P = .007). Sinus tachycardia was higher in the last available hospital ECG than CV event ECG (37.5% vs. 20.4%; P = .031). Admission ECG QTc was significantly associated with admission troponin levels (R = 0.52, P < .001). The last available hospital ECG showed non-survivors had longer QRS duration than survivors (114.6 vs. 91.2 ms; P = .026), and higher heart rate was associated with longer ICU length of stay (Spearman ρ = 0.339, P = .032). Conclusions In hospitalized COVID-19 patients who suffered cardiovascular events, ECGs at various stages of COVID-19 hospitalization showed significantly different features with dissimilar clinical outcome correlations.

Background Hypertrophic cardiomyopathy (HCM) is caused by rare variants in sarcomere-encoding genes, but little is known about the clinical significance of these variants in the general population. Objectives The goal of this study was to compare lifetime outcomes and cardiovascular phenotypes according to the presence of rare variants in sarcomere-encoding genes among middle-aged adults. Methods This study analyzed whole exome sequencing and cardiac magnetic resonance imaging in UK Biobank participants stratified according to sarcomere-encoding variant status. Results The prevalence of rare variants (allele frequency, Central Illustration

A 71-year-old-lady presented with breathlessness, general tiredness and orthopnea. Echocardiography and electrocardiogram were suspicious for cardiac…, A 71-year-old-woman presented with breathlessness, general tiredness and orthopnea. Echocardiography and electrocardiogram were suspicious for cardiac amyloidosis. This case illustrates contemporary evaluation to confirm the diagnosis and distinguish between different types of amyloid. (Level of Difficulty: Beginner.), Graphical abstract

The Conserved Oligomeric Golgi (COG) complex, a multi-subunit vesicle tethering complex of the CATCHR (Complexes Associated with Tethering Containing Helical Rods) family, controls several aspects of cellular homeostasis by orchestrating retrograde vesicle traffic within the Golgi. The COG complex interacts with all key players regulating intra-Golgi trafficking, namely SNAREs, SNARE-interacting proteins, Rabs, coiled-coil tethers, and vesicular coats. In cells, COG deficiencies result in the accumulation of non-tethered COG-complex dependent (CCD) vesicles, dramatic morphological and functional abnormalities of the Golgi and endosomes, severe defects in N- and O- glycosylation, Golgi retrograde trafficking, sorting and protein secretion. In humans, COG mutations lead to severe multi-systemic diseases known as COG-Congenital Disorders of Glycosylation (COG-CDG). In this report, we review the current knowledge of the COG complex and analyze COG-related trafficking and glycosylation defects in COG-CDG patients., Graphical abstract Unlabelled Image, Highlights • Intracellular membrane trafficking and glycosylation. • COG complex structure and functions. • COG-CDGs: clinical presentation and molecular analysis.

Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac disease. The disease is characterized by marked variability in morphological expression and natural history, ranging from asymptomatic to heart failure or sudden cardiac death. Left ventricular hypertrophy and abnormal ventricular configuration result in dynamic left ventricular outflow obstruction in most patients. The goal of pharmacological therapy in HCM is to alleviate the symptoms, and it includes pharmacotherapies and septal reduction therapies. In this review, we summarize the relevant clinical issues and treatment options of HCM.

Objectives The goal of this study was to explore sex differences in myocardial remodeling in aortic stenosis (AS) by using echocardiography, cardiac magnetic resonance (CMR), and biomarkers. Background AS is a disease of both valve and left ventricle (LV). Sex differences in LV remodeling are reported in AS and may play a role in disease phenotyping. Methods This study was a prospective assessment of patients awaiting surgical valve replacement for severe AS using echocardiography, the 6-min walking test, biomarkers (high-sensitivity troponin T and N-terminal pro–brain natriuretic peptide), and CMR with late gadolinium enhancement and extracellular volume fraction, which dichotomizes the myocardium into matrix and cell volumes. LV remodeling was categorized into normal geometry, concentric remodeling, concentric hypertrophy, and eccentric hypertrophy. Results In 168 patients (age 70 ± 10 years, 55% male, indexed aortic valve area 0.40 ± 0.13 cm2/m2, mean gradient 47 ± 4 mm Hg), no sex or age differences in AS severity or functional capacity (6-min walking test) were found. CMR captured sex dimorphism in LV remodeling not apparent by using 2-dimensional echocardiography. Normal geometry (82% female) and concentric remodeling (60% female) dominated in women; concentric hypertrophy (71% male) and eccentric hypertrophy (76% male) dominated in men. Men also had more evidence of LV decompensation (pleural effusions), lower left ventricular ejection fraction (67 ± 16% vs. 74 ± 13%; p < 0.001), and higher levels of N-terminal pro–brain natriuretic peptide (p = 0.04) and high-sensitivity troponin T (p = 0.01). Myocardial fibrosis was higher in men, with higher focal fibrosis (late gadolinium enhancement 16.5 ± 11.2 g vs. 10.5 ± 8.9 g; p < 0.001) and extracellular expansion (matrix volume 28.5 ± 8.8 ml/m2 vs. 21.4 ± 6.3 ml/m2; p < 0.001). Conclusions CMR revealed sex differences in associations between AS and myocardial remodeling not evident from echocardiography. Given equal valve severity, the myocardial response to AS seems more maladaptive in men than previously reported. (Regression of Myocardial Fibrosis After Aortic Valve Replacement [RELIEF-AS]; NCT02174471), Graphical abstract

Background: Brugada syndrome (BrS) is an inherited electroclinical syndrome and can be occasionally precipitated by fever. The prevalence of Brugada-type electrocardiographic patterns (BTEP) due to febrile illnesses have not been previously studied in India. Materials and methods: Between June 2014 and December 2015, 525 consecutive patients admitted to a government hospital with acute febrile illness were retrospectively enrolled. In addition to their investigations for workup of fever, ECGs were analyzed and BTEP types 1 and 2 were noted. Daily ECGs if available were perused to document reversal. Results: BTEP was seen in 23 (4% 95%CI: 2.9–6.5%): BTEP type 1 (Brugada syndrome) in 11 patients (2%; 95%CI 1.2–3.7%) and BTEP type 2 in 12. All patients with BrS (BTEP type1) were males; mean age and temperature were 37.7 years (SD: 17.6) and 38.8 °C (SD: 0.6), respectively. There were no significant differences in age, temperature or ECG parameters between patients with BTEP and those without. These patients neither had cardiac symptoms nor family history of sudden cardiac deaths. Bacterial infections were the commonest cause of fever in patients with BrS. All BTEP changes resolved with defervesence of fever except in one. Conclusion: The prevalence of the fever induced BrS is higher in our study group and is comparable to estimates in Southeast Asian populations. An ECG should be considered in all febrile patients. Further studies are required for better characterization and risk stratification of these patients. Keywords: Brugada syndrome, Brugada-type ECG pattern, India, Fever, Prevalence

The annual incidence of sudden cardiac death (SCD) in athletes is significantly lower than the general population. However, when SCD occurs in an athlete during sporting event or training, it sends shockwaves in the society and raises questions about cardiovascular effects of sports and exercise. This document reviews the causes and mechanism of SCD in sports and exercise in young and older athletes. In the Indian context, we suggest a 'pre-participation screening' of young and older athletes and consider a 'supervised, graded exercise regime' for the uninitiated, older sports participant. Finally, the document proposes medical infrastructure required to successfully revive a victim of sudden cardiac arrest during a sporting event.

Background Left ventricular (LV) hypertrophy, a key process in human cardiac disease, results from cellular (hypertrophy) and extracellular matrix expansion (interstitial fibrosis). Objectives This study sought to investigate whether human myocardial interstitial fibrosis in aortic stenosis (AS) is plastic and can regress. Methods Patients with symptomatic, severe AS (n = 181; aortic valve area index 0.4 ± 0.1 cm2/m2) were assessed pre–aortic valve replacement (AVR) by echocardiography (AS severity, diastology), cardiovascular magnetic resonance (CMR) (for volumes, function, and focal or diffuse fibrosis), biomarkers (N-terminal pro–B-type natriuretic peptide and high-sensitivity troponin T), and the 6-min walk test. CMR was used to measure the extracellular volume fraction (ECV), thereby deriving matrix volume (LV mass × ECV) and cell volume (LV mass × [1 − ECV]). Biopsy excluded occult bystander disease. Assessment was repeated at 1 year post-AVR. Results At 1 year post-AVR in 116 pacemaker-free survivors (age 70 ± 10 years; 54% male), mean valve gradient had improved (48 ± 16 mm Hg to 12 ± 6 mm Hg; p < 0.001), and indexed LV mass had regressed by 19% (88 ± 26 g/m2 to 71 ± 19 g/m2; p < 0.001). Focal fibrosis by CMR late gadolinium enhancement did not change, but ECV increased (28.2 ± 2.9% to 29.9 ± 4.0%; p < 0.001): this was the result of a 16% reduction in matrix volume (25 ± 9 ml/m2 to 21 ± 7 ml/m2; p < 0.001) but a proportionally greater 22% reduction in cell volume (64 ± 18 ml/m2 to 50 ± 13 ml/m2; p < 0.001). These changes were accompanied by improvement in diastolic function, N-terminal pro–B-type natriuretic peptide, 6-min walk test results, and New York Heart Association functional class. Conclusions Post-AVR, focal fibrosis does not resolve, but diffuse fibrosis and myocardial cellular hypertrophy regress. Regression is accompanied by structural and functional improvements suggesting that human diffuse fibrosis is plastic, measurable by CMR and a potential therapeutic target. (Regression of Myocardial Fibrosis After Aortic Valve Replacement; NCT02174471), Central Illustration

Background Myocardial fibrosis occurs in aortic stenosis (AS) as part of the hypertrophic response. It can be detected by LGE, which is associated with an adverse prognosis in the form of increased mortality and morbidity. Objectives To assess the prevalence of LGE patterns using cardiac magnetic resonance (CMR) in severe AS patients and to study its prognostic significance. Methods Patients enrolled into the study from June 2012 to November 2014. All the patients underwent CMR and various patterns of LGE studied. These patients if symptomatic were advised AVR and others were managed conservatively. All patients were followed up and watched for outcomes like mortality, heart failure/hospitalization for cardiovascular cause, fall in left ventricular ejection fraction (LVEF) ≥20% and arrhythmia. Results A total of 109 patients (mean age-57.7 ± 12.5yrs) underwent CMR with 63 males. These patients were followed up for a mean of 13 months. Among 38 patients who underwent AVR, 6 died (5–cardiovascular cause, 1–non cardiovascular). 71 patients were managed conservatively out of which 18 died (17-cardiovascular cause, 1-non cardiovascular cause). LGE patterns were seen in 46 patients (43%); mid myocardial enhancement was seen in 31.1% of cases (33 patients). No LGE pattern was seen in 57%(63 patients). Basal and mid regions were maximally involved with mid myocardial enhancement in 66% & 68.3% respectively. LV ejection fraction (p = 0.002), peak aortic systolic velocity (p = 0.01) and peak aortic systolic gradient (p = 0.02) were the main predictors of LGE. Main predictors of primary outcome were NYHA class [OR- 13.4(2.8–26.1), p ≤ 0.001], age- 62 ± 9.6yrs(p = 0.001), EF simpson-50.9 ± 13%(p ≤ 0.001), LGE[OR 2.8 (1.27–6.47),p = 0.01], number of segments involved [2.37 ± 2.1,P ≤ 0.001] & CMR LV mass (151.73 ± 32 gms, p = 0.007). LGE predicted heart failure/hospitalization for cardiovascular cause [OR- 3.8(1.2–11.9), p = 0.01] and fall in LVEF [OR- 5.8(1.5–22.5), p = 0.005]. Patients with LGE had 2.87 times risk of adverse outcomes and patients with more than 3 segment LGE involvement had again increased chances for adverse outcomes. Conclusions LGE was detected by CMR in 43% of patients with severe AS. It predicted recurrent heart failure, hospitalization for cardiovascular cause and fall in LV ejection fraction. Our study has laid a path to larger prospective studies with long term follow up to assess the prognostic impact of CMR in patients with severe AS.

Aims: Taller stature has been associated with increased risk of atrial fibrillation (AF). AF and heart failure (HF) often co-occur but the association between height and risk of HF in older adults has not been well studied. We have examined the association between height and incident AF and incident HF in older adults. Methods: Prospective study of 3346 men aged 60-79 years with no diagnosed HF, myocardial infarction or stroke at baseline (1998-2000) followed up for a mean period of 16 years, in whom there were 294 incident HF cases and 456 incident AF. Men were divided into 5 height groups: 183.0 cms based on the 25th, 50th, 75th and 95th centiles distribution of height. Results: CVD risk factors tended to decrease with increasing height but a positive association was seen between height and electrocardiographic QRS duration and incident AF. Both short stature (183.0 cm) was associated with significantly increased risk of HF in age-adjusted analysis compared to those in the second height quartile [HR (95 %CI) = 1.62 (1.15, 2.26) and 2.04 (1.23, 3.39) respectively]. In short men the increased risk remained after adjustment for adverse CVD risk factors; in tall men the association was largely associated with AF and QRS duration. Conclusion: Tall stature is associated with significantly increased risk of AF leading to increased risk of HF. Short stature was associated with increased HF risk which was not explained by known adverse CVD risk factors.

Objectives Cardiac magnetic resonance (CMR) was used to investigate the extracellular compartment and myocardial fibrosis in patients with aortic stenosis, as well as their association with other measures of left ventricular decompensation and mortality. Background Progressive myocardial fibrosis drives the transition from hypertrophy to heart failure in aortic stenosis. Diffuse fibrosis is associated with extracellular volume expansion that is detectable by T1 mapping, whereas late gadolinium enhancement (LGE) detects replacement fibrosis. Methods In a prospective observational cohort study, 203 subjects (166 with aortic stenosis [69 years; 69% male]; 37 healthy volunteers [68 years; 65% male]) underwent comprehensive phenotypic characterization with clinical imaging and biomarker evaluation. On CMR, we quantified the total extracellular volume of the myocardium indexed to body surface area (iECV). The iECV upper limit of normal from the control group (22.5 ml/m2) was used to define extracellular compartment expansion. Areas of replacement mid-wall LGE were also identified. All-cause mortality was determined during 2.9 ± 0.8 years of follow up. Results iECV demonstrated a good correlation with diffuse histological fibrosis on myocardial biopsies (r = 0.87; p, Graphical abstract

Background Enzyme replacement therapy (ERT) with recombinant human α-galactosidase has been available for the treatment of Fabry disease since 2001 in Europe and 2003 in the USA. Treatment outcomes with ERT are dependent on baseline patient characteristics, and published data are derived from heterogeneous study populations. Methods We conducted a comprehensive systematic literature review of all original articles on ERT in the treatment of Fabry disease published up until January 2017. This article presents the findings in adult male patients. Results Clinical evidence for the efficacy of ERT in adult male patients was available from 166 publications including 36 clinical trial publications. ERT significantly decreases globotriaosylceramide levels in plasma, urine, and in different kidney, heart, and skin cell types, slows the decline in estimated glomerular filtration rate, and reduces/stabilizes left ventricular mass and cardiac wall thickness. ERT also improves nervous system, gastrointestinal, pain, and quality of life outcomes. Conclusions ERT is a disease-specific treatment for patients with Fabry disease that may provide clinical benefits on several outcomes and organ systems. Better outcomes may be observed when treatment is started at an early age prior to the development of organ damage such as chronic kidney disease or cardiac fibrosis. Consolidated evidence suggests a dose effect. Data described in male patients, together with female and paediatric data, informs clinical practice and therapeutic goals for individualized treatment., Highlights • This article provides a systematic review of the available clinical evidence on ERT in adult male Fabry patients. • The patient population heterogeneity highlights the need for standardized reporting and population-specific guidelines. • ERT may slow down progression of cardiac and renal disease and has a positive effect on other outcomes. • Treatment effects can be optimized when ERT is started as early as possible before the onset of major organ damage. • Consolidated evidence suggests a dose effect of ERT. • Therapeutic goals for the treatment of Fabry disease with ERT help advance disease management.

Background Cardiac involvement determines outcome in patients with systemic amyloidosis. There is major unmet need for quantification of cardiac amyloid burden, which is currently only met in part through semi-quantitative bone scintigraphy or Cardiovascular Magnetic Resonance (CMR), which measures ECVCMR. Other accessible tests are needed. Objectives To develop cardiac computed tomography to diagnose and quantify cardiac amyloidosis by measuring the myocardial Extracellular Volume, ECVCT. Methods Twenty-six patients (21 male, 64 ± 14 years) with a biopsy-proven systemic amyloidosis (ATTR n = 18; AL n = 8) were compared with twenty-seven patients (19 male, 68 ± 8 years) with severe aortic stenosis (AS). All patients had undergone echocardiography, bone scintigraphy, NT-pro-BNP measurement and EQ-CMR. Dynamic Equilibrium CT (DynEQ-CT) was performed using a prospectively gated cardiac scan prior to and after (5 and 15 minutes) a standard Iodixanol (1 ml/kg) bolus to measure ECVCT. ECVCT was compared to the reference ECVCMR and conventional amyloid measures: bone scintigraphy and clinical markers of cardiac amyloid severity (NT-pro-BNP, Troponin, LVEF, LV mass, LA and RA area). Results ECVCT and ECVCMR results were well correlated (r2 = 0.85 vs r2 = 0.74 for 5 and 15 minutes post bolus respectively). ECVCT was higher in amyloidosis than AS (0.54 ± 0.11 vs 0.28 ± 0.04, p, Highlights • Cardiac involvement determines outcome in amyloidosis. • There is major unmet need for quantification of cardiac amyloid burden. • Dynamic Equilibrium CT (DynEQ-CT) is a 5-minute contrast-enhanced CT scan. • DynEQ-CT measures the extracellular volume fraction, which increases in amyloid. • DynEQ-CT has major potential for diagnosis and quantification of cardiac amyloidosis.

Outcomes from 5 years of treatment with agalsidase alfa enzyme replacement therapy (ERT) for Fabry disease in patients enrolled in the Fabry Outcome Survey (FOS) were compared with published findings for untreated patients with Fabry disease. Data were extracted from FOS, a Shire-sponsored database, for comparison with data from three published studies. Outcomes evaluated were the annualized rate of change in estimated glomerular filtration rate (eGFR) and left ventricular mass indexed to height (LVMI) as well as time to and ages at a composite morbidity endpoint and at death. FOS data were extracted for 740 treated patients who were followed for a median of ~ 5 years. Compared with no treatment, patients treated with agalsidase alfa demonstrated slower decline in renal function and slower progression of left ventricular hypertrophy. Treated male patients with baseline eGFR < 60 mL/min/1.73 m 2 had a mean (standard error of the mean [SEM]) annualized change in eGFR of − 2.86 (0.53) mL/min/1.73 m 2 /y compared with − 6.8 (1.5) in the published untreated cohort. The mean (SEM) rate of LVMI increase with treatment was 0.33 (0.10) g/m 2.7 /y in males and 0.48 (0.09) in females, compared with 4.07 (1.03) in untreated males and 2.31 (0.81) in untreated females. Morbidity occurred later in treated patients, with ~ 16% risk of a composite morbidity event (26% in males) after 24 months with ERT versus ~ 45% without treatment, with first events and deaths also occurring at older ages in patients administered ERT (e.g., estimated median survival in treated males was 77.5 years versus 60 years in untreated males). Findings from these retrospective comparisons of observational data and published literature support the long-term benefits of ERT with agalsidase alfa for Fabry disease in slowing the progression of renal impairment and cardiomyopathy. Treatment also appeared to delay the onset of morbidity and mortality. Interpretation of these findings should take into account that they are based on retrospective comparisons with previously published data.

Background Mild hypertrophy but increased arrhythmic risk characterizes the stereotypic phenotype proposed for hypertrophic cardiomyopathy (HCM) caused by thin-filament mutations. However, whether such clinical profile is different from more prevalent thick-filament–associated disease is unresolved. Objectives This study aimed to assess clinical features and outcomes in a large cohort of patients with HCM associated with thin-filament mutations compared with thick-filament HCM. Methods Adult HCM patients (age >18 years), 80 with thin-filament and 150 with thick-filament mutations, were followed for an average of 4.5 years. Results Compared with thick-filament HCM, patients with thin-filament mutations showed: 1) milder and atypically distributed left ventricular (LV) hypertrophy (maximal wall thickness 18 ± 5 mm vs. 24 ± 6 mm; p < 0.001) and less prevalent outflow tract obstruction (19% vs. 34%; p = 0.015); 2) higher rate of progression to New York Heart Association functional class III or IV (15% vs. 5%; p = 0.013); 3) higher prevalence of systolic dysfunction or restrictive LV filling at last evaluation (20% vs. 9%; p = 0.038); 4) 2.4-fold increase in prevalence of triphasic LV filling pattern (26% vs. 11%; p = 0.002); and 5) similar rates of malignant ventricular arrhythmias and sudden cardiac death (p = 0.593). Conclusions In adult HCM patients, thin-filament mutations are associated with increased likelihood of advanced LV dysfunction and heart failure compared with thick-filament disease, whereas arrhythmic risk in both subsets is comparable. Triphasic LV filling is particularly common in thin-filament HCM, reflecting profound diastolic dysfunction.

Background LFA-1/JAM-A interaction plays a significant role in early steps of leukocyte transendothelial migration (diapedesis) which takes part in atherosclerosis pathogenesis. In this population-based case–control study, the frequencies of JAM-A rs790056 and LFA-1 rs8058823 gene polymorphisms in patients with coronary heart disease (CHD) and healthy subjects were investigated and the correlations between the different genotypes and cardiovascular risk factors were analyzed. Methods The JAM-A and LFA-1 genotypes were determined in 153 patients with CHD and 124 controls by PCR–RFLP assay. Results In CHD patient group, the frequency of JAM-A rs790056 TT genotype and the frequency of T allele were higher when compared with the control group (p = 0.03 and p = 0.007,respectively). In patient groups, the frequency of LFA-1 rs8058823 AA genotype was higher (p = 0.000), and the frequency of AG genotype was lower when compared with the control group (p = 0.031). In the control group, LFA-1 rs8058823 G allele carriers had higher SBP than subjects with AA genotype (p = 0.038), whereas in the CHD patient group, G allele carriers had lower DBP than subjects with AA genotype (p = 0.007). The multivariate logistic regression analysis confirmed that the JAM-A rs790056 TT genotype (OR = 2.472, p = 0.045) and LFA-1 rs8058823 AA genotype (OR = 6.751, p = 0.000) were risk factors for CHD development. Conclusion These results suggest that the wild type genotypes and alleles of JAM-A rs790056 (TT genotype and T allele) and LFA-1 rs8058823 (AA genotype and A allele) were found to be risk factors for CHD, whereas rare genotypes and alleles were found to be higher in healthy controls thus being protective., Highlights • JAM-A common genotype and allele were more frequent in CHD group than controls. • LFA-1 common genotype was more frequent in CHD group than controls. • LFA-1 rare allele had lower DBP than subjects with common genotype. • JAM-A and LFA-1 common genotypes were risk factors for CHD development.