Association of Pulmonary Hypertension and Monoclonal Gammopathy of Undetermined Significance.

Objective: To determine the prevalence of monoclonal gammopathy of undetermined significance (MGUS) in patients with PH as well as precapillary PH. Methods: Olmsted County residents with PH, diagnosed between 1/1/1995 and 9/30/2017, were identified, and age and sex were matched to a normal control group. The PH group and normal control group were then cross-referenced with the Mayo Clinic MGUS database. Charts were reviewed to verify MGUS and PH. Heart catheterization data were then analyzed in these patients for reference to the gold standard for diagnosis. Results: There were 3419 patients diagnosed with PH by echocardiography between 1995 and 2017 in Olmsted County that met the criteria of our study. When the PH group (N = 3313) was matched to a normal control group (3313), a diagnosis of MGUS was significantly associated with PH 10.2% (OR = l.84 [95% CI 1.5-2.2], p < 0.001), compared with controls 5.8% based on echo diagnosis. Using heart catheterization data (484 patients), a diagnosis of MGUS was associated with PH 13.0% (OR = 3.94 [95% CI 2.28-6.82], p < 0.001). For pulmonary artery hypertension (N = 222), a diagnosis of MGUS was associated with PH at similar 12.2% (OR = 4.50 [95%CI 1.86-10.90], p < 0.001. Conclusions: There is a higher prevalence of MGUS in patients with PH and precapillary PH compared with normal controls. This association cannot be explained fully by other underlying diagnoses associated with PH. Assessing for this in patients with PH of unclear etiology may be reasonable in the workup of patients found to have PH.

Thrombocytopenia independently predicts death in idiopathic PAH.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a progressive vascular disorder with a high mortality. Clinical experience and small case series suggest thrombocytopenia may be frequent in this population and associated with a poor prognosis. We sought to estimate the prevalence of thrombocytopenia in patients with PAH and characterize its association with disease characteristics and patient outcome. METHODS: Single center cohort study of 714 incident adult patients with Group 1 PH who were evaluated for baseline platelet count at the time of diagnosis. Pts were stratified into three groups: normal platelet count (>150 × 109/L), Grade 1 thrombocytopenia (75-149 × 109/L) and Grade 2-4 thrombocytopenia (<75 × 109/L). RESULTS: The median platelet count was 209 × 109/L (IQR 163, 264). There were 572 (80%) pts without thrombocytopenia, 107 (15%) with Grade 1 and 35 (5%) with Grade 2-4 thrombocytopenia. The median pt age was 55 years (IQR 44-65) with no difference between platelet groups (p = 0.85). Men were more likely to have thrombocytopenia (62, 34%) than women (80, 15%, p < 0.0001). Thrombocytopenia was frequent with portopulmonary PAH (84%) as opposed to idiopathic PAH (iPAH; 14%) or connective tissue disease associated PAH (12%). Platelet counts were not associated with functional class symptoms, the degree of right ventricular enlargement or dysfunction or tricuspid regurgitation by echocardiography. Invasive hemodynamics of right atrial pressure, mean pulmonary artery pressure and pulmonary vascular resistance were also similar between platelet groups. Thrombocytopenia was associated with higher mortality in iPAH patients (age- and sex-adjusted 5 year mortality [HR 1.95 (1.20, 3.08) p = 0.008] but not in other etiology groups. In a multivariate model of iPAH patients (adjusted for age, sex, DLCO, PVR, creatinine and 6MW distance) thrombocytopenia was most predictive of 5-year mortality [HR 1.68 (1.32, 2.12), p < 0.0001]. CONCLUSION: Thrombocytopenia in the context of iPAH portends a poor prognosis and is a simple independent factor to consider in judging severity of disease.

Incidence and Management of Hemopericardium: Impact of Changing Trends in Invasive Cardiology.

OBJECTIVE: As invasive cardiovascular care has become increasingly complex, cardiac perforation leading to hemopericardium is a progressively prevalent complication. We sought to assess the frequency, etiology, and outcomes of hemorrhagic pericardial effusions managed through a nonsurgical echo-guided percutaneous strategy. PATIENTS AND METHODS: Over a 10-year period (January 1, 2007, to December 31, 2016), 1097 unique patients required pericardiocentesis for clinically important pericardial effusions. Of these 411 had drainage of hemorrhagic effusions (defined as a pericardial hemoglobin level >50% of serum hemoglobin or frank blood in the setting of cardiac perforation). Clinical characteristics, echocardiographic data, details of the procedure, and outcomes were determined. RESULTS: Median patient age was 67 years (interquartile range, 56-76 years), and 60% were men. The procedure was emergent in 83% and elective in 17%. The site of pericardiocentesis was determined by echo-guidance in all: 68% from the left para-apical region, 18% from the left or right parasternal areas, and 14% were subxyphoid. Half (n=215 [52%]) occurred after cardiac perforation with percutaneous interventional procedure (ablation, n=94; device lead implantation, n=65; percutaneous coronary intervention, n=22; other, n=34), whereas 30% followed cardiac or thoracic surgery. Pericardial fluid volume drained was 546±440 mL. In 94% of cases, echo-guided pericardiocentesis was the only treatment of the effusion needed, whereas definitive surgery was required in 25 (6%) cases for persistent bleeding or acute management of the underlying etiology. There was no procedural mortality. Late mortality was better for hemorrhagic effusions compared with a contemporary cohort with nonhemorrhagic effusions. CONCLUSION: Echocardiographic guidance allows rapid successful pericardiocentesis in the setting of hemopericardium related to microperforation with interventional procedures, malignancy, or pericarditis, with most not requiring surgical intervention. Surgery should remain the first-line approach for aortic dissection or myocardial rupture.

Safety and Outcome of Percutaneous Drainage of Pericardial Effusions in Patients with Cancer.

Malignancy is a common cause of pericardial effusions. The findings, immediate safety and longer-term outcomes of pericardiocentesis are less well defined. We reviewed the cases of all patients with malignancy that underwent pericardiocentesis at our institution over a 10-year period. From January 1, 2007 to December 31, 2016, 171 patients with cancer underwent echo-guided pericardiocentesis. A total of 53% were male with a mean age of 60 ± 15 years. The average volume drained was 485 (IQR 350 to 719) ml. The procedure was technically successful in 170/171 (99.4%) of patients without significant complications; there were no procedure-related deaths. A total of 20% had hemorrhagic, 48% had serosanguinous, and 31% serous pericardial effusions. The type of effusion was not associated with outcome. Cytology (measured in 164) was positive in 58% and only weakly related to outcome (median survival nine versus 18 weeks, p = 0.04). Per our institutional practice, a pericardial catheter was left in place until there were less than 50 ml of net drainage in 24 hours (average 3 ± 2 days). A total of 135 patients had metastatic carcinoma, 23 patients had lymphoma or chronic leukemia and 4 metastatic sarcoma. Patients with either lymphoma or chronic leukemia had better survival than those with carcinoma or sarcoma (median survival 102 vs 12 weeks, p < 0.0001) with a 46% vs 3% 5-year survival, p < 0.0001). Echoguided pericardiocentesis with extended pericardial catheter placement is safe and effective in cancer patients with pericardial effusions. However, overall outcomes are poor in cancer patients with pericardial effusions that required drainage, particularly in those with carcinoma or sarcoma.

Left ventricular non-compaction cardiomyopathy: Incidental diagnosis after ST-elevation myocardial infarction.

Left ventricular non-compaction cardiomyopathy is a rare congenital cardiomyopathy, which usually presents early in life but may also manifest into adulthood. We present the case of an elderly woman with left ventricular non-compaction cardiomyopathy, which was discovered incidentally following an ST-elevation myocardial infarction.

Imaging Findings of Congestive Hepatopathy.

Congestive hepatopathy (CH) refers to hepatic abnormalities that result from passive hepatic venous congestion. Prolonged exposure to elevated hepatic venous pressure may lead to liver fibrosis and cirrhosis. Liver dysfunction and corresponding clinical signs and symptoms typically manifest late in the disease process. Recognition of CH at imaging is critical because advanced liver fibrosis may develop before the condition is suspected clinically. Characteristic findings of CH on conventional images include dilatation of the inferior vena cava and hepatic veins; retrograde hepatic venous opacification during the early bolus phase of intravenous contrast material injection; and a predominantly peripheral heterogeneous pattern of hepatic enhancement due to stagnant blood flow. Extensive fibrosis can be seen in chronic or severe cases. Hyperenhancing regenerative nodules that may retain hepatobiliary contrast agents are often present. Magnetic resonance (MR) elastography can show elevated liver stiffness and may be useful in evaluation of fibrosis in CH because it can be incorporated easily into routine cardiac MR imaging. Preliminary experience with MR elastography suggests its future use in initial evaluation of patients suspected of having CH, for monitoring of disease, and for assessment after therapy. To facilitate appropriate workup and treatment, radiologists should be familiar with findings suggestive of CH at radiography, ultrasonography, computed tomography, MR imaging, and MR elastography. In addition, knowledge of underlying pathophysiology, comparative histologic abnormalities, and extrahepatic manifestations is useful to avoid diagnostic pitfalls and suggest appropriate additional diagnostic testing. (©)RSNA, 2016.

Evaluation of liver stiffness with magnetic resonance elastography in patients with constrictive pericarditis: Preliminary findings.

PURPOSE: To evaluate with magnetic resonance elastography (MRE) whether patients with constrictive pericarditis (CP) have increased hepatic stiffness. CP results in reduced pericardial compliance, ventricular interdependence, and right heart failure. Patients with untreated CP may develop liver fibrosis and ultimately cirrhosis due to chronic venous congestion. Chronic venous congestion ± fibrosis may lead to increased liver stiffness. MATERIALS AND METHODS: Prospectively, patients with suspected CP underwent 2D transthoracic echocardiography, cardiac MRI, and liver MRE. An automated method was used to draw regions of interest (ROIs) on the stiffness maps to calculate the mean liver stiffness in kilopascals (kPa). A t-test with α = 0.05 was performed between stiffness values of patients with positive and negative CP findings based on previously published echocardiography criteria. RESULTS: Nineteen patients met inclusion criteria with a mean ± standard deviation (SD) age of 51 ± 16 years. Nine patients (47%) had CP. Mean liver stiffness trended higher in patients with CP compared to those without CP (4.04 kPa vs. 2.46; P = 0.045). Liver stiffness correlated with MRI septal bounce (P = 0.04), inferior vena cava size (P = 0.003), echo abnormal septal motion (P = 0.04), and echo mitral inflow variation >25% (P = 0.02). Only MRI septal bounce predicted CP by echocardiography (P < 0.001). CONCLUSION: CP was associated with increased liver stiffness. The increased stiffness is most likely secondary to chronic hepatic venous congestion and/or fibrosis. MRE may be useful for noninvasive liver stiffness assessment in CP. J. Magn. Reson. Imaging 2016;44:81-88.

Pulmonary Hypertension in Hereditary Hemorrhagic Telangiectasia.

BACKGROUND: A subset of patients with hereditary hemorrhagic telangiectasia (HHT) develops pulmonary hypertension (PH) by mechanisms including pulmonary arterial hypertension, high flow, and elevated pulmonary arterial wedge pressure (PAWP). We aimed to describe echocardiographic and hemodynamic characteristics of patients with coexisting HHT and PH. METHODS: We conducted a single-center cohort study of patients with confirmed HHT who underwent right-sided heart catheterization (RHC) and transthoracic two-dimensional echocardiography for suspected PH between June 1, 2003 and September 1, 2013 at Mayo Clinic Rochester, Minnesota. RESULTS: Of 38 patients with confirmed HHT who underwent RHC and echocardiography, 28 (74%) had a mean pulmonary artery pressure (MPAP) ≥ 25 mm Hg. Of those 28, 12 (43%) had pulmonary arterial hypertension. Two patients had normal PAWP and pulmonary vascular resistance (PVR), with PH secondary to either an atrial septal defect or high cardiac flow. Fourteen patients (50%) had elevated PAWP (≥ 15 mm Hg), nine with evidence of high flow. RHC in all 28 patients demonstrated a MPAP of 41 ± 11 mm Hg, PAWP of 17 ± 10 mm Hg, and PVR of 4.5 ± 4.2 Wood units. Echocardiography demonstrated moderate/severe right ventricular dysfunction in nine patients (32%). The presence of PH trended toward worse survival (P = .06). CONCLUSIONS: PH in patients with HHT occurs by different mechanisms, and there is a trend toward worse survival in patients who develop PH despite the mechanism. The equal predilection toward all subtypes of PH illustrates the necessity of RHC to clarify the hemodynamics.

Severe reversible pulmonary hypertension in smoldering multiple myeloma: two cases and review of the literature.

An association between pulmonary hypertension (PH) and POEMS syndrome (characterized by polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) as well as other plasma cell dyscrasias, including multiple myeloma (MM), has been shown to exist. Recent case reports have identified a reversible form of PH that occurs outside of previously identified etiologies. We report two cases of PH in the setting of smoldering MM (SMM) that resolved with chemotherapy and stem cell transplantation. Although other features were individualized among the cases (dermatomyositis, scleromyxedema), treatment of MM and SMM resulted in a normalization of right ventricular systolic pressure and improvement in right ventricular dysfunction that was previously unresponsive to PH therapies. The magnitude and sustained nature of reversibility in these four cases could offer clues about the pathophysiology and treatment of PH.

Increase in pulmonary arterial pressure after atrial fibrillation ablation: incidence and associated findings.

PURPOSE: The stiff left atrial (LA) syndrome is defined as pulmonary hypertension (PH) secondary to reduced LA compliance and has recently been shown to be one cause of PH after atrial fibrillation (AF) ablation. We aimed to determine the incidence of an increase in pulmonary arterial (PA) pressure post-ablation and examine the clinical and echocardiographic associations. METHODS: Patients who underwent AF ablation between 1999 and 2011 were included if they had both an echocardiogram pre-ablation and 3 months post-ablation. Patients were then separated into two groups with the increased PA pressure group defined as patients with >10 mmHg increase in right ventricular systolic pressure (RVSP) post-ablation and a post-ablation RVSP >35 mmHg. RESULTS: Of the 499 patients meeting the study criteria, 41 (8.2%) had an increase in RVSP >10 mmHg and RVSP >35 mmHg post-ablation. On echocardiogram, the two groups had similar E/A and E/e' ratios pre-ablation. However, post-ablation, the increased PA pressure group had higher E/A (2.12 vs. 1.49, p < 0.01) and E/e' (14.7 vs. 11.2, p < 0.01) ratios. LA expansion index values were lower in the increased PA pressure group pre-ablation (51 vs. 92%, p < 0.01), but not significantly different post-ablation (82 vs. 88%, p = 0.44). CONCLUSIONS: Around 8% of patients develop an increase in estimated PA pressure after AF ablation. Echocardiographic parameters suggest that patients who develop increased PA pressure are developing (or unmasking) left ventricular diastolic dysfunction.

Physician attitudes toward palliative care for patients with pulmonary arterial hypertension: results of a cross-sectional survey.

Pulmonary arterial hypertension (PAH) is a chronic, symptomatic, life-threatening illness; however, it is complex, with variable expression regarding impact on quality of life (QOL). This study investigated attitudes and comfort of physicians regarding palliative care (PC) for patients with PAH and explored potential barriers to PC in PAH. An internet-based, mixed-methods survey was distributed to Pulmonary Hypertension Clinicians and Researchers, a professional organization within the Pulmonary Hypertension Association. Only responses from physicians involved in clinical care of patients with PAH were analyzed. Of 355 clinicians/researchers, 79 (22%) returned surveys, including 76 (21%) providers involved in clinical care. Responding physicians were mainly pulmonologists (67%), practiced in university/academic medical centers (89%), had been in practice a mean of 12 ± 7 years, cared for a median of 100 PAH patients per year, and reported a high level of confidence in managing PAH (87%), advanced PAH-specific pharmacologic interventions (95%), and end-of-life care (88%). Smaller proportions were comfortable managing pain (62%) and QOL issues (78%). Most physicians (91%) reported utilizing PC consultation at least once in the prior year, primarily in the setting of end-of-life/active dying (59%), hospice referral (46%), or symptomatic dyspnea/impaired QOL (40%). The most frequent reasons for not referring patients to PC included nonapproval by the patient/family (51%) and concern that PC is "giving up hope" (43%). PAH may result in symptoms that impair QOL despite optimal PAH therapy; however, PC awareness and utilization for PAH providers is low. Opportunities may exist to integrate PC into care for PAH patients.

Pericardial effusions in pulmonary arterial hypertension: characteristics, prognosis, and role of drainage.

BACKGROUND: The presence and size of a pericardial effusion in pulmonary arterial hypertension (PAH) and its association with outcome is unclear. METHODS: In this single-center cohort study of 577 patients with group 1 PAH seen between January 1, 1995, and December 31, 2005, all patients underwent transthoracic echocardiography and were followed for ≥ 5 years. Echocardiography-guided pericardiocentesis was performed as needed. RESULTS: Pericardial effusions on index echocardiography occurred in 150 patients (26%); 128 patients had small and 22 had moderate-sized or larger effusions. Most of the moderate or greater effusions occurred in patients who had connective tissue disease (82%). Mean right atrial pressure was 13.4 ± 4.4 mm Hg (no effusion), 15.1 ± 4.4 mm Hg (small effusion), and 17.0 ± 4.0 mm Hg (moderate or greater effusion) (P < .0001). Median survival for patients with moderate or greater effusion, mild effusion, or no effusion was 11.3 months, 42.3 months, and 76.5 months, respectively. Four of the 22 patients with moderate or greater pericardial effusions eventually required echocardiography-guided pericardiocentesis because of clinical and echocardiographic evidence of hemodynamic impact. When drained, the effusions were large (858 ± 469 mL) and generally serous. All pericardiocenteses were performed cautiously under echocardiographic guidance by a highly experienced echocardiologist, with low immediate morbidity and mortality. CONCLUSIONS: Pericardial effusions are relatively common but rarely of hemodynamic significance in patients with PAH. However, even modest degrees of pericardial fluid are associated with a significant increase in mortality and appear to reflect the presence of associated collagen vascular disease and high right atrial pressure.

Impaired left ventricular mechanics in pulmonary arterial hypertension: identification of a cohort at high risk.

BACKGROUND: Pulmonary arterial hypertension (PAH) is characterized by pulmonary vascular remodeling and right heart failure. The right (RV) and left ventricles (LV) do not function in isolation, sharing a common pericardial sac and interventricular septum. We sought to define the clinical and prognostic significance of ventricular interdependence in PAH and its association with LV filling patterns through speckle-tracking strain echocardiography. METHODS AND RESULTS: Echocardiography was performed in 71 adults with a new diagnosis of PAH. To analyze LV and RV function separately, we measured peak systolic longitudinal and circumferential strain of the LV and RV. Survival was assessed >2 years. Patients had dilated right-sided chambers (right atrial volume index, 44 ± 19 mL/m(2); RV end-diastolic area, 34 ± 9 cm(2)), and reduced RV function (RV fractional area change, 28 ± 12%). Speckle-tracking echocardiography revealed significant reductions in RV free wall peak systolic strain (-15 ± 3%). Despite normal LV size and normal conventional measures of LV systolic function (end-diastolic dimension, 42 ± 6 mm; ejection fraction, 65 ± 8%; cardiac index, 2.6 ± 0.8 L/min per m(2)), patients had reduced LV free wall systolic strain (-15 ± 3%). Decreased LV free wall systolic strain was associated with a delayed relaxation mitral inflow Doppler pattern, P=0.0002. During 2-year follow-up, 19 patients (27%) died. LV strain was associated with increased mortality (unadjusted hazard ratio, 2.40 per 5% decrease in LV free wall strain, 1.22-4.68), which remained significant when adjusted for age, sex, World Health Organization functional class, and PAH pathogenesis (hazard ratio, 3.11, 1.38-7.20). CONCLUSIONS: The pressure loading in PAH results in geometric alterations and functional decline of the RV, with marked reduction in RV systolic strain. Despite preservation of LV ejection fraction, LV systolic strain was also reduced and associated with early mortality, highlighting the significance of ventricular interdependence in PAH.

RETRACTED: Syncope in adults with pulmonary arterial hypertension.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). This article has been retracted at the request of the authors, because of a data entry error which is fundamental to the study findings. As background, this was a clinical study where a specific variable was tested in a large database. The process involved merging a variable (presence or absence of syncope) from one electronic source with an alternate electronic database of patients with pulmonary arterial hypertension and assessing associations and outcomes. In proceeding to design a follow-up study to this work Dr. Le, went back to the original source file to abstract new data. In doing this she identified a 'cut-and paste' error in which the column of syncope data was transferred incorrectly where syncope/no syncope variables were assigned to wrong subjects. This led to a critical error that then got carried forward and a fundamental misclassification of syncope in the final study group. This error fundamentally affects the results which now do not fully support the conclusions.

Managing impairment in patients with allergic rhinitis.

Allergic rhinitis is a common medical problem in both the adult and the pediatric population. A main complication of this disease is a reduction in the patient's quality of life. Individuals with either seasonal or perennial allergic rhinitis often are impaired, adversely affecting work and/or school performance. This impairment can result from the disease itself and the treatment thereof. Oral antihistamines are the mainstay of treatment for allergic disease. First-generation antihistamines are considered sedating and frequently are impairing even when sedation is absent. Second-generation antihistamines show some class variability regarding impairment but as a group are clearly less impairing than their first-generation predecessors. Second-generation antihistamines are the preferred medication when antihistamines are necessary.