Annalisa Turco

Analyses of Longitudinal and of Transverse Right Ventricular Function Provide Different Clinical Information in Patients with Pulmonary Hypertension

We tested the hypothesis that analysis of longitudinal right ventricular (RV) function and analysis of transverse RV function by echocardiography provide different clinical information in patients with pulmonary hypertension (PH). Indices of longitudinal and transverse RV function were obtained with different echocardiographic techniques in 30 patients with idiopathic pulmonary arterial hypertension, 28 patients with systolic left ventricular dysfunction and PH (sLVD PH), 27 patients with sLVD and normal pulmonary pressure (sLVD no PH) undergoing right heart catheterization and 20 healthy patients. Indices of RV transverse function were significantly worse in patients with PH than in patients without PH and did not statistically differ between patients with normal and those with reduced cardiac index; RV diameter shortening at mid-segment correlated best with mean pulmonary artery pressure (h = 0.63, p < 0.001). Indices of longitudinal function were poorly related to severity of PH, but a tricuspid annular plane systolic excursion <15 mm predicted a cardiac index <2.5 L/min/m(2) with 80% sensitivity and 93% specificity (area under curve = 0.85). In conclusion, in patients with PH, reduced transverse RV function is a reliable indicator of the presence of high pulmonary artery pressure, whereas reduced RV longitudinal function is associated with impairment of cardiac function.

Prognostic value of TAPSE after therapy optimisation in patients with pulmonary arterial hypertension is independent of the haemodynamic effects of therapy

Objective To evaluate the prognostic significance of right ventricular function assessed by echocardiography after start or escalation of targeted therapy in patients with pulmonary arterial hypertension. Methods Study design: longitudinal study. Setting: tertiary referral centre for pulmonary hypertension. Patients: 81 consecutive patients with pulmonary arterial hypertension (33 naive and 48 prevalent). Interventions: right heart catheterisation and echocardiography performed prior to starting or escalating targeted therapy and repeated in 55 patients after 4–12 months of therapy. Main outcome measure: survival after follow-up examinations. Results 11 patients died and 7 were lost to follow-up during the first year; 8 patients underwent first follow-up evaluation beyond 1 year. 55 patients were re-evaluated after therapy; during the subsequent follow-up period of 25 months, 9 patients died, 7 worsened from WHO I/II to III/IV and 15 remained in WHO III/IV despite therapy. A baseline tricuspid annular plane systolic excursion (TAPSE) ≥15 mm was associated with a lower risk of death (HR=0.32; 95% CI 0.12 to 0.83, p=0.012). Attaining a TAPSE≥15 mm after therapy was associated with a significantly lower risk of death or clinical worsening (HR=0.2; 95% CI 0.1 to 0.6, p=0.002) and a lower risk of death which approached statistical significance (HR=0.3; 95% CI 0.2 to 1.1, p=0.075). Per cent changes in TAPSE were loosely related to changes in pulmonary vascular resistances after therapy (R=0.37). Conclusions In patients with pulmonary arterial hypertension, the evaluation of right ventricular function by TAPSE after targeted therapy is useful to predict subsequent prognosis, regardless of the haemodynamic effects of therapy.

Relationship between electrocardiographic findings and Cardiac Magnetic Resonance phenotypes in patients with Hypertrophic Cardiomyopathy

Background Q waves and negative T waves are common electrocardiographic (ECG) abnormalities in patients with Hypertrophic Cardiomyopathy (HCM). Several studies correlated ECG findings with presence and extent of fibrosis and hypertrophy; however, their significance remains incompletely clarified. Our study aimed to explain the mechanism behind Q and negative T waves by comparing their positions on a 12-lead ECG with phenotypes observed at Late Gadolinium Enhancement (LGE) Cardiac Magnetic Resonance (CMR). Methods 12-lead ECG and LGE-CMR were performed in 88 consecutive patients with HCM (42 SD 16 years, 65 males). Using Delta Thickness ratio (DT ratio), and “global” and “parietal” LGE at CMR, the extent and distribution of myocardial hypertrophy and fibrosis were studied in correlation with ECG abnormalities. Results Q waves in different leads were not associated with “parietal” LGE score. Lateral Q waves correlated with an increased DT ratio Inferior Septum/Lateral wall (p = 0.01). A similar correlation between inferior Q waves and an increased DT Ratio Anterior wall/Inferior wall was of borderline statistical significance (p = 0.06). As expected, ECG signs of LV hypertrophy related to a raised Left Ventricular Mass Index (LVMI) (p < 0.0001) and mean wall thickness (p = 0.01). Depolarization disturbances, including negative T waves in lateral (p = 0.044) and anterior (p = 0.031) leads correlated with “parietal” LGE scores while QT dispersion (p = 0.0001) was associated with “global” LGE score. Conclusion In HCM patients, Q waves are generated by asymmetric hypertrophy rather than by myocardial fibrosis, while negative T waves result from local LGE distribution at CMR.

Dobutamine stress echocardiography in pulmonary arterial hypertension

BACKGROUND There is a growing interest in exploring the concept of right ventricular functional reserve in patients with pulmonary arterial hypertension. However, it is still unclear how it should be assessed. Aim of the study was to investigate the determinants of the changes in cardiac output and in pulmonary pressure during dobutamine stress echocardiography in pulmonary arterial hypertension. METHODS Low-dose dobutamine stress echocardiography was performed in 55 patients and 28 controls. Tricuspid annular plane systolic excursion, its ratio to systolic pulmonary artery pressure, right ventricular area change, degree of tricuspid regurgitation, right ventricular end-systolic pressure-area ratio, cardiac output were assessed at rest and at peak stress. RESULTS According to the stress induced increase in cardiac output, patients were classified into 2 groups: above/equal to the median of 2.8 L/min (high cardiac output) or below the median (low cardiac output). High cardiac output patients were characterized by a greater increase in heart rate (+45.1 ± 17.5 vs +21.3 ± 17.7 bpm), a greater improvement in tricuspid annular plane systolic excursion (+4.2 ± 3.3 vs +1.9 ± 2.6 mm, P = 0.005) and a decrease in tricuspid regurgitation (P = 0.010) as compared to low cardiac output patients. Changes in pulmonary pressure were not associated with changes in indicators of right ventricular function but only with changes in heart rate. CONCLUSIONS The increase in cardiac output during dobutamine is associated with an improvement in longitudinal right ventricular function, a decrease in tricuspid regurgitation and an increase in heart rate. Changes in pulmonary pressure only reflect the changes in heart rate.

Clinical Presentation and Outcome in a Contemporary Cohort of Patients with Acute Myocarditis: The Multicenter Lombardy Registry

Background: There is controversy about the outcome of patients with acute myocarditis (AM), and data are lacking on how patients admitted with suspected AM are managed. We report characteristics, in-hospital management, and long-term outcome of patients with AM based on a retrospective multicenter registry from 19 Italian hospitals. Methods: A total of 684 patients with suspected AM and recent onset of symptoms (<30 days) were screened between May 2001 and February 2017. Patients >70 years of age and those >50 years of age without coronary angiography were excluded. The final study population comprised 443 patients (median age, 34 years; 19.4% female) with AM diagnosed by either endomyocardial biopsy or increased troponin plus edema and late gadolinium enhancement at cardiac magnetic resonance. Results: At presentation, 118 patients (26.6%) had left ventricular ejection fraction <50%, sustained ventricular arrhythmias, or a low cardiac output syndrome, whereas 325 (73.4%) had no such complications. Endomyocardial biopsy was performed in 56 of 443 (12.6%), and a baseline cardiac magnetic resonance was performed in 415 of 443 (93.7%). Cardiac mortality plus heart transplantation rates at 1 and 5 years were 3.0% and 4.1%. Cardiac mortality plus heart transplantation rates were 11.3% and 14.7% in patients with complicated presentation and 0% in uncomplicated cases (log-rank P<0.0001). Major AM-related cardiac events after the acute phase (postdischarge death and heart transplantation, sustained ventricular arrhythmias treated with electric shock or ablation, symptomatic heart failure needing device implantation) occurred in 2.8% at the 5-year follow-up, with a higher incidence in patients with complicated forms (10.8% versus 0% in uncomplicated AM; log-rank P<0.0001). &bgr;-Adrenoceptor blockers were the most frequently used medications both in complicated (61.9%) and in uncomplicated forms (53.8%; P=0.18). After a median time of 196 days, 200 patients had follow-up cardiac magnetic resonance, and 8 of 55 (14.5%) with complications at presentation had left ventricular ejection fraction <50% compared with 1 of 145 (0.7%) of those with uncomplicated presentation. Conclusions: In this contemporary study, overall serious adverse events after AM were lower than previously reported. However, patients with left ventricular ejection fraction <50%, ventricular arrhythmias, or low cardiac output syndrome at presentation were at higher risk compared with uncomplicated cases that had a benign prognosis and low risk of subsequent left ventricular systolic dysfunction.

Changes in surface electrocardiogram in patients with chronic thromboembolic pulmonary hypertension undergoing pulmonary endarterectomy. Correlations with hemodynamic and echocardiographic improvements after surgery.

BACKGROUND The aim of the present study was to evaluate the changes of electrocardiographic (ECG) markers of right ventricular (RV) hypertrophy/overload in patients with chronic thromboembolic pulmonary hypertension (CTEPH) undergoing pulmonary endarterectomy (PEA). METHODS AND RESULTS We evaluated 99 CTEPH patients who underwent PEA. P wave amplitude in DII, R wave amplitude in V1 and the number of patients with negative T wave in V1-V3 decreased significantly at 1month after surgery with no further change at 1year, in parallel with the rapid improvement in right heart hemodynamics. S wave amplitude in V1, R:S wave ratio in lead V6 and prevalence of SIQIII pattern improved significantly at 1year, in parallel with the progressive reverse remodeling of the right ventricle at echocardiography. CONCLUSIONS The study shows that some of the ECG markers of RV hypertrophy/overload better reflect RV hemodynamic overload while others better reflect the pathologic remodeling of the right ventricle.

Mutazione del gene per la lamina A/C associata a ipoplasia apicale del ventricolo sinistro: un nuovo fenotipo di laminopatia?

: Isolated left ventricular (LV) apical hypoplasia is a rare anomaly characterized by a dysfunctioning, spherical left ventricle and elongated right ventricle wrapping around the deficient LV apex. The etiology is unknown; it is presumed to be a rare congenital developmental defect during partitioning of the ventricles, caused by an in-utero infection. We describe for the first time a case of isolated LV apical hypoplasia associated with lamin A/C gene mutation. Echocardiography showed a mildly dilated left ventricle with spherical configuration and impaired systolic function, and an elongated right ventricle wrapping around the deficient LV apex. Magnetic resonance imaging also identified fatty replacement of the LV apical myocardium. Late gadolinium enhancement imaging showed mid-wall fibrosis in the interventricular septum. Family screening by ECG and echocardiography failed to identify heart disease in the patients family; however, the probands father and daughter were found to carry the same mutation. This case report highlights the difficulties of a correct interpretation of genetic mutations in a single patient with cardiomyopathy. Indeed, the causative role of a mutation needs to be confirmed by co-segregation analysis. Although the etiology of LV apical hypoplasia remains unknown, the first hypothesis is an acquired process interfering with the early development of the heart, the new one is a genetic defect.

EXPRESS: MitraClip procedure as “bridge to list”, the ultimate therapeutic option for end-stage heart failure patients not eligible for heart transplantation due to severe pulmonary hypertension

Patients with end-stage heart failure (HF), pulmonary hypertension and elevated pulmonary vascular resistance (PVR) despite medical therapy are not eligible for heart transplantation (HTx). In this ‘proof of concept’ case series, we demonstrate the feasibility and efficacy of the MitraClip procedure as ‘bridge to list’ in end-stage HF patients not eligible for HTx. In fact, in the three patients reported, who were initially excluded from the HTx list because of elevated PVR, the MitraClip procedure was followed by a sustained improvement of PVR, allowing the patients’ risk to be reclassified, and they were then considered eligible for HTx.

Different forms of pulmonary hypertension in a family with clinical and genetic evidence for hereditary hemorrhagic teleangectasia type 2

Hereditary hemorrhagic telangiectasia (HTT) is an autosomal dominant disease, most frequently caused by a mutation in either ENG or ACVRL1, which can be associated with pulmonary arterial hypertension (PAH). In this report, we describe a new unpublished ACVRL1 mutation segregating in three members of the same family, showing three different types of pulmonary hypertension (PH) in the absence of BMPR2 mutations. The first patient has a form of heritable PAH (HPAH) in the absence of hepatic arteriovenous malformations (AVMs); the second one has a severe form of portopulmonary hypertension (PoPAH) associated with multiple hepatic AVMs; the third one has hepatopulmonary syndrome (HPS) with numerous hepatic arteriovenous fistulas and a form of post-capillary PH due to high cardiac output. In summary, a single mutation in the ACVRL1 gene can be associated, in the same family, with an extreme phenotypic variability regarding not only the clinical presentation of HHT but also the type of PH in the absence of BMPR2 mutations. More studies are needed to evaluate if this variability can be explained by the presence of additional variants in other genes relevant for the pathogenesis of HHT.

Right Ventricular Arrhythmogenic Dysplasia in Cardiac Arrest. An Echocardiographic Pattern Not to Forget

Right Ventricular Arrhythmogenic Dysplasia in Cardiac Arrest An Echocardiographic Pattern Not to Forget Guido Tavazzi, Gabriele Via, Annalisa Turco, and Francesco Mojoli University of Pavia, Anesthesia, Intensive Care and Pain Therapy, Pavia, Italy; Anesthesia and Intensive Care, Emergency Department, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo, Pavia, Italy; and Foundazione Policlinico San Matteo, Istituti di Ricovero e Cura a Carattere Scientifico, Cardiology Unit, Pavia, Italy