Hereditary Transthyretin Amyloidosis: How to Differentiate Carriers and Patients Using Speckle-Tracking Echocardiography.

BACKGROUND: Hereditary transthyretin amyloidosis is a rare disease caused by transthyretin (TTR) gene mutations. The aim of our study was to identify early signs of cardiac involvement in patients with a TTR gene mutation in order to differentiate carriers from patients with neurological or cardiac disease. METHODS: A case-control study was carried out on 31 subjects with the TTR mutation. Patients were divided into three groups: 23% with cardiac amyloidosis and polyneuropathy (group A), 42% with only polyneuropathy (group B) and 35% carriers (group C). Speckle-tracking echocardiography (left-ventricular global longitudinal strain-GLS, atrial stiffness) was performed in all patients. The apical/basal longitudinal strain ratio (SAB) and relative apical sparing (RAS) were assessed in all subjects. RESULTS: Analyzing groups C and B, we only found a significant difference in the SAB (p-value 0.001) and RAS (p-value 0.039). These parameters were significantly more impaired in group A compared to group B (SAB p-value 0.008; RAS p-value 0.002). Also, atrial stiffness was significantly impaired in groups A and B compared to group C. CONCLUSIONS: Our study suggests the diagnostic role of the SAB and RAS in cardiac amyloidosis. The SAB and RAS showed a gradual increase from carriers to patients with neurological and cardiac diseases. Thus, these parameters, in addition to atrial stiffness, could be used to monitor carriers. More extensive data are needed.

Contractile Reserve in Heart Failure with Preserved Ejection Fraction.

Background: Diastolic stress echocardiography (SE) is useful for confirming the diagnosis of heart failure with preserved left ventricular ejection fraction (HFpEF) when it is uncertain. The aim of this study was to assess the value of new echocardiographic parameters during diastolic SE in patients with dyspnea and suspected HFpEF. Methods: Sixty-two patients with exertional dyspnea and inconclusive rest echocardiography for a diagnosis of HFpEF were enrolled. Exercise SE was performed in all patients. Contractile reserve (LVCR) was assessed by measuring: 1. changes in the left ventricular ejection fraction (LVEF) between rest and peak stress; 2. stress-to-rest ratio of force (force was defined as the ratio between systolic arterial pressure and left ventricular end-systolic volume); and 3. mechanical reserve, defined as the change in systolic strain (GLS) between rest and peak stress. Results: Diagnosis of HFpEF was performed by SE in 26 patients. Comparing patients with a diagnosis of HFpEF (group A) to patients with other causes of dyspnea (group B), we found a significant increase in the E/e' ratio in group A at peak stress. LV GLS was significantly reduced in group A compared to group B at rest and stress (p value 0.01 at rest; p value 0.04 at stress). At peak stress, GLS did not significantly increase in group A, while it increased in group B (p value 0.04). LVEF increased significantly in both groups. Conclusion: Patients with HFpEF have impaired LVCR when assessed using GLS. Thus, the assessment of mechanical reserve could give additional diagnostic information during stress tests in patients with HFpEF.

The prognostic role of CMR using global planimetric criteria in patients with excessive left ventricular trabeculation.

OBJECTIVES: Although cardiovascular magnetic resonance (CMR) is widely used in the assessment of left ventricular non-compaction (LVNC), there are no universally accepted diagnostic criteria and limited data regarding their prognostic value. We assessed the long-term prognostic role of the planimetric global Grothoff's criteria and of the CMR findings in predicting adverse cardiovascular events (CE). METHODS: We prospectively enrolled 78 patients (46.7 ± 18.7 years, 33.3% females) with documented positive Jenni's echocardiographic criteria for LVNC. Cine images were used to quantify function parameters and to assess for the presence of all four quantitative Grothoff's criteria (global Grothoff's criteria). Late gadolinium enhancement (LGE) images were acquired to detect the presence of replacement myocardial fibrosis. RESULTS: Petersen's CMR criterion for LVNC (NC/C ratio > 2.3 in at least one myocardial segment) was fulfilled in the whole population. Twenty-six patients fulfilled the global Grothoff's criteria (four out of four). The mean duration of the follow-up was 44.2 ± 27.4 months and 28 CE were registered: 10 ventricular tachycardias, 12 episodes of heart failure (HF), four strokes, and two cardiac deaths. In the multivariate analysis, the independent predictive factors for CE were positive global Grothoff's criteria (hazard ratio, HR = 3.33, 95% CI = 1.52-7.29; p = 0.003) and myocardial fibrosis (HR = 2.41, 95% CI = 1.08-5.36; p = 0.032). CONCLUSIONS: Positive global Grothoff's criteria and myocardial fibrosis were powerful predictors of CE in patients with a diagnosis of LVNC by CMR Petersen's criterion. Thus, we strongly suggest a step approach confirming the diagnosis of LVNC by using the global planimetric Grothoff's criteria, which showed a prognostic impact. KEY POINTS: • Positive global Grothoff's criteria and replacement myocardial fibrosis were powerful predictors of cardiovascular events in patients with a diagnosis of LVNC by CMR Petersen's criterion. • Positive global Grothoff's criteria were associated with a higher frequency of ventricular arrhythmias in patients with a diagnosis of LVNC by CMR Petersen's criterion.

Iatrogenic pulmonary artery dissection in patient with ostium secundum interatrial septum defect.

Pulmonary artery dissection is a rare and lethal condition. Few cases are reported in the literature, and most are derived from autopsies. In most cases, pulmonary artery dissection is a complication of chronic pulmonary hypertension leading to pulmonary artery aneurysm but there are other causes. We describe a case of iatrogenic pulmonary artery dissection in an elderly patient with ostium secundum defect. In particular, we describe the role of cardiac magnetic resonance in making this diagnosis and guiding future therapeutic decisions.

Cardiovascular Toxicity in Cancer Patients Treated with Tyrosine Kinase Inhibitors: A Real-World Single-Center Experience.

BACKGROUND: Target therapy can cause various cardiovascular complications. The aim of this study was to evaluate the burden of cardiovascular complications related to treatment with anti-BCR-ABL tyrosine kinase inhibitors (TKIs) and to determine if there are differences between the latest- and first-generation TKIs. METHODS: A retrospective observational study was carried out on 55 patients (39 men, 16 women; mean age ± SD: 58 ± 11 years) treated with TKIs targeting Bcr-Abl for a median period of 3.5 years. Patients were divided in two groups according to the type of treatment. Group A included patients treated with latest-generation TKI (nilotinib, dasatinib, and ponatinib), while group B included patients treated with first-generation TKI (imatinib). Cardiological evaluation included electrocardiogram, echocardiogram with global longitudinal strain of left ventricle (GLS), and carotid ultrasound scan with arterial stiffness measurement (pulse wave velocity, PWV). Adverse cardiovascular events were recorded in both groups. RESULTS: Statistical analysis showed that cardiovascular adverse events (myocardial ischemia, peripheral artery disease, deep vein thrombosis, and pleural effusion) were significantly more frequent in group A than group B (p value = 0.044). Moreover, there was a significant reduction in GLS and PWV in group A when compared to group B (respectively, p = 0.03 and p = 0.004). CONCLUSIONS: Our study confirms that imatinib is a relatively safe drug, while it reveals that the latest-generation TKIs may cause a burden of cardiovascular complications. GLS and PWV allow detection of early signs of cardiac and vascular toxicity in oncohematologic patients treated with TKI, and their use is advisable.

The planimetric Grothoff's criteria by cardiac magnetic resonance can improve the specificity of left ventricular non-compaction diagnosis in thalassemia intermedia.

We differentiated the left ventricle non-compaction (LVNC) from hypertrabeculated myocardium due to a negative remodeling in thalassemia intermedia (TI) patients applying linear and planimetric criteria and comparing the cardiovascular magnetic resonance (CMR) findings. CMR images were analyzed in 181 TI patients enrolled in the Myocardial Iron Overload in Thalassemia Network and 27 patients with proved LVNC diagnosis. The CMR diagnostic criteria applied in TI patients were: a modified linear CMR Petersen's criterion based on a more restrictive ratio of diastolic NC/C > 2.5 at segmental level and the combination of planimetric Grothoff's criteria (percentage of trabeculated LV myocardial mass LV-MM ≥ 25% of global LV mass and total LV-MMI NC ≥ 15 g/m2). Seventeen TI patients showed at least one positive NC/C segment. Compared to LVNC patients, these patients showed a lower frequency of segments with non-compaction areas (2.41 ± 1.33 vs 5.48 ± 2.26; P < 0.0001), significantly lower LV-MM NC percentage (10.99 ± 4.09 vs 28.20 ± 4.27%; P < 0.0001), LV-MMI (7.58 ± 4.86 vs 19.88 ± 5.02 g/m2; P < 0.0001) and extension of macroscopic fibrosis (0.44 ± 0.18 vs 4.65 ± 2.89; P = 0.004), and significantly higher LV ejection fraction (61.29 ± 5.17 vs 48.50 ± 17.55%; P = 0.016) and cardiac index (4.80 ± 1.49 vs 3.46 ± 1.11 l/min/m2; P = 0.002). No TI patient fulfilled the Grothoff's criteria. All TI patients with an NC/C ratio > 2.5 showed morphological and functional CMR parameters significantly different from the patients with a proved diagnosis of LVNC. Differentiation of LVNC from hypertrabeculated LV in ß-TI patients due to a negative heart remodeling depends on the selected CMR criterion. We suggest using planimetric Grothoff's criteria to improve the specificity of LVNC diagnosis.

Subclinical cardiovascular damage in patients with HCV cirrhosis before and after treatment with direct antiviral agents: a prospective study.

BACKGROUND: Cirrhosis is associated with morpho-functional cardiovascular alterations. AIMS: To detect early features of cardiovascular damage in HCV-compensated cirrhotic patients using myocardial deformation indices and carotid arterial stiffness, and, further, to evaluate their short-term behaviour after HCV eradication with direct antiviral agents (DAAs). METHODS: Thirty-nine consecutive patients with HCV cirrhosis, without previous cardiovascular events, were studied and matched for age, gender and cardiovascular risk factors to 39 controls without liver or cardiovascular disease. Patients and controls underwent a baseline echocardiographic evaluation including global longitudinal strain and ultrasound scan of carotid arteries. HCV-cirrhotics were reassessed by echocardiography and carotid ultrasound after obtaining sustained virological response (SVR) on DAAs. RESULTS: HCV-cirrhotics showed at baseline a significantly reduced global longitudinal strain compared to controls -18.1 (16.3-20.5) vs -21.2 (20.4-22.3), P < 0.001. They also had a significantly higher pulse wave velocity 8.6 (7.7-9.1) m/s vs 6.6 (6.0-7.1) m/s, P = 0.0001, and ß-stiffness index 12.4 (11.1-13.5) vs 8.6 (8.0-9.2) P = 0.0001. At multiple regression analysis, diabetes and HCV cirrhosis were independent predictors of global longitudinal strain. All HCV-cirrhotic patients had SVR on DAAs. Follow-up available in 32 of 39 (82%) at 9 (8-10) months showed a significant improvement of tricuspid annular plane systolic excursion (P = 0.01) and lateral E' velocity compared to baseline (P = 0.001). CONCLUSIONS: HCV-cirrhotics show a significant rate of subclinical cardiac and vascular abnormalities. At a time when their survival is less linked to progression of liver disease, due to viral eradication on DAAs, cardiovascular morbidity and mortality may take a significant role.

Non-compact myocardium assessment by cardiac magnetic resonance: dependence on image analysis method.

To compare image analysis methods for the assessment of left ventricle non-compaction from cardiac magnetic resonance (CMR) imaging. CMR images were analyzed in 20 patients and 10 normal subjects. A reference model of the MR signal was introduced and validated based on image data. Non-compact (NC) myocardium size and distribution were assessed by tracing a single, continuous contour delimiting trabeculated region (Jacquier) or by one-by-one selection of trabeculae (Grothoff). The global non-compact/compact (NC/C) ratio, the NC mass, and the segmental NC/C ratio were assessed. Results were compared with the reference model. A significant difference between Grothoff and Jacquier approaches in the estimation of NC/C ratio (32.08 ± 6.63 vs. 19.81 ± 5.72, p < 0.0001) and NC mass (26.59 ± 8.36 vs. 14.15 ± 5.73 g/m2, p < 0.0001) was found. The Grothoff approach better matches the expected signal distribution. Inter-observer reproducibility of both Grothoff and Jacquier methods was adequate (9.71 and 8.22%, respectively) with no significant difference between observers. Jacquier and Grothoff approaches are not interchangeable so that specific diagnostic thresholds should be used for different image analysis methods. Grothoff method seems to better capture the true extension of trabeculated tissue.

[Cardiovascular risk profile of patients with psoriasis]. / Profilo di rischio cardiovascolare nei pazienti con psoriasi.

The aim of this study was to assess the cardiovascular risk profile of patients with psoriasis compared to patients without psoriasis. A case-control assay was performed using 143 cases (psoriasis patients) and 104 controls (patients without psoriasis). We assessed the presence of hypertension, lipid profile (HDL, triglycerides), diabetes, and body mass index in both cases and controls. Psoriasis patients showed an unfavorable cardiovascular risk profile and a higher risk of cardiovascular events and metabolic syndrome than patients without psoriasis.

Risk factors for contrast induced nephropathy: a study among Italian patients.

This study aimed to make a profile of patients at highest risk of developing contrast induced nephropathy (CIN) in order to take appropriate prevention measures. 591 patients undergoing coronary procedures were divided into two groups: patients with (CIN-group) and without (no-CIN) an increase in creatinine level equal or more than 25% from baseline values within 24-48 h after the coronary procedure. All patients underwent an accurate anamnesis, objective exam, hematochemical measurements, and diagnostic exams. The results of this study while confirming that, average age (p = 0.01), diabetes mellitus (p < 0.0001), base line renal insufficiency (p = 0.0001), diuretic therapy (p = 0.002), higher contrast doses (p = 0.01), are associated with a higher risk of contrast-induced nephropathy, also demonstrated that both clinical (p = 0.01) and subclinical (p < 0.0001) atherosclerosis, and higher preprocedural high sensitive C-reactive protein levels (hs- CRP) (p = 0.02) are risk factors for CIN.

Impact of dual antiplatelet therapy with proton pump inhibitors on the outcome of patients with acute coronary syndrome undergoing drug-eluting stent implantation.

This study aimed to assess if proton pump inhibitors (PPIs) may reduce the effectiveness of clopidogrel, than H2 antagonist (anti-H2) in order to determine rehospitalization for acute coronary syndrome (re-ACS), target vessel revascularization (TVR) and cardiac death. This case-control study included 176 patients with ACS undergoing angioplasty (PCI) with drug-eluting stent implantation. The population was divided into two groups: PPI group (n = 121) consisting of patients receiving at discharge dual antiplatelet therapy (DAT) plus PPI and anti-H2 group (n = 55), consisting of patients receiving at discharge DAT + H2 receptor antagonist (H2RA). In a followup of 36 months the prevalence of ACS event (P = 0.014), TVR (P = 0.031) was higher in the PPI group than in the anti-H2 group; instead there was no statistically significant difference between groups for death. The variables independently associated with ACS were the diabetes, omeprazole, and esomeprazole; instead the variables independently associated with TVR were only omeprazole. Our data shows that the use of omeprazole and esomeprazole, with clopidogrel, is associated with increased risk of adverse outcomes after PCI with drug-eluting stent implantation.

Early detection of coronary artery flow and myocardial perfusion impairment in hypertensive patients evidenced by myocardial blush grade (MBG) and thrombolysis in myocardial infarction (TIMI) frame count (TFC).

OBJECTIVE: In hypertensive patients with typical chest pain but absence of coronary stenosis the coronary microcirculation may be impaired, thus, our study aimed to appraise, in these subjects, the role of the coronary microcirculation, assessed by Myocardial Blush Grade (MBG) and Thrombolysis in Myocardial Infarction (TIMI) Frame Count (TFC). METHODS: A total of 95 subjects with chest pain and uninjured coronary arteries were recruited into the study: 80 subjects were hypertensive while 15 subjects were normotensive. The hypertensive subjects were divided into two subgroups: hypertensive subjects with positive scintigraphy and hypertensive subjects with negative scintigraphy. The TFC, a quantitative method of assessing coronary artery flow, the MBG, an assessment of the level of tissue perfusion, and the Total Myocardial Blush Score (TMBS), the sum of the myocardial blush grades of each coronary territory, were evaluated on the coronary angiogram of every patient. RESULTS: The TFC was higher (p<0.05) in hypertensive subjects than in normotensive subjects. The MBG and the TMBS were lower (p<0.05) in hypertensive subjects than in normotensive subjects. The TFC was higher (p<0.05) in positive scintigraphy than in negative scintigraphy. The MBG was lower (p<0.05) in positive scintigraphy than in negative scintigraphy. The Spearman rank correlation test showed that the TFC and the MBG was inversely associated. CONCLUSION: The hypertensive subjects had impaired coronary artery flow and myocardial perfusion, documented by the TFC, MBG and myocardial perfusion scintigraphy. These methods may be universally applicable, in fact they are validated and most catheterization laboratories have access to them.

Chemotherapy-induced cardiotoxicity: role of the tissue Doppler in the early diagnosis of left ventricular dysfunction.

Cardiotoxicity is a common complication of chemotherapy. The aim of this study was to assess the cardiotoxicity of anticancer drugs using tissue Doppler imaging. A prospective study was carried out using patients with early breast cancer (72 women, median age: 57 ± 12 year) and other inclusion and exclusion criteria. Inclusion criteria were treatment with epirubicin, trastuzumab, fluorouracil, cyclophosphamide, taxotere, and taxolo; left ventricular ejection fraction (LVEF) of more than 50%; and absence of important pathologies. Exclusion criteria were presence of known heart disease, earlier exposure to mediastinal irradiation, and earlier chemotherapy. On the basis of treatment, patients were divided into five groups: A=fluorouracil-epirubicin-cyclophosphamide (FEC), B = FEC + trastuzumab, C = trastuzumab, D = FEC + taxotere, and E = FEC + taxol + trastuzumab. Cardiological evaluation including electrocardiogram and echocardiogram was carried out at baseline, 3 months, and 6 months after the start of chemotherapy in all patients. The Doppler patterns were integrated with other echo parameters (tissue Doppler). Significant changes (P < 0.05) in the echo parameters of the tissue Doppler were observed in treated patients during follow-up but not in LVEF. In conclusion, the tissue Doppler is more sensitive than standard Doppler in the study of diastolic function and LVEF in the study of systolic function. The tissue Doppler should integrate conventional echocardiography in the study of left ventricular function in patients treated with anticancer drugs. It is very important to reduce the risk of cardiovascular complications, especially heart failure, in breast cancer survivors.