Stefano Leuzzi

Demonstrable cardiac reinnervation after human heart transplantation by carotid baroreflex modulation of RR interval.

BACKGROUND After heart transplantation, respiration-synchronous fluctuations (0.18 to 0.35 Hz, high frequency [HF]) in RR interval may result from atrial stretch caused by changes in venous return, but slower fluctuations (0.03 to 0.15 Hz, low frequency [LF]) not due to respiration suggest reinnervation. In normal subjects, sinusoidal neck suction selectively stimulates carotid baroreceptors and causes reflex oscillations of RR interval. METHODS AND RESULTS To evaluate the presence of reinnervation, we measured the power of RR-LF and RR-HF in 26 heart transplant recipients and 16 control subjects before and during sinusoidal neck suction at 0.1 Hz and 0.20 Hz (similar to but distinct from that of controlled respiration, 0.25 Hz) and before and during administration of atropine or beta-blocker (esmolol hydrochloride) by spectral analysis. All transplant recipients showed small respiratory HF fluctuations. Nonrespiratory LF fluctuations were present in 13 of 26 transplant recipients and increased with months since transplantation (r = .53, P < .01). HF neck suction induced a 0.20-Hz component in all 16 control subjects and none of the 26 transplant subjects. LF neck suction increased RR-LF (from 0.73 +/- 0.20 to 1.30 +/- 0.26 ln ms2, P < .001), similar to but less than in control subjects (from 6.12 +/- 0.21 to 8.27 +/- 0.21 ln ms2, P < .001). Atropine reduced all fluctuations in control subjects and blocked the HF increase caused by 0.20-Hz neck suction but not the LF increase during 0.10-Hz stimulation. Neck suction-induced changes in LF fluctuations persisted after administration of atropine in transplant recipients but were attenuated by esmolol hydrochloride, suggesting sympathetic rather than vagal reinnervation. CONCLUSIONS The presence of baroreceptor-induced RR oscillations is evidence of functional, although incomplete, autonomic reinnervation.

Cardiovascular autonomic modulation in essential hypertension. Effect of tilting.

To better understand the role played by the autonomic nervous system in essential hypertension, we used autoregressive power spectrum analysis to study the noncasual oscillations in RR interval, blood pressure, and skin blood flow in 40 subjects with mild to moderate hypertension and in 25 age-matched control subjects at low frequency (index of sympathetic activity to the heart and the peripheral circulation) and high frequency, respiratory related (index of vagal tone to the heart). RR interval, respiration, noninvasive systolic blood pressure, and skin arteriolar blood flow were simultaneously and continuously recorded with subjects in the supine position and immediately after tilting. The low-frequency component was not significantly different in the two groups either at the cardiac level (control versus hypertensive subjects: 39.1 +/- 4.3 versus 39.9 +/- 3.7 normalized units [NU]) or at the vascular level (1.52 +/- 0.17 versus 1.69 +/- 0.13 ln mm Hg2). After head-up tilting, the RR interval fluctuations were less in hypertensive subjects (low-frequency components from 39.9 +/- 3.7 to 48.4 +/- 4.1 NU, P < .05; high-frequency components from 53.9 +/- 3.7 to 44 +/- 4 NU, P < .05) than in control subjects (low-frequency components from 39.1 +/- 4.3 to 64.4 +/- 4.9 NU, P < .001; high-frequency components from 56.0 +/- 4.5 to 31.2 +/- 4.6 NU, P < .001); the low-frequency components in systolic blood pressure increased similarly in hypertensive subjects (to 2.43 +/- 0.17 ln mm Hg2, P < .0001) and in control subjects (to 2.44 +/- 0.21 ln mm Hg2, P < .01), but the low-frequency components in skin blood flow increased only in control subjects (from 5.34 +/- 0.45 to 6.55 +/- 0.53 mm Hg2, P < .01), not in hypertensive subjects (from 5.55 +/- 0.34 to 5.60 +/- 0.35 ln mm Hg2). In hypertensive subjects with left ventricular hypertrophy, the low-frequency components in systolic blood pressure did not increase after tilting (from 1.75 +/- 0.33 to 2.05 +/- 0.41 ln mm Hg2). Baroreflex sensitivity, as assessed by spectrum analysis, was significantly lower in hypertensive than in control subjects (5.17 +/- 0.49 versus 13.18 +/- 2.44 ms/mm Hg, P < .001. Power spectrum analysis did not reveal an increased sympathetic activity or reactivity either at the cardiac or at the vascular level. The decreased baroreceptor sensitivity in hypertensive subjects could explain the reduced change in sympathovagal balance in the tilt position at the cardiac level. In hypertensive subjects without left ventricular hypertrophy, cardiopulmonary reflex deactivation induced by tilting and/or amplification of sympathetic nervous tone by arteriolar structural change could have preserved the sympathetic activation at the vascular level.

Good Prognosis for Pericarditis With and Without Myocardial Involvement Results From a Multicenter, Prospective Cohort Study

Background— The natural history of myopericarditis/perimyocarditis is poorly known, and recently published studies have presented contrasting data on their outcomes. The aim of the present article is to assess the prognosis of myopericarditis/perimyocarditis in a multicenter, prospective cohort study. Methods and Results— A total of 486 patients (median age, 39 years; range, 18–83 years; 300 men) with acute pericarditis or a myopericardial inflammatory syndrome (myopericarditis/perimyocarditis; 85% idiopathic, 11% connective tissue disease or inflammatory bowel disease, 5% infective) were prospectively evaluated from January 2007 to December 2011. The diagnosis of acute pericarditis was based on the presence of 2 of 4 clinical criteria (chest pain, pericardial rubs, widespread ST-segment elevation or PR depression, and new or worsening pericardial effusion). Myopericardial inflammatory involvement was suspected with atypical ECG changes for pericarditis, arrhythmias, and cardiac troponin elevation or new or worsening ventricular dysfunction on echocardiography and confirmed by cardiac magnetic resonance. After a median follow-up of 36 months, normalization of left ventricular function was achieved in >90% of patients with myopericarditis/perimyocarditis. No deaths were recorded, as well as evolution to heart failure or symptomatic left ventricular dysfunction. Recurrences (mainly as recurrent pericarditis) were the most common complication during follow-up and were recorded more frequently in patients with acute pericarditis (32%) than in those with myopericarditis (11%) or perimyocarditis (12%; P<0.001). Troponin elevation was not associated with an increase in complications. Conclusions— The outcome of myopericardial inflammatory syndromes is good. Unlike acute coronary syndromes, troponin elevation is not a negative prognostic marker in this setting.Background— The natural history of myopericarditis/perimyocarditis is poorly known, and recently published studies have presented contrasting data on their outcomes. The aim of the present article is to assess the prognosis of myopericarditis/perimyocarditis in a multicenter, prospective cohort study. Methods and Results— A total of 486 patients (median age, 39 years; range, 18–83 years; 300 men) with acute pericarditis or a myopericardial inflammatory syndrome (myopericarditis/perimyocarditis; 85% idiopathic, 11% connective tissue disease or inflammatory bowel disease, 5% infective) were prospectively evaluated from January 2007 to December 2011. The diagnosis of acute pericarditis was based on the presence of 2 of 4 clinical criteria (chest pain, pericardial rubs, widespread ST-segment elevation or PR depression, and new or worsening pericardial effusion). Myopericardial inflammatory involvement was suspected with atypical ECG changes for pericarditis, arrhythmias, and cardiac troponin elevation or new or worsening ventricular dysfunction on echocardiography and confirmed by cardiac magnetic resonance. After a median follow-up of 36 months, normalization of left ventricular function was achieved in >90% of patients with myopericarditis/perimyocarditis. No deaths were recorded, as well as evolution to heart failure or symptomatic left ventricular dysfunction. Recurrences (mainly as recurrent pericarditis) were the most common complication during follow-up and were recorded more frequently in patients with acute pericarditis (32%) than in those with myopericarditis (11%) or perimyocarditis (12%; P <0.001). Troponin elevation was not associated with an increase in complications. Conclusions— The outcome of myopericardial inflammatory syndromes is good. Unlike acute coronary syndromes, troponin elevation is not a negative prognostic marker in this setting. # Clinical Perspective {#article-title-31}

Aetiological diagnosis in acute and recurrent pericarditis: when and how.

The cause of acute and recurrent pericarditis is often a major concern for the clinicians in clinical practice. Several possible causes of pericarditis can be listed, as the pericardium may be involved in a large number of systemic disorders or may be diseased, as an isolated process. The reported diagnostic yield of extensive laboratory evaluation and pericardiocentesis is low in the absence of cardiac tamponade or suspected neoplastic, tuberculous, and purulent pericarditis. Patients with pericarditis can be safely managed on an outpatient basis without a thorough diagnostic evaluation unless a specific cause is suspected or the patient has high-risk features, or both. A targeted aetiological search should be directed to the most common cause on the basis of the clinical background, epidemiological issues or specific presentations. In developed countries the clinicians should rule out neoplastic, tuberculous, and purulent pericarditis, as well as pericarditis related to a systemic disease.

Late gadolinium enhancement on cardiac magnetic resonance and phenotypic expression in hypertrophic cardiomyopathy

BACKGROUND Cardiac magnetic resonance (CMR) imaging with late gadolinium enhancement (LGE) can identify areas of myocardial fibrosis in vivo in patients with hypertrophic cardiomyopathy (HCM). The aim of this study was to examine the association between clinical-morphological variables, risk factor for sudden death, and LGE findings in a consecutive, unselected population of HCM patients. METHODS From January 2005 to August 2009, 124 HCM patients (53 ± 17 years, 86 men) were prospectively evaluated with CMR examination, assessing left ventricular (LV) hypertrophy, function, and LGE. RESULTS In univariate analysis, patients were divided into tertiles according to the number of segments positive for LGE (first tertile, 0.3 ± 0.4; second tertile, 2.2 ± 0.4; third tertile, 5.2 ± 1.9 segments). Male gender (P = .05), maximum LV wall thickness (P = .002), nonsustained ventricular tachycardia (P = .001), ejection fraction <50% (P = .02), LV mass (P = .02), left atrium dilation (P = .04), perfusion defects (P ≤ .001), and telesystolic volume (P = .04) were all positively related with the number of segments of LGE. In multivariable analysis, male gender (P = .007), maximum LV wall thickness (P = .006), LV mass (P = .031), and perfusion alterations (P = .017) were independent predictors of LGE extent. CONCLUSIONS Our study shows an independent association, even at multivariate analysis, between the entity of LGE and maximum LV wall thickness, mass, and perfusion defects in patients with HCM. Whether the presence and the extent of LGE translates into clinical events later on awaits further long-term follow-up studies.

Response to Letter Regarding Article, “Good Prognosis for Pericarditis With and Without Myocardial Involvement: Results From a Multicenter, Prospective Cohort Study”

We thank Drs Mewton and Bresson for their interest in our article.1 The issues raised by the authors are essentially 3: the diagnosis being based on subjective criteria, the exclusion of patients with systemic inflammatory diseases, and the rationale for the definition of perimyocarditis and myopericarditis not being based on solid pathophysiological evidence. First, in clinical practice, a spectrum of myopericardial syndromes can be encountered, ranging from pure pericarditis to increasing degrees of inflammatory myocardial involvement (myopericarditis and perimyocarditis) to pure myocarditis.2,3 Diagnostic criteria for acute pericarditis are well recognized and established.3–5 Although not supported by guidelines and consensus documents, myopericarditis and perimyocarditis definitions also have been proposed on the basis of clinical criteria.3 Myopericarditis is a primarily pericardial inflammatory syndrome occurring when clinical diagnostic criteria …

Good Prognosis for Pericarditis With and Without Myocardial InvolvementClinical Perspective: Results From a Multicenter, Prospective Cohort Study

Background— The natural history of myopericarditis/perimyocarditis is poorly known, and recently published studies have presented contrasting data on their outcomes. The aim of the present article is to assess the prognosis of myopericarditis/perimyocarditis in a multicenter, prospective cohort study. Methods and Results— A total of 486 patients (median age, 39 years; range, 18–83 years; 300 men) with acute pericarditis or a myopericardial inflammatory syndrome (myopericarditis/perimyocarditis; 85% idiopathic, 11% connective tissue disease or inflammatory bowel disease, 5% infective) were prospectively evaluated from January 2007 to December 2011. The diagnosis of acute pericarditis was based on the presence of 2 of 4 clinical criteria (chest pain, pericardial rubs, widespread ST-segment elevation or PR depression, and new or worsening pericardial effusion). Myopericardial inflammatory involvement was suspected with atypical ECG changes for pericarditis, arrhythmias, and cardiac troponin elevation or new or worsening ventricular dysfunction on echocardiography and confirmed by cardiac magnetic resonance. After a median follow-up of 36 months, normalization of left ventricular function was achieved in >90% of patients with myopericarditis/perimyocarditis. No deaths were recorded, as well as evolution to heart failure or symptomatic left ventricular dysfunction. Recurrences (mainly as recurrent pericarditis) were the most common complication during follow-up and were recorded more frequently in patients with acute pericarditis (32%) than in those with myopericarditis (11%) or perimyocarditis (12%; P<0.001). Troponin elevation was not associated with an increase in complications. Conclusions— The outcome of myopericardial inflammatory syndromes is good. Unlike acute coronary syndromes, troponin elevation is not a negative prognostic marker in this setting.Background— The natural history of myopericarditis/perimyocarditis is poorly known, and recently published studies have presented contrasting data on their outcomes. The aim of the present article is to assess the prognosis of myopericarditis/perimyocarditis in a multicenter, prospective cohort study. Methods and Results— A total of 486 patients (median age, 39 years; range, 18–83 years; 300 men) with acute pericarditis or a myopericardial inflammatory syndrome (myopericarditis/perimyocarditis; 85% idiopathic, 11% connective tissue disease or inflammatory bowel disease, 5% infective) were prospectively evaluated from January 2007 to December 2011. The diagnosis of acute pericarditis was based on the presence of 2 of 4 clinical criteria (chest pain, pericardial rubs, widespread ST-segment elevation or PR depression, and new or worsening pericardial effusion). Myopericardial inflammatory involvement was suspected with atypical ECG changes for pericarditis, arrhythmias, and cardiac troponin elevation or new or worsening ventricular dysfunction on echocardiography and confirmed by cardiac magnetic resonance. After a median follow-up of 36 months, normalization of left ventricular function was achieved in >90% of patients with myopericarditis/perimyocarditis. No deaths were recorded, as well as evolution to heart failure or symptomatic left ventricular dysfunction. Recurrences (mainly as recurrent pericarditis) were the most common complication during follow-up and were recorded more frequently in patients with acute pericarditis (32%) than in those with myopericarditis (11%) or perimyocarditis (12%; P <0.001). Troponin elevation was not associated with an increase in complications. Conclusions— The outcome of myopericardial inflammatory syndromes is good. Unlike acute coronary syndromes, troponin elevation is not a negative prognostic marker in this setting. # Clinical Perspective {#article-title-31}

Good Prognosis for Pericarditis With and Without Myocardial InvolvementClinical Perspective

Background— The natural history of myopericarditis/perimyocarditis is poorly known, and recently published studies have presented contrasting data on their outcomes. The aim of the present article is to assess the prognosis of myopericarditis/perimyocarditis in a multicenter, prospective cohort study. Methods and Results— A total of 486 patients (median age, 39 years; range, 18–83 years; 300 men) with acute pericarditis or a myopericardial inflammatory syndrome (myopericarditis/perimyocarditis; 85% idiopathic, 11% connective tissue disease or inflammatory bowel disease, 5% infective) were prospectively evaluated from January 2007 to December 2011. The diagnosis of acute pericarditis was based on the presence of 2 of 4 clinical criteria (chest pain, pericardial rubs, widespread ST-segment elevation or PR depression, and new or worsening pericardial effusion). Myopericardial inflammatory involvement was suspected with atypical ECG changes for pericarditis, arrhythmias, and cardiac troponin elevation or new or worsening ventricular dysfunction on echocardiography and confirmed by cardiac magnetic resonance. After a median follow-up of 36 months, normalization of left ventricular function was achieved in >90% of patients with myopericarditis/perimyocarditis. No deaths were recorded, as well as evolution to heart failure or symptomatic left ventricular dysfunction. Recurrences (mainly as recurrent pericarditis) were the most common complication during follow-up and were recorded more frequently in patients with acute pericarditis (32%) than in those with myopericarditis (11%) or perimyocarditis (12%; P<0.001). Troponin elevation was not associated with an increase in complications. Conclusions— The outcome of myopericardial inflammatory syndromes is good. Unlike acute coronary syndromes, troponin elevation is not a negative prognostic marker in this setting.Background— The natural history of myopericarditis/perimyocarditis is poorly known, and recently published studies have presented contrasting data on their outcomes. The aim of the present article is to assess the prognosis of myopericarditis/perimyocarditis in a multicenter, prospective cohort study. Methods and Results— A total of 486 patients (median age, 39 years; range, 18–83 years; 300 men) with acute pericarditis or a myopericardial inflammatory syndrome (myopericarditis/perimyocarditis; 85% idiopathic, 11% connective tissue disease or inflammatory bowel disease, 5% infective) were prospectively evaluated from January 2007 to December 2011. The diagnosis of acute pericarditis was based on the presence of 2 of 4 clinical criteria (chest pain, pericardial rubs, widespread ST-segment elevation or PR depression, and new or worsening pericardial effusion). Myopericardial inflammatory involvement was suspected with atypical ECG changes for pericarditis, arrhythmias, and cardiac troponin elevation or new or worsening ventricular dysfunction on echocardiography and confirmed by cardiac magnetic resonance. After a median follow-up of 36 months, normalization of left ventricular function was achieved in >90% of patients with myopericarditis/perimyocarditis. No deaths were recorded, as well as evolution to heart failure or symptomatic left ventricular dysfunction. Recurrences (mainly as recurrent pericarditis) were the most common complication during follow-up and were recorded more frequently in patients with acute pericarditis (32%) than in those with myopericarditis (11%) or perimyocarditis (12%; P <0.001). Troponin elevation was not associated with an increase in complications. Conclusions— The outcome of myopericardial inflammatory syndromes is good. Unlike acute coronary syndromes, troponin elevation is not a negative prognostic marker in this setting. # Clinical Perspective {#article-title-31}

First pass perfusion MRI identifies microvascular anatomical damage in patients with hypertrophic cardiomyopathy

Introduction Sudden death (SD) and progressive left ventricular (LV) impairment are serious possible consequences occurring in patients with hypertrophic cardiomyopathy (HCM). Interstitial fibrosis and scarring are associated with progressive LV dysfunction and with markers of SD, and are usually associated with small-vessel disease and a reduction of the number of vessels related to interstitial fibrosis and scarring.