Currently adopted diagnostic flow charts consider transthyretin and light-chain cardiac amyloidosis as mutually exclusive. Here, we report for the first time, to our knowledge, the demonstration of a ...biopsy-proven dual pathology in an 80-year-old man with sequential development of both wild-type transthyretin amyloidosis and light-chain cardiac amyloidosis cardiomyopathy over a 3-year timespan. (
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Large trials using noninvasive mechanical ventilation to treat central apnea (CA) occurring at night (“sleep apnea”) in patients with systolic heart failure (HF) have failed to improve prognosis. The ...prevalence and prognostic value of CA during daytime and over an entire 24-h period are not well described.
This study evaluated the occurrence and prognostic significance of nighttime, daytime, and 24-h CA episodes in a large cohort of patients with systolic HF.
Consecutive patients receiving guideline-recommended treatment for HF (n = 525; left ventricular ejection fraction LVEF of 33 ± 9%; 66 ± 12 years of age; 77% males) underwent prospective evaluation, including 24-h respiratory recording, and were followed-up using cardiac mortality as an endpoint.
The 24-h prevalence of predominant CAs (apnea/hypopnea index AHI ≥5 events/h, with CA of >50%) was 64.8% (nighttime: 69.1%; daytime: 57.0%), whereas the prevalence of predominant obstructive apneas (OA) was 12.8% (AHI ≥5 events/h with OAs >50%; nighttime: 14.7%; daytime: 5.9%). Episodes of CA were associated with neurohormonal activation, ventricular arrhythmic burden, and systolic/diastolic dysfunction (all p < 0.05). During a median 34-month follow-up (interquartile range IQR: 17 to 36 months), 50 cardiac deaths occurred. Nighttime, daytime, and 24-h moderate-to-severe CAs were associated with increased cardiac mortality (AHI of </≥15 events/h; log-rank: 6.6, 8.7, and 5.3, respectively; all p < 0.05; central apnea index CAI of </≥10 events/h; log-rank 8.9, 11.2, and 10.9, respectively; all p < 0.001). Age, B-type natriuretic peptide level, renal dysfunction, 24-h AHI, CAI, and time with oxygen saturation of <90% were independent predictors of outcome.
In systolic HF patients, CAs occurred throughout a 24-h period and were associated with a neurohormonal activation, ventricular arrhythmic burden, and worse prognosis.
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Cheyne-Stokes respiration (CSR) is believed to only occur in supine and sleeping conditions, and thus, CSR treatment is applied to those specific states. Although CSR has also been described in ...patients with heart failure (HF) during wakefulness, its persistence in an upright position is still unknown.
The purpose of this study was to assess the predictors, clinical correlates, and prognostic value of diurnal CSR in upright position.
Outpatients with systolic HF underwent a comprehensive evaluation, including short-term respiratory monitoring with a head-up tilt test to investigate the presence of upright CSR, assessment of chemoreflex response to hypoxia and hypercapnia, and 24-h cardiorespiratory recording. At follow-up, cardiac death was considered as the endpoint.
Of 574 consecutive patients (left ventricular ejection fraction 32 ± 9%; age 65 ± 13 years; 80% men), 195 (34%) presented supine CSR only, 82 (14%) presented supine and upright CSR, and 297 patients (52%) had normal breathing. Patients with upright CSR had the greatest apnea-hypopnea and central apnea index (at daytime and nighttime), the worst hemodynamic profile and exercise performance, increased plasma norepinephrine and N-terminal pro-B-type natriuretic peptide, and chemosensitivity to hypercapnia, which was the only independent predictor of upright CSR (odds ratio: 3.96; 95% confidence interval CI: 1.45 to 10.76; p = 0.007 vs. normal breathing; odds ratio: 4.01; 95% CI: 1.54 to 10.46; p = 0.004 vs. supine CSR). At 8-year follow-up, patients with upright CSR had the worst outcome (log-rank = 14.05; p = 0.001) and the presence of upright CSR independently predicted 8-year cardiac death (hazard ratio: 2.39; 95% CI: 1.08 to 5.29; p = 0.032).
Upright CSR in HF patients is predicted by increased chemosensitivity to hypercapnia and is associated with worse clinical conditions and with a greater risk of cardiac death.
Evidence of sympathetic and renin-angiotensin-aldosterone system activation provided a rationale for neurohormonal antagonism in heart failure with reduced ejection fraction (HFrEF), while no data ...are available in patients with milder degree of systolic dysfunction. We aimed to investigate neurohormonal function in HF with preserved and mid-range EF (HFpEF/HFmrEF).
Three cohorts (n = 189/each) of stable HFpEF, HFmrEF and HFrEF patients were selected (median age 70, 67 and 67 years; male 56%, 73% and 74%, respectively). Patients received a baseline clinical assessment including plasma renin activity (PRA), aldosterone, catecholamines, and N-terminal fraction of pro-B-type natriuretic peptide (NT-proBNP) assays, and were followed-up for all-cause death.
Neuroendocrine profile was similar between HFpEF and HFmrEF, while all neurohormones except epinephrine were higher in HFrEF than in HFmrEF (NT-proBNP 2332 ng/L, IQR 995–5666 vs 575 ng/L, 205–1714; PRA 1.7 ng/mL/h, 0.4–5.6 vs 0.6 ng/mL/h, 0.2–2.6; aldosterone 153 ng/L, 85–246 vs 113 ng/L, 72–177; norepinephrine 517 ng/L, 343–844 vs 430 ng/L, 259–624; all p < 0.001, epinephrine 31 ng/L, 10–63 vs 25 ng/L, 10–44; p = 0.319). These findings were unrelated to treatment heterogeneity. Ten percent of HFpEF patients had elevated PRA, aldosterone and norepinephrine vs. 8% in HFmrEF and 21% in HFrEF. During a 5-year follow-up, survival decreased with the number of neurohormones elevated (HFpEF: log-rank 7.8, p = 0.048; HFmrEF: log-rank 11.8, p = 0.008; HFrEF: log-rank 8.1, p = 0.044).
Neurohormonal activation is present only in a subset of patients with HFpEF and HFmrEF, and may hold clinical significance. Neurohormonal antagonism may be useful in selected HFpEF/HFmrEF population.
•Neurohormonal activation has been well documented in HFrEF.•There is limited evidence on neurohormonal activation in HFpEF and HFmrEF.•Sympathetic and RAAS activation is present only in a group of HFpEF/HFmrEF patients.•Neurohormonal blockade may be useful only in a subset of HFpEF/HFmrEF patients.
Abstract Background Impairment of kidney function is frequently observed in chronic heart failure (CHF). It correlates with clinical and neurohormonal status, and affects prognosis. We aimed to ...identify the prognostic impact of plasma renin activity (PRA) in patients affected by CHF with chronic kidney disease (CKD). Methods We enrolled 996 consecutive CHF patients (age 65 ± 13 years, mean ± SD, left ventricular ejection fraction, LVEF, 33 ± 10%), who underwent a complete clinical and neurohormonal characterization and were then followed-up (median 36 months) for the end point of cardiac death. Results A stage ≥ 3 CKD (estimated glomerular filtration rate < 60 mL/min/1.73 m2 ) was found in 437 patients. Impaired renal function was associated with worse symptoms, lower LVEF, higher plasma norepinephrine, NT-proBNP and PRA (all p < 0.001). As compared to patients with preserved renal function, those with CKD had higher cardiac mortality 106 (24%) vs 53 (9.5%), p < 0.001. In CKD patients, at Cox multivariate analysis, only ejection fraction (HR 0.91, 95% CI 0.84–0.97, p = 0.008), NT-proBNP (2.53, 1.45–4.41, p = 0.001) and PRA (1.73, 1.16–2.58, p = 0.007) were independent predictors of cardiac death. ROC analysis identified a cut-off value for PRA of 3.29 ng/mL/h that predicted prognosis with the greatest accuracy. Finally, the elevation of both NT-proBNP and PRA identified a subset of patients with the highest risk of cardiac death. Conclusions PRA has an independent prognostic value in CHF patients with CKD comorbidity. The combination of PRA and NT-proBNP identifies a group of high risk patients, who might benefit of a more intensive care, targeted to enhance renin–angiotensin system antagonism.
Circulating concentrations of N-terminal fragment of the prohormone of brain natriuretic peptide (NT-proBNP) are influenced by age and common age-related comorbidities, such as renal dysfunction. ...Therefore, utility of NT-proBNP for prediction of prognosis in the aged has been questioned. We aimed to investigate the prognostic value of NT-proBNP across age classes in a cohort of patients with chronic systolic HF.
We enrolled 2364 consecutive outpatients with HF and left ventricular ejection fraction ≤50%. Patients were classified according to age quartiles, and a very elderly subgroup was identified, aged ≥85 years. After baseline assessment (including NT-proBNP testing), patients were followed-up for the composite of cardiovascular death, heart transplantation or ventricular assistance device implantation (primary outcome) and for all-cause death (secondary outcome). Patients in the fourth quartile (Q4, age ≥ 77 years, n = 638) and in the very elderly subgroup (age ≥ 85 years, n = 153), had higher NT-proBNP (p < .001 vs Q1). NT-proBNP was independently associated with primary and secondary outcome at 1- and 5-years follow-up in the whole population, as well as in Q4 and in the very elderly subgroup (all p < .05). Compared to the whole population, Q4 and very elderly had higher NT-proBNP cut-off for prediction of 1-year primary (4188 and 9729 ng/l, respectively vs 3710 ng/l) and secondary outcome (4296 and 7634 ng/l, respectively vs 3056 ng/l).
NT-proBNP predicts mortality in elderly and very elderly patients with chronic systolic HF, both at mid- and long-term follow-up. Higher NT-proBNP prognostic cut-off should be considered in the aged HF population.
•NT-proBNP predicts outcome in elderly and very elderly patients with heart failure.•Risk associated with high NT-proBNP increases with age, peaking in the oldest old.•Higher NT-proBNP cut-offs are to be considered in elderly patients.•Circulating NT-proBNP has different clinical correlates depending on patients' age.
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