Advances in cardiac imaging have resulted in greater recognition of cardiac amyloidosis in everyday clinical practice, but the diagnosis continues to be made in patients with late-stage disease, ...suggesting that more needs to be done to improve awareness of its clinical manifestations and the potential of therapeutic intervention to improve prognosis. Light chain cardiac amyloidosis, in particular, if recognized early and treated with targeted plasma cell therapy, can be managed very effectively. For patients with transthyretin amyloidosis, there are numerous therapies that are currently in late-phase clinical trials. In this review, we address common questions encountered in clinical practice regarding etiology, clinical presentation, diagnosis, and management of cardiac amyloidosis, focusing on recent important developments in cardiac imaging and biochemical diagnosis. The aim is to show how a systematic approach to the evaluation of suspected cardiac amyloidosis can impact the prognosis of patients in the modern era.
Pulmonary Hypertension in Chronic Lung Diseases Seeger, Werner, MD; Adir, Yochai, MD; Barberà, Joan Albert, MD ...
Journal of the American College of Cardiology,
12/2013, Letnik:
62, Številka:
25
Journal Article, Conference Proceeding
Recenzirano
Odprti dostop
Chronic obstructive lung disease (COPD) and diffuse parenchymal lung diseases (DPLD), including idiopathic pulmonary fibrosis (IPF) and sarcoidosis, are associated with a high incidence of pulmonary ...hypertension (PH), which is linked with exercise limitation and a worse prognosis. Patients with combined pulmonary fibrosis and emphysema (CPFE) are particularly prone to the development of PH. Echocardiography and right heart catheterization are the principal modalities for the diagnosis of COPD and DPLD. For discrimination between group 1 PH patients with concomitant respiratory abnormalities and group 3 PH patients (PH caused by lung disease), patients should be transferred to a center with expertise in both PH and lung diseases for comprehensive evaluation. The task force encompassing the authors of this article provided criteria for this discrimination and suggested using the following definitions for group 3 patients, as exemplified for COPD, IPF, and CPFE: COPD/IPF/CPFE without PH (mean pulmonary artery pressure mPAP <25 mm Hg); COPD/IPF/CPFE with PH (mPAP ≥25 mm Hg); PH-COPD, PH-IPF, and PH-CPFE); COPD/IPF/CPFE with severe PH (mPAP ≥35 mm Hg or mPAP ≥25 mm Hg with low cardiac index CI <2.0 l/min/m2 ; severe PH-COPD, severe PH-IPF, and severe PH-CPFE). The “severe PH group” includes only a minority of chronic lung disease patients who are suspected of having strong general vascular abnormalities (remodeling) accompanying the parenchymal disease and with evidence of an exhausted circulatory reserve rather than an exhausted ventilatory reserve underlying the limitation of exercise capacity. Exertional dyspnea disproportionate to pulmonary function tests, low carbon monoxide diffusion capacity, and rapid decline of arterial oxygenation upon exercise are typical clinical features of this subgroup with poor prognosis. Studies evaluating the effect of pulmonary arterial hypertension drugs currently not approved for group 3 PH patients should focus on this severe PH group, and for the time being, these patients should be transferred to expert centers for individualized patient care.
The presence of mutations leading to amino acid substitutions in TTR destabilizes the tetramer, promoting amyloid fibril formation. In an approach targeting fibril removal from tissue, the ...combination of doxycycline and the bile acid derivative tauroursodeoxycholic acid was effective in a murine model of FAP (8), and it stabilized N-terminal pro-B-type natriuretic peptide and echocardiographic parameters in an open-label pilot study of patients with wt-ATTR and mt-ATTR (9).
Cinaciguat (BAY 58-2667) is a novel soluble guanylate cyclase activator. This study evaluated the haemodynamic effect and safety of cinaciguat added to standard therapy in patients with acute ...decompensated heart failure (ADHF).
In this placebo-controlled, phase IIb study (NCT00559650), 139 patients admitted with ADHF, pulmonary capillary wedge pressure (PCWP) ≥18 mmHg, left ventricular ejection fraction <40%, and a pre-existing need for invasive haemodynamic monitoring were randomized 2:1 to cinaciguat:placebo (continuous i.v. infusion). The dose was titrated for 8 h and maintained for 16-40 h (starting dose: 100 μg/h). At 8 h, mean PCWP changed from 25.7 ± 5.0 mmHg by -7.7 mmHg with cinaciguat and from 25.0 ± 5.3 mmHg by -3.7 mmHg with placebo (P < 0.0001). The mean right atrial pressure changed from 12.4 ± 5.3 mmHg by -2.7 mmHg with cinaciguat and from 11.8 ± 4.9 mmHg by -0.6 mmHg with placebo (P= 0.0019). Cinaciguat also decreased the pulmonary and systemic vascular resistance and the mean arterial pressure, and increased the cardiac index (all P < 0.0001 vs. placebo). Systolic blood pressure changed by -21.6 ± 17.0 mmHg with cinaciguat and -5.0 ± 14.5 mmHg with placebo. Adverse events were experienced by 71 and 45% of patients receiving cinaciguat and placebo, respectively. No adverse effects on the 30-day mortality were seen; however, the trial was stopped prematurely due to an increased occurrence of hypotension at cinaciguat doses ≥200 µg/h.
Cinaciguat unloaded the heart in patients with ADHF. However, high doses were associated with hypotension.
IMPORTANCE: Iron deficiency is present in approximately 50% of patients with heart failure with reduced left ventricular ejection fraction (HFrEF) and is an independent predictor of reduced ...functional capacity and mortality. However, the efficacy of inexpensive readily available oral iron supplementation in heart failure is unknown. OBJECTIVE: To test whether therapy with oral iron improves peak exercise capacity in patients with HFrEF and iron deficiency. DESIGN, SETTING, AND PARTICIPANTS: Phase 2, double-blind, placebo-controlled randomized clinical trial of patients with HFrEF (<40%) and iron deficiency, defined as a serum ferritin level of 15 to 100 ng/mL or a serum ferritin level of 101 to 299 ng/mL with transferrin saturation of less than 20%. Participants were enrolled between September 2014 and November 2015 at 23 US sites. INTERVENTIONS: Oral iron polysaccharide (n = 111) or placebo (n = 114), 150 mg twice daily for 16 weeks. MAIN OUTCOMES AND MEASURES: The primary end point was a change in peak oxygen uptake (V̇o2) from baseline to 16 weeks. Secondary end points were change in 6-minute walk distance, plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels, and health status as assessed by Kansas City Cardiomyopathy Questionnaire (KCCQ, range 0-100, higher scores reflect better quality of life). RESULTS: Among 225 randomized participants (median age, 63 years; 36% women) 203 completed the study. The median baseline peak V̇o2 was 1196 mL/min (interquartile range IQR, 887-1448 mL/min) in the oral iron group and 1167 mL/min (IQR, 887-1449 mL/min) in the placebo group. The primary end point, change in peak V̇o2 at 16 weeks, did not significantly differ between the oral iron and placebo groups (+23 mL/min vs −2 mL/min; difference, 21 mL/min 95% CI, −34 to +76 mL/min; P = .46). Similarly, at 16 weeks, there were no significant differences between treatment groups in changes in 6-minute walk distance (−13 m; 95% CI, −32 to 6 m), NT-proBNP levels (159; 95% CI, −280 to 599 pg/mL), or KCCQ score (1; 95% CI, −2.4 to 4.4), all P > .05. CONCLUSIONS AND RELEVANCE: Among participants with HFrEF with iron deficiency, high-dose oral iron did not improve exercise capacity over 16 weeks. These results do not support use of oral iron supplementation in patients with HFrEF. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT02188784
Patients with decompensated heart failure and cardiorenal syndrome were randomly assigned to ultrafiltration or diuretic therapy. Ultrafiltration was inferior to diuretics with respect to the primary ...end point, a bivariate measure of change in creatinine and body weight.
The acute cardiorenal syndrome (type 1) is defined as worsening renal function in patients with acute decompensated heart failure.
1
It occurs in 25 to 33% of patients with acute decompensated heart failure and is associated with poor outcomes.
1
,
2
Multiple processes contribute to the development of the acute cardiorenal syndrome, including extrarenal hemodynamic changes, neurohormonal activation, intrarenal microvascular and cellular dysregulation, and oxidative stress.
1
In some cases, intravenous diuretics, which are often administered in patients with acute decompensated heart failure,
3
may directly contribute to worsening renal function.
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,
4
,
5
The use of diuretics to treat persistent congestion after the onset . . .
...the diagnosis of AL cardiac amyloidosis necessitates that the clinician be aware of the possibility that HF due to an infiltrative cardiomyopathy is leading to symptoms of dyspnea, fatigue, and ...edema in a middle-aged patient without a history of coronary disease or its risk factors. Because bortezomib administration can have transient myocardial and renal depressant effects, the effect of LV ejection fraction as a predictor of successful BDEX+AA needs to be assessed. ...a comparative effectiveness study is initiated, the ideal patient to be considered for chemotherapy would be one whose extracardiac amyloid burden is relatively small, has a good functional capacity, and whose cardiac dysfunction can be medically managed.
In a randomized trial involving 110 patients with heart failure with a preserved ejection fraction, those who received 120 mg of isosorbide mononitrate daily for 6 weeks had a lower daily activity ...level than those who received placebo, as assessed by accelerometry.
Approximately half of patients with heart failure have a preserved ejection fraction.
1
Exercise intolerance is a cardinal feature of this syndrome and perpetuates sedentary behavior, deconditioning, and frailty.
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–
4
In early studies in patients with heart failure with a reduced ejection fraction, long-acting nitrates improved activity tolerance, as assessed by submaximal
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,
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or maximal
7
exercise tests. Although nitrates are commonly prescribed for symptom relief in heart failure,
8
–
12
the effects of nitrates in patients with heart failure and a preserved ejection fraction have not been extensively studied. The hemodynamic effects of nitrates might attenuate pulmonary congestion with exertion and improve . . .
BACKGROUND—Pulmonary hypertension caused by systolic left ventricular dysfunction is associated with significant morbidity and mortality; however, no treatment is approved for this indication. We ...hypothesized that riociguat, a novel soluble guanylate cyclase stimulator, would have beneficial hemodynamic effects in patients with pulmonary hypertension caused by systolic left ventricular dysfunction.
METHODS AND RESULTS—Overall, 201 patients with heart failure resulting from pulmonary hypertension caused by systolic left ventricular dysfunction were randomized to double-blind treatment with oral placebo or riociguat (0.5, 1, or 2 mg 3 times daily) for 16 weeks in 4 parallel arms. The primary outcome was the placebo-corrected change from baseline at week 16 in mean pulmonary artery pressure. Although the decrease in mean pulmonary artery pressure in the riociguat 2 mg group (−6.1±1.3 mm Hg; P<0.0001 versus baseline) was not significantly different from placebo (P=0.10), cardiac index (0.4 L·min·m; 95% confidence interval, 0.2–0.5; P=0.0001) and stroke volume index (5.2 mL·m; 95% confidence interval, 2.0–8.4; P=0.0018) were significantly increased without changes in heart rate or systemic blood pressure compared with placebo. Both pulmonary (−46.6 dynes·s·cm; 95% confidence interval, –89.4 to –3.8; P=0.03) and systemic vascular resistance (−239.3 dynes·s·cm; 95% confidence interval, –363.4 to –115.3; P=0.0002) were significantly reduced with riociguat 2 mg. Riociguat reduced the Minnesota Living With Heart Failure score (P=0.0002). Discontinuation of treatment was similar between treatment groups.
CONCLUSIONS—Although the primary end point of the study was not met, riociguat was well tolerated in patients with pulmonary hypertension caused by systolic left ventricular dysfunction and improved cardiac index and pulmonary and systemic vascular resistance.
CLINICAL TRIAL REGISTRATION—URLhttp://www.clinicaltrials.gov. Unique identifierNCT01065454.
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