Comparison of cardiac involvement, extracardiac manifestations and outcomes between homozygote and heterozygote transthyretin p.Val142Ile (V122I) variant in patients with hereditary transthyretin amyloidosis: a cohort study.

BACKGROUND: Hereditary transthyretin (ATTRv) p.Val142Ile (V122I) mutation is the most common inherited cause of cardiac amyloidosis and little is known about the phenotype and outcome of the rare homozygotic genotype. This study aimed to compare phenotypic characteristics and outcomes between heterozygous and homozygous patients with ATTRv V122I amyloidosis. MATERIAL AND METHODS: This monocentric, observational, retrospective study conducted at the French National Referral Centre for Cardiac Amyloidosis (Henri Mondor Hospital, Créteil), described clinical, electrocardiographic, cardiac imaging features and prognostic data for patients with ATTRv V122I amyloidosis. RESULTS: Among 185 ATTRv V122I patients identified, 161 were heterozygous and 24 were homozygous. The homozygous frequency was 13%. Onset occured significantly earlier in the homozygotes compared to heterozygotes with earlier median age at diagnosis (67[63-71] years vs 76[70-79] years, p < .001), age at first cardiac symptom (66[61-71] years vs 74[68-78] years, p < .001) and age at first extracardiac symptom (59[52-70] years vs 69[62-75] years, p = .003). Homozygous ATTRv V122I was also associated with greater disease burden with earlier events (death, transplant or hospitalisation for acute heart failure) compared with heterozygotes (71[67-74] vs 78[76-79] years, p = .018). CONCLUSION: This rare, homozygous V122I cohort confirmed the earlier age of onset, death and cardiac events in this population.

Resting Left Ventricular Global Longitudinal Strain to Identify Silent Myocardial Ischemia in Asymptomatic Patients with Diabetes Mellitus.

BACKGROUND: Screening for silent coronary artery disease in asymptomatic patients with diabetes mellitus (DM) is challenging and controversial. In this context, it seems crucial to identify early markers of coronary artery disease. METHODS: The aim of this study was to investigate the incremental value of resting left ventricular (LV) global longitudinal strain (GLS) for the prediction of positive results on stress (exercise or dobutamine) transthoracic echocardiography in 273 consecutive asymptomatic high-risk patients with DM. Positive results on stress transthoracic echocardiography were defined as stress-induced LV wall motion abnormalities (new or worsening preexisting abnormalities). RESULTS: Compared with patients with negative stress results, those with positive stress results (n = 28 [10%]) more frequently had cardiovascular risk factors, complications of DM, vascular disease, moderate and severe calcification of the aortic valve and mitral annulus, and worse resting LV GLS (-16.7 ± 2.9% vs -19.0 ± 1.9%, P < .001). On multivariable logistic regression analysis, DM duration > 10 years, diabetic retinopathy, LV hypertrophy, and impaired LV GLS (odds ratio, 1.39 [95% CI, 1.14-1.70] per percentage increase; odds ratio, 5.16 [95% CI, 1.96-13.59] for LV GLS worse than -18%) were independently associated with positive results on stress transthoracic echocardiography. The area under the curve to predict positive results was 0.74 for LV GLS with a cutoff of -18.0% (sensitivity 68%, specificity 78%). The area under the curve of the multivariable model to predict test results was improved by the addition of LV GLS (P < .001), with a bias-corrected area under the curve after bootstrapping of 0.842 [95% CI, 0.753-0.893]. CONCLUSIONS: The present findings show that resting LV GLS is associated with the presence of silent ischemia and could be useful to better identify asymptomatic patients with DM who might benefit from coronary artery disease screening.

Basal Takotsubo syndrome with transient severe mitral regurgitation caused by drug use: a case report.

BACKGROUND: Takotsubo syndrome (TTS) is a reversible cardiomyopathy. Little is known regarding its basal form and possible complications. CASE SUMMARY: A 31-year-old woman with no medical history was hospitalized for attempted suicide by ingestion of cocaine, benzodiazepine, and methadone. Initially, the patient received intensive care for coma and bradypnoea. After naloxone administration, the neurological situation improved, but the patient developed acute pulmonary oedema. Transthoracic echocardiography (TTE) revealed left ventricular systolic dysfunction with the basal wall's akinesia associated with moderate to severe restrictive mitral regurgitation. Global longitudinal strain (GLS) was impaired mainly in the basal segments. A coronary computed tomography ruled out coronary artery disease. Symptoms improved quickly under diuretic treatment. Transthoracic echocardiography at Day 6 showed improved basal wall contraction, with a left ventricular ejection fraction (LVEF) of 50% and moderate mitral regurgitation. TTE at Day 30 confirmed the diagnosis of myocardial infarction with non-obstructive coronary arteries related to a basal TTS after complete recovery of the LVEF, normalization of the wall motion and GLS, and the absence of residual mitral regurgitation. DISCUSSION: We report a case of acute pulmonary oedema due to basal TTS complicated by severe transient mitral regurgitation associated with moderate left ventricular dysfunction. Measuring strain by speckle-tracking can be useful to diagnose and monitor this entity. The use of coronary computed tomography is informative in young patients to rule-out coronary artery disease.