Umeå University's logo

Background: Cardiac amyloidosis (CA) is an under-recognized cause of heart failure in elderly patients. While diagnosis has traditionally relied on echocardiographic red flags and bone scintigraphy, novel tools may provide enhanced disease characterization.

Case summary: We present the case of a 78-year-old man with progressive symptoms of heart failure who was diagnosed with wild-type transthyretin cardiac amyloidosis (ATTRwt-CM) through conventional and advanced multimodal imaging. Initial clues included a discordance between QRS voltages on electrocardiography and increased left ventricular wall thickness on echocardiography, along with signs of elevated filling pressures. Speckle-tracking echocardiography revealed impaired regional myocardial deformation, global function, and work energetics. Serum and urine immunofixation excluded light chain (AL) amyloidosis. DPD scintigraphy confirmed amyloid deposition with a characteristic distribution. Genetic testing ruled out hereditary variants. PET imaging demonstrated myocardial uptake suggestive of amyloid infiltration and microcalcification. Cardiac MR revealed elevated native T1 and extracellular volume fractions. Invasive pressure–volume loop assessment confirmed biventricular stiffness and impaired contractile reserve, despite clinical compensation at rest. These findings supported early initiation of Tafamidis in a minimally symptomatic patient.

Discussion: This case highlights the role of advanced diagnostics in refining cardiac amyloidosis phenotyping and guiding individualized therapeutic decisions.

BACKGROUND: Right ventricular-pulmonary arterial (RV-PA) uncoupling is central to prognosis in precapillary pulmonary hypertension (PH). While the tricuspid annular plane systolic excursion tosystolic pulmonary artery pressure (TAPSE/sPAP) ratio is an established bedside surrogate of RV-PA coupling, novel energetic markers such as three-dimensional (3D)-derived right ventricular (RV) global wasted work (GWW) may provide complementary insight into maladaptive RV remodeling.

OBJECTIVES: To contextualize the prognostic value of RV GWW relative to TAPSE/sPAP and clarify their mechanistic and clinical complementarity.

METHODS AND RESULTS: Patients with elevated GWW (≥38 mmHg/%) exhibited evidence of RV-PA uncoupling, including a reduced RV end-systolic elastance to arterial elastance (Ees/Ea) ratio (0.47 [0.34-0.73] vs. 0.71 [0.50-0.91]; p = 0.007) and lower TAPSE/sPAP ratio (0.21 [0.18-0.32] vs. 0.34 [0.22- 0.45] mm/Hg; p = 0.003) compared with lower GWW. In secondary analyses, a TAPSE/sPAP ratio below the median was associated with increased risk of death or lung transplantation (hazard ratio [HR] 3.20; 95% CI: 1.45-7.08), remaining significant after adjustment for age and sex (adjusted HR 2.97; 95% CI: 1.27-6.94). Discrimination was modest and comparable for TAPSE/sPAP (C-statistic 0.63; 95% CI: 0.53-0.73) and GWW (C-statistic 0.61), with no significant difference between metrics (ΔC = -0.02; p = 0.68).

CONCLUSIONS: TAPSE/sPAP remains a robust and clinically valuable surrogate of macroscopic RV-PA coupling. However, GWW offers complementary information by quantifying myocardial inefficiency related to paradoxical and postsystolic deformation, capturing energetic consequences of afterload mismatch that may not be reflected by displacement-based indices alone. Integrating energetic and mechanical markers may enable a more granular assessment of RV performance, particularly in intermediate-risk PH, and warrants evaluation in larger multicenter studies.

Hypertrophic cardiomyopathy (HCM) is a primary cardiac muscle disorder with unique pathophysiology, heterogeneous expression, and diverse clinical presentations, with an overall mortality rate for untreated patients of approximately 1.3% per year. It is probably the most common genetically transmitted heart disease. HCM is often familial, of autosomal dominant transmission, and has a high degree of variable clinical penetrance. The latter is age related with typical features developing during adolescence. Approximately 50–70% of patients present mutations in one of the genes that encode different components of the cardiac sarcomere.

Left atrial reservoir strain (LASr) offers diagnostic and prognostic value in patients with heart failure. However, LASr may be technically challenging and is not available to all clinical echocardiographers. Since LASr is a consequence of left atrial (LA) stretch during apical descent of the mitral annulus, we hypothesized that a ratio between mitral annular plane systolic excursion (MAPSE) and LA volume (LAV) may offer similar diagnostic value as LASr. We aimed to investigate the relationship between MAPSE/LAV and LASr and evaluate the diagnostic performance of MAPSE/LAV to identify patients with elevated LV filling pressure. MAPSE/LAV and LA strain measures were obtained in patients referred for echocardiography due to aortic stenosis, and in patients who had undergone clinically indicated right heart catheterization (RHC) with simultaneous echocardiography. In 93 patients with moderate aortic stenosis, MAPSE/LAV was moderately correlated with LASr (r = 0.57) but was lower in patients with elevated compared to normal LV filling pressure by echocardiography (0.11 vs. 0.16 mm/mL, p < 0.001). In 72 patients who had undergone RHC and simultaneous echocardiography, MAPSE/LAV and LASr correlated weakly with pulmonary artery wedge pressure (PAWP) (r=-0.44 and r = 0.37). MAPSE/LAV was lower in patients with elevated (> 15 mmHg) vs. normal PAWP (0.14 mm/mL vs. 0.27 mm/mL). Accuracy for detection of elevated PAWP was similar for MAPSE/LAV (area under the curve MAPSE/LAV: 0.75 [0.58-0.92] and LASr: 0.75 [0.57-0.90]). Despite a moderate correlation with LASr, MAPSE/LAV provided similar diagnostic value as LASr in predicting elevated LV filling pressures as determined by echocardiography and RHC.

Aim: Right ventricular (RV) function determines symptom burden and clinical outcomes in pulmonary hypertension (PH). Global wasted work (GWW) quantifies mechanical inefficiencies in RV performance associated with elevated afterload, but is inadequately characterized in precapillary PH. We assessed the association of GWW with echocardiographic indices of RV remodeling, RV–PA coupling and invasive hemodynamics, and evaluated its prognostic significance in precapillary PH.

Methods and Results: Myocardial work indices were measured by 3D echocardiography in patients with well-defined precapillary PH who underwent right heart catheterization within 24 hours. Patients with poor image quality, significant valvular lesions and associated left heart disease were excluded. Among 61 patients, those with GWW ≥ 38 mmHg/% (n = 31) exhibited larger RV end-systolic volume (60 [42–71] vs. 42 [35–46] mL/m2, p = 0.009), lower TAPSE (17 [16–20] vs. 20 [17–23] mm, p = 0.04), higher Ea (1.32[0.98–1.57] vs. 0.92 [0.64–1.29] mmHg/mL, p = 0.02) and higher pulmonary vascular resistance (11.1 [8.1–14.2] vs. 5.4 [3.4–8.7]WU, p = 0.002). GWW decreased as RV longitudinal strain and RV—PA coupling improved and increased with lower cardiac index and higher pulmonary vascular resistance. GWW outperformed conventional right ventricular indices in identifying patients at risk of death or transplantation (HR: 2.5 [1.1–5.7], p = 0.02).

Conclusions: Elevated GWW is associated with RV remodeling, worsening RV function and reduced survival in precapillary PH. Our results suggest that GWW may offer incremental prognostic value over conventional RV metrics, with potential implications for risk stratification and therapy management. Larger studies are warranted to validate these findings.

Pulmonary hypertension describes raised pulmonary circulatory pressure, venous or arterial. Venous pulmonary hypertension is more common in daily practice than primary arterial hypertension. The rise in pulmonary venous and arterial pressure represents pressure overload for the right ventricle. With the right ventricular myocardial thickness being thin, it responds to the pressure afterload by giving way and stretching, hence the enlargement of the right ventricular and right atrial cavities. Severe cases of raised right ventricular pressure will eventually affect left ventricular function through the ventricular interaction mechanism.

Restrictive cardiomyopathy is a condition characterized by normal or subnormal left ventricular cavity size and systolic function but with increased myocardial stiffness. This makes the ventricle incompliant with predominant filling in early diastole. When atrial systolic function is maintained, the ventricle may accommodate a small volume of blood during atrial systole but at the expense of a further rise in end diastolic pressure. These physiological disturbances are associated with raised left atrial pressure, atrial enlargement, and arrhythmias.

Aims: Transthyretin cardiomyopathy (ATTR-CM) is a progressive, life-threatening infiltrative disorder with reportedly lower prevalence in women. While echocardiographic red flags for identifying ATTR-CM have been established in populations overrepresented by men, their diagnostic utility is inadequately studied in women. We assessed the diagnostic accuracy of echocardiographic red flags and electrocardiography in a well-characterized, female population with hypertrophied left ventricles to differentiate ATTR-CM from left ventricular hypertrophy (LVH).

Methods and results: We compared echocardiographic red flags and electrocardiography in 62 female patients with an interventricular septal thickness of >12 mm, divided equally into well-defined ATTR-CM (n = 31) and age-matched LVH. ATTR-CM displayed higher relative wall thickness (RWT), higher values for relative apical sparing (RELAPS), and lower S-wave in lead aVR (SaVR) than LVH. Left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS) did not differ between groups. RWT/SaVR ratio displayed stronger diagnostic performance to identify ATTR-CM (AUC = 0.97) when compared with RELAPS (AUC = 0.83) and RWT (AUC = 0.82). Further, RELAPS demonstrated lower and SaVR higher optimal diagnostic cut-offs than those previously published in predominant male cohorts.

Conclusion: In a well-characterized, single-centre, female population with hypertrophied left ventricles, RWT/SaVR outperformed conventional echocardiographic red flags and shows promise for diagnosing ATTR-CM. Our findings also highlight the need for sex-specific cut-offs, but generalizability is limited by a single-centre design and predominance of the Val30Met genotype. Validation in larger prospective cohorts is warranted.

Background: Right ventricular (RV) function is inadequately investigated and routinely overlooked in transthyretin amyloid cardiomyopathy (ATTR-CM). Novel imaging distinguishers between intrinsic RV myocardial disease in ATTR-CM and primary RV overload disorder phenotypes may enhance mechanistic and pathophysiological understanding of RV dysfunction. We aimed to investigate RV performance in ATTR-CM employing comprehensive 2D and 3D echocardiography, and to compare these indices with primary RV afterload disease.

Methods: We investigated conventional and novel indices of RV contractile function, myocardial work and ventricular–vascular coupling in 21 well-characterized ATTR-CM patients, 10 PAH patients and 12 healthy controls. RV long axis function and pulmonary artery (PA) systolic pressure were evaluated using 2D Doppler echocardiography. RV ejection fraction (RVEF), volumes, global longitudinal strain (GLS) and novel myocardial work indices were analyzed by 3D echocardiography. RV elastance (E_es), afterload (E_a) and RV-PA coupling (E_es/E_a) were estimated using the single-beat volume method.

Results: ATTR-CM showed lower RVEF, GLS and E_es, and a higher RV global myocardial work index (GWI), constructive work (GCW), E_a and RV-PA coupling compared with controls. RV EF, stroke volume, GLS and circumferential strain did not differ between ATTR-CM and PAH. However, GWI, GCW, E_es and E_a were lower in ATTR-CM. RV–pulmonary coupling displayed strong association with RV 3D strain (r = 0.84, p < 0.001), whereas RV E_es (contractility) was related to RV GWI (r = 0.54, p < 0.001).

Conclusions: ATTR-CM displayed lower RV performance, higher global myocardial work and higher RV-PA coupling than controls. Myocardial work indices E_es and E_a are novel distinguishers of RV dysfunction phenotypes. The clinical and prognostic value of these novel variables warrant further investigation.