Stefano Del Pace

Cardiac resynchronization therapy : Gender related differences in left ventricular reverse remodeling

Cardiac resynchronization refers to pacing techniques that change the degree of atrial and ventricular electromechanical asynchrony in patients with major atrial and ventricular conduction disorders. Atrial and ventricular resynchronization is usually accomplished by pacing from more than one site in an electrical chamber--atrium or ventricle--and occasionally by stimulation at a single unconventional site. Resynchronization produces beneficial hemodynamic and antiarrhythmic effects by providing a more physiologic pattern of depolarization. Atrial resynchronization may prevent atrial fibrillation in selected patients with underlying bradycardia or interatrial block. Its antiarrhythmic effect in the absence of bradycardia is unclear. Ventricular resynchronization is of far greater clinical value than atrial resynchronization. Biventricular (or single-chamber left ventricular) pacing is beneficial for patients with congestive heart failure, severe left ventricular systolic dysfunction, dilated cardiomyopathy (either ischemic or idiopathic), and a major left-sided intraventricular conduction disorder, such as left bundle branch block. The change in electrical activation from resynchronization, which has no positive inotropic effect as such, is translated into mechanical improvement with a more coordinated left ventricular contraction. Several recent randomized trials and a number of observational studies have demonstrated the long-term effectiveness of ventricular resynchronization in the above group of patients. The high incidence of sudden death among these patients has encouraged ongoing clinical trials to evaluate the benefit of a system that combines biventricular pacing and cardioversion-defibrillation into a single implantable device.Aim: Gender related differences in epidemiology, treatment, and prognosis of heart failure (HF) have been reported. We examined the sex influence in patients treated with cardiac resynchronization therapy (CRT).

Tako-Tsubo-like syndrome during anaphylactic reaction

Tako‐Tsubos syndrome (apical ballooning or broken heart syndrome) is a reversible left ventricular dysfunction due to apical asynergy that occurs typically after sudden emotional stress in a subject without coronary disease. It is characterized by acute onset of chest pain or dyspnoea or both and is associated with electrocardiographic changes such as ST segment elevation and/or T wave inversion. Myocardial biomarkers may be normal or slightly elevated.

Tissue Doppler and strain imaging: a new tool for early detection of cardiac amyloidosis.

Using traditional echocardiography, the diagnosis of cardiac amyloidosis (CA) is often only possible in advanced stage when recommended therapies may have adverse effects. The aim of our study was to evaluate whether additional information can be derived from Tissue and strain Doppler imaging (TDI and SDI). Forty patients with systemic amyloidosis and 24 healthy subjects underwent traditional, tissue and strain Doppler echocardiography. Patients were classified having CA if mean wall thickness (mT), was half of the sum septum and posterior wall thickness, was ≥12 mm. The following parameters were evaluated: peak early diastolic velocity (Em) as index of ventricular relaxation, mitral E-wave to Em ratio (E/Em) as index of left ventricular (LV) filling pressure and mean LV strain peak curves (mSt) as global long-axis contraction index. In non cardiac amyloidosis (NCA), both Em and mSt were lower than in age matched controls (p < 0.01, p < 0.05, respectively) and higher than in CA (p < 0.01 and p < 0.01, respectively). Both Em and mSt were related to mT (p < 0.001). A significant (p < 0.01) nonlinear relation was observed between plasma terminal of pro B-natriuretic peptide and mT, Em, E/Em and mSt. TDI and SDI are able to detect amyloid myocardial involvement in such an early stage that cannot be evidenced by using traditional echocardiography.

Abnormal coronary reserve and left ventricular wall motion during cold pressor test in patients with previous left ventricular ballooning syndrome

AIMS To investigate whether and how cold pressor test (CPT) could affect myocardial perfusion and left ventricular (LV) function in patients with previous LV ballooning syndrome (LVBS). METHODS AND RESULTS Cold pressor test (3 min hand immersion in ice-water) was performed in 17 women with previous LVBS and in 7 age- and risk factor-matched women with chest pain and normal coronary arteries. At baseline and peak CPT, global and regional LV function, and myocardial perfusion were quantitatively assessed by real-time three-dimensional echocardiography (RT3DE) and myocardial contrast (SonoVue, Bracco) 2D echocardiography (MCE), respectively (Philips iE33 machine, X3-1 and S5-1 probes). Data were analysed off-line (QLab 6.0 software). Peripheral venous catecholamines were assayed by high performance liquid chromatography with electrochemical detection. Cold pressor test induced similar haemodynamic changes and catecholamine increase in controls and LVBS patients. Left ventricular ejection fraction decreased and transient new mid-ventricular and apical motion abnormalities developed in LVBS patients only (quantitative RT3D analysis), without corresponding perfusion defects (MCE). At peak CPT, coronary blood flow and velocity increased (quantitative MCE analysis) in control subjects only. CONCLUSION Cold pressor test induced LV wall motion abnormalities unmatched to regional coronary flow reduction in LVBS patients only. The reduced coronary reserve in response to CPT suggests microvascular dysfunction in LVBS patients.

ACE Insertion/Deletion, But Not −240A>T Polymorphism, Modulates the Severity in Heart Failure

Objective ACE gene is reported to be a candidate gene in heart failure. The insertion/deletion (I/D) polymorphism has been observed to be a predictor of mortality in this disease, but no data are available concerning the role of ACE −240A>T polymorphism. In this study, we investigated the role of ACE I/D and −240A>T polymorphisms in influencing both severity and clinical outcomes in patients with heart failure, according to New York Heart Association (NYHA) class. Patients We studied 323 patients with heart failure (258 men/65 women; age, 70.8 ± 11.5 years) followed-up for 11.9 ± 6.6 months. Results The ACE D and −240T allele frequency significantly increased according to the NYHA functional class (P = 0.0002 and P < 0.0001, respectively). No significant difference in ACE polymorphism genotype distribution and allele frequency according to N-terminal pro-brain natriuretic peptide tertiles was observed. At multinomial regression analysis, ACE D but not −240T allele has been evidenced to be a significant and independent predictor of severity for both NYHA III and IV classes (P = 0.01 and P = 0.004, respectively). The ACE D allele prevalence was higher, even if not significantly in both death and rehospitalization groups in comparison with survivors and nonrehospitalized (P = 0.6 and P = 0.9, respectively). No difference in −240T allele frequency has been observed for the ACE −240A>T polymorphism, in relation to both death and rehospitalization (P = 0.1 and P = 0.6, respectively). Conclusions This study suggests that ACE I/D polymorphism might represent a predisposing factor to severe heart failure, independently of well-known prognostic markers.

Abnormal response to mental stress in patients with Takotsubo cardiomyopathy detected by gated single photon emission computed tomography

PurposePersistent abnormalities are usually not detected in patients with Takotsubo cardiomyopathy (TTC). Since sympathetically mediated myocardial damage has been proposed as a causative mechanism of TTC, we explored whether mental stress could evoke abnormalities in these patients.MethodsOne month after an acute event, 22 patients fulfilling all TTC diagnostic criteria and 11 controls underwent resting and mental stress gated single photon emission computed tomography (SPECT). Perfusion, wall motion, transient ischaemic dilation (TID) and left ventricular (LV) ejection fraction (EF) were evaluated.ResultsNone of the controls showed stress-induced abnormalities. Mental stress evoked regional changes (perfusion defects and/or wall motion abnormality) in 16 TTC subjects and global abnormalities (LVEF fall >5% and/or TID >1.10) in 13; 3 had a completely negative response. TID, delta LVEF and delta wall motion score were significantly different in TTC vs control patients: 1.08 ± 0.20 vs 0.95 ± 0.11 (p < 0.05), −1.7 ± 6% vs 4 ± 5% (p < 0.02) and 2.5 (0, 4.25) vs 0 (0, 0) (p < 0.002), respectively.ConclusionMental stress may evoke regional and/or global abnormalities in most TTC patients. The abnormal response to mental stress supports the role of sympathetic stimulation in TTC. Mental stress could thus be helpful for TTC evaluation.

Age as a Prognostic Factor in Patients with Acute Coronary Syndrome undergoing Urgent/Emergency Cardiac Surgery

BACKGROUND Patients presenting with acute coronary syndrome (ACS) who require urgent/emergency coronary artery bypass grafting (CABG) are increasing, as is the complexity of their clinical characteristics, one of which is advanced age. We evaluated the prognostic role of age in patients undergoing urgent/emergency cardiac surgery for ACS. METHODS From January to December 2013, 452 consecutive patients underwent CABG at our institution. Among these, 213 presented with ACS, were enrolled in the study and divided into tertiles of age: First: 40-65 years old (n=73), Second: 66-74 (n=70), Third: 75-89 (n=70). Patients were followed post-operatively for 30 days. RESULTS No differences between tertiles were found for baseline clinical and angiographic characteristics. Off-pump interventions were 67.6%. Older patients more frequently required an associate intervention to CABG for a mechanical complication of ACS. Overall 30-day all-cause mortality was 4.7% (n=10); 0.6% (n=1) in patients undergoing isolated CABG (n=168, 78.9%). The STEMI diagnosis was an independent risk factor for 30-day mortality, and age was not. CONCLUSIONS The 30-day mortality rate of older ACS patients who undergo urgent/emergency CABG is comparable to that of younger ones. Pre-operative risk assessment should rely on evaluation of the clinical complexity of each patient independent of their chronological age, to customise the therapeutic strategy.

Impact of renal function impairment assessed by CKDEPI estimated glomerular filtration rate on early and late outcomes after coronary artery bypass grafting

BACKGROUND We explore the association between short- and long- term adverse outcomes following coronary artery bypass grafting (CABG) and the degree of preoperative renal dysfunction classified on glomerular fraction estimated with Chronic Kidney Disease-Epidemiology Collaboration equation (eGFRCKD-EPI). We also try to identify cut-off values of eGFRCKD-EPI able to predict post-CABG unfavorable events and assess whether a reclassification with new thresholds is necessary. METHODS One-thousand-one-hundred-eighty-six consecutive patients undergoing CABG between 2005 and 2014 were categorized in 4 groups according to the eGFRCKD-EPI: Group 1 (≥60ml/min/1.73m2; n=1199), Group 2 (45-59ml/min/1.73m2; n=358), Group 3 (30-44ml/min/1.73m2; n=171) and Group 4 (≤29ml/min/1.73m2; n=126). Median follow-up was 66months [IQR 46-84]. RESULTS eGFRCKD-EPI ≤30ml/min/1.73m2, ≤41ml/min/1.73m2, ≤27ml/min/1.73m2 and ≤29ml/min/1.73m2 were strong predictors of early mortality (OR 5.88 [95% CI 2.59-11.25]), stroke (2.59 [1.43-3.71]), prolonged length of stay (3.49 [1.24-5.92]) and postoperative dialysis (3.68 [1.34-4.91]), respectively. In addition, eGFRCKD-EPI ≤26ml/min/1.73m2, ≤25ml/min/1.73m2, ≤35ml/min/1.73m2 and ≤29ml/min/1.73m2 predicted all-cause death (hazard ratio 2.74 [95% CI 2.10-3.92] cardiovascular death (sub-hazard ratio 2.11 [95% CI 1.42-3.90]), myocardial infarction (2.01 [1.32-3.70]) and heart failure (2.24 [1.41-3.93]), respectively. Analyses corrected by age and left ventricular ejection fraction confirmed these findings. CONCLUSIONS In our experience, the use of the eGFRCKD-EPI equation led to categorization with a significantly lower number of patients at risk for post-CABG complications. This might have important clinical repercussions on allocation of healthcare resources and more targeted prevention and management of CABG complications.

Anomalous origin of circumflex arteries evaluated with MDCT

To date, coronary angiography (CA) is the gold standard technique for the evaluation of coronary vessels (CVs). However, CA provides only a two-dimensional view of the CVs and sometimes fails to clearly visualise the relationship between CVs and surrounding structures. This issue becomes critical when anomalous CVs must be visualised. Moreover, it is not always easy to selectively engage the anomalous CV which may lead to the erroneous assumption that the CV is occluded. Congenital coronary artery anomalies are rare and occur in 0.17% of the autopsy cases. The incidence of anomalous origin of the CVs is higher in the population of patients referred for CA (0.6–1.3%) [1]. Although anomalous CVs lack clinical significance, in the majority of the patients, there are some ‘‘malignant’’ anomalies that may cause non-fatal or fatal acute myocardial infarction or sudden death especially in young athletes without atherosclerotic coronary artery disease (CAD). In older patients, both CAD and CV anomalies may be present and in these cases it is difficult to clarify the exact mechanism of myocardial ischaemia. In the last few years, several studies showed the usefulness of non-invasive modalities for the detection of CV anomalies such as magnetic resonance imaging, electron beam computed tomography (EBCT) and especially multidetector computed tomography (MDCT). Although the clinical role of MDCT is under discussion, several studies have been published where MDCT with retrospective ECG-gating was used as a non-invasive tool to visualise coronary anatomy. In clinical practice, MDCT is being used for the detection of CV lesions in symptomatic patients with low–intermediate pre-test probability to have CAD, to follow-up CAD patients treated with bypass surgery or percutaneous angioplasty [2]. This is possible because MDCT has an excellent spatial resolution which allows a good assessment of the atherosclerotic plaque. In the recent scientific statement of the American Heart Association, MDCT was pointed as a class IIa technique (level of evidence C) for the visualisation of CV anomalies [3]. In the literature, there are several interesting papers where MDCT was successfully used to visualise anomalous CVs [4, 5]. In this paper, we describe the anomalous origin and course of two circumflex arteries.

A 72-year-old man with intermittent fever, anemia and a history of coronary and peripheral artery disease

Dr. Del Pace: A 72-year-old man with history of coronary and peripheral artery disease was admitted to this hospital with fever, fatigue and loss of weight. He had hypertension, type 2 diabetes mellitus and hyperlipidemia. He suffered from an ischemic cardiomyopathy with a low ejection fraction (33%). Fifty years prior he had undergone subtotal gastroresection for peptic ulcer. Seventeen years prior to this current admission (PTA), he had an aortobifemoral bypass grafting for symptomatic peripheral artery disease, and 8 years prior he had a myocardial infarction. Three vessel coronary disease was detected and coronary-artery bypass grafting had been carried out. One year PTA, he experienced an episode of sustained ventricular tachycardia, treated with stenting of the anterior descending coronary artery, followed by an internal cardiac defibrillator (ICD) implantation. Ten months PTA, he had a massive enteric bleeding complicated by hemorrhagic shock. A colonoscopy revealed ulcerated cecal angiodysplasia that was treated with an application of metallic clips. During the following months, he was admitted several times for sideropenic anemia without evidence of acute gastrointestinal bleeding, and iron therapy was administrated. Two colonoscopies were performed but no source of active bleeding was detected. Two months PTA, he developed a low-grade fever resistent to a 2-week course of antibiotic therapy with levofloxacin. Laboratory tests showed a normocytic anemia (8.1 g/dL) with normal levels of B12 and folic acid, with low levels of sideremia (13 lg/dL), and a normal haptoglobin. An esophagogastroduodenoscopy was normal. Neoplastic markers (NSE, CA 125, CA 15-3, CA 72-4, CA 19-9, CYFRA 21-1, CEA, alfa-FP) were all in the normal range. Antinuclear antibody, ANCA, rheumatoid factor were negative as well as immunofixation in serum and urine. A computed tomography (CT scan) of the abdomen with contrast material confirmed ceacum angiodysplasia, but did not reveal active enteral bleeding. Transesophageal echocardiography was performed, and a vegetation on the ICD catheter was found. One blood culture was positive for Streptococcus intermedius. Treatment with amoxicillin was started, and during the hospital stay, the fever disappeared. Removal of the pacemaker was suggested, but the patient refused it. After discharge, he completed a 4-week cycle of antibiotic therapy, but after 1 week of withdrawal, fever developed again with malaise, fatigue and weight loss. He was readmitted to this hospital. On examination, the patient appeared in mild distress. He had low-grade fever (37.5 C). The Blood pressure was 100/50 mmHg, pulse rate 70 beats/min and oxygen saturation 98% while he was breathing ambient air. A grade 2/6 S. Del Pace A. Savino (&) G. F. Gensini Department of Heart and Vessels, Careggi Hospital, University of Florence, Viale Morgagni 85, 50139 Florence, Italy e-mail: savino.andrea@gmail.com