Cardiac amyloidosis usually presents with heart failure, but rarely leads to coronary insuffi ciency. The authors report a case of a 69-year-old Japanese woman with cardiac amyloidosis presenting as microvascular angina. She had exertional angina with positive exercise test and normal coronary angiograms. However, heart failure developed, and she died 3 years after symptom onset. On autopsy, coronary arteries were patent. In contrast to that of the epicar dial coronary arteries, histologic examination of the heart revealed severe obstructive alter ations of the intramural coronary arteries with amyloid. Furthermore, amyloid was present mainly in the endocardium and the intramural coronary arteries, but there was little present in the myocardium. This case was a rare AL amyloidosis. There have been only 4 reported cases of cardiac amyloidosis that presented with exertional angina, a positive exercise test, and normal coronary angiograms and histologic examination.

β-Blocker (BB) use is a mainstay for the treatment of heart failure (HF) with reduced ejection fraction (HFrEF), whereas its efficacy for heart failure with preserved ejection fraction (HFpEF) remains controversial. Women outnumber men in HFpEF, whereas men outnumber women in HFrEF. Plasma B-type natriuretic peptide (BNP) is established as a biomarker for HF. We examined whether BB use is associated with plasma BNP levels differently in men and women with HFpEF. The study subjects comprised 721 patients with HFpEF [left ventricular ejection fraction (LVEF) ≥ 50%] (184 men, mean age 78.2 ± 9.2 yr and 537 women, mean age 83.1 ± 8.8 yr), 179 on BB (66 men and 113 women) and 542 no BB (118 men and 424 women), 583 in sinus rhythm (SR) and 138 in atrial fibrillation (AF). A multivariable logistic regression test was used. Plasma BNP levels were higher (P = 0.0005), systolic blood pressure and LVEF lower (P = 0.0003, and P = 0.0059, respectively) on BBs than on no BBs in women, whereas in men, plasma BNP levels, systolic blood pressure, and LVEF were not altered significantly (P = 0.0849, P = 0.9129, and P = 0.4718, respectively) on BBs compared with no BBs in patients with SR. Multivariable logistic regression analysis revealed that BB use and women were a positive and a negative predictor for high BNP levels (P = 0.003 and P = 0.032, respectively) in SR but not in AF. BB use was associated with high-plasma BNP levels and lower LVEF in women but not in men with HFpEF and SR, suggesting that the pathogenesis and treatment of HFpEF may differ in men and women in SR. NEW & NOTEWORTHY Pathogenesis and treatment for heart failure with preserved ejection fraction (HFpEF) may differ in men and women in sinus rhythm (SR).

Background: After the discovery of the Klotho gene, phosphate came into focus as a pathogenetic aging agent. Phosphate homeostasis is controlled by phosphate-regulating hormones: fibroblast growth factor 23 (FGF23), vitamin D3, and parathyroid hormone. This study investigated the relationship between the deterioration in phosphate homeostasis and arterial stiffness by measuring serum FGF23 concentrations.Methods and Results: The study subjects comprised 82 hospitalized patients (31 males, 51 females; mean [±SD] age 78.6±10.5 years). All patients underwent chest computed tomography, measurement of central blood pressure (BP), and blood chemistry tests. Arterial calcification and/or stiffness was evaluated using the Agatston calcification score (ACS) and pulse wave velocity (PWV). PWV was significantly correlated with age (t=23.47, P<0.0001), estimated glomerular filtration rate (eGFR; t=−4.40, P<0.0001), and ACS (t=4.36, P<0.0001). Serum FGF23 concentrations were significantly correlated with age (t=2.52, P=0.014), eGFR (t=−3.37, P<0.001), serum inorganic phosphorus concentrations (t=3.49, P<0.001), serum vitamin D3concentrations (t=−4.57, P<0.001), ACS (t=2.30, P=0.025), augmentation pressure (t=2.48, P=0.015), central systolic BP (t=2.00, P=0.049), plasma B-type natriuretic peptide (BNP) concentrations (t=3.48, P<0.001), and PWV (t=2.99, P=0.004). PWV was positively related to augmentation pressure (t=4.09, P<0.001), central systolic BP (t=3.13, P=0.002), and plasma BNP concentrations (t=3.54, P<0.001).Conclusions: This study shows that the increase in serum FGF23 concentrations reflects deterioration of phosphate homeostasis and is an important predictor for arterial stiffness, which intensifies cardiac afterload.

Heart failure with preserved ejection fraction (HFpEF) is a major health concern. There is a growing recognition of the causal interplay between arterial stiffness and HFpEF. We recently reported that phosphate retention is a trigger for arterial stiffness. This study focuses on whether arterial stiffness due to phosphate retention could be a predictor for HFpEF. Methods: The subjects of this study were 158 patients (68 males and 90 females, mean age 74.8 ± 11.2). HFpEF was defined according to the guidelines of the ESC 2019. Pulse wave velocity (PWV) and central systolic blood pressure (CSBP) were used as markers for arterial stiffness and afterload, respectively. We measured serum levels of fibroblast growth factor 23 (FGF23) as a marker of phosphate retention. Results: The serum levels of FGF23 had a significant relationship with PWV. PWV had significant relationships with LV mass index, plasma BNP levels, and relative wall thickness, e′, and E/e′ (p < 0.001, respectively). Multivariate logistic regression analysis revealed that higher PWV values and hypertension were significant predictors for the dependent factor (HFpEF). Arterial stiffness amplified afterload, leading to LV concentric hypertrophy and diastolic dysfunction. This study presents that arterial stiffness is a key predictor of HFpEF, and that phosphate retention is involved in the pathology of HFpEF.

BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is a major health concern. There is a growing recognition of the causal interplay between arterial stiffness and HFpEF. We recently reported that the deterioration of phosphate homeostasis is a trigger for both arterial stiffness. This study focuses on whether arterial stiffness due to phosphate retention could be a predictor for HFpEF. METHODS: The study subjects were 158 patients (68 males and 90 females, mean age 74.8±11.2). They received echocardiography, central blood pressure (BP) and blood biochemistry tests. HFpEF was defined according to the guidelines of the European Society of Cardiology 2021. Pulse wave velocity (PWV) and central systolic blood pressure (CSBP) were used as markers for arterial stiffness and cardiac afterload, respectively. We measured serum levels of fibroblast growth factor 23 (FGF23) as markers of phosphate retention. RESULTS: The serum levels of FGF23 had significant relationship with PWV (t=3.33, p<0.001). PWV had a significant positive relationship with CSBP (t=4.54, p<0.001). PWV furthermore had significant relationships with LV mass index (t=4.74), plasma BNP levels (t=5.44), and relative wall thickness (t=3.83), e’ (t=-4.21) and E/e’ (t=7.88) (p<0.001, respectively). Multivariate logistic regression analysis using independent factors, including PWV higher values, sex and hypertension, revealed that PWV higher values (t=5.89, p<0.0001) and hypertension (t=2.17, p=0.031) were significant predictors for the dependent factor (HFpEF). CONCLUSIONS: Arterial stiffness amplified cardiac afterload, leading to LV concentric hypertrophy and LV diastolic dysfunction. This study presents that arterial stiffness due to phosphate retention, and hypertension are important predictors of HFpEF. What is New?: Arterial stiffness is an important predictor for HFpEF. Arterial stiffness is caused by an increase in phosphate retention due to aging and CKD via kidney nephron loss. Arterial stiffness amplifies cardiac afterload leading to LV concentric hypertrophy and LV diastolic dysfunction. What are the Clinical Implications?: Arterial calcification and/or stiffness should be a new target in cardiovascular diseases. Phosphate is thought to be an important aging accelerating factor. Phosphate regulating medications, phosphate restriction diets, and osteoporosis therapies may all be protective against aging related diseases including HFpEF.