A man in his seventies with fatigue and renal failure. / En mann i 70-årene med utmattelse og nyresvikt.

A man in his seventies underwent routine heart examinations as part of workup for kidney transplantation. Unexpected findings led to more extensive investigations and revealed two rare systemic diseases as causes of his heart failure.

Bone scintigraphy reduces the need for biopsy in suspected cardiac amyloidosis. / Skjelettscintigrafi reduserer behovet for biopsi ved mistanke om kardial amyloidose.

The gold standard to diagnose suspected cardiac amyloidosis is myocardial biopsy. In recent years, bone scintigraphy has partly replaced myocardial biopsy.

First Norwegian case of hereditary ATTR amyloidosis with a novel transthyretin variant.

An earlier healthy 64-year-old man with previous surgery for bilateral carpal tunnel syndrome (CTS) in his 50s, presented with dyspnoea on exertion. Cardiac amyloidosis was suspected due to "red flag" signs and symptoms. Further investigations with scintigraphy and genetic testing confirmed the diagnosis of hereditary ATTR variant (ATTRv) amyloidosis. This is the first case report of ATTRv amyloidosis in a patient of Norwegian origin and is caused by the mutation E54A (p.E74A) in the transthyretin (TTR) gene. This mutation is previously not reported in international databases. Transthyretin amyloid cardiomyopathy (ATTR-CM) is an underdiagnosed disease with a poor prognosis. Early recognition remains essential to afford the best treatment efficacy.

Increased LV apical untwist during preload reduction in healthy humans: an echocardiographic speckle tracking study during lower body negative pressure.

We sought to investigate the effect of reduced preload on left ventricle (LV) untwist and early diastolic filling in healthy individuals. Twelve healthy men, 22 (22, 23) years of age, were examined at rest and during applied lower body negative pressure (LBNP) of -20 mmHg and -40 mmHg, respectively. Regional untwist and untwist rate during IVRT were calculated at LV basal, papillary, subpapillary, and apical short axis levels by two dimensional speckle tracking echocardiography. Left ventricle early diastolic filling was assessed by transmitral E-wave (E) peak velocity by pulsed Doppler and flow propagation velocity (Vp) by color M-mode Doppler and early diastolic pulsed Doppler tissue velocities (E') from septal and lateral mitral annulus. From rest to LBNP -40 mmHg, the LV untwist and untwist rate at subpapillary level increased from 2.3 (1.4, 3.5) to 4.5 (3.1, 7.6) degrees and from -36 (-51, -25) to -69 (-127, -42) °/s (P < 0.001, P = 0.003), respectively, while apical untwist and untwist rate increased from 3.9 (2.3, 4.3) to 7.6 (6.4, 10.5) degrees and from -51 (-69, -40) to -118 (-170, -84) °/s (P < 0.001, P < 0.001), respectively. Since untwist and untwist rate at the basal level were unchanged, this created markedly larger base to apical untwist and untwist rate gradients from rest to LBNP -40 mmHg. E, Vp, and E' were reduced by 34, 32, and 39%, respectively. LV untwist and untwist rate during IVRT were increased at apical levels, which might be a physiological mechanism to minimize the impairment in LV early diastolic filling during preload reduction.

Regional LV deformation in healthy individuals during isovolumetric contraction and ejection phases assessed by 2D speckle tracking echocardiography.

PURPOSE: The main purpose of the this human study was by speckle tracking imaging to characterize the regional and temporal distribution of normal left ventricular (LV) deformation and the LV geometry during isovolumetric contraction (IVC) and the ejection phase. METHODS: Twelve healthy young men [22 (2·3) years] were included. Longitudinal and circumferential strain and local twist angle were measured at four LV short-axis levels: basal, papillary, subpapillary and apical level during IVC and ejection phases. In addition, LV length from apex to the atrio-ventricular level, two diameters at LV basal short-axis level and atrio-ventricular plane displacement (AVPD) were measured to characterize LV shape during IVC. RESULTS: During IVC, longitudinal and circumferential shortening was demonstrated at all four short-axis levels from base to apex, while the LV made a basal counterclockwise and apical clockwise rotation representing untwist. In addition, there was a reduction in LV length and changes in short-axis diameters at basal level and AVPD from end-diastole to end-IVC, reflecting that the LV changed from an oval to a more spherical shape. At end-systole, longitudinal and circumferential shortening and local twist angle were significantly increased towards apex (P<0·05). CONCLUSION: This study demonstrated that the IVC in healthy humans is characterized by regional longitudinal and circumferential shortening and LV untwist, which occurs parallel to geometric changes of the LV into a spherical shape. During ejection, increased regional gradients of LV deformation towards apex in LV longitudinal and circumferential shortening and local and net twist angle were demonstrated.

Reduced preload elicits increased LV twist in healthy humans: an echocardiographic speckle-tracking study during lower body negative pressure.

BACKGROUND: In normal left ventricles (LV), counterclockwise rotation (CCR) and net twist angle (NTA) have shown important roles during ejection. We investigated the effect of reduced preload by lower body negative pressure (LBNP) on CCR and NTA. METHODS AND RESULTS: Twelve healthy men were examined at rest, LBNP -20 and -40 mmHg. By two-dimensional speckle-tracking imaging, we measured rotation at four short-axis levels: basal, papillary, sub-papillary and apical. LV NTA was calculated as apex-to-base difference in rotation. Additionally, regional end-diastolic (EDA) and end-systolic area (ESA) were measured and regional area fraction (RAF) calculated [(EDA-ESA)/EDA] × 100). From rest to LBNP -40 mmHg, rotation at basal and papillary levels was unchanged. At sub-papillary level, rotation increased from 3·2 ± 3·6 to 5·8 ± 4·7° (P<0·05), while apical rotation increased from 9·3 ± 3·4 to 12·8 ± 4·7° (P<0·05). Correspondingly, LV NTA increased for each load reduction by 1·6 ± 1·8° (P<0·05) and 4·2 ± 2·3° (P<0·05). RAF increased at sub-papillary and apical levels from 57·6 ± 3·7 to 64·7 ± 8·8% and from 63·4 ± 8·8 to 74·8 ± 10·1%, respectively (P<0·05). From rest to LBNP -40 mmHg, changes in rotation and RAF correlated significantly at sub-papillary and apical levels (r = 0·94, P<0·01, and r = 0·63, P<0·05, respectively). CONCLUSIONS: Preload reduction in normal LV elicits increased systolic CCR and regional area fraction at sub-papillary and apical levels as well as net twist angle. These findings might be of physiological importance to minimize reduction in stroke volume and maintain arterial blood pressure.

Medical and ventilatory treatment of acute heart failure: new insights.

BACKGROUND: The traditional medical treatment of acute heart failure (AHF) has remained unchanged for many years. It has been based on oxygen supplementation and mechanical ventilatory support as well as the administration of morphine, diuretics, nitrates and inotropic agents. In 2005 the European Society of Cardiology (ESC) published new guidelines on the diagnosis and treatment of AHF. Also, new therapies have been introduced recently, giving rise to changes in therapeutic concepts. MATERIAL/METHOD: Based on these new guidelines and recent studies selected from the literature we here describe the new ESC classification of AHF including its epidemiology and pathophysiology. We further present a state-of-the-art status of the choices of medical treatment for patients with acute decompensated heart failure and pulmonary edema. RESULTS: Mechanical ventilatory support reduces the number of patients who require endotracheal intubation. Nitrates in dosages higher than employed today appear to be beneficiary to patients with pulmonary congestion, probably because of the pronounced afterload-reducing effect. Nesiritide, a synthetic brain natriuretic peptide, has shown better hemodynamic effects than common nitrate dosages in patients with congestive heart failure. Tezosentan, an endothelin antagonist, was tested in the biggest AHF trial ever, which, however, was terminated prematurely because it was futile to proceed given the endpoints dyspnea and death. The beta1-adrenergic drug dobutamine and the phosphodiestherase inhibitor milrinone are associated with increased mortality in patients with pronounced chronic and acute congestive heart failure. Levosimendan, a new inotropic drug, has shown lower mortality compared to dobutamine in patients with acute congestive heart failure. CONCLUSION: New concepts have finally emerged, including the application of old drugs such as nitrates in new (i.e., higher) dosages, as well as the novel compound levosimendan, recommended for patients with AHF and hypoperfused organs. The new ESC classification of AHF provides a valuable and long-awaited guideline to diagnose and treat this severe condition.

[Medical and ventilatory treatment of acute heart failure]. / Medikamentell og ventilatorisk behandling ved akutt hjertesvikt.

BACKGROUND: Traditional medical treatment of acute heart failure has remained unchanged for many years. It has been based on oxygen supplementation and mechanical ventilatory support as well as the administration of morphine, diuretics, nitrates and inotropic agents. In 2005 the European Society of Cardiology published new guidelines on diagnosis and treatment. Also, new therapies have been introduced recently, giving rise to changes in therapeutic concepts. MATERIAL AND METHOD: The article is based on these new guidelines and recent studies selected from the literature. RESULTS: Mechanical ventilatory support reduces the number of patients who require endotracheal intubation. Nitrates in higher dosages than employed today appear to be beneficial to patients with pulmonary congestion, probably because of the pronounced afterload reducing effect. Nesiritide has shown better haemodynamic effects than common nitrate dosages in patients with congestive heart failure. Tezosentan was tested in the biggest trial ever which, however, was terminated prematurely, because of futility with regard to the endpoints dyspnoea and death. Dobutamine and milrinone are associated with increased mortality in patients with pronounced chronic and acute congestive heart failure. Levosimendan has shown lower mortality compared to dobutamine in patients with acute congestive heart failure. INTERPRETATION: New concepts have finally emerged, including the application of old drugs such as nitrates in new (i.e., higher) dosages, as well as the novel compound levosimendan, and hypoperfused organs without severe hypotension. The new European Society of Cardiology classification provides a valuable and long-awaited guideline to diagnosis and treatment.

Effect of thalidomide on cardiac remodeling in chronic heart failure: results of a double-blind, placebo-controlled study.

BACKGROUND: Inflammation and matrix degradation may play a pathogenic role in chronic heart failure (CHF), and therefore, we examined whether thalidomide, a drug with potential immunomodulating and matrix-stabilizing properties, could improve left ventricular (LV) function in patients with CHF secondary to idiopathic dilated cardiomyopathy (IDCM) or coronary artery disease (CAD). METHODS AND RESULTS: Fifty-six patients with CHF and an LV ejection fraction (LVEF) <40% who were already on optimal conventional cardiovascular treatment were randomized to thalidomide (25 mg QD increasing to 200 mg QD) or placebo and followed up for 12 weeks. Our main findings were as follows: (1) During thalidomide treatment but not during placebo, there was a marked increase in LVEF (&7 EF units) along with a significant decrease in LV end-diastolic volume and heart rate. (2) This improvement in LVEF was accompanied by a decrease in matrix metalloproteinase-2 without any changes in its endogenous tissue inhibitor, suggesting a matrix-stabilizing net effect. (3) Thalidomide also induced a decrease in total neutrophil count and an increase in plasma levels of tumor necrosis factor-alpha, suggesting both proinflammatory and antiinflammatory effects. (4) The effect of thalidomide on LVEF was more marked in IDCM than in CAD, possibly partly reflecting that the former group was able to tolerate a higher thalidomide dosage. CONCLUSIONS: Although our results must be confirmed in larger studies that also examine the effects on morbidity and mortality, our findings suggest a role for thalidomide in the management of CHF in addition to traditional cardiovascular medications.