Relation of QRS duration to response to cardiac resynchronization therapy.

Left bundle branch block (LBBB) is the most reliable electrocardiographic predictor of responsiveness to cardiac resynchronization therapy (CRT). However, not all patients with LBBB will respond to CRT. Our aim was to investigate the interaction between QRS duration, LBBB-type morphology, and the responsiveness to CRT. We retrospectively analyzed electrocardiograms of 243 patients who underwent CRT implantation according to current clinical indications. A 6-month reduction of left ventricular end-systolic volume >15% was used to identify CRT responders. The clinical end point consisted of death, hospitalization for heart failure and sustained rapid ventricular tachyarrhythmias. An LBBB morphology was present in 169 patients (70%) and 101 of these (60%) were responders to CRT. Analyzing the interaction between QRS duration and CRT responsiveness in patients with LBBB, a "U shaped" distribution resulted, with nonresponders clustered between 120 and 130 ms and above 180 ms. The receiver operating characteristic curve analysis identified 178 ms as the optimal cut-off value of QRS to predict a nonresponsiveness to CRT (area under the curve = 0.67 [95% confidence interval 0.57 to 0.76]). At multivariate analysis, only an ischemic cause and a QRS ≥178 ms were independent predictors of nonresponsiveness to CRT (area under the curve = 0.75). Patients with LBBB with QRS ≥178 ms had greater likelihood of adverse clinical events during a mean follow-up of 32 months (p = 0.049). In conclusion, in patients with LBBB undergoing CRT, a marked QRS widening (i.e., ≥178 ms) is related to worse echocardiographic responsiveness and lower event free survival rate compared with patients with an intermediate QRS widening.

[Focal acute myocarditis mimicking ST-elevation myocardial infarction: a case report and literature review]. / Miocardite acuta focale simulante un infarto miocardico con sopraslivellamento del tratto ST: descrizione di un caso clinico e revisione della letteratura.

Myocarditis is associated with a broad spectrum of clinical and electrocardiographic manifestations, ranging from completely asymptomatic courses to signs of myocardial infarction or cardiogenic shock. Endomyocardial biopsy is considered the gold standard for the diagnosis of myocarditis; however, in clinical practice, cardiovascular magnetic resonance (CMR) plays a leading role, being the most accurate noninvasive method for tissue characterization. We report the case of a 22-year-old patient hospitalized for acute precordial pain associated with ST-segment elevation in leads DI and aVL, mimicking acute myocardial infarction, in whom CMR led to the correct diagnosis of acute focal myocarditis.

Interactions between cardiovascular and cerebrovascular disease.

OPININION STATEMENT: All patients with ischemic stroke should undergo a comprehensive assessment of cardiovascular risk. Patients with carotid artery disease, symptoms of cerebral ischemia and high cardiovascular risk profiles should be considered for noninvasive testing for coronary artery disease (CAD). Routine testing for CAD before carotid endarterctomy is not recommended. Patients with coexisting coronary and carotid artery disease should be more aggressively treated for reducing their "very high" risk of cardiovascular events. In patients candidates to carotid revascularization, a preoperative coronary angiography and coronary revascularization are not recommended. Warfarin is recommended in all patients with moderate to high risk of stroke. Novel oral anticoagulants represent an attractive alternative to warfarin. However, their place in therapy in clinical practice is not yet established. Percutaneous closure of the left atrial appendage for stroke prophylaxis may be considered in selected patients with atrial fibrillation and contraindications for oral anticoagulant therapy. Warfarin is not indicated in patients with heart failure who are in sinus rhythm. Percutaneous closure of patent foramen does not seem to be superior to medical therapy for the prevention of recurrences in patients with cryptogenic stroke.

[After ACC/AHA and ESC Guidelines: Pre-operative cardiological evaluation in non-cardiac surgery: certainties, controversial areas and opportunities for a team approach]. / Dopo le Linee Guida ACC/AHA ed ESC: La valutazione cardiologica preoperatoria nella chirugia non cardiaca: le certezze, le aree controverse e le opportunità di una gestione in team.

A standardized and evidence-based approach to the cardiological management of patients undergoing noncardiac surgery has been recently defined by Task Forces of the American Heart Association (AHA), American College of Cardiology (ACC) and the European Society of Cardiology (ESC) that published their guidelines in 2007 and 2009, respectively. Both the recommendations moved from risk indices to a practical, stepwise approach of the patient, which integrates clinical risk factors and test results with the estimated stress of the planned surgical procedure. In the present paper the main topics of the guidelines are discussed, and moreover, emphasis is placed on four controversial issues such as the use of prophylactic coronary revascularization in patients with myocardial ischemia, the perioperative management of patients with congestive heart failure, the routine use of betablockers and statins, and, finally, the management of antiplatelet therapies in patients with coronary stents. In addition to promoting an improvement of immediate perioperative care, the preoperative cardiological evaluation should be a challenge for identifying subjects with enhanced risk of cardiovascular events, who should be treated and monitored during a long-term follow-up.

[Role of statins in patients with acute coronary syndromes]. / La riduzione del rischio di nuovi eventi dopo sindrome coronarica acuta: qual è il ruolo delle statine?

After 10 years of studies on statins in acute coronary syndromes what have we learned? (1) The use of statins in acute coronary syndromes reduces coronary events during follow-up; (2) an "intensive" strategy based on the use of potent high dosage statins is effective on 4 to 6 months prognosis, nevertheless side effects and drug withdrawal are frequent; (3) beyond the usual paradigm "the lower the better", the new paradigm of "long term sustainability" should be developed, adopting adequate strategies; (4) a target-oriented study on statins in acute coronary syndrome is desirable, to evaluate which LDL values should be achieved or maintained for the best prognostic benefit.

[Pulmonary arterial hypertension. Part II: Medical and surgical treatment]. / L'ipertensione arteriosa polmonare. Parte II: Terapia medica e chirurgica.

Treatment of pulmonary arterial hypertension (group 1 of clinical classification) has been recently characterized by important progresses, particularly in pharmacological therapy. Only until few years ago, patients with pulmonary arterial hypertension were treated with non-specific drugs, such as diuretics and digoxin for right heart failure and calcium-channel blockers in the minority of cases, responders to the acute vasoreactivity test. In addition, use of oral anticoagulant treatment was supported by uncontrolled studies. In the last 15 years (in particular in the last 8 years) different randomized controlled trials assessing the functional, clinical and hemodynamic efficacy of three classes of targeted drugs (prostanoids, endothelin receptor antagonists and phosphodiesterase type 5 inhibitors) with pulmonary vascular dilating and antiproliferative effects have been performed. This information has allowed the proposal of an evidence-based treatment algorithm. Treatment starts with general measures (physical activity, fertility control, respiratory tract infection, etc.) and supportive therapy (anticoagulant therapy, diuretics, oxygen, digoxin). Patients who respond to the acute vasoreactivity test (10% of idiopathic form) are treated with high doses of calcium-channel blockers, non-responders with targeted therapies either on monotherapy or combination. Usually an oral active drug is initiated and a second compound of a different class is combined in case of non-satisfactory response to the first treatment. Combination therapy should be performed only in specialized centers with large experience on use of targeted therapies and their relevant side effects. In case of failure of medical therapy, possible options are balloon atrial septostomy and/or listing for lung or heart-lung transplantation. As available treatments do not constitute a cure for pulmonary arterial hypertension, further progresses are expected in the near future.

[Pulmonary arterial hypertension. Part I: pathobiologic, pathophysiologic, clinical and diagnostic aspects]. / L'ipertensione arteriosa polmonare. Parte I: patobiologia, fisiopatologia, aspetti clinici e diagnostici.

Pulmonary hypertension is a pathophysiologic condition characterized by the increase of mean pulmonary arterial pressure > or =25 mmHg. A concomitant increase of pulmonary wedge pressure >15 mmHg may be present (post-capillary pulmonary hypertension) or not (precapillary pulmonary hypertension). The increase of pulmonary arterial pressure and of pulmonary vascular resistance and consequent elevation of the right ventricular afterload lead to right ventricular failure after variable periods of time. Pulmonary hypertension is present in multiple clinical conditions which have been classified in five groups. Pulmonary arterial hypertension (group 1) includes the familial and the idiopathic form and the forms associated with anorexigen drug use, connective tissue diseases, congenital heart diseases, HIV infection and portal hypertension. Group 2 includes all left heart diseases characterized by the increase of left atrial pressure and pulmonary wedge pressure (post-capillary pulmonary hypertension). Group 3 includes parenchymal lung diseases (chronic obstructive lung disease, lung fibrosis, ecc). Chronic thromboembolic pulmonary hypertension (group 4) is characterized by the obstruction of elastic pulmonary arteries at different levels by organized thromboembolism. Group 5 includes heterogeneous conditions such as sarcoidosis and histiocytosis X. These clinical groups are characterized by different pathobiologic and pathophysiologic mechanisms and therapeutic strategies. The exact pathobiologic mechanisms leading to pulmonary arterial hypertension (group 1) are unknown. Genetic factors (inheritable forms), predisposing factors (female gender) and exogenous factors (drugs, antibodies, viruses, congenital heart disease, etc). Endothelial dysfunction of lung microcirculation is invariably present and is characterized by the reduction of vasodilator and antiproliferative substances (prostacyclin, nitric oxide) and by the increase of vasoconstrictor and mitogenic factors (endothelin, thromboxane A2). Current approved therapies are targeted to the correction of this imbalance, which leads to the progressive increase of pulmonary vascular resistance. Different therapeutic strategies that are effective in diverse groups require an appropriate diagnostic algorithm in order to identify the precise group and specific conditions within the group. Evaluation of vasoreactivity and assessment of the severity of functional and hemodynamic changes are also required in pulmonary arterial hypertension for an appropriate therapeutic decision-making and estimate of results.

[The JUPITER study: critical review of final results]. / Lo studio JUPITER: analisi critica dei risultati.

Major clinical evidence obtained in the last 15-20 years with statins is reviewed. A tight correlation between LDL cholesterol and occurrence of major cardiovascular events has been observed. Moreover, favorable effects have been shown also in subjects with normal cholesterol blood levels and high levels of high-sensitivity C-reactive protein (hsCRP), a predictive marker of cardiovascular events. In two studies involving patients with acute coronary artery disease the prognosis was better in subjects with cholesterol levels < 70 mg/dl or hsCRP < 2 mg/I. These studies provide the background for the JUPITER trial, a double-blind randomized controlled "globalized" study with rosuvastatin 20 mg in primary prevention, including 17 802 normal cholesterolemic males and females with increased risk for hsCRP > 2 mg/I. The combined primary endpoint included myocardial infarction, stroke, arterial revascularization, hospitalization for unstable angina, or death from cardiovascular causes. Rosuvastatin reduced LDL cholesterol levels by 50% and hsCRP levels by 37%. The trial was stopped after a median follow-up period of 1.9 years, due to a significant superiority of rosuvastatin on the incidence of major cardiovascular events. Moreover, long-term adherence to randomized treatment was excellent, and safety was consistent in the two groups. Eligible patients were more than one fourth of the outpatients attending a cardiology clinic; median age of 66 is 5-6 years lower than age of patients admitted to Italian intensive cardiac care units for acute coronary disease, suggesting the usefulness of a primary prevention program with rosuvastatin in this clinical setting. Practical and healthcare planning implications deriving from this study are currently under evaluation by scientific societies and healthcare authorities.

Management of pulmonary arterial hypertension associated with congenital systemic-to-pulmonary shunts and Eisenmenger's syndrome.

A large proportion of patients with congenital heart disease (CHD), in particular those with relevant systemic-to-pulmonary shunts, will develop pulmonary arterial hypertension (PAH) if left untreated. Persistent exposure of the pulmonary vasculature to increased blood flow, as well as increased pressure, may result in pulmonary obstructive arteriopathy, which leads to increased pulmonary vascular resistance that, if it approaches or exceeds systemic resistance, will result in shunt reversal. Eisenmenger's syndrome, the most advanced form of PAH associated with CHD, is defined as CHD with an initial large systemic-to-pulmonary shunt that induces severe pulmonary vascular disease and PAH, with resultant reversal of the shunt and central cyanosis. The histopathological and pathobiological changes seen in patients with PAH associated with congenital systemic-to-pulmonary shunts, such as endothelial dysfunction of the pulmonary vasculature, are considered similar to those observed in idiopathic or other associated forms of PAH. A pathological and pathophysiological classification of CHD with systemic-to-pulmonary shunt leading to PAH has been developed that includes specific characteristics, such as the type, dimensions and direction of the shunt, extracardiac abnormalities and repair status. A clinically oriented classification has also been proposed. The prevalence of PAH associated with congenital systemic-to-pulmonary shunts in Western countries has been estimated to range between 1.6 and 12.5 cases per million adults, with 25-50% of this population affected by Eisenmenger's syndrome. Clinically, Eisenmenger's syndrome presents with multiple organ involvement, with progressive deterioration of function over time. The signs and symptoms of Eisenmenger's syndrome in the advanced stages include central cyanosis, dyspnoea, fatigue, haemoptysis, syncope and right-sided heart failure. Survival of patients with Eisenmenger's syndrome is clearly less than that of the general population, but appears to be better than that of patients with idiopathic PAH in a comparable functional class. The treatment strategy for patients with PAH associated with congenital systemic-to-pulmonary shunts and, in particular, those with Eisenmenger's syndrome is based mainly on clinical experience rather than being evidence based. General measures include recommendations for physical activity, pregnancy, infections, air travel, exposure to high altitudes and elective surgery, and that psychological assistance be provided as necessary. Phlebotomies are required only when hyperviscosity of the blood is evident, usually when the haematocrit is >65%. The use of supplemental oxygen therapy is controversial and it should be used only in patients in whom it produces a consistent increase in arterial oxygen saturation. Oral anticoagulant treatment with warfarin can be initiated in patients with pulmonary artery thrombosis and absent, or only mild, haemoptysis. The following three classes of drugs targeting the correction of abnormalities in endothelial dysfunction have been approved recently for the treatment of PAH: (i) prostanoids; (ii) endothelin receptor antagonists; and (iii) phosphodiesterase-5 inhibitors. The efficacy and safety of these compounds have been confirmed in uncontrolled studies in patients with PAH associated with corrected and uncorrected congenital systemic-to-pulmonary shunts, as well as in patients with Eisenmenger's syndrome. One randomized controlled trial reported favourable short- and long-term outcomes of treatment with the orally active dual endothelin receptor antagonist bosentan in patients with Eisenmenger's syndrome. Lung transplantation with repair of the cardiac defect or combined heart-lung transplantation are options for Eisenmenger's syndrome patients with a poor prognosis. A treatment algorithm based on the one used in the treatment of PAH patients is proposed for patients with PAH associated with corrected and uncorrected congenital systemic-to-pulmonary shunts and Eisenmenger's syndrome.