Sodium nitroprusside for advanced heart failure. A metanalysis of literature data.

Advanced heart failure (HF) is associated with a very poor prognosis and places a big burden on health-care services. The gold standard treatment, i.e. long-term mechanical circulatory support or heart transplantation, is precluded in many patients but observational studies suggest that the use of SNP might be associated with favourable long-term clinical outcomes. We performed a metanalysis of published studies that compared sodium nitroprusside (SNP) with optimal medical therapy to examine the safety and efficacy of SNP as part of the treatment regimen of patients hospitalized for advanced heart failure (HF). We searched PUBMED, EMBASE and WEB OF SCIENCE for studies that compared SNP with optimal medical therapy in advanced HF on July 2022. After screening 700 full-text articles, data from two original articles were included in a combined analysis. The analysis demonstrated a 66% reduction in the odds of death in advanced HF patients treated with SNP. The results show the potential importance of the inclusion of SNP in the treatment regimen of patients hospitalized because of advanced HF and underlines that controlled, randomized studies are still required in this condition.

Iatrogenic atrial septal defect does not affect acute hemodynamic modifications after transcatheter edge-to-edge repair in patients with functional mitral regurgitation.

OBJECTIVE: The correction of functional mitral regurgitation (FMR) with transcatheter edge-to-edge repair (TEER) can favorably affect patients' hemodynamic profile. However, the procedure requires inter-atrial trans-septal access and the hemodynamic relevance of the residual iatrogenic atrium septal defect (iASD) is still debated. This study aimed at investigating the hemodynamic modifications during TEER with MitraClip, before and after the iASD creation, in patients with heart failure with reduced ejection fraction (HFrEF) and severe FMR. METHODS: Thirty-nine HFrEF patients with 3+ or 4+/4+ FMR were included. Right heart catheterization was performed at baseline after general anesthesia induction and at the end of TEER, both before and after removing the device guiding catheter. RESULTS: Compared with baseline, MitraClip positioning was followed by a significant immediate improvement in cardiac output (respectively: 3.36 vs 5.05 ml/min), pulmonary artery wedge pressure (23.7 vs 18.2 mmHg), mean pulmonary artery pressure (34.4 vs 27.7 mmHg) and pulmonary vascular resistance (3.6 vs 2.2 Wood Units) (all p < 0.001). No further significant modifications occurred after removing the device guiding catheter. CONCLUSIONS: Our data suggest that the acute hemodynamic modifications after TEER are not influenced by the induction of iASD in patients with FMR.

Left atrial dilatation in systolic heart failure: a marker of poor prognosis, not just a buffer between the left ventricle and pulmonary circulation.

BACKGROUND: The relation between systolic pulmonary pressure (sPAP) and left atrium in patients with heart failure (HF) is unclear. Diastolic dysfunction, expressed as restrictive mitral filling pattern (RMP), and functional mitral regurgitation (FMR) are associated with both LA enlargement and increased sPAP. We aimed to evaluate whether atrial dilation might modulate the consequences of RMP and FMR on the pulmonary circulation of patients with HF with reduced ejection fraction (HFrEF). METHODS: 1256 HFrEF patients were retrospectively recruited in four Italian centers. Left ventricular (LVD) and atrial (LAD) diameters were measure by m-mode, and EF were measured. RMP was defined as E-wave deceleration time lower than 140 ms. FMR was quantitatively measured. sPAP was evaluated based on maximal tricuspid regurgitant velocity and estimated right atrial pressure. RESULTS: Final study population was formed by 1005 patients because of unavailability of sPAP in 252 patients. Mean EF was 33 ± 3, 35% had RMP, 67% had mild, and 26% moderate-to-severe FMR. 69% of patients had increased sPAP. A significant association was observed between sPAP and EF, RMP, FMR, and LAD (p < 0.0001 for all). At multivariate analysis, LAD was positively associated with sPAP (p < 0.0001) independently of EF, RMP, and FMR. Analogously, LAD (p < 0.05) was associated with more severe symptoms and worse prognosis after adjustment for LV function and FMR. CONCLUSION: LA dilation was positively associated with sPAP independently of EF, RMP, and FMR. This highlights that LA size should be considered a marker of the severity of the disease.

Effects on survival of loop diuretic dosing in ambulatory patients with chronic heart failure using a propensity score analysis.

OBJECTIVE: To ascertain whether increasing doses of orally administered furosemide are associated with impaired survival in outpatients with chronic heart failure (CHF) and left ventricular (LV) systolic dysfunction. METHODS: Transthoracic echo-Doppler examination was carried out at baseline in 813 consecutive CHF outpatients with LV ejection fraction ≤ 45%. The total daily dose of furosemide was assessed for each patient. Chronic kidney disease (CKD) was defined by a glomerular filtration rate < 60 ml/min/1.73 m(2). The end-point was all-cause mortality. To control the prognostic effect of furosemide for the propensity of using high doses of the drug, the Cox model was stratified by the propensity score, itself computed from a multivariable logistic model. Mean follow up was 44 months. RESULTS: After stratification for the propensity score, the risk of death increased linearly across quartiles of furosemide dose (HR 1.38, 95% CI 1.14-1.68, p < 0.001). A daily dose of 50 mg was identified as the best threshold value to predict a high risk of death within 3 years with an area under the ROC curve of 0.68 (95% CI 0.64-0.72). Increasing doses of furosemide were associated with an increased risk of death regardless of LV filling pattern, CKD and background therapy with ACE-inhibitors or beta-blockers. CONCLUSIONS: In outpatients with CHF, after stratification for the propensity score, the risk of death increased linearly across quartiles of furosemide daily dose. A threshold furosemide dose of 50 mg was related with the worse outcome.

The tailored medical therapy in patients with advanced heart failure referred for cardiac transplantation.

INTRODUCTION: Optimal pharmacologic management of heart transplant (HT) candidates is required prior to evaluation so as to obtain a reliable prognostic stratification and to address the donor shortage. The aim of this study was to determine whether a tailored medical approach was effectively achieved before HT waiting list enrollment. MATERIALS AND METHODS: This study concerned 40 consecutive patients referred for HT evaluation who underwent a clinical assessment, including hemodynamic, echocardiographic, and brain natriuretic peptide determinations. Medical therapy was optimized according to the clinical assessment to improve neurohormonal and hemodynamic profiles. We analyzed the distribution of the different drugs between the first and the following evaluation to demonstrate whether a significant improvement of medical therapy could be achieved in advanced chronic heart failure (ACHF). RESULTS: The mean age was 53 years, including 93% males. The etiology of disease was ischemic in 40% and idiopathic in 45%. The mean left ventricular ejection fraction was 23%, mean values of hemodynamic data were cardiac index (CI) 2+/-0.6 L/min/m(2), mean pulmonary arterial pressure (mPAP) 30+/-10 mm Hg, wedge pressure (PWP) 23+/-8 mm Hg; mean BNP was 618 pg/mL. Median follow-up was 397 days; 82% of candidates underwent HT waiting-list enrollment. The medical treatment was modified as follows: beta-blockers were introduced or uptitrated in 32%, angiotensin receptor blockers (ARB) were introduced in 7.5%, spironolactone was started in 42%, nitrates were introduced in 20%, and diuretics were uptitrated in 35% of patients. CONCLUSION: In patients with ACHF referred for HT, a further effort in the assessment of the medical treatment is strongly recommended.

Microvascular changes in the lower extremities of paraplegics with heterotopic ossification.

OBJECTIVES: To investigate the morphological aspects of blood microvasculature of the skin and subcutaneous tissues in subjects with paraplegia with heterotopic ossification (HO). METHODS: In two patients with traumatic spinal cord injury and HO, punch biopsies of skin and hypodermic soft tissue in the region of HO near the hip were studied with histological and ultrastructural methods. RESULTS: Alterations of endothelial cell and basement membrane of capillaries and small vessels were observed. Hyperactive endothelium, thickening and reduplication of the basement membrane, changes of the perivascular connective tissues and microcalcifications in the subcutaneous fat tissue were also seen. CONCLUSIONS: This present study indicates microvascular changes in the skin and subcutaneous tissue in the region of HO near the hip of two subjects with paraplegia. In our opinion the described vascular changes may induce hypoxiemic alterations of the soft para-articular tissues leading metabolic changes which may contribute to the development of HO. Therefore, it cannot be concluded whether these changes are directly responsible for HO induction.

Evidence-based diagnosis of familial non-X-linked dilated cardiomyopathy. Prevalence, inheritance and characteristics.

AIMS: To assess the prevalence of familial non-X-linked dilated cardiomyopathy, to diagnose early asymptomatic cases evaluate inheritance and characterize clinical phenotypes. METHODS AND RESULTS: We screened 472 relatives of 104 consecutive patients diagnosed with dilated cardiomyopathy; males with X-linked dilated cardiomyopathy were excluded based on systematic immunohistochemical and molecular analysis. Relatives underwent clinical examination, electrocardiography, echocardiography and serum creatine-phosphokinase determination. Twenty-six index patients (25%) had familial disease: four youths (< or = 20 years) had rapidly progressive outcome and underwent emergency transplantation. In a sib-pair, the onset was with atrioventricular block. Inheritance was autosomal dominant in 15, undetermined in seven (four sib-pairs); mitochondrial DNA pathological mutations were found in four. The screening identified 23 newly diagnosed relatives in the familial group. Transplantation (P = 0.04) and atrial fibrillation (P = 0.04) were more frequent, and left bundle branch block (P = 0.04) less frequent in index patients with familial than in those with non-familial disease. Several non-affected relatives had instrumental abnormalities potentially useful as pre-clinical markers: their prevalence was similar in both groups. CONCLUSIONS: The prevalence of familial, non X-linked dilated cardiomyopathy was 25%. The immediate benefits of screening family members of index patients was early diagnosis in unaware symptomless affected relatives.

Five-minute recording of heart rate variability in severe chronic heart failure: correlates with right ventricular function and prognostic implications.

BACKGROUND: In advanced chronic heart failure (CHF), correlation between heart rate variability (HRV) and parameters of disease severity is still unclear. A reduced HRV has been related to left but not to right ventricular function parameters. Moreover, the prognostic role of spectral measures is not fully defined. We sought to assess HRV by using a short electrocardiographic recording in ambulatory patients with severe CHF to investigate the relation of HRV with clinical neurohormonal and hemodynamic parameters and to determine its predictive prognostic power. METHODS AND RESULTS: HRV was obtained from 5-minute electrocardiographic recordings in 75 ambulatory patients with CHF referred for heart transplantation screening. Standard frequency-domain parameters (total power, low-frequency power, and high-frequency power) were calculated. Prognostic value of these autonomic markers and their correlation with clinical and instrumental parameters were also assessed. A low low-frequency/high-frequency ratio was an independent predictor of cardiac events (P =.015). No correlation was found between New York Heart Association class and HRV, whereas significant correlations were identified between norepinephrine plasma levels, several hemodynamic parameters, and spectral measures (P < or =.03). A reduced HRV, particularly a low-frequency power reduction (P =.000), was highly related to indexes of right ventricular dysfunction. CONCLUSIONS: The current data indicate that spectral analysis of HRV, calculated from short electrocardiographic recordings, may represent a simple but effective means contributing to risk stratification of patients with severe CHF. Autonomic information obtained from this analysis suggests that right ventricular dysfunction may be a critical element determining autonomic imbalance in patients with severe CHF.

Structure of the initial lymphatics of the human urinary bladder with invasive urothelial tumors.

The ability of urothelial tumors of the urinary bladder to metastasize via the lymphatic circulation and the extent of metastatic involvement of regional lymph nodes is an important parameter in the staging and prognosis of these neoplasms. Accordingly, we examined the site and morphology of initial lymphatic vessels in the mucosa of the human urinary bladder in patients with invasive transitional cell carcinoma. Lymphatics in the papillary tumoral mass was also examined. Endoscopic transurethral biopsies from the urinary bladder of 120 patients with invasive transitional cell papillary carcinoma were utilized for this study. Biopsy from the uninvolved lateral wall of the same patient was utilized as a control. On histopathology of biopsies of neoplastic tissues, initial lymph vessels were seen in the deeper region of the mucosa but not in the subepithelial layer nor in the stroma of the tumoral papillae. The latter were often associated with arteriolar and venular vessels. When edema and inflammation occurred in peritumoral regions, lymphatics showed a dilated lumen, non-indented wall with dissociated perivascular collagen and elastic fibers. Tumoral permeation or embolization of lymphatics was seen in 12% of patients with invasive tumors, and these lymphatic vessels did not display significant morphologic changes. The absence of initial lymphatics in the stroma of tumoral papillae and in infiltrated subepithelial regions of the urinary bladder may explain the absence of lymph node metastasis in early-stage invasive urothelial tumors.

Structure of the lymphatic microcirculation in the human urinary bladder with different intraluminal pressure and distension.

The localization, morphology and fine structure of initial lymphatic vessels in the mucosa of the empty and distended urinary bladder were studied. Endoscopic transurethral biopsies of the empty (collapsed) bladder showed under light and electron microscopy numerous intramural lymphatics with a dilated lumen and thin profile. Contacts between endothelial cells were single, overlapping, interlocking, and open while the perivascular connective tissue was filled by fascicles of collagen fibers. In the most superficial layer (subepithelial mucosa), lymphatics were not seen. Biopsies obtained under elevated intraluminal pressure and distension showed on light and electron microscopy lymphatic vessels with small lumens characteristically reduced to irregular slits. Endothelial cell contacts were simple or overlapping; open junctions were rare. The perivascular connective tissue was dense and collagen and elastic fibers often abutted one another. These findings support that with a distended or expanded urinary bladder, the effect of increased intraluminal pressure on the superficial (mucosal) layer radially pulls on the connective tissue that in turn compresses the initial lymphatics thereby restricting lymph transport.

Langerhans' cell granulomatosis and Hodgkin's lymphoma. Report of a case.

A 48-year-old female with a history of accentuated dyspnea, pleural thickening in anteromedial portion with left patchy parenchymal shadowing invading adjoining parasternal structure of the rib cage, presented 13 months later marked superclavicular, anterior mediastinic and parahilar left lymphadenopathy. Open surgical biopsies on the pleural lesion invading the hypodermic tissues of parasternal region showed morphological and immunocytochemical patterns of Langerhans' cell histiocytosis (LCH). 13 months later the superclavicular lymph node biopsy diagnosed Hodgkin's lymphoma (HD), mixed cellularity type II, stage AE. On a total of 29 cases with association of LCH and HD, the described case in the second case that shows morphologically demonstrated LCh with subsequent development of HD. It is postulated that the development of HD in a patient with LCH, might represent malignant evolution of this hyperplastic process.

Detection and morphology of thymic remnants after video-assisted thoracoscopic extended thymectomy (VATET) in patients with myasthenia gravis.

Thymectomy is often an extremely useful therapeutic procedure in myasthenia gravis (MG) and is usually indicated for adult patients with generalized disease. Because remnants of thymus may remain in extrathymic fat, an extended thymectomy is recommended. A new surgical approach without sternotomy: video-assisted thoracoscopic extended thymectomy (VATET) was performed in 30 MG patients. The weight of removed thymus ranged from 10.8 to 113 grams. The weight of fatty tissue removed from pretracheal, anterior mediastinal and costophrenic areas ranged from 6.3 to 74.8 grams. Histological examination revealed thymic remnants in 14.8% of pretracheal fat samples and in 33.3% of samples from anterior mediastinal plus costophrenic areas. These findings indicate that VATET is a radical procedure and may be the first choice surgery for young female MG patients, since aesthetic sequelae are reduced compared to procedures involving sternotomy.

Morphological changes in the skin microlymphatics in recently injured paraplegic patients with ilio-femoral venous thrombosis.

Based on morphological features of the lymphatic microcirculation of the skin from healthy subjects, and from paraplegic patients who had no evidence of ilio-femoral venous thrombosis (thromboembolic disease: TED), the leg terminal lymphatic vessels from skin biopsies of five male paraplegic patients with acute traumatic spinal cord lesions and with documented TED were studied. Paraplegic patients with TED had lymph vessels with a dilated lumen surrounded by a rarefacted perivascular connective tissue characterized by dissociation and disruption of collagen and elastic fibres. The lymphatic wall was generally attenuated and some open junctions and channels delimited by endothelial protrusions were observed. The venous outflow obstruction caused by deep venous thrombosis accompanied by the absence of ambulatory venous pressure in the paretic leg determines skin microlymphatic dilatation, lymph stasis and changes in the interstitial connective tissues. These alterations may be considered to be the morphological aspect of the dystrophic alterations seen in the skin of legs from paraplegic patients with TED. The results are discussed in view of the correct rehabilitative medical treatment necessary, and adequate prophylaxis of TED.

Morphological changes of dermal blood and lymphatic vessels in chronic venous insufficiency of the leg.

Morphological changes of dermal blood and lymphatic microcirculation in skin biopsies from patients affected by Chronic Venous Insufficiency (CVI) associated with stasis dermatitis of the lower limbs, are reported here. Blood vessels are characterized by an occluded lumen, thickening and reduplication of the basement membrane. The structural changes in dermal lymphatic vessels are: (i) collapsed lumen of lymphatics located in the papillar dermis; (ii) numerous and complex interdigitations between contiguous endothelial cells and lack of open junctions; (iii) derangement of the anchoring filaments that normally pull the lymphatic lumen open. The connective matrix is characterized by fibrosis with formation of dense bundles of collagen and elastic fibers. These results suggest that the dermal lymphatic and blood microcirculation in CVI are connected to a reduced fluid exchange capacity because of the structural changes occurred in the vascular and lymphatic wall and in the surrounding connective tissue.