Evaluation of potential links between phenotypic features and genetic variants in left ventricular outflow tract obstruction in hypertrophic cardiomyopathy using cardiovascular magnetic resonance imaging.

This study aimed to identify the phenotypic features contributing to the development of left ventricular outflow tract obstruction (LVOTO) in patients with hypertrophic cardiomyopathy (HCM) and to evaluate the genotype‒phenotype relationship. This cross-sectional study included 96 patients diagnosed with HCM (mean age: 56.9 ± 13.5 years, 32.3% female). The patients were divided into hypertrophic nonobstructive cardiomyopathy (HNCM; n = 60) and hypertrophic obstructive cardiomyopathy (HOCM; n = 36) groups. All patients underwent CMR. Patients (n = 77) who had previously provided formal approval underwent a genetic examination that included 18 genes. The anterior mitral leaflet (AML) length/LVOT diameter ratio, posterior mitral leaflet (PML) length/LVOT diameter ratio, and anterolateral papillary muscle (AL-PM) mobility were associated with LVOTO, independent of the basal IVS thickness, abnormal chordal attachment, and bifid PM. An AML length/LVOT diameter ratio of ≥ 2.30, a PML length/LVOT diameter ratio of ≥ 1.83, and an AL-PM mobility of ≥ 57.7% were predictors of LVOTO, with good sensitivity and specificity. Positive variants (VUS, LP, and P) were detected in 37.7% (29 of 77) of the patients who underwent genetic testing. The LP/P variant was detected in 20.8% (16 of 77) of patients. Three groups (variant-negative, VUS, and LP/P groups) had significant differences in the LVOT diameter (median 14, 12, and 10 mm, respectively; p = 0.021), AML length (mean 25.3, 26.5, and 27.5 mm, respectively; p = 0.029), AML length/LVOT diameter ratio (median 1.74, 2.33, and 2.85, respectively; p = 0.006), PML length/LVOT diameter ratio (median 1.29, 1.82, and 2.10, respectively; p = 0.045), and abnormal chordal attachment (6.3%, not observed, and 31.3%, respectively; p = 0.009). The AML length/LVOT diameter ratio, PML length/LVOT diameter ratio, and AL-PM mobility were associated with LVOTO. In addition, genetic testing results may provide information regarding the phenotypic expression of patients with HCM.

The Definition of Sarcomeric and Non-Sarcomeric Gene Mutations in Hypertrophic Cardiomyopathy Patients: A Multicenter Diagnostic Study Across Türkiye.

BACKGROUND: Hypertrophic cardiomyopathy is a common genetic heart disease and up to 40%-60% of patients have mutations in cardiac sarcomere protein genes. This genetic diagnosis study aimed to detect pathogenic or likely pathogenic sarcomeric and non-sarcomeric gene mutations and to confirm a final molecular diagnosis in patients diagnosed with hypertrophic cardiomyopathy. METHODS: A total of 392 patients with hypertrophic cardiomyopathy were included in this nationwide multicenter study conducted at 23 centers across Türkiye. All samples were analyzed with a 17-gene hypertrophic cardiomyopathy panel using next-generation sequencing technology. The gene panel includes ACTC1, DES, FLNC, GLA, LAMP2, MYBPC3, MYH7, MYL2, MYL3, PLN, PRKAG2, PTPN11, TNNC1, TNNI3, TNNT2, TPM1, and TTR genes. RESULTS: The next-generation sequencing panel identified positive genetic variants (variants of unknown significance, likely pathogenic or pathogenic) in 12 genes for 121 of 392 samples, including sarcomeric gene mutations in 30.4% (119/392) of samples tested, galactosidase alpha variants in 0.5% (2/392) of samples and TTR variant in 0.025% (1/392). The likely pathogenic or pathogenic variants identified in 69 (57.0%) of 121 positive samples yielded a confirmed molecular diagnosis. The diagnostic yield was 17.1% (15.8% for hypertrophic cardiomyopathy variants) for hypertrophic cardiomyopathy and hypertrophic cardiomyopathy phenocopies and 0.5% for Fabry disease. CONCLUSIONS: Our study showed that the distribution of genetic mutations, the prevalence of Fabry disease, and TTR amyloidosis in the Turkish population diagnosed with hypertrophic cardiomyopathy were similar to the other populations, but the percentage of sarcomeric gene mutations was slightly lower.

Non-dominant right coronary artery (RCA) is associated with suspected inferior ischemia on SPECT in patients without significant coronary artery disease (CAD).

OBJECTIVE: There is a huge uncertainty in the medical community regarding the significance of non-dominant right coronary artery (RCA) in patients with inferior wall ischemia on myocardial perfusion single-photon emission computed tomography (SPECT). The purpose of this study is to determine the effect of non-dominant RCA on myocardial perfusion SPECT (MPS) with respect to the misleading detection of ischemia in the inferior wall of the myocardium. METHODS: This is a retrospective study of 155 patients, who had undergone elective coronary angiography owing to an indication of inferior wall ischemia by MPS between 2012 and 2017. Patients were divided into two groups based on the coronary dominance: group 1 (n = 107), if RCA is the dominant artery, and group 2 (n = 48), if there are dominance of left artery and codominance of both arteries. Obstructive CAD was diagnosed in the case of stenosis that had severity greater than 50%. The positive predictive value (PPV), which was calculated as per the correlation between the inferior wall ischemia in MPS and obstruction level in RCA, was compared in both groups. RESULTS: Majority of patients were male (109, 70%) and the mean age was 59.5 ± 10.2. There were 45 patients with obstructive RCA disease (PPV: 42%) among 107 patients in group 1, whereas there were only 8 patients with obstructive coronary artery disease (CAD) in RCA among 48 patients in group 2, (PPV: 16% and p = 0.004). CONCLUSIONS: The results demonstrated that non-dominant RCA is associated with false-positive detection of inferior wall ischemia via MPS.

Percutaneous Treatment of Left Main Coronary Artery Compression in a Pulmonary Artery Hypertension Patient Associated with Atrial Septal Defect.

Pulmonary arterial hypertension is still a fatal disease persisting with poor prognosis, despite all the advances in treatment (new agents and new combination strategies) in recent years. Patients present with different symptoms which are not specific to the disease (dyspnea, angina, palpitation, and syncope). Angina may occur secondary to myocardial ischemia due to increased right ventricular after load (oxygen supply and demand mismatch) or external compression on the left main coronary artery. Left main coronary artery compression is associated with post-exercise sudden cardiac death in pulmonary arterial hypertension patients. It should be kept in mind in the differential diagnosis of angina in patients with pulmonary arterial hypertension and should be treated immediately. Here, we report a pulmonary arterial hypertension patient associated with secundum-type atrial septal defect presented with ostial left main coronary artery compression caused by an enlarged pulmonary artery and treated with intravascular ultrasound-guided percutaneous coronary intervention.