Myocardial structural and functional changes in cardiac amyloidosis: insights from a prospective observational patient registry.

AIMS: The pathophysiological hallmark of cardiac amyloidosis (CA) is the deposition of amyloid within the myocardium. Consequently, extracellular volume (ECV) of affected patients increases. However, studies on ECV progression over time are lacking. We aimed to investigate the progression of ECV and its prognostic impact in CA patients. METHODS AND RESULTS: Serial cardiac magnetic resonance (CMR) examinations, including ECV quantification, were performed in consecutive CA patients. Between 2012 and 2021, 103 CA patients underwent baseline and follow-up CMR, including ECV quantification. Median ECVs at baseline of the total (n = 103), transthyretin [(ATTR) n = 80], and [light chain (AL) n = 23] CA cohorts were 48.0%, 49.0%, and 42.6%, respectively. During a median period of 12 months, ECV increased significantly in all cohorts [change (Δ) +3.5% interquartile range (IQR): -1.9 to +6.9, P < 0.001; Δ +3.5%, IQR: -2.0 to +6.7, P < 0.001; and Δ +3.5%, IQR: -1.6 to +9.1, P = 0.026]. Separate analyses for treatment-naïve (n = 21) and treated (n = 59) ATTR patients revealed that the median change of ECV from baseline to follow-up was significantly higher among untreated patients (+5.7% vs. +2.3%, P = 0.004). Survival analyses demonstrated that median change of ECV was a predictor of outcome [total: hazard ratio (HR): 1.095, 95% confidence interval (CI): 1.047-1.0145, P < 0.001; ATTR: HR: 1.073, 95% CI: 1.015-1.134, P = 0.013; and AL: HR: 1.131, 95% CI: 1.041-1.228, P = 0.003]. CONCLUSION: The present study supports the use of serial ECV quantification in CA patients, as change of ECV was a predictor of outcome and could provide information in the evaluation of amyloid-specific treatments.

Functional capacity testing in patients with pulmonary hypertension (PH) using the one-minute sit-to-stand test (1-min STST).

BACKGROUND: The one-minute sit-to-stand-test (1-min STST) is a quick, space saving test to evaluate functional capacity. Exercise testing plays an important role in the long-term follow-up of pulmonary hypertension (PH) patients and is currently evaluated using the six-minute-walk-test (6MWT). The aim of the study was to assess the convergent validity of the 1-min STST in patients with PH and its association with markers of PH severity. METHODS: We evaluated 106 PH patients with the 1-min-STST and 6MWT and measured cardiorespiratory parameters (heart rate, blood pressure, oxygen saturation) before and after test conduction. N-terminal pro brain-type natriuretic peptide (NT-proBNP), WHO functional class (WHO-FC) and mean pulmonary artery pressure (mPAP) were defined as markers of PH severity. RESULTS: Strong correlation was found between performances of 1-min STST and 6MWT (r = .711, p < .001), indicating convergent validity. Both tests were inversely associated with NT-proBNP (STST: r = -.405, p < .001; 6MWT: r = -.358, p < .001), WHO-FC (STST: r = -.591, p < .001; 6MWT: r = -.643, p < .001) and mPAP (STST: r = -.280, p < .001; 6MWT: r = -.250, p < .001). Significant changes in cardiorespiratory parameters were observed in both tests (all p < 0.001). Further the post-exercise cardiorespiratory parameters correlated strongly between the 1-min STST and 6MWT (all r ≥ .651, all p < .001). CONCLUSION: The 1-min STST demonstrated good convergent validity with the 6MWT and was associated with markers of PH severity. Furthermore, both exercise tests caused similar cardiorespiratory responses.

Cardiac amyloidosis: a significant blind spot of the H2FPEF score.

BACKGROUND: Cardiac amyloidosis (CA) often mimics heart failure with preserved ejection fraction (HFpEF). Due to very different treatment strategies, an exact diagnosis and differentiation between pure HFpEF and CA-related heart failure (HF) is important. In the present study, we assessed the recently published H2FPEF score in patients with pure HFpEF, transthyretin (ATTR), as well as light chain (AL) amyloidosis-related HFpEF and tested whether it differentiates between these entities. METHODS: The H2FPEF scores consists of easy-to-assess clinical (Body Mass Index, number of hypertensive drugs, presence of atrial fibrillation, age) and echocardiographic (systolic pulmonary arterial pressure, E/E´) parameters. It can be computed in a categorical way resulting in scores between 0 and 9 points (0-1: HFpEF rule out, 2-5: further testing required, 6-9: HFpEF rule in), or in a continual way providing an exact percentage of a patient's HFpEF probability. Continuous and categorical variables were compared using the Kruskal-Wallis, Mann-Whitney-U, and χ2-tests. Diagnostic accuracy was computed from 2x2 tables. Survival analysis was performed with Kaplan-Meier curves. A P value of <0.05 was set as the level of significance. RESULTS: A total of 100 patients with pure HFpEF, 53 patients with ATTR, and 34 patients with AL CA were included in the present study. Median age (HFpEF: 71.5 years; ATTR CA: 77.0 years; AL CA: 60.0 years; P<0.001), gender distribution (HFpEF [female]: 73.0%, ATTR (female): 18.9%, AL [female]: 38.2%; P<0.001), and N-terminal prohormone of brain natriuretic peptide (HFpEF: 1045pg/mL; ATTR CA: 1927pg/mL; AL CA: 4308pg/mL; P<0.001) differed significantly between study cohorts. Median H2FPEF scores were highest among HFpEF (categorical: 5.0 points; continual: 95.1%), followed by ATTR (categorical: 4.0 points; continual: 89.0%), and AL CA (categorical: 3.0 points; continual: 31.2%). Respective P values were <0.001. Low H2FPEF scores (0-1 points) were found among patients in the AL CA cohort (29.4%), but not among HFpEF or ATTR CA patients (P<0.001). The majority of patients, irrespective of disease entity were in the intermediate score range (2-5 points, HFpEF: 80.0% ATTR CA: 94.3%, AL CA: 67.9%; P=0.006). High scores (6-9 points) were most often found among HFpEF patients (20.0%), followed by ATTR CA (5.7%) and AL CA (2.9%), (P=0.007). CONCLUSIONS: The H2FPEF score should be used with caution, as there is a significant overlap between HFpEF and CA-related HF.

Impact of Tafamidis and Optimal Background Treatment on Physical Performance in Patients With Transthyretin Amyloid Cardiomyopathy.

BACKGROUND: In patients with transthyretin amyloid cardiomyopathy, tafamidis was shown to slow the decline in 6-minute walking distance as compared with placebo. We aimed to define the impact of tafamidis and optimal background treatment on functional capacity as determined by cardiopulmonary exercise testing (CPET). METHODS: Seventy-eight consecutive patients were enrolled in the study. They underwent CPET at baseline, and outcome defined as death or heart failure hospitalization was obtained for a time period of up to 30 months. Fifty-four patients completed a follow-up CPET at 9±3 months (range, 4-16 months). Improvement in peak VO2 at follow-up was defined as ∆peak VO2≥1.0 mL/(kg·min), stable peak VO2 was defined as 0≤∆peak VO2<1.0 mL/(kg·min), and decline in peak VO2 was defined by ∆peak VO2<0 mL/(kg·min). RESULTS: Baseline peak VO2>14 mL/(kg·min) as well as minute ventilation/carbon dioxide production slope≤34 were associated with a lower risk of death or heart failure hospitalization (P=0.002, P=0.007, respectively). In 54 patients, who received tafamidis and underwent repeat CPET testing, an improvement in physical performance (P=0.002) was observed at follow-up. When comparing pre and post-treatment parameters, 29 patients (54%) showed an increase in percent predicted peak VO2 (P<0.0001), an improvement of peak VO2 (P<0.0001), and better physical performance at follow-up (P<0.0001). Patients with stable or improved peak VO2 had less advanced heart disease at baseline (P=0.046). CONCLUSIONS: Our findings demonstrate that baseline peak VO2 and baseline minute ventilation/carbon dioxide production slope predict outcomes and an improvement in physical performance as measured by CPET was observed in patients receiving tafamidis, who had less advanced disease at baseline, emphasizing the importance of early diagnosis.

Exercise capacity assessed with the one-minute sit-to-stand test (1-min STST) and echocardiographic findings in patients with heart failure with preserved ejection fraction (HFpEF).

BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is a major cause of morbidity and mortality. Precise risk stratification remains challenging. The one-minute sit-to-stand-test (1-min STST), a quick, objective test of functional capacity may be helpful for stratification of clinical profile in HFpEF patients. OBJECTIVE: The aim of this initial investigation was to prospectively examine whether the 1-min STST can be used for the evaluation of exercise capacity in HFpEF patients and whether it is in line with echocardiographic as well as quality of life (QoL) findings. METHODS: 39 HFpEF patients were prospectively studied. Functional performance was examined with the 1-min STST and QoL with the CAMPHOR questionnaire. Clinical parameters including echocardiographic measurements [estimated pulmonary artery systolic pressure (ePASP), tricuspid regurgitation velocity (TRV)] were obtained. Patients were divided into two groups based on their number of 1-min STST repetitions (Group I: ≤50% of predicted 1-min STST repetitions using the norm-reference values developed by Strassmann et al. for healthy people, N=24; Group II: >50% of predicted 1-min STST repetitions, N=15). RESULTS: Patients in group I with limited 1-min STST performance showed worse echocardiographic parameters [higher ePASP (p=0.038), higher TRV (p=0.018) and more reduced tricuspid annular plane systolic excursion (TAPSE) (p=0.001)], worse six-minute walk test (6MWT) (p<0.001) and worse QoL (p<0.001) compared to patients in group II. CONCLUSION: Our study shows potential usefulness of the 1-min STST as an evaluative tool for exercise capacity in HFpEF patients, because patients with worse 1-min STST performance have worse clinical parameters and QoL.

The utility and complications of plasma administration in cirrhotic patients undergoing minimally invasive procedures.

Patients with cirrhosis have coagulopathy often necessitating correction with blood products, such as plasma products (fresh frozen plasma and plasma frozen within 24 h) prior to certain invasive procedures. However, plasma administration has the potential for substantial negative adverse effects such as volume overload, transfusion-related lung injury and allergic/anaphylactic reactions. In addition, its effectiveness in preventing bleeding is similarly unclear. The purpose of this study was to determine the safety and efficacy of plasma administration in cirrhotic patients undergoing minimally invasive procedures, specifically vascular access placement, transjugular liver biopsies, renal biopsies and thoracenteses. In this retrospective cohort study, we identified patients receiving plasma products in preparation for an invasive procedure, with the primary outcomes of volume overload and bleeding. Of the 145 transfusion events that met the criteria from 2015 to 2018, the median INR decreased from 2.7 to 2.2 pre and post plasma administration and 13.8% of recipients had complications of volume overload. The cost of acquisition of plasma administered below clinically impactful doses accumulates to an estimated 19 000 dollars over this time period, not including nursing preparation or production costs. Plasma products minimally, if at all, improved laboratory values of coagulation and in some patients led to adverse effects.

Low serum potassium levels and diabetes - An unfavorable combination in patients with heart failure and preserved ejection fraction.

BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is among the most common forms of heart failure (HF). We aimed to investigate the prognostic significance of serum potassium levels and its interaction with type-2 diabetes mellitus in patients with HFpEF. METHODS: Consecutive HFpEF patients were prospectively included in a registry study. The primary endpoint was a composite of cardiac death or HF hospitalization. RESULTS: 363 HFpEF patients were enrolled (median age: 73.0 years; females: 70.3%). Median serum potassium (K+) was 4.3 mmol/L. A total of 128 (35.3%) patients had type-2 diabetes mellitus, of whom 92 were treated with oral anti-diabetic drugs and 35 with insulin. The study population was divided into two groups, according to their serum potassium levels. Significant differences between the groups were detected with regards to combined endpoint [n = 27 (61.4%) versus n = 87 (27.3%); p < 0.0001]. Lower serum potassium levels were significantly associated with adverse outcome in the Cox proportional hazard analysis [hazard ratio (HR): 1.83; 95% confidence interval (CI) 1.14-2.94; p = 0.0118]. Further independent predictors of adverse outcome were a history of HF hospitalizations (HR: 2.77; 95% CI 1.82-4.21; p < 0.0001), higher NT-pro BNP (HR: 1.93; 95% CI 1.82-4.21; p = 0.0084) as well as type-2 diabetes mellitus (HR: 1.57; 95% CI 1.05-2.34; p = 0.0027). Patients with diabetes and K+ ≤ 3.71 mmol/L faced the worst outcome as compared to the remainder of the group (p = 0.0001). CONCLUSION: In HFpEF patients, the combination of diabetes and low serum potassium levels are associated with an adverse outcome.

Determinants of Bioprosthetic Aortic Valve Degeneration.

OBJECTIVES: The aim of the present long-term study was to assess the incidence and mode of valve hemodynamic deterioration (VHD) of bioprosthetic aortic valves, as well as associated factors. BACKGROUND: Modern definitions of bioprosthetic valve deterioration recommend the use of echocardiography for the assessment of transprosthetic gradients and valvular regurgitation. METHODS: A total of 466 consecutive patients (mean age 73.5 ± 7.5 years, 56.0% women) underwent surgical bioprosthetic aortic valve replacement between 1994 and 2014. Clinical assessment, transthoracic echocardiography, and laboratory testing were performed at baseline and follow-up. VHD was defined as mean transprosthetic gradient ≥30 mm Hg and/or at least moderate valvular regurgitation on echocardiography. Patient-prosthesis mismatch was defined as an effective orifice area indexed to body surface area ≤0.8 cm2/m2. RESULTS: Patients were followed for a median of 112.3 months (interquartile range: 57.7 to 147.7 months). Among patients with complete follow-up (n = 383), 70 subjects (18.3%; 4.8% per valve-year) developed VHD after a median of 32.4 months (interquartile range: 12.9 to 87.2 months; stenosis, n = 45; regurgitation, n = 16; both, n = 9). Factors associated with VHD by multivariate regression analysis were serum creatinine >2.1 mg/dl (hazard ratio [HR]: 4.143; 95% confidence interval [CI]: 1.740 to 9.866; p = 0.001), porcine tissue valves (HR: 2.241; 95% CI: 1.356 to 3.706; p = 0.002), arterial hypertension (HR: 3.022; 95% CI: 1.424 to 6.410; p = 0.004), and patient-prosthesis mismatch (HR: 1.931; 95% CI: 1.102 to 3.384; p = 0.022). By Kaplan-Meier analysis, elderly subjects showed faster development of VHD (age <70 years, 133.5 months [95% CI: 116.2 to 150.8 months]; 70 to 80 years, 129.1 months [95% CI: 112.4 to 145.7 months]; >80 years, 100.3 months [95% CI: 63.6 to 136.9 months]; p = 0.023). By multivariate Cox regression, age, diabetes, concomitant coronary artery bypass grafting, creatinine, and VHD (p < 0.05) were significantly associated with mortality. CONCLUSIONS: On the basis of echocardiography, every fifth patient developed VHD after surgical bioprosthetic heart valve replacement. VHD was associated with renal impairment, the use of porcine tissue valves, arterial hypertension, and patient-prosthesis mismatch. Patients younger than 70 years were not affected by faster VHD.

Syncope: The Underestimated Threat in Severe Aortic Stenosis.

OBJECTIVES: Decision making in severe aortic stenosis (AS) requires a comprehensive pre-operative evaluation of the risk-to-benefit ratio. The aim of this study was to assess whether certain pre-operative symptoms are associated with outcome after surgical aortic valve replacement (SAVR). BACKGROUND: The cardinal symptoms of AS indicating a need for intervention are angina, symptoms of heart failure, and syncope. Nevertheless, it remains unknown whether the presence of these more advanced symptoms conveys an increased risk after SAVR and whether the detection of early symptoms in patients with asymptomatic AS should be emphasized more in routine clinical practice. METHODS: A total of 625 patients with isolated severe AS undergoing elective SAVR were prospectively enrolled in this long-term observational study. RESULTS: Patients experiencing syncope had significantly smaller left ventricular diameters (p = 0.02), left atrial diameters (p = 0.043), right ventricular diameters (p = 0.04), and right atrial diameters (p = 0.001), smaller aortic valve areas (p = 0.048), and lower indexed stroke volumes (p = 0.043) compared with patients without syncope. Syncope conveyed an increased risk for mortality after SAVR that persisted after multivariate adjustment for a bootstrap-selected confounder model, with an adjusted hazard ratio of 2.27 (95% confidence interval: 1.04 to 4.95; p = 0.04) for 1-year short-term mortality and an adjusted hazard ratio of 2.11 (95% confidence interval: 1.39 to 3.21; p < 0.001) for 10-year long-term mortality. In contrast, pre-operative dyspnea, angina, and reduced left ventricular function were not significantly associated with outcomes. CONCLUSIONS: This long-term observational study in a large contemporary cohort of patients with AS for the first time demonstrates that syncope represents an underestimated threat in aortic stenosis, associated with poor prognosis after SAVR. Importantly, other primary indications for SAVR (i.e., dyspnea, angina, and decreased left ventricular function) were associated with significantly better post-operative outcomes than syncope. Patients experiencing syncope displayed a specific pathophysiologic phenotype characterized by a smaller aortic valve area, smaller cardiac cavities, and lower stroke volumes.

Evaluation of the effect of trimetazidine on Tc-99m methoxyisobutyl isonitrile gated scintigraphy in patients with coronary artery ectasia.

OBJECTIVE: Coronary artery ectasia (CAE) is the abnormal dilatation of a segment of the coronary artery to a diameter of at least 1.5 times that of normal adjacent segments. Symptoms are variable, and its prognosis and treatment modalities are unclear. The aim of this study is to evaluate the effect of trimetazidine (TMZ) on ischemic left ventricular function by rest-stress Tc-99m methoxyisobutyl isonitrile (Tc-99m MIBI) myocardial scintigraphy in symptomatic patients with CAE. METHODS: We included patients with ectasia admitted to our Cardiology Department, Turkey, between 2003 and 2004 in this study. All patients underwent coronary angiography and diagnosed with CAE, before and 4 weeks after TMZ administration. Seventeen patients (9 men, 8 women) underwent gated single-proton emission tomographic (SPECT) using Tc-99m MIBI. We performed quantitative global and regional ventricular functional analysis using quantitative gated SPECT software. RESULTS: The global ejection fraction increased from 59.9%+/-8.9% to 62.6%+/-8.3% after therapy (p=0.033). In addition, the end systolic volume and the end diastolic volume decreased after therapy (101.7+/-23.5 ml to 95.1+/-22.9 ml, p=0.002; from 41.1+/-14.3 to 36.4+/-13.6, p=002). In all segments, we observed significant post-therapy increases in relative tracer uptake. Percentage of MIBI uptake was 71.2+/-15.3 at baseline stress and 73.2+/-15 post-TMZ (p=0.001). As global function parameters, the total wall motion normal areas changed significantly (67-74% p=0.01) after therapy, but the total wall thickness did not changed significantly(49-45%, p=0.21). CONCLUSION: The results of this study demonstrate that TMZ improves myocardial function by rest-stress Tc-99m MIBI gated SPECT during stress-induced ischemia in patients with CAE. Also, the outcomes revealed improvement in functional parameters, and percentage of MIBI uptake post TMZ administration. We can use this procedure to monitor the effect of TMZ in CAE patients.