A Cautionary Tale of Hypertrophic Cardiomyopathy-From "Benign" Left Ventricular Hypertrophy to Stroke, Atrial Fibrillation, and Molecular Genetic Diagnostics: A Case Report and Review of Literature

Abstract

This case report concerns a 48-year-old man with a history of ischemic stroke at the age of 41 who reported cardiac hypertrophy, registered in his twenties when explained by increased physical activity. Family history was positive for a mother with permanent atrial fibrillation from her mid-thirties. At the age of 44, he had a first episode of persistent atrial fibrillation, accompanied by left atrial thrombosis while on a direct oral anticoagulant. He presented at our clinic at the age of 45 with another episode of persistent atrial fibrillation and decompensated heart failure. Echocardiography revealed a dilated left atrium, reduced left ventricular ejection fraction, and an asymmetric left ventricular hypertrophy. Cardiac magnetic resonance was positive for a cardiomyopathy with diffuse fibrosis, while slow-flow phenomenon was present on coronary angiography. Genetic testing by whole-exome sequencing revealed three variants in the patient, c.309C > A, p.His103Gln in the ACTC1 gene, c.116T > G, p.Leu39Ter in the PLN gene, and c.5827C > T, p.His1943Tyr in the SCN5A gene, the first two associated with hypertrophic cardiomyopathy and the latter possibly with familial atrial fibrillation. This case illustrates the need for advanced diagnostics in unexplained left ventricular hypertrophy, as hypertrophic cardiomyopathy is often overlooked, leading to potentially debilitating health consequences.

Keywords: ACTC1; PLN; SCN5A; atrial fibrillation; cardiac magnetic resonance; coronary slow-flow phenomenon; genetic testing; hypertrophic cardiomyopathy; left ventricular hypertrophy; whole-exome sequencing.

Figure 1

(A) Electrocardiogram (ECG) at admission showing atrial fibrillation with a frequency of about 90 beats per minute, right axis deviation, and a right bundle branch block with a QRS complex duration of 134 ms. A single ventricular extrasystole is noted. (B) Chest X-ray of the patient at admission showing cardiomegaly and pulmonary congestion.

Figure 1

(A) Electrocardiogram (ECG) at admission showing atrial fibrillation with a frequency of about 90 beats per minute, right axis deviation, and a right bundle branch block with a QRS complex duration of 134 ms. A single ventricular extrasystole is noted. (B) Chest X-ray of the patient at admission showing cardiomegaly and pulmonary congestion.

Figure 2

Transthoracic echocardiography findings: (A) Parasternal long axis view showing hypertrophy of the septum, visibly more pronounced, compared to the posterior wall of the left ventricle (16 mm vs. 8 mm) with an estimated asymmetricity index of 2. (B) Speckle tracking global longitudinal strain of the left ventricle (LV GLS) showing an average value of 12.2% with regionally reduced strain values at the basal and mid-portions of the septum, the inferior wall, and the anteroseptal wall. Peak systolic dispersion (PSD) was 57.2 ms. Abbreviations of the left ventricular segments from (B) SEPT—septum; ANT SEPT—anterior septal wall; ANT—anterior wall; LAT—lateral wall; POST—posterior wall; INF—inferior wall.

Figure 3

Cardiac magnetic resonance findings. Four chamber (first line) and three chamber (second line) SSFP CINE images in the end diastole (A,C) and end systole (B,D). Mildly thickened middle and partially basal septum (up to 16 mm, arrows in (A,C)) with the borderline thinned myocardium along the apical free wall and at the apex (arrow in (D)). Pericardial effusion along the free wall of the left ventricle (Arrow in (B)).

Figure 4

Cardiac magnetic resonance findings. Short-axis T1 (A) and T2 (B) mapping and LGE images (C,D). Variably prolonged T1 relaxation time (mean 1140 ms, (A)) and T2 relaxation time (mean 53 ms, (B)) along the septum and the free wall of the left ventricle. Patchy and linear LGE in depth along the basal and middle septum and along the lateral and lower-lateral wall of the left ventricle. Limited subepicardial LGEI was also detected.

Figure 5

Transesophageal echocardiography showing thrombosis of the left atrial appendage (arrow).

Figure 6

Molecular genetic analysis by whole-exome sequencing and a targeted panel of 242 cardiomyopathy-associated genes revealed 3 variants in the proband: c.309C > A, p.His103Gln in the ACTC1 gene (A) and c.116T > G, p.Leu39Ter in the PLN gene (B), as well as c.5827C > T, p.His1943Tyr in the SCN5A gene (C). The ACTC1, PLN, and SCN5A gene variants wre reported using RefSeq NM_005159.5, NM_002667.5, and NM_001160161.2, respectively. (A) ACMG/AMP classification: likely pathogenic (categories: PP3, PM5, PM2, PP2). (B) ACMG/AMP classification: pathogenic (categories: PVS1, PP5, PM2). (C) ACMG/AMP classification: variant of uncertain significance (category: PM2).