Understanding and recognition of the right ventricular function and dysfunction via a numerical study.

The role played by the right ventricular (RV) dysfunction has long been underestimated in clinical practice. Recent findings are progressively confirming that when the RV efficiency deteriorates both the right and the left circulation is (significantly) affected, but studies dedicated to a detailed description of RV hemodynamic role still lack. In response to such a gap in knowledge, this work proposes a numerical model that for the first time evaluates the effect of isolated RV dysfunction on the whole circulation. Lumped parameter modelling was applied to represent the physio-pathological hemodynamics. Different grades of impairment were simulated for three dysfunctions i.e., systolic, diastolic, and combined systolic and diastolic. Hemodynamic alterations (i.e., of blood pressure, flow, global hemodynamic parameters), arising from the dysfunctions, are calculated and analysed. Results well accord with clinical observations, showing that RV dysfunction significantly affects both the pulmonary and systemic hemodynamics. Successful verification against in vivo data proved the clinical potentiality of the model i.e., the capability of identifying the degree of RV impairment for given hemodynamic conditions. This study aims at contributing to the improvement of RV dysfunction recognition and treatment, and to the development of tools for the clinical management of pathologies involving the right heart.

Aortic stenosis severity assessment: how to match non-invasive to invasive metrics.

This article underscores the importance of the haemodynamic principles of the methods of measurement, as well as inherited limitations of each method, to adequately manage differing data between invasive and non-invasive tests.

Thrombus burden and myocardial damage during primary percutaneous coronary intervention.

Large thrombus burden (LTB) lesions in the context of primary percutaneous coronary intervention (p-PCI) have been related to unsuccessful angiographic reperfusion and unfavorable clinical outcomes. However, the hazard of LTB treatment on myocardial damage has not been evaluated. We investigated the impact of LTB on myocardial damage using contrast-enhanced cardiac magnetic resonance (CE-CMR) in the setting of p-PCI. In 327 patients, who underwent p-PCI without thrombus aspiration within 12 hours from symptom onset, we prospectively assessed the impact of LTB on infarct size and microvascular damage using CE-CMR. LTB was defined by the presence of Thrombolysis In Myocardial Infarction thrombus score ≥3 in patent infarct-related artery (IRA); or by "cut-off" occlusion pattern and/or large reference vessel diameter (≥3.5 mm) in occluded IRA. One hundred ninety-seven patients (60.2%) showed LTB and 130 (39.8%) did not. Distal embolization occurred in 18.8% patients with versus 6.9% without LTB (p = 0.003). At CE-CMR, patients with LTB had larger infarct size index (27.5 ± 11.1 vs 22.1 ± 17.5, p = 0.009) and more often transmural necrosis (70.5% vs 55.4%, p = 0.008) compared with patients without LTB. Excluding patients with distal embolization, patients with LTB still had larger necrosis. At multivariate analysis, occluded (IRA) at baseline, anterior infarction, and presence of LTB predicted transmural necrosis. In conclusion, LTB in the setting of p-PCI is related to larger myocardial damage as detected by CE-CMR, regardless of angiographic detectable distal embolization.

The left ventricle as a mechanical engine: from Leonardo da Vinci to the echocardiographic assessment of peak power output-to-left ventricular mass.

The interpretation of the heart as a mechanical engine dates back to the teachings of Leonardo da Vinci, who was the first to apply the laws of mechanics to the function of the heart. Similar to any mechanical engine, whose performance is proportional to the power generated with respect to weight, the left ventricle can be viewed as a power generator whose performance can be related to left ventricular mass. Stress echocardiography may provide valuable information on the relationship between cardiac performance and recruited left ventricular mass that may be used in distinguishing between adaptive and maladaptive left ventricular remodeling. Peak power output-to-mass, obtained during exercise or pharmacological stress echocardiography, is a measure that reflects the number of watts that are developed by 100 g of left ventricular mass under maximal stimulation. Power output-to-mass may be calculated as left ventricular power output per 100 g of left ventricular mass: 100× left ventricular power output divided by left ventricular mass (W/100 g). A simplified formula to calculate power output-to-mass is as follows: 0.222 × cardiac output (l/min) × mean blood pressure (mmHg)/left ventricular mass (g). When the integrity of myocardial structure is compromised, a mismatch becomes apparent between maximal cardiac power output and left ventricular mass; when this occurs, a reduction of the peak power output-to-mass index is observed.

Alström syndrome: cardiac magnetic resonance findings.

BACKGROUND: Alström Syndrome (ALMS) is an extremely rare multiorgan disease caused by mutations in ALMS1. Dilated cardiomyopathy (DCM) is a common finding but only one series has been investigated by Cardiac Magnetic Resonance (CMR). METHODS: Eight genetically proven ALMS patients (ages 11-41) underwent CMR performed by standard cine steady state, T1, T2 and late gadolinium enhancement (LGE) sequences. Ejection fraction (EF), Diastolic Volume (EDV) and Systolic Volume normalized for body surface area (ESV), and mass indices were determined, as well as EDV/Mass ratio, an index expressing the adequacy of cardiac mass to heart volume. Regional fibrosis was assessed by LGE; diffuse fibrosis was measured by a TI scout sequence acquired at 5, 10 and 15 min after gadolinium by comparing inversion time values (TI) at null time in ALMS and control group. RESULTS: In one patient severe DCM was present with diffuse LGE. There were seven cases without clinical DCM. In these patients, EF was at lower normal limits or slightly reduced and ESV index increased; six patients had decreased mass index and EDV/Mass ratio. Mild regional non ischemic fibrosis was detected by LGE in three cases; diffuse fibrosis was observed in all cases, as demonstrated by shorter TI values in ALMS in comparison with controls (5 min: 152 ± 12 vs 186 ± 16, p 0.0002; 10 min: 175 ± 8 vs 204 ± 18, p 0.0012; 15 min: 193 ± 9 vs 224 ± 16, p 0.0002). CONCLUSIONS: Cardiac involvement in ALMS is characterized by progressive DCM, associated with systolic dysfunction, myocardial fibrosis and reduced myocardial mass.

Time-dependent detrimental effects of distal embolization on myocardium and microvasculature during primary percutaneous coronary intervention.

OBJECTIVES: The authors sought to investigate the impact of distal embolization (DE) on myocardial damage and microvascular reperfusion, according to time-to-treatment, using contrast-enhanced cardiac magnetic resonance (CE-CMR). BACKGROUND: DE, occurring during primary percutaneous coronary intervention (p-PCI), appears to increase myocardial necrosis and to worsen microvascular perfusion, as shown by surrogate markers. However, data regarding the behavior of DE on jeopardized myocardium, and in particular on necrosis extent and distribution, are still lacking. METHODS: In 288 patients who underwent p-PCI within 6 h from symptom onset, the authors prospectively assessed the impact of DE on infarct size and microvascular damage, using CE-CMR. The impact of DE was assessed according to time-to-treatment: for group 1, <3 h; for group 2, ≥3 and ≤6 h. RESULTS: DE occurred in 41 (14.3%) patients. Baseline clinical characteristics were not different between the 2 groups. At CE-CMR, patients with DE showed larger infarct size (p = 0.038) and more often transmural necrosis compared with patients without DE (p = 0.008) when time-to-treatment was <3 h, but no impact was proven after this time (p = NS). Patients with DE showed more often microvascular obstruction, as evaluated at first-pass enhancement, than patients without DE (100% vs. 66.5%, p = 0.001) up to 6 h from symptom onset. CONCLUSIONS: These findings suggest that the detrimental impact of DE occurring during p-PCI on myocardial damage is largely influenced by ischemic time, increasing the extent of necrosis in patients presenting within the first hours after symptom onset, and having limited or no impact after this time window.

Risk stratification and prognostic assessment by myocardial perfusion-gated SPECT in patients with left bundle-branch block and low-intermediate cardiac risk.

OBJECTIVE: In high-risk patients with left bundle-branch block (LBBB), functional but not perfusion parameters yield incremental prognostic information. The aim of our study was to evaluate the prognostic value of gated single photon emission computed tomography (SPECT) in low-intermediate risk LBBB patients. METHODS: One hundred seventy-six subjects underwent stress-rest dual-day protocol 99mTc sestamibi-gated SPECT and were dichotomized in two groups: without LBBB (Group 1, n = 86) and with LBBB (Group 2, n = 90). Patients were followed for 32 ± 18 months. Cox regression multivariate analysis was used to determine which variable was the best predictor of cardiac event. Event-free survival curves were computed by Kaplan-Meier method. RESULTS: Myocardial perfusion scintigraphy was abnormal in 32 and 60 patients for Groups 1 and 2, respectively (37 vs. 67 %, p < 0.001). In Groups 1 and 2, the mean summed stress score (SSS) was 3.7 ± 5.6 versus 6.7 ± 6.4, while the mean summed difference score (SDS) was 1.6 ± 2.5 versus 2.7 ± 3.3 (both p < 0.005); therefore 34 % of patients in Group 1 and 53 % of those in Group 2 presented myocardial ischemia. All functional parameters were significantly different between the two subsets (all p < 0.005). Follow-up was completed in 161 patients (92 %); 10 events occurred in Group 1 and 20 in Group 2 (14 vs. 25 %). The event-free survival was significantly higher in patients with normal than in those with abnormal scan (85 vs. 63 %, p < 0.005); moreover, the prognosis of patients with LBBB was significantly worse. At multivariate analysis, SDS was found to be the only independent predictor of cardiac events both in all patients and in LBBB population (HR 3.08, and HR 4.99, p < 0.05). CONCLUSIONS: This is the first study to assess the prognostic value of gated SPECT in patients with LBBB and low-intermediate cardiac risk. Both perfusion and functional data obtained by gated SPECT are different between patients with and without LBBB. However, SDS is the only predictor of events. Thus, the amount of reversible ischemia at gated SPECT has a discriminative power in stratifying the cardiac risk of LBBB population.

Prognostic value of myocardial perfusion scintigraphy in elderly patients with hypertension: a 10-year follow-up analysis.

PURPOSE: The aim of the study was to assess the role of myocardial perfusion scintigraphy (MPS) in the prediction of future cardiac events in elderly hypertensive patients and to investigate if its prognostic value is maintained during a 10-year follow-up period. METHODS: A total of 229 consecutive patients ≥ 65 years old (range 65-88 years) with arterial hypertension, who were referred to our institution for stress/rest (99m)Tc-sestamibi MPS between January 2000 and November 2001, were followed up for 10-12 years. Cardiac death, myocardial infarction and a coronary revascularization procedure were considered as events. Survival curves were computed by the Kaplan-Meier method. A stepwise Cox proportional hazards analysis was used to identify predictors of events. RESULTS: Follow-up was completed in 221 (96.5 %) patients; 26 patients experienced cardiac death, 29 myocardial infarction and 51 coronary revascularization. Annual event rates for cardiac death, cardiac death/myocardial infarction and cardiac death/myocardial infarction/coronary revascularization were, respectively, 0, 0.2 and 0.4 % for patients with a normal scan and 1.5, 3.0 and 5.3 % after an abnormal MPS. Event-free survival was significantly different according to extent and severity of perfusion defects (all p < 0.01). An increase in global chi-square in predicting cardiac events occurred when MPS data were added to pre-scan information (from 47.28 to 88.87; p < 0.001). CONCLUSION: MPS provides incremental prognostic information for the prediction of cardiac events in elderly patients with hypertension. Subjects with a normal scan have an excellent 10-year outcome, and the risk of experiencing a cardiac event increases with extension and severity of stress perfusion defect.

Diagnostic and prognostic value of gated myocardial perfusion single-photon emission computed tomography in low-risk patients with left bundle-branch block.

BACKGROUND: The abnormal left ventricular activation pattern in patients with a left bundle-branch block (LBBB) frequently induces myocardial perfusion defects, decreasing the specificity of noninvasive coronary-risk stratification with stress testing. We assessed the diagnostic and prognostic impact of gated single-photon emission computed tomography (SPECT) in low-risk patients with LBBB. METHODS: A total of 114 patients underwent dual-day protocol Tc-99m sestamibi gated SPECT and were divided into two subsets: without LBBB (group 1, n = 57) and with LBBB (group 2, n = 57). Sixty-eight (60%) patients had negative coronary angiography and 46 (40%) were at a low risk for coronary artery disease. The variables incorporating the extent and severity of perfusion defects were calculated: summed stress score, summed rest score and summed difference score, end-diastolic volume (EDV), end-systolic volume (ESV), and left ventricular ejection fraction. The mean variations in EDV and ESV were computed as follows: rest volume-poststress volume. Cardiac events were classified as major and minor. RESULTS: Gated SPECT was positive in eight (14%) patients of group 1 and 33 (58%) patients of group 2 (P<0.001). The summed stress score was significantly higher in group 2 than in group 1 (4.7 ± 4.8 vs. 0.9 ± 1.8, P<0.001); similarly, EDV and ESV were significantly higher in LBBB patients (P<0.05 in both). The mean variation in EDV was -2.21 ml for group 1 and 1.32 ml for group 2 (P<0.05). After a mean follow-up period of 32 ± 19 months, cardiac events occurred in 22 (23%) patients, six of group 1 and 16 of group 2 (12 vs. 35%, P<0.01). CONCLUSION: Functional and perfusion parameters obtained by gated SPECT are different between patients with and without LBBB. In LBBB patients, the decrease in EDV between rest and poststress could be considered an early marker of diastolic dysfunction that might anticipate left ventricular ejection fraction reduction and may have an impact on prognosis.

Valve replacement for severe aortic stenosis with low transvalvular gradient and left ventricular ejection fraction exceeding 0.50.

BACKGROUND: Severe aortic stenosis with a low transvalvular gradient and preserved left ventricular ejection fraction (LVEF) is often misdiagnosed, leading to undertreatment of such patients with no clear indication for surgical intervention. This study investigated the outcome of aortic valve replacement (AVR) in patients with severe aortic stenosis and a low transvalvular gradient despite normal LVEF. METHODS: Between 1985 and 2008, we evaluated 73 patients who underwent AVR compared with 29 patients who did not. Overall, aortic valve area was 1.0 cm2 or smaller, LVEF was 0.50 or higher, and transvalvular gradient was 30 mm Hg or less. Multivariate and Cox analyses were used to compare these two groups according to AVR. RESULTS: Compared with controls, AVR patients were younger and with higher body mass index. Coronary artery bypass grafting was performed simultaneously in 38 AVR patients (52%). At follow-up (median, 42 months; interquartile range, 23 to 75 months), survival was longer in AVR patients. By Cox analysis, AVR remained a major predictor of lower mortality (hazard ratio, 0.237; 95% confidence interval, 0.119 to 0.470; p<0.0001). CONCLUSIONS: In patients with severe aortic stenosis and low transvalvular gradient despite a normal LVEF, AVR was associated with significant improvement in long-term survival and functional status and with a low operative mortality.

Incidence, predictors, and outcome of conduction disorders after transcatheter self-expandable aortic valve implantation.

The aims of the present study were to investigate the incidence and characteristics of conduction disorders (CDs) after transcatheter aortic valve implantation (TAVI), to analyze the predictors of permanent pacemaker (PPM) implantation, and to evaluate the outcomes of CDs over time. In particular, we sought to investigate whether the depth of deployment and other technical aspects of valve implantation might predict the need for PPM implantation after TAVI. TAVI has been reported to favor the onset or worsening of CDs often requiring PPM implantation. A total of 70 patients with aortic stenosis due to dystrophic calcification underwent TAVI with third-generation CoreValve Revalving System from May 2007 to April 2009. We collected electrocardiograms at baseline, during TAVI, during hospitalization and at the 1-, 3-, 6-, and 12-month follow-up visits thereafter. The clinical, anatomic, and procedural variables were tested to identify the predictors of PPM implantation. The PPM dependency at follow-up was analyzed. Six patients were excluded from the analysis because of a pre-existing PPM. Of the 64 patients, 32 (50%) had one or more atrioventricular-intraventricular CDs at baseline. TAVI induced a worsening in the CDs in 49 (77%) of the 64 patients, with 25 (39%) requiring in-hospital PPM implantation. On multivariate analysis, the independent predictors of PPM implantation were the depth of the prosthesis implantation (p = 0.039) and the pre-existing right bundle branch block (p = 0.046). A trend in the recovery of the CDs over time was recorded, although 2 patients required PPM implantation 1 month after discharge for late complete atrioventricular block. In conclusion, TAVI often induces or worsens CDs, requiring PPM in more than one third of patients, although a trend in the recovery of CDs during the midterm was recorded. The independent predictors of PPM implantation were the depth of prosthesis implantation and pre-existing right bundle branch block.

Relation of aortic valve weight to severity of aortic stenosis.

The purpose of this study was to analyze the relation of aortic valve weight to transvalvular gradient and area, with special regard to valve anatomy, size of calcific deposits, gender, and body size. Two hundred forty-two surgically excised stenotic aortic valves of patients (139 men, mean age 72 ± 9 years) who had undergone preoperative cardiac catheterization and echocardiography were weighed and examined with respect to number of cusps (tricuspid vs bicuspid), size of calcium deposits (microaggregates vs nodular macroaggregates), and presence of cholesterol clefts. The relation among valve weight, gradient, and area was studied. Transvalvular gradient was independent of gender or valve anatomy and was linearly correlated with valve weight absolutely (r = 0.33, p <0.01) or normalized by body surface area (r = 0.40, p <0.01). No correlation was evident between valve area and weight. Calcium macroaggregates were mainly present in men (51%) and in bicuspid valves (67%) and were seen to be strong determinants of valve weight (2.84 ± 1.03 g with macroaggregates vs 1.63 ± 0.56 g with microaggregates, p <0.001) but not of transvalvular gradient. Calcium microaggregates characterized tricuspid valves (62%), where transvalvular gradient was determined by valve weight (p = 0.0026). In conclusion, the heavier the valve, the less frequent were hypercholesterolemia, valve cholesterol clefts, hypertension, and diabetes mellitus.

Impact of multivessel coronary artery disease on early ischemic injury, late clinical outcome, and remodeling in patients with acute myocardial infarction treated by primary coronary angioplasty.

OBJECTIVE: The mechanism through which multivessel coronary artery disease (MVD) adversely affects the outcome of patients with ST-elevation myocardial infarction (STEMI) is poorly characterized. We assessed whether the impact of MVD on outcome of STEMI patients is because of ischemic damage after primary percutaneous coronary intervention (PPCI) or to late ischemic events. METHODS: From August 2005 to 2007, 288 STEMI patients treated by (bare metal) stent-PPCI were prospectively enrolled. The ischemic injury early after PPCI (evaluated by multiparametric approach) and the incidence of late adverse cardiovascular events were compared between the two groups. RESULTS: Compared with single vessel coronary artery disease, MVD patients (n=134) were older, with higher prevalence of diabetes, prior MI, anterior MI and higher collateral score. Myocardial perfusion as assessed by myocardial blush and SigmaST-segment resolution was similar in the two groups as well as the infarct size and microvascular obstruction as assessed by Troponin I and by the delayed enhancement of cardiac magnetic resonance. At clinical (98% complete) and echocardiogaphic (94% complete) follow-up (median 32 months) MVD patients showed a higher incidence of re-MI (6.1 vs. 1.3%), and urgent revascularization (8.3 vs. 2.7%) and worse left ventricular remodeling than single vessel disease patients. At propensity adjusted analysis MVD was an independent predictor of re-MI (odds ratio: 5.7) and ventricular remodeling (odds ratio: 2.2). CONCLUSION: The impact of MVD on clinical outcome and remodeling of STEMI patients is not because of the extent of ischemic damage observed after PPCI, but to recurrent ischemic events during follow-up.

Acceptable reperfusion delay to prefer primary angioplasty over fibrin-specific thrombolytic therapy is affected (mainly) by the patient's mortality risk: 1 h does not fit all.

AIMS: The mortality benefit of primary percutaneous coronary angioplasty (PPCI) is time-dependent. We explored the relationship between risk and PPCI delay, adjusted for the delay at presentation, which leads to equivalent 30-day mortality between PPCI and fibrin-specific thrombolytic therapy (TT). METHODS AND RESULTS: Sixteen randomized trials were analysed. The mortality rate in the TT arm was interpreted as a proxy for mortality risk. We calculated the PPCI-related delay as the difference between 'door-to-balloon minus door-to-needle' time and PPCI survival benefit as 30-day mortality after TT minus 30-day mortality after PPCI. Baseline mortality risk (P = 0.004), PPCI delay (P = 0.006), and presentation delay (P = 0.03) were correlated with 30-day survival benefit of PPCI. By the regression analysis, the following equation: Z = 0.59X - 0.033Y - 0.0003W - 1.3 (where Z is the absolute reduction in mortality of PPCI over TT, X the mortality risk, Y the PPCI-delay, and W the presentation delay), can be calculated. According to this equation, acceptable angioplasty-related delay shows a wide range based mainly on the different risk profiles. CONCLUSION: Baseline mortality risk of ST elevation myocardial infarction patients is a major determinant of the acceptable time delay to choose the most appropriate therapy. Although a longer delay lowers the survival advantage of PPCI, a longer PPCI-related delay could be acceptable in high-risk STEMI patients.

The C-reactive protein levels in left ventricular dysfunction of different etiology.

BACKGROUND: We have investigated variations in the C-reactive protein levels in groups of patients with left ventricular dysfunction of various causes. MATERIALS AND METHODS: We have studied 59 patients (ranging from 40 to 80 years, mean age of 64, SD 9) with left ventricular dysfunction caused by dilated cardiomyopathy, valvular heart disease, chronic ischemic cardiomyopathy. These patients have been compared to 30 healthy subjects and to 15 others with acute myocardial infarction. The C-reactive protein levels have been analyzed and correlated to echocardiographic index of the left ventricular function as well as to the clinical parameters. RESULTS: The levels of C-reactive protein show a statistically significant difference between healthy controls and patients with chronic left ventricular dysfunction (0.95mg/l +-0.9 vs 10.17+-13.77; p <0.0001); a statistically significant difference between patients with chronic left ventricular dysfunction and patients with acute myocardial infarction (10.17mg/l+-13.7 vs 30.78+-22.53, p<0.0001), and a statistically significant difference between the group of patients with chronic left ventricular dysfunction of both ischemic and non ischemic origin (15.39mg/l +-18.19 vs 6.83+-8.77, p = 0.0095). When all chronic patients were analyzed together, the levels of C-reactive protein correlated with the New York Heart Association class (r = 0.282, p = 0.015), age (r = 0.231, p = 0.039) and with the end diastolic volume of left ventricle (r = -0.230, p = 0.040). CONCLUSIONS: As shown by increment of C-reactive protein values, the immune system is activated in patients with the chronic left ventricular dysfunction. The patients with the chronic left ventricular dysfunction of an ishemic origin have higher levels of C-reactive protein than those of a non-ischemic origin. This difference could depend on the atherosclerotic process present presumably only in the first group.

Interleukin-6 and tumor necrosis factor-alpha as biochemical markers of heart failure: a head-to-head clinical comparison with B-type natriuretic peptide.

BACKGROUND: The reliability of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) as biochemical markers of heart failure in comparison to B-type natriuretic peptide (BNP) has not been investigated in depth. AIM: To compare the correlations between IL-6, TNF, BNP plasma concentrations and some clinical and instrumental variables and their prognostic value in heart failure patients. METHODS: In 79 patients with heart failure, the correlations between IL-6, TNF and BNP plasma concentrations and a series of 18 variables were studied. Outcome events were death from any cause and combined death and heart transplantation. RESULTS: At univariate analysis, BNP and IL-6 plasma concentrations correlated with each other (r = 0.4828; P < 0.0001), with New York Heart Association class, fluid retention, left ventricular ejection fraction, mean right atrial pressure, mean pulmonary pressure and cardiac index. All these correlations were stronger with BNP. TNF plasma concentration correlated only with New York Heart Association class and left ventricular ejection fraction.During follow-up, 1-32 months, 14 patients died and nine underwent heart transplantation. At univariate analysis, both BNP and IL-6 plasma concentrations were predictors of death and heart transplantation, but only BNP was a predictor of death; however, only creatinine plasma level was an independent predictor of prognosis. CONCLUSION: IL-6 and TNF are less reliable biochemical markers than BNP in heart failure patients.