RESUMO
BACKGROUND: Current echocardiographic scoring systems for percutaneous mitral valvuloplasty (PMV) have limitations. This study examined new, more quantitative methods for assessing valvular involvement and the combination of parameters that best predicts immediate and long-term outcome after PMV. METHODS AND RESULTS: Two cohorts (derivation n=204 and validation n=121) of patients with symptomatic mitral stenosis undergoing PMV were studied. Mitral valve morphology was assessed by using both the conventional Wilkins qualitative parameters and novel quantitative parameters, including the ratio between the commissural areas and the maximal excursion of the leaflets from the annulus in diastole. Independent predictors of outcome were assigned a points value proportional to their regression coefficients: mitral valve area ≤1 cm(2) (2), maximum leaflets displacement ≤12 mm (3), commissural area ratio ≥1.25 (3), and subvalvular involvement (3). Three risk groups were defined: low (score of 0-3), intermediate (score of 5), and high (score of 6-11) with observed suboptimal PMV results of 16.9%, 56.3%, and 73.8%, respectively. The use of the same scoring system in the validation cohort yielded suboptimal PMV results of 11.8%, 72.7%, and 87.5% in the low-, intermediate-, and high-risk groups, respectively. The model improved risk classification in comparison with the Wilkins score (net reclassification improvement 45.2%; P<0.0001). Long-term outcome was predicted by age and postprocedural variables, including mitral regurgitation, mean gradient, and pulmonary pressure. CONCLUSIONS: A scoring system incorporating new quantitative echocardiographic parameters more accurately predicts outcome following PMV than existing models. Long-term post-PMV event-free survival was predicted by age, degree of mitral regurgitation, and postprocedural hemodynamic data.
Assuntos
Valvuloplastia com Balão , Ecocardiografia Doppler/métodos , Estenose da Valva Mitral/diagnóstico por imagem , Estenose da Valva Mitral/cirurgia , Valva Mitral/diagnóstico por imagem , Valva Mitral/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Ecocardiografia Doppler/normas , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Estenose da Valva Mitral/epidemiologia , Análise Multivariada , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Fatores de Risco , Adulto JovemRESUMO
BACKGROUND: Ischemic mitral regurgitation (MR) is a frequent complication of myocardial infarction associated with left ventricular (LV) dilatation and dysfunction, which doubles mortality. At the molecular level, moderate ischemic MR is characterized by a biphasic response, with initial compensatory rise in prohypertrophic and antiapoptotic signals, followed by their exhaustion. We have shown that early MR repair 30 days after myocardial infarction is associated with LV reverse remodeling. It is not known whether MR repair performed after the exhaustion of compensatory mechanisms is also beneficial. We hypothesized that late repair will not result in LV reverse remodeling. METHODS AND RESULTS: Twelve sheep underwent distal left anterior descending coronary artery ligation to create apical myocardial infarction and implantation of an LV-to-left atrium shunt to create standardized moderate volume overload. At 90 days, animals were randomized to shunt closure (late repair) versus sham (no repair). LV remodeling was assessed by 3-dimensional echocardiography, dP/dt, preload-recruitable stroke work, and myocardial biopsies. At 90 days, animals had moderate volume overload, LV dilatation, and reduced ejection fraction (all P<0.01 versus baseline, P=NS between groups). Shunt closure at 90 days corrected the volume overload (regurgitant fraction 6 ± 5% versus 27 ± 16% for late repair versus sham, P<0.01) but was not associated with changes in LV volumes (end-diastolic volume 106 ± 15 versus 110 ± 22 mL; end-systolic volume 35 ± 6 versus 36 ± 6 mL) or increases in preload-recruitable stroke work (41 ± 7 versus 39 ± 13 mL mm Hg) or dP/dt (803 ± 210 versus 732 ± 194 mm Hg/s) at 135 days (all P=NS). Activated Akt, central in the hypertrophic process, and signal transducer and activator of transcription 3 (STAT3), a critical node in the hypertrophic stimulus by cytokines, were equally depressed in both groups. CONCLUSIONS: Late correction of moderate volume overload after myocardial infarction did not improve LV volume or contractility. Upregulation of prohypertrophic intracellular pathways was not observed. This contrasts with previously reported study in which early repair (30 days) reversed LV remodeling. This suggests a window of opportunity to repair ischemic MR after which no beneficial effect on LV is observed, despite successful repair.
Assuntos
Insuficiência da Valva Mitral/cirurgia , Isquemia Miocárdica/cirurgia , Remodelação Ventricular/fisiologia , Animais , Insuficiência da Valva Mitral/fisiopatologia , Isquemia Miocárdica/fisiopatologia , Ovinos , Método Simples-Cego , Fatores de TempoRESUMO
BACKGROUND: Undersized ring annuloplasty for ischemic mitral regurgitation (MR) is associated with variable results and >30% MR recurrence. We tested whether subvalvular repair by severing second-order mitral chordae can improve annuloplasty by reducing papillary muscle tethering. METHODS AND RESULTS: Posterolateral myocardial infarction known to produce chronic remodeling and MR was created in 28 sheep. At 3 months, sheep were randomized to sham surgery versus isolated undersized annuloplasty versus isolated bileaflet chordal cutting versus the combined therapy (n=7 each). At baseline, chronic myocardial infarction (3 months), and euthanasia (6.6 months), we measured left ventricular (LV) volumes and ejection fraction, wall motion score index, MR regurgitation fraction and vena contracta, mitral annulus area, and posterior leaflet restriction angle (posterior leaflet to mitral annulus area) by 2-dimensional and 3-dimensional echocardiography. All groups were comparable at baseline and chronic myocardial infarction, with mild to moderate MR (MR vena contracta, 4.6±0.1 mm; MR regurgitation fraction, 24.2±2.9%) and mitral annulus dilatation (P<0.01). At euthanasia, MR progressed to moderate to severe in controls but decreased to trace with ring plus chordal cutting versus trace to mild with chordal cutting alone versus mild to moderate with ring alone (MR vena contracta, 5.9±1.1 mm in controls, 0.5±0.08 with both, 1.0±0.3 with chordal cutting alone, 2.0±0.4 with ring alone; P<0.01). In addition, LV end-systolic volume increased by 108% in controls versus 28% with ring plus chordal cutting, less than with each intervention alone (P<0.01). In multivariate analysis, LV end-systolic volume and mitral annulus area most strongly predicted MR (r(2)=0.82, P<0.01). CONCLUSIONS: Comprehensive annular and subvalvular repair improves long-term reduction of both chronic ischemic MR and LV remodeling without decreasing global or segmental LV function at follow-up.
Assuntos
Anuloplastia da Valva Mitral/métodos , Insuficiência da Valva Mitral/fisiopatologia , Insuficiência da Valva Mitral/cirurgia , Remodelação Ventricular/fisiologia , Animais , Seguimentos , Valva Mitral/diagnóstico por imagem , Valva Mitral/cirurgia , Insuficiência da Valva Mitral/diagnóstico por imagem , Distribuição Aleatória , Ovinos , Fatores de Tempo , UltrassonografiaRESUMO
BACKGROUND: Mitral regurgitation (MR) generally accompanies inferobasal myocardial infarction (MI), with leaflet tethering by displaced papillary muscles. Mitral regurgitation is also reported with anteroapical MI without global dilatation or inferior wall motion abnormalities. We hypothesized that anteroapical MI extending to the inferior apex displaces the papillary muscles, tethering the mitral leaflets to cause MR. METHODS AND RESULTS: In the retrospective part of the study, consecutive anteroapical MI patients were studied. Moderate-severe MR occurred in 9% of 234 patients with only anteroapical MI versus 17% of 242 with inferoapical extension (P<0.001). Ejection fraction was only mildly different (41 ± 4% versus 46 ± 5%; P<0.01). In the human mechanistic portion of the study, 60 anteroapical MI patients (20 with only 2 apical segments involved and 40 with involvement of all 4 apical segments; 20 with MR and 20 without MR) were compared with 20 normal controls. Those with MR (≥ moderate) had higher systolic papillary muscle-to-annulus tethering length (P < 0.01). Mitral regurgitation grade correlated most strongly with tethering length (r = 0.70) and its diminished systolic shortening (r = -0.65). In the animal study, 9 sheep with left anterior descending coronary artery ligation were analyzed. Four sheep that developed MR had inferoapical MI extension with tethering length increasing over 1.5 months (2.1 ± 0.4 to 2.9 ± 0.4 cm, P < 0.001) versus no significant increase in 5 sheep without MR (2.0 ± 0.4 to 2.1 ± 0.3 cm, P not statistically significant). In MR sheep, the normal decrease in tethering length from diastole to systole was eliminated (P < 0.01). CONCLUSIONS: Anteroapical MI with inferoapical extension can mechanically displace papillary muscles, causing MR despite the absence of basal and midinferior wall motion abnormalities. This suggests the possibility of repositioning treatments for this condition.
Assuntos
Insuficiência da Valva Mitral/etiologia , Insuficiência da Valva Mitral/fisiopatologia , Infarto do Miocárdio/complicações , Músculos Papilares/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Animais , Estudos de Casos e Controles , Vasos Coronários/cirurgia , Ecocardiografia Doppler , Feminino , Humanos , Ligadura/efeitos adversos , Masculino , Pessoa de Meia-Idade , Valva Mitral/diagnóstico por imagem , Valva Mitral/fisiopatologia , Insuficiência da Valva Mitral/diagnóstico por imagem , Modelos Animais , Infarto do Miocárdio/diagnóstico por imagem , Infarto do Miocárdio/etiologia , Músculos Papilares/diagnóstico por imagem , Estudos Retrospectivos , Ovinos , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/fisiopatologiaRESUMO
BACKGROUND AND AIM OF THE STUDY: Ischemic mitral regurgitation (IMR) often persists, despite annular ring reduction. It has been hypothesized that persistent IMR following ring annuloplasty was related to a continued tethering of the mitral leaflets, as defined by the distance by which the papillary muscles (PMs) were displaced outside the mitral annular ring. METHODS: Seven sheep (four acute, three chronic) with persistent mitral regurgitation (MR) following ring annuloplasty for IMR were studied using three-dimensional (3D) echocardiography to examine the mitral valve geometry. The three stages examined were: Stage 1, baseline; Stage 2, post myocardial infarction (via ligation of the obtuse marginal branches); and Stage 3, post undersized ring annuloplasty. The 3D echocardiography measurements included mitral annular area, tethering distance from the ischemic PM to the anterior annulus, and the outside displacement of the PM relative to ring PM displacement. RESULTS: Persistent moderate MR remained in these seven sheep following undersized ring annuloplasty (MR vena contracta change (pre versus post ring): 7.0 versus 5.8 +/- 2.4 mm, p = NS), despite a reduction in the mitral annular area of 50 +/- 18% (10.3 +/- 6.3 versus 4.7 +/- 1.3 cm2). Ring annuloplasty shifted the posterior annulus towards the anterior annulus, such that the infarcted PM became displaced outside the mitral annulus. The projected displacement distance of the PM outside versus inside the annular ring was 8.4 +/- 2.4 mm outside mitral annulus post ring versus 3.6 +/- 2.5 mm within mitral annulus pre ring, p < 0001). The displacement distance from the infarcted PM to the mitral annulus restricted the ability of the posterior leaflet to move anteriorly, preventing effective coaptation. By multivariate analysis, this displacement distance was an important determinant of residual MR (p < 0.02). CONCLUSION: Persistent MR following ring annuloplasty for IMR relates to persistently abnormal leaflet tethering, with restricted posterior leaflet motion due to PM displacement outside of the mitral annulus.
Assuntos
Anuloplastia da Valva Mitral , Insuficiência da Valva Mitral/etiologia , Complicações Pós-Operatórias/etiologia , Animais , Insuficiência da Valva Mitral/fisiopatologia , Músculos Papilares/fisiopatologia , Complicações Pós-Operatórias/fisiopatologia , OvinosRESUMO
BACKGROUND: Ischemic mitral regurgitation (MR) is primarily caused by left ventricle deformation, but leaflet thickening with fibrotic changes are also observed in the valve. Increased levels of 5-hydroxytryptamine (5-HT; ie, serotonin) are described after myocardial infarction (MI); 5-HT can induce valve fibrosis through the 5-HT type 2B receptor (5-HT2BR). OBJECTIVES: This study aims to test the hypothesis that post-MI treatment with cyproheptadine (5-HT2BR antagonist) can prevent ischemic MR by reducing the effect of serotonin on mitral biology. METHODS: Thirty-six sheep were divided into 2 groups: inferior MI and inferior MI treated with cyproheptadine (0.5 mg/kg/d). Animals were followed for 90 days. Blood 5-HT, infarct size, left ventricular volume and function, MR fraction and mitral leaflet size were assessed. In a complementary in vitro study, valvular interstitial cells were exposed to pre-MI and post-MI serum collected from the experimental animals. RESULTS: Increased 5-HT levels were observed after MI in nontreated animals, but not in the group treated with cyproheptadine. Infarct size was similar in both groups (11 ± 3 g vs 9 ± 5 g; P = 0.414). At 90 days, MR fraction was 16% ± 7% in the MI group vs 2% ± 6% in the cyproheptadine group (P = 0.0001). The increase in leaflet size following MI was larger in the cyproheptadine group (+40% ± 9% vs +22% ± 12%; P = 0.001). Mitral interstitial cells overexpressed extracellular matrix genes when treated with post-MI serum, but not when exposed to post-MI serum collected from treated animals. CONCLUSIONS: Cyproheptadine given after inferior MI reduces post-MI 5-HT levels, prevents valvular fibrotic remodeling, is associated with larger increase in mitral valve size and less MR.
Assuntos
Estenose da Valva Aórtica , Calcinose , Insuficiência da Valva Mitral , Infarto do Miocárdio , Animais , Valva Aórtica , Células Cultivadas , Ciproeptadina/farmacologia , Ciproeptadina/uso terapêutico , Fibrose , Valva Mitral/diagnóstico por imagem , Insuficiência da Valva Mitral/etiologia , Infarto do Miocárdio/complicações , Infarto do Miocárdio/tratamento farmacológico , Serotonina , Ovinos , Remodelação Ventricular/fisiologiaRESUMO
BACKGROUND: Analyzing the determinants of systolic anterior motion of the mitral valve and consequent left ventricular outflow tract (LVOT) obstruction in patients with asymmetrical septal hypertrophy requires a comprehensive 3-dimensional analysis of mitral leaflet (ML) area, papillary muscle (PM) geometry, and the distribution of left ventricular hypertrophy. METHODS AND RESULTS: Real-time 3-dimensional echocardiography was performed in 47 patients with asymmetrical septal hypertrophy and 32 normal controls. Patients included 20 with resting LVOT obstruction (group I) and 27 without (group II). Customized software (Omni 4D) provided a validated measure of ML surface area, LVOT area, mitral annular area and nonplanarity, LVOT hypertrophy index by topography (percent area with wall thickness >16 mm), and 3-dimensional PM positions relative to annulus. ML area was more than twice as large in group I than normal and 1.4 times normal in group II (P<0.001). Group I patients were also characterized by higher LVOT hypertrophy index and medial and anterior displacements of both PMs, resulting in a shorter inter-PM distance. Independent determinants of LVOT obstruction were indexed total ML area (adjusted odds ratio, 5.651; 95% confidence interval, 1.573 to 20.304; P=0.008) and inter-PM distance (adjusted odds ratio, 0.416; 95% confidence interval, 0.203 to 0.854; P=0.0169). Minimal LVOT area during systole correlated well with peak LVOT pressure gradient (R(2)=0.83, P<0.001); its independent determinants were left ventricular end-systolic volume (P=0.0183), indexed total ML area (P=0.0108), inter-PM distance (P=0.0378), annular height (P=0.0047), and LVOT hypertrophy index (P=0.0098). CONCLUSIONS: Myocardium is not the only tissue affected in patients with asymmetrical septal hypertrophy, and primary changes of the mitral apparatus, including ML area increase and PM displacement, are independent determinants of LVOT obstruction and provide a comprehensive mechanism that determines leaflet slack and anteriorly directed motion. Abnormal PM-mitral valve geometry assessed by real-time 3-dimensional echocardiography can provide reasonable new targets for individualized intervention.
Assuntos
Ecocardiografia Tridimensional , Septos Cardíacos/diagnóstico por imagem , Septos Cardíacos/patologia , Valva Mitral/diagnóstico por imagem , Disfunção Ventricular Esquerda/diagnóstico por imagem , Obstrução do Fluxo Ventricular Externo/fisiopatologia , Feminino , Frequência Cardíaca , Septos Cardíacos/fisiopatologia , Ventrículos do Coração/anormalidades , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Valva Mitral/anormalidades , Disfunção Ventricular Esquerda/fisiopatologia , Obstrução do Fluxo Ventricular Externo/diagnóstico por imagemRESUMO
BACKGROUND: Ischemic mitral regurgitation is caused by systolic traction on the mitral leaflets related to ventricular distortion. Little is known about how chronic tethering affects leaflet area, in part because it cannot be measured repeatedly in situ. Recently, a new method for 3D echocardiographic measurement of mitral leaflet area was developed and validated in vivo against sheep valves, later excised. Clinical studies (n=80) showed that mitral leaflet area increased by >30% in patients with inferior myocardial infarction and dilated cardiomyopathy versus normal; greater adaptation independently predicted less mitral regurgitation. This study explored whether mitral valve area changes over time within the same heart with ischemic mitral regurgitation. METHODS AND RESULTS: Twelve sheep were studied at baseline and 3 months after inferior myocardial infarction by 3D echocardiography; 6 were untreated and 6 were treated initially with an epicardial patch to limit left ventricular dilation and mitral regurgitation. Untreated sheep developed left ventricular dilation at 3 months, with global dysfunction (mean+/-SD ejection fraction, 24+/-10% versus 44+/-10% with patching, P=0.02) and moderate mitral regurgitation (vena contracta, 5.0+/-1.0 versus 0.8+/-1.0 mm, P<0.0002). In untreated sheep, total diastolic leaflet area increased from 13.1+/-1.3 to 18.1+/-2.5 cm(2) (P=0.0001). In patched sheep, leaflet area at 3 months was not significantly different from baseline sheep values (13.0+/-1.1 versus baseline, 12.1+/-1.8 cm(2), P=0.31). CONCLUSIONS: Mitral valve area, independent of systolic stretch, increases over time as the left ventricular remodels after inferior myocardial infarction. This increase, however, fails to compensate adequately for tethering to prevent mitral regurgitation. Understanding the mechanism of valve adaptation can potentially suggest new biological and surgical therapeutic targets.
Assuntos
Insuficiência da Valva Mitral/patologia , Valva Mitral/patologia , Isquemia Miocárdica/complicações , Remodelação Ventricular , Animais , Modelos Animais de Doenças , Hemodinâmica , Insuficiência da Valva Mitral/fisiopatologia , OvinosRESUMO
BACKGROUND: In patients with left ventricular infarction or dilatation, leaflet tethering by displaced papillary muscles frequently induces mitral regurgitation, which doubles mortality. Little is known about the biological potential of the mitral valve (MV) to compensate for ventricular remodeling. We tested the hypothesis that MV leaflet surface area increases over time with mechanical stretch created by papillary muscle displacement through cell activation, not passive stretching. METHODS AND RESULTS: Under cardiopulmonary bypass, the papillary muscle tips in 6 adult sheep were retracted apically short of producing mitral regurgitation to replicate tethering without confounding myocardial infarction or turbulence. Diastolic leaflet area was quantified by 3-dimensional echocardiography over 61+/-6 days compared with 6 unstretched sheep MVs. Total diastolic leaflet area increased by 2.4+/-1.3 cm(2) (17+/-10%) from 14.3+/-1.9 to 16.7+/-1.9 cm(2) (P=0.006) with stretch with no change in the unstretched valves despite sham open heart surgery. Stretched MVs were 2.8 times thicker than normal (1.18+/-0.14 versus 0.42+/-0.14 mm; P<0.0001) at 60 days with an increased spongiosa layer. Endothelial cells (CD31(+)) coexpressing alpha-smooth muscle actin were significantly more common by fluorescent cell sorting in tethered versus normal leaflets (41+/-19% versus 9+/-5%; P=0.02), indicating endothelial-mesenchymal transdifferentiation. alpha-Smooth muscle actin-positive cells appeared in the atrial endothelium, penetrating into the interstitium, with increased collagen deposition. Thickened chordae showed endothelial and subendothelial alpha-smooth muscle actin. Endothelial-mesenchymal transdifferentiation capacity also was demonstrated in cultured MV endothelial cells. CONCLUSIONS: Mechanical stresses imposed by papillary muscle tethering increase MV leaflet area and thickness, with cellular changes suggesting reactivated embryonic developmental pathways. Understanding such actively adaptive mechanisms can potentially provide therapeutic opportunities to augment MV area and reduce ischemic mitral regurgitation.
Assuntos
Adaptação Fisiológica/fisiologia , Insuficiência da Valva Mitral/diagnóstico por imagem , Insuficiência da Valva Mitral/fisiopatologia , Valva Mitral/fisiologia , Animais , Carneiro Doméstico , UltrassonografiaRESUMO
BACKGROUND: Mitral leaflet enlargement has been identified as an adaptive mechanism to prevent mitral regurgitation in dilated left ventricles (LVs) caused by chronic aortic regurgitation (AR). This enlargement is deficient in patients with functional mitral regurgitation, which remains frequent in the population with ischemic cardiomyopathy. Maladaptive fibrotic changes have been identified in post-myocardial infarction (MI) mitral valves. It is unknown if these changes can interfere with valve growth and whether they are present in other valves. OBJECTIVES: This study sought to test the hypothesis that MI impairs leaflet growth, seen in AR, and induces fibrotic changes in mitral and tricuspid valves. METHODS: Sheep models of AR, AR + MI, and controls were followed for 90 days. Cardiac magnetic resonance, echocardiography, and computed tomography were performed at baseline and 90 days to assess LV volume, LV function, mitral regurgitation and mitral leaflet size. Histopathology and molecular analyses were performed in excised valves. RESULTS: Both experimental groups developed similar LV dilatation and dysfunction. At 90 days, mitral valve leaflet size was smaller in the AR + MI group (12.8 ± 1.3 cm2 vs. 15.1 ± 1.6 cm2, p = 0.03). Mitral regurgitant fraction was 4% ± 7% in the AR group versus 19% ± 10% in the AR + MI group (p = 0.02). AR + MI leaflets were thicker compared with AR and control valves. Increased expression of extracellular matrix remodeling genes was found in both the mitral and tricuspid leaflets in the AR + MI group. CONCLUSIONS: In these animal models of AR, the presence of MI was associated with impaired adaptive valve growth and more functional mitral regurgitation, despite similar LV size and function. More pronounced extracellular remodeling was observed in mitral and tricuspid leaflets, suggesting systemic valvular remodeling after MI.
Assuntos
Insuficiência da Valva Mitral/fisiopatologia , Valva Mitral/diagnóstico por imagem , Infarto do Miocárdio/complicações , Remodelação Ventricular , Animais , Insuficiência da Valva Aórtica/complicações , Ecocardiografia Tridimensional , Matriz Extracelular/metabolismo , Feminino , Fibrose , Imageamento por Ressonância Magnética , Masculino , Isquemia Miocárdica/complicações , Ovinos , Tomografia Computadorizada por Raios X , Valva Tricúspide/diagnóstico por imagemRESUMO
BACKGROUND: Functional mitral regurgitation (MR) is caused by systolic traction on the mitral leaflets related to ventricular distortion. Little is known about whether chronic tethering causes the mitral leaflet area to adapt to the geometric needs imposed by tethering, in part because of inability to reconstruct leaflet area in vivo. Our aim was to explore whether adaptive increases in leaflet area occur in patients with functional MR compared with normal subjects and to test the hypothesis that leaflet area influences MR severity. METHODS AND RESULTS: A new method for 3-dimensional echocardiographic measurement of mitral leaflet area was developed and validated in vivo against 15 sheep heart valves, later excised. This method was then applied in 80 consecutive patients from 3 groups: patients with normal hearts by echocardiography (n=20), patients with functional MR caused by isolated inferior wall-motion abnormality or dilated cardiomyopathy (n=29), and patients with inferior wall-motion abnormality or dilated cardiomyopathy but no MR (n=31). Leaflet area was increased by 35+/-20% in patients with LV dysfunction compared with normal subjects. The ratio of leaflet to annular area was 1.95+/-0.40 and was not different among groups, which indicates a surplus leaflet area that adapts to left-heart changes. In contrast, the ratio of total leaflet area to the area required to close the orifice in midsystole was decreased in patients with functional MR compared with those with normal hearts (1.29+/-0.15 versus 1.78+/-0.39, P=0.001) and compared with patients with inferior wall-motion abnormality or dilated cardiomyopathy but no MR (1.81+/-0.38, P=0.001). After adjustment for measures of LV remodeling and tethering, a leaflet-to-closure area ratio <1.7 was associated with significant MR (odds ratio 23.2, 95% confidence interval 2.0 to 49.1, P=0.02). CONCLUSIONS: Mitral leaflet area increases in response to chronic tethering in patients with inferior wall-motion abnormality and dilated cardiomyopathy, but the development of significant MR is associated with insufficient leaflet area relative to that demanded by tethering geometry. The varying adequacy of leaflet adaptation may explain in part the heterogeneity of this disease among patients. The results suggest the need to understand the mechanisms that underlie leaflet adaptation and whether leaflet area can potentially be modified as part of the therapeutic approach.
Assuntos
Insuficiência da Valva Mitral/patologia , Valva Mitral/patologia , Remodelação Ventricular , Idoso , Animais , Estudos de Casos e Controles , Ecocardiografia Tridimensional , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Valva Mitral/fisiopatologia , Insuficiência da Valva Mitral/etiologia , Estudos Prospectivos , OvinosRESUMO
BACKGROUND: Ischemic mitral regurgitation (MR) relates to displacement of the papillary muscles from ischemic ventricular distortion. We tested the hypothesis that repositioning of the papillary muscles can be achieved by injection of polyvinyl-alcohol (PVA) polymer, a biologically inert biomaterial that has been specially formulated to produce an encapsulated, stable, resilient gel once injected into the myocardium. The purpose is to materially support the infarcted myocardium while at the same time repositioning the papillary muscles that become apically tethered in MR. METHODS AND RESULTS: Nine sheep underwent ligation of circumflex branches to produce acute ischemic MR. PVA polymer was then injected by echo guidance into the myocardium underlying the infarcted papillary muscle. Hemodynamic data, left ventricular ejection fraction, elastance, tau (relaxation constant), left ventricular stiffness coefficient, and 2-dimensional and 3-dimensional echocardiograms were obtained post-MR and post-PVA injection. One animal died after coronary ligation and 2 did not develop MR. In the remaining 6, moderate MR developed. With PVA injection, the MR decreased significantly from moderate to trace-mild (vena contracta: 5+/-0.4 mm versus 2+/-0.7 mm, post-MR versus post-PVA injection; P<0.0001). This was associated with a decrease in infarcted papillary muscle-to-mitral annulus tethering distance (27+/-4 to 24+/-4 mm, post-MR versus post-PVA, P<0.001). Importantly, PVA injection was not associated with significant decreases in left ventricular ejection fraction (43+/-6% versus 37+/-4%, post-MR versus post-PVA, P=nonsignificant), elastance (3.5+/-1.4 versus 2.9+/-1.3; post-MR versus post-PVA injection, P=nonsignificant). Measures of left ventricular diastolic function, tau (100+/-51 ms to 84+/-37 ms, post-MR versus post-PVA; P=nonsignificant), and left ventricular stiffness coefficient (0.18+/-0.12 versus 0.14+/-0.08, post-MR versus post-PVA; P=nonsignificant) did not increase post-PVA. CONCLUSIONS: PVA polymer injection resulted in acute reverse remodeling of the ventricle with papillary muscle repositioning to decrease MR. This was not associated with an adverse effect on left ventricular systolic and diastolic function. This new approach to alter pathological anatomy after infarction may offer an alternative strategy for relieving ischemic MR by correcting the position of the affected papillary muscle, thus relieving apical tethering.
Assuntos
Insuficiência da Valva Mitral/etiologia , Insuficiência da Valva Mitral/fisiopatologia , Isquemia Miocárdica/complicações , Músculos Papilares/efeitos dos fármacos , Álcool de Polivinil/administração & dosagem , Remodelação Ventricular/efeitos dos fármacos , Animais , Imagem de Difusão por Ressonância Magnética , Ecocardiografia Tridimensional , Géis , Hemodinâmica , Injeções , Insuficiência da Valva Mitral/diagnóstico , Infarto do Miocárdio/patologia , Infarto do Miocárdio/fisiopatologia , Miocárdio , Álcool de Polivinil/química , Álcool de Polivinil/farmacologia , Ovinos , Função Ventricular EsquerdaRESUMO
AIMS: Two-dimensional echocardiographic (2DE) assessment of right ventricular (RV) function is difficult, often resulting in inconsistent RV evaluation. Real-time three-dimensional echocardiography (RT3DE) allows the RV to be viewed in multiple planes, which can potentially improve RV assessment and limit interobserver variability when compared with 2DE. METHODS AND RESULTS: Twenty-five patients underwent 2DE and RT3DE. Views of 2DE (RV inflow, RV short axis, and apical four-chamber) were compared with RT3DE views by four readers. RT3DE data sets were sliced from anterior-posterior (apical view) and from base to apex (short axis) to obtain six standardized planes. Readers recorded the RV ejection fraction (RVEF) from 2DE and RT3DE images. RVEF recorded by RT3DE (RVEF(3D)) and 2D (RVEF(2D)) were compared with RVEF by disc summation (RVEF(DS)), which was used as a reference. Interobserver variability among readers of RVEF(3D) and RVEF(2D) was then compared. Overall, mean RVEF(DS), RVEF(3D), and RVEF(2D) were 37 +/- 11%, 38 +/- 10%, 41 +/- 10%, respectively. The mean difference of RVEF(3D)-RVEF(DS) was significantly less than RVEF(2D)-RVEF(DS) (3.7 +/- 4% vs. 7.1 +/- 5%, P = 0.0066, F-test). RVEF(3D) correlated better with RVEF(DS) (r = 0.875 vs. r = 0.69, P = 0.028, t-test). RVEF(3D) was associated with a 39% decrease in interobserver variability when compared with RVEF(2D) [standard deviation of mean difference: 3.7 vs. 5.1, (RT3DE vs. 2DE), P = 0.018, t-test]. CONCLUSIONS: RT3DE provides improved accuracy of RV function assessment and decreases interobserver variability when compared with 2D views.
Assuntos
Ecocardiografia Tridimensional , Função Ventricular Direita , Feminino , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Estudos ProspectivosRESUMO
PURPOSE: MitraClip is the sole percutaneous device approved for functional mitral regurgitation (MR; FMR) but MR recurs in over one third of patients. As device-induced mechanical effects are a potential cause for MR recurrence, we tested the hypothesis that MitraClip increases leaflet stress and procedure-related strain in sub-valvular left ventricular (LV) myocardium in FMR associated with coronary disease (FMR-CAD). METHODS: Simulations were performed using finite element models of the LV + mitral valve based on MRI of 5 sheep with FMR-CAD. Models were modified to have a 20% increase in LV volume (↑LV_VOLUME) and MitraClip was simulated with contracting beam elements (virtual sutures) placed between nodes in the center edge of the anterior (AL) and posterior (PL) mitral leaflets. Effects of MitraClip on leaflet stress in the peri-MitraClip region of AL and PL, septo-lateral annular diameter (SLAD), and procedure-related radial strain (Err) in the sub-valvular myocardium were calculated. RESULTS: MitraClip increased peri-MitraClip leaflet stress at end-diastole (ED) by 22.3±7.1 kPa (p<0.0001) in AL and 14.8±1.2 kPa (p<0.0001) in PL. MitraClip decreased SLAD by 6.1±2.2 mm (p<0.0001) and increased Err in the sub-valvular lateral LV myocardium at ED by 0.09±0.04 (p<0.0001)). Furthermore, MitraClip in ↑LV_VOLUME was associated with persistent effects at ED but also at end-systole where peri-MitraClip leaflet stress was increased in AL by 31.9±14.4 kPa (p = 0.0268) and in PL by 22.5±23.7 kPa (p = 0.0101). CONCLUSIONS: MitraClip for FMR-CAD increases mitral leaflet stress and radial strain in LV sub-valvular myocardium. Mechanical effects of MitraClip are augmented by LV enlargement.
Assuntos
Análise de Elementos Finitos , Insuficiência da Valva Mitral/cirurgia , Valva Mitral/cirurgia , Modelos Cardiovasculares , Miocárdio/patologia , Instrumentos Cirúrgicos , Animais , Simulação por Computador , Diástole , Valva Mitral/fisiopatologia , Insuficiência da Valva Mitral/fisiopatologia , Ovinos , Estresse Mecânico , SístoleRESUMO
OBJECTIVES: This study hypothesized that compensatory mitral leaflet area (MLA) adaptation occurs in patients with persistent atrial fibrillation (AF) without left ventricular (LV) dysfunction but has limitations that augment mitral regurgitation (MR). The study also explored whether asymmetrical annular dilation is matched by relative leaflet enlargement. BACKGROUND: Functional MR occurs in patients with AF and isolated annular dilation, but the relationship of MLA adaptation with annular area (AA) is unknown. METHODS: Three-dimensional echocardiographic images were acquired from 86 patients with quantified MR: 53 with nonvalvular persistent AF (23 MR+ with moderate or greater MR, 30 MR-) without LV dysfunction or dilation and 33 normal controls. Comprehensive 3-dimensional analysis included total diastolic MLA, adaptation ratios of MLA to annular area and MLA to leaflet closure area, and annular and tenting geometry. RESULTS: Total MLA was 22% larger in patients with AF than in controls, thus paralleling the increased AA. However, as AA increased, adaptive indices (MLA/AA ratio and ratio of MLA to closure area) plateaued, becoming lowest in MR+ patients (ratio of MLA to closure area = 1.63 ± 0.17 controls, 1.60 ± 0.11 MR-, 1.32 ± 0.10 MR+; p < 0.001). MR increased as the ratio of MLA to closure area decreased (R2 = 0.68; p < 0.001). The posterior-to-anterior MLA ratio remained constant, whereas the posterior-to-anterior mitral annulus perimeter increased (1.21 ± 0.16 controls, 1.32 ± 0.20 MR-, 1.46 ± 0.19 MR+; p < 0.001). Multivariate MR determinants were annular area, total MLA to closure area, and posterior-to-anterior perimeter ratios. CONCLUSIONS: MLA adaptively increases in AF with isolated annular dilation and normal LV function. This compensatory enlargement becomes insufficient with greater annular dilation, and the leaflets fail to match asymmetrical annular remodeling, thereby increasing MR. These findings can potentially help optimize therapeutic options and motivate basic studies of adaptive growth processes.
Assuntos
Fibrilação Atrial/fisiopatologia , Função do Átrio Esquerdo , Insuficiência da Valva Mitral/fisiopatologia , Valva Mitral/fisiopatologia , Adaptação Fisiológica , Idoso , Fibrilação Atrial/complicações , Fibrilação Atrial/diagnóstico , Estudos de Casos e Controles , Ecocardiografia Tridimensional , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valva Mitral/diagnóstico por imagem , Insuficiência da Valva Mitral/diagnóstico por imagem , Insuficiência da Valva Mitral/etiologia , Prognóstico , Fatores de Risco , Função Ventricular EsquerdaRESUMO
BACKGROUND: Recurrent ischemic mitral regurgitation (IMR) is frequent despite initial reduction by annuloplasty because continued LV remodeling increases tethering to the infarcted papillary muscle (PM). We have previously shown that PM repositioning by an external patch device can acutely reduce IMR. In this study, we tested the hypothesis that IMR reduction persists despite possible continued LV remodeling. METHODS AND RESULTS: In 7 sheep, we used a chronic ischemic posterior infarct model that produces LV dilatation and MR over 10 weeks. An epicardial patch device was adjusted under echo guidance to reduce MR, with follow-up over a further 8 weeks and evaluation by 3D echo and sonomicrometry. In all 7 sheep, moderate IMR resolved with acute patch application and PM repositioning (6.5+/-1.8 mm to 0.6+/-1.3 mm proximal jet width, P<0.001) without decrease in LVEF (43+/-3% to 44+/-8%). Eight weeks after PM repositioning, MR was not significantly greater (0.6+/-1.3 mm versus 1.0+/-1.0 mm, P=NS) despite an increase in LV volumes in 3 animals (2 had increases of 50+/-15%). On average, LV volumes did not change significantly (ESV: 46+/-8 mL versus 49+/-15 mL; P=NS and EDV: 85+/-16 mL versus 89+/-30 mL; P=NS). LVEF was unchanged from acute to chronic patch (44+/-8% versus 43+/-8%). Contractility as end-systolic elastance did not decrease from the chronic MI to the acute and chronic patch stages, nor were there any significant changes in dP/dt, LV stiffness constant, or time constant of LV relaxation (Tau). CONCLUSION: PM repositioning is persistently effective in reducing moderate chronic IMR, even when LV volume increases. This may reflect structural stabilization by an external patch device of the papillary muscle-LV wall complex that controls mitral valve tethering.
Assuntos
Procedimentos Cirúrgicos Cardíacos/métodos , Insuficiência da Valva Mitral/cirurgia , Isquemia Miocárdica/cirurgia , Músculos Papilares/cirurgia , Disfunção Ventricular Esquerda/cirurgia , Animais , Insuficiência da Valva Mitral/diagnóstico por imagem , Isquemia Miocárdica/diagnóstico por imagem , Músculos Papilares/diagnóstico por imagem , Radiografia , Ovinos , Disfunção Ventricular Esquerda/diagnóstico por imagemRESUMO
BACKGROUND: Mitral regurgitation (MR) doubles postmyocardial infarction (MI) mortality. We have shown that moderate MR augments remodeling in an apical MI model (no intrinsic MR) with independent left ventricle-to-left atrial MR-type flow. We hypothesized that repairing moderate MR 1 month after MI reverses this remodeling. METHODS AND RESULTS: Anteroapical MIs were created in 18 sheep, and a left ventricle-to-left atrial shunt implanted in 12 (regurgitant fraction, 30%). Six sheep had the shunt closed at 1 month (repair group). Sheep were compared at baseline, and at 1 and 3 months. Sheep in the MI+MR (unrepaired) and repaired groups remodeled during the first month (120% increased left ventricular end-systolic volume [ESV; P<0.01]), but shunt closure reversed remodeling at 3 months, with end-diastolic volume (EDV) and ESV 135% and 128% of baseline versus 220% and 280% without repair (P<0.001). At 3 months, dP/dt and preload-recruitable stroke work were relatively maintained in the repaired and MI-only groups versus nearly 50% decreases without repair. Prohypertrophic gp130 and antiapoptotic pAkt increased followed by exhaustion below baseline without repair, but remained elevated at 3 months with repair or MI only. With repair, matrix metalloproteinase-2 decreased to < or = 50% that without repair in remote and border zones at 3 months, and the matrix metalloproteinase inhibitor TIMP-4 increased dramatically. CONCLUSIONS: Early repair of moderate MR in the setting of apical MI substantially reverses the otherwise progressive remodeling process, with reduced left ventricular volumes, relatively maintained contractility, persistently activated intracellular signals promoting hypertrophy and opposing apoptosis, and reduced matrix proteolytic activity. These findings are of interest for the current controversy regarding potential benefits of repair of MR after MI.
Assuntos
Insuficiência da Valva Mitral/cirurgia , Isquemia Miocárdica/cirurgia , Remodelação Ventricular/fisiologia , Animais , Proteínas da Matriz Extracelular/biossíntese , Masculino , Insuficiência da Valva Mitral/metabolismo , Insuficiência da Valva Mitral/fisiopatologia , Isquemia Miocárdica/metabolismo , Isquemia Miocárdica/fisiopatologia , OvinosRESUMO
BACKGROUND: Tricuspid regurgitation (TR) is an important predictor of morbidity and mortality in heart failure. We aimed to examine the 3D geometry of the tricuspid valve annulus (TVA) in patients with functional TR, comparing them with patients with normal tricuspid valve function and relating annular geometric changes to functional TR. METHODS AND RESULTS: TVA shape was examined by real-time 3D echocardiography in 75 patients: 35 with functional TR and 40 with normal tricuspid valve function (referent group). The 3D shape of the TVA was reconstructed from rotated 2D planes, and the annular plane was computed by least-squares fitting. Annular area and mediolateral, anteroposterior, and high (superior)-low (inferior) distances were calculated. TR was assessed by vena contracta width. The normal TVA has a bimodal pattern (high-low distance=7.23+/-1.05 mm). High points were located anteroposteriorly, and low points were located mediolaterally. With moderate or greater TR (vena contracta width 5.80+/-2.62 mm), the TVA became dilated (17.24+/-4.75 versus 9.83+/-2.18 cm2, P<0.0001, TR versus referent), more planar with decreased high-low distance (4.14+/-1.05 mm), and more circular with decreased ratio of mediolateral/anteroposterior (1.11+/-0.09 versus 1.32+/-0.09, P<0.0001, TR versus referent). CONCLUSIONS: The normal TVA has a bimodal shape with distinct high points located anteroposteriorly and low points located mediolaterally. With functional TR, the annulus becomes larger, more planar, and circular. These changes in annular shape with TR have potentially important mechanistic and therapeutic implications for tricuspid valve repair.
Assuntos
Ecocardiografia Tridimensional , Insuficiência da Valva Tricúspide/diagnóstico por imagem , Arritmias Cardíacas , Ecocardiografia , Coração/anatomia & histologia , Átrios do Coração/anatomia & histologia , Insuficiência Cardíaca/diagnóstico por imagem , Insuficiência Cardíaca/etiologia , Humanos , Processamento de Imagem Assistida por Computador , Seleção de PacientesRESUMO
BACKGROUND: During the development of heart failure (HF), the changes of contraction timing pattern and temporal heterogeneity of segmental contraction happen early and may precede both symptomatic HF and the decrease in left ventricular ejection fraction (LVEF). In patients treated with anthracyclines, both symptomatic HF and the decrease of LVEF are detected once significant myocardial injury has occurred. The aim of the current study was to investigate whether changes in the timing of contraction can be detected early after anthracyclines therapy. METHODS: Forty-one women (50 ± 11 years old) with newly diagnosed breast cancer were prospectively enrolled in two centers and underwent an echocardiogram before and after anthracyclines. Peak longitudinal myocardial systolic strain was measured on the apical four- and two-chamber views. The time to peak systolic longitudinal strain (TP), ejection time (ET), isovolumic contraction time (IVCT), systolic time, and diastolic time were measured using strain curves and Doppler tracings and compared before and after anthracyclines. The heterogeneity of contraction (dyssynchrony) was measured by the SD of the TP of all segments. RESULTS: Anthracyclines treatment was associated with an increase in heart rate (HR) and a decrease in TP. TP was correlated with HR. TP/ET was independent of HR and inversely correlated to peak strain both at baseline and after anthracyclines. TP/ET increased after anthracyclines (1.26 ± 0.19 to 1.31 ± 0.22; P < .001), and this increase was correlated with the decrease in strain. The increase in TP/ET was due to an increase in IVCT/ET. A similar degree of dyssynchrony was found at baseline and after anthracyclines. CONCLUSIONS: Anthracyclines treatment induces an increase in the duration of contraction, mainly by increasing the IVCT. This increase is correlated to the decrease in strain and may therefore have additional prognostic value.
Assuntos
Antraciclinas/administração & dosagem , Antraciclinas/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Contração Miocárdica/efeitos dos fármacos , Disfunção Ventricular Esquerda/induzido quimicamente , Disfunção Ventricular Esquerda/fisiopatologia , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Boston , Neoplasias da Mama/fisiopatologia , Estudos Controlados Antes e Depois , Acoplamento Excitação-Contração/efeitos dos fármacos , Feminino , Insuficiência Cardíaca/induzido quimicamente , Insuficiência Cardíaca/diagnóstico por imagem , Insuficiência Cardíaca/fisiopatologia , Humanos , Pessoa de Meia-Idade , Quebeque , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Volume Sistólico , Resultado do Tratamento , Ultrassonografia/métodos , Disfunção Ventricular Esquerda/diagnóstico por imagemRESUMO
BACKGROUND: Ischemic mitral regurgitation (MR) is classically ascribed to functional restriction of normal leaflets, but recent studies have suggested post-myocardial infarction (MI) mitral valve (MV) leaflet fibrosis and thickening, challenging valve normality. Progression of leaflet thickness post-MI has not been studied. We hypothesized that excessive MV remodeling post-MI contributes to MR. Our objectives are to characterize MV changes after MI and relate them to MR. METHODS AND RESULTS: Three groups of 40 patients with serial echocardiograms over a mean of 23.4 months were identified from an echocardiography database: patients first studied early (6±12 days) and late (12±7 years) after an inferior MI and normal controls. MV thickness was correlated with MR. We studied the mechanisms for MV changes in a sheep model (6 apical MI versus 6 controls) followed for 8 weeks, with MV cellular and histopathologic analyses. Early post-MI, leaflet thickness was found to be similar to controls (2.6±0.5 vs 2.5±0.4 mm; P=0.23) but significantly increased over time (2.5±0.4 to 2.9±0.4 mm; P<0.01). In this group, patients tolerating maximal doses of renin-angiotensin blocking agents had less thickening (25% of patients; P<0.01). The late-MI group had increased thickness (3.2±0.5 vs 2.5±0.4 mm; P<0.01) without progression. At follow-up, 48% of post-MI patients had more than mild MR. Increased thickness was independently associated with MR. Experimentally, 8 weeks post-MI, MVs were 2-fold thicker than controls, with increased collagen, profibrotic transforming growth factor-ß, and endothelial-to-mesenchymal transformation, confirmed by flow cytometry. CONCLUSIONS: MV thickness increases post-MI and correlates with MR, suggesting an organic component to ischemic MR. MV fibrotic remodeling can indicate directions for future therapy.