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Heart failure with preserved ejection fraction (HFpEF) is frequently attributed etiologically to an underlying left ventricular (LV) diastolic dysfunction, although its pathophysiology is far more complex and can exhibit significant variations among patients. This review endeavours to systematically unravel the pathophysiological heterogeneity by illustrating diverse mechanisms leading to an impaired cardiac output reserve, a central and prevalent haemodynamic abnormality in HFpEF patients. Drawing on previously published findings from our research group, we propose a pathophysiology-guided phenotyping based on the presence of: (1) LV diastolic dysfunction, (2) LV systolic pathologies, (3) arterial stiffness, (4) atrial impairment, (5) right ventricular dysfunction, (6) tricuspid valve regurgitation, and (7) chronotopic incompetence. Tailored to each specific phenotype, we explore various potential treatment options such as antifibrotic medication, diuretics, renal denervation and more. Our conclusion underscores the pivotal role of cardiac output reserve as a key haemodynamic abnormality in HFpEF, emphasizing that by phenotyping patients according to its individual pathomechanisms, insights into personalized therapeutic approaches can be gleaned.
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BACKGROUND: Recent trial data suggest that stratification of patients with heart failure with preserved ejection fraction (HFpEF) according to left ventricular ejection fraction (LVEF) provides a means for dissecting different treatment responses. However, the differential pathophysiologic considerations have rarely been described. METHODS: This prospective, single-center study analyzed consecutive symptomatic patients with HFpEF diagnosed according to the 2016 European Society of Cardiology heart failure guidelines. Patients were grouped into LVEF 50% to 60% and LVEF >60% cohorts. All patients underwent cardiac magnetic resonance imaging. Transfemoral cardiac catheterization was performed to derive load-dependent and load-independent left ventricular (LV) properties on pressure-volume loop analyses. RESULTS: Fifty-six patients with HFpEF were enrolled and divided into LVEF 50% to 60% (n=21) and LVEF >60% (n=35) cohorts. On cardiac magnetic resonance imaging, the LVEF >60% cohort showed lower LV end-diastolic volumes (P=0.019) and end-systolic volumes (P=0.001) than the LVEF 50% to 60% cohort; stroke volume (P=0.821) did not differ between the cohorts. Extracellular volume fraction was higher in the LVEF 50% to 60% cohort than in the LVEF >60% cohort (0.332 versus 0.309; P=0.018). Pressure-volume loop analyses demonstrated higher baseline LV contractility (end-systolic elastance, 1.85 vs 1.33 mm Hg/mL; P<0.001) and passive diastolic stiffness (ß constant, 0.032 versus 0.018; P=0.004) in the LVEF >60% cohort. Ventriculo-arterial coupling (end-systolic elastance/arterial elastance) at rest was in the range of optimized stroke work in the LVEF >60% cohort but was impaired in the LVEF 50% to 60% cohort (1.01 versus 0.80; P=0.005). During handgrip exercise, patients with LVEF >60% had higher increases in end-systolic elastance (1.85 versus 0.82 mm Hg/mL; P=0.023), attenuated increases in indexed end-systolic volume (-1 versus 7 mL/m²; P<0.004), and more exaggerated increases in LV filling pressures (8 vs 5 mm Hg; P=0.023). LV stroke volume decreased in the LVEF >60% cohort (P=0.007) under exertion. CONCLUSIONS: Patients with HFpEF in whom LVEF ranged from 50% to 60% demonstrated reduced contractility, impaired ventriculo-arterial coupling, and higher extracellular volume fraction. In contrast, patients with HFpEF and a LVEF >60% demonstrated a hypercontractile state with excessive LV afterload and diminished preload reserve. A LVEF-based stratification of patients with HFpEF identified distinct morphologic and pathophysiologic subphenotypes.
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Insuficiência Cardíaca , Função Ventricular Esquerda , Força da Mão/fisiologia , Insuficiência Cardíaca/diagnóstico por imagem , Insuficiência Cardíaca/terapia , Humanos , Estudos Prospectivos , Volume Sistólico/fisiologia , Função Ventricular Esquerda/fisiologiaRESUMO
BACKGROUND: Both radiofrequency and ultrasound endovascular renal sympathetic denervation (RDN) have proven clinical efficacy for the treatment of hypertension. We performed a head-to-head comparison of these technologies. METHODS: Patients with resistant hypertension were randomly assigned in a 1:1:1 manner to receive either treatment with (1) radiofrequency RDN of the main renal arteries; (2) radiofrequency RDN of the main renal arteries, side branches, and accessories; or (3) an endovascular ultrasound-based RDN of the main renal artery. The primary end point was change in systolic daytime ambulatory blood pressure at 3 months. RESULTS: Between June 2015 and June 2018, 120 patients were enrolled (mean age, 64±9 years±SD; mean daytime blood pressure, 153/86±12/13 mm Hg). Of these, 39 were randomly assigned to radiofrequency main renal artery ablation, 39 to combined radiofrequency ablation of the main artery and branches, and 42 to ultrasound-based treatment. Baseline daytime blood pressure, clinical characteristics, and treatment were well balanced between the groups. At 3 months, systolic daytime ambulatory blood pressure decreased by 9.5±12.3 mm Hg ( P<0.001) in the whole cohort. Although blood pressure was significantly more reduced in the ultrasound ablation group than in the radiofrequency ablation group of the main renal artery (-13.2±13.7 versus -6.5±10.3 mm Hg; mean difference, -6.7 mm Hg; global P=0.038 by ANOVA, adjusted P=0.043), no significant difference was found between the radiofrequency ablation groups (-8.3±11.7 mm Hg for additional side branch ablation; mean difference, -1.8 mm Hg; adjusted P>0.99). Similarly, the blood pressure reduction was not found to be significantly different between the ultrasound and the side branch ablation groups. Frequencies of blood pressure response ≥5 mm Hg were not significantly different (global P=0.77). CONCLUSIONS: In patients with resistant hypertension, endovascular ultrasound-based RDN was found to be superior to radiofrequency ablation of the main renal arteries only, whereas a combined approach of radiofrequency ablation of the main arteries, accessories, and side branches was not. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02920034.
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Pressão Sanguínea , Ablação por Cateter , Hipertensão/cirurgia , Rim/irrigação sanguínea , Artéria Renal/inervação , Simpatectomia , Procedimentos Cirúrgicos Ultrassônicos , Idoso , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Ablação por Cateter/efeitos adversos , Ablação por Cateter/instrumentação , Resistência a Medicamentos , Feminino , Humanos , Hipertensão/diagnóstico , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Método Simples-Cego , Simpatectomia/efeitos adversos , Simpatectomia/instrumentação , Simpatectomia/métodos , Fatores de Tempo , Resultado do Tratamento , Procedimentos Cirúrgicos Ultrassônicos/efeitos adversos , Procedimentos Cirúrgicos Ultrassônicos/instrumentaçãoRESUMO
BACKGROUND: Experimental trials suggest improved outcome by mild therapeutic hypothermia for cardiogenic shock after acute myocardial infarction. The objective of this study was to investigate the hemodynamic effects of mild therapeutic hypothermia in patients with cardiogenic shock complicating acute myocardial infarction. METHODS: Patients (n=40) with cardiogenic shock undergoing primary percutaneous coronary intervention without classic indications for mild therapeutic hypothermia underwent randomization in a 1:1 fashion to mild therapeutic hypothermia for 24 hours or control. The primary end point was cardiac power index at 24 hours; secondary end points included other hemodynamic parameters and serial measurements of arterial lactate. RESULTS: No relevant differences were observed for the primary end point of cardiac power index at 24 hours (mild therapeutic hypothermia versus control: 0.41 [interquartile range, 0.31-0.52] versus 0.36 [interquartile range, 0.31-0.48] W/m2; P=0.50; median difference, -0.025 W/m2; 95% CI, -0.12 to 0.06). Similarly, all other hemodynamic measurements were not statistically different. Arterial lactate levels at 6, 8, and 10 hours were significantly higher in patients in the mild therapeutic hypothermia group with a slower decline ( P for interaction=0.03). There were no differences in 30-day mortality (60% versus 50%; hazard ratio, 1.27; 95% CI, 0.55-2.94; P=0.55). CONCLUSIONS: In this randomized trial, mild therapeutic hypothermia failed to show a substantial beneficial effect on cardiac power index at 24 hours in patients with cardiogenic shock after acute myocardial infarction. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01890317.
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Hipotermia Induzida/métodos , Infarto do Miocárdio/terapia , Intervenção Coronária Percutânea , Choque Cardiogênico/terapia , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Feminino , Alemanha , Hemodinâmica , Humanos , Hipotermia Induzida/efeitos adversos , Hipotermia Induzida/mortalidade , Ácido Láctico/sangue , Masculino , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/mortalidade , Infarto do Miocárdio/fisiopatologia , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/mortalidade , Estudos Prospectivos , Recuperação de Função Fisiológica , Choque Cardiogênico/diagnóstico , Choque Cardiogênico/mortalidade , Choque Cardiogênico/fisiopatologia , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Previous randomised renal denervation studies did not show consistent efficacy in reducing blood pressure. The objective of our study was to evaluate the effect of renal denervation on blood pressure in the absence of antihypertensive medications. METHODS: SPYRAL HTN-OFF MED was a multicentre, international, single-blind, randomised, sham-controlled, proof-of-concept trial. Patients were enrolled at 21 centres in the USA, Europe, Japan, and Australia. Eligible patients were drug-naive or discontinued their antihypertensive medications. Patients with an office systolic blood pressure (SBP) of 150 mm Hg or greater and less than 180 mm Hg, office diastolic blood pressure (DBP) of 90 mm Hg or greater, and a mean 24-h ambulatory SBP of 140 mm Hg or greater and less than 170 mm Hg at second screening underwent renal angiography and were randomly assigned to renal denervation or sham control. Patients, caregivers, and those assessing blood pressure were blinded to randomisation assignments. The primary endpoint, change in 24-h blood pressure at 3 months, was compared between groups. Drug surveillance was done to ensure patient compliance with absence of antihypertensive medication. The primary analysis was done in the intention-to-treat population. Safety events were assessed at 3 months. This study is registered with ClinicalTrials.gov, number NCT02439749. FINDINGS: Between June 25, 2015, and Jan 30, 2017, 353 patients were screened. 80 patients were randomly assigned to renal denervation (n=38) or sham control (n=42) and followed up for 3 months. Office and 24-h ambulatory blood pressure decreased significantly from baseline to 3 months in the renal denervation group: 24-h SBP -5·5 mm Hg (95% CI -9·1 to -2·0; p=0·0031), 24-h DBP -4·8 mm Hg (-7·0 to -2·6; p<0·0001), office SBP -10·0 mm Hg (-15·1 to -4·9; p=0·0004), and office DBP -5·3 mm Hg (-7·8 to -2·7; p=0·0002). No significant changes were seen in the sham-control group: 24-h SBP -0·5 mm Hg (95% CI -3·9 to 2·9; p=0·7644), 24-h DBP -0·4 mm Hg (-2·2 to 1·4; p=0·6448), office SBP -2·3 mm Hg (-6·1 to 1·6; p=0·2381), and office DBP -0·3 mm Hg (-2·9 to 2·2; p=0·8052). The mean difference between the groups favoured renal denervation for 3-month change in both office and 24-h blood pressure from baseline: 24-h SBP -5·0 mm Hg (95% CI -9·9 to -0·2; p=0·0414), 24-h DBP -4·4 mm Hg (-7·2 to -1·6; p=0·0024), office SBP -7·7 mm Hg (-14·0 to -1·5; p=0·0155), and office DBP -4·9 mm Hg (-8·5 to -1·4; p=0·0077). Baseline-adjusted analyses showed similar findings. There were no major adverse events in either group. INTERPRETATION: Results from SPYRAL HTN-OFF MED provide biological proof of principle for the blood-pressure-lowering efficacy of renal denervation. FUNDING: Medtronic.
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Ablação por Cateter/métodos , Resistência a Medicamentos , Hipertensão/cirurgia , Simpatectomia/métodos , Adulto , Fatores Etários , Idoso , Anti-Hipertensivos/uso terapêutico , Austrália , Determinação da Pressão Arterial , Europa (Continente) , Feminino , Humanos , Hipertensão/diagnóstico , Hipertensão/tratamento farmacológico , Internacionalidade , Masculino , Pessoa de Meia-Idade , Segurança do Paciente , Prognóstico , Valores de Referência , Medição de Risco , Índice de Gravidade de Doença , Fatores Sexuais , Método Simples-Cego , Resultado do Tratamento , Estados UnidosAssuntos
Cateterismo Cardíaco/métodos , Comunicação Interatrial/cirurgia , Valva Mitral/cirurgia , Idoso , Idoso de 80 Anos ou mais , Ecocardiografia Transesofagiana/métodos , Feminino , Seguimentos , Comunicação Interatrial/diagnóstico por imagem , Humanos , Masculino , Valva Mitral/diagnóstico por imagem , Resultado do Tratamento , Teste de Caminhada/métodosRESUMO
BACKGROUND: For patients with high-risk pulmonary artery embolism (PE), catheter-directed therapies pose a viable alternative treatment option to systemic thrombolysis or anticoagulation. Right now, there are multiple devices available which have been proven to be safe and effective in lower-risk settings. There is, however, little data comparing their efficacies in high-risk PE. METHODS: We performed a retrospective, single-center study on patients with high-risk PE undergoing catheter interventional treatment. Patients receiving large-bore catheter thrombectomy were compared to patients receiving alternative treatment forms. RESULTS: Of the 20 patients included, 9 received large-bore thrombectomy, and 11 received alternative interventional treatments. While the baseline characteristics were comparable between the two groups, periprocedural and in-hospital mortality tended to be significantly lower with large-bore thrombectomy when compared to other treatment forms (0 vs. 55% and 33 vs. 82%, p = 0.07 and 0.01, respectively). CONCLUSIONS: In this small, retrospective study, large-bore thrombectomy was associated with lower mortality as compared to alternative treatment forms. Future prospective research is needed to corroborate these findings.
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AIMS: The aim of this study was to assess the pathophysiological implications of severe tricuspid regurgitation (TR) in patients with heart failure with preserved ejection fraction (HFpEF) by using tricuspid transcatheter edge-to-edge repair (T-TEER) as a model of right ventricular (RV) volume overload relief. METHODS AND RESULTS: This prospective interventional single arm trial (NCT04782908) included patients with invasively diagnosed HFpEF. The following parameters were prospectively assessed before and after T-TEER: left ventricular (LV) diastolic properties by invasive pressure-volume loop recordings; biventricular time-volume curves and function as well as septal curvature by cardiac magnetic resonance imaging; strain analyses for timing of septal motion. Overall, 20 patients (median age 78, interquartile range [IQR] 72-83 years, 65% female) were included. T-TEER reduced TR by a median of 2 (of 5) grades (IQR 2-1). T-TEER increased LV stroke volume and LV end-diastolic volume (LVEDV) (p < 0.001), without increasing LV end-diastolic pressure (LVEDP) (p = 0.094), consequently diastolic function improved with a reduction in LVEDP/LVEDV (p = 0.001) and a rightward shift of the end-diastolic pressure-volume relationship. The increase in LVEDV correlated with a decrease in RV end-diastolic volume (p < 0.001) and LV transmural pressure increased (p = 0.028). Secondary to a decrease in early RV filling, improvements in early LV filling were observed, correlating with an alleviation of leftwards bowing of the septum (p < 0.01, respectively). CONCLUSION: Diastolic LV properties in patients with HFpEF and severe TR are importantly determined by ventricular interaction in the setting of RV volume overload. T-TEER reduces RV volume overload and improves biventricular interaction and physiology.
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Insuficiência Cardíaca , Volume Sistólico , Insuficiência da Valva Tricúspide , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Cateterismo Cardíaco/métodos , Diástole , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/complicações , Ventrículos do Coração/fisiopatologia , Ventrículos do Coração/diagnóstico por imagem , Imagem Cinética por Ressonância Magnética/métodos , Estudos Prospectivos , Volume Sistólico/fisiologia , Insuficiência da Valva Tricúspide/fisiopatologia , Insuficiência da Valva Tricúspide/complicações , Disfunção Ventricular Direita/fisiopatologia , Função Ventricular Esquerda/fisiologia , Função Ventricular Direita/fisiologiaRESUMO
BACKGROUND: The SPYRAL HTN-ON MED (Global Clinical Study of Renal Denervation With the Symplicity Spyral Multi-electrode Renal Denervation System in Patients With Uncontrolled Hypertension in the Absence of Antihypertensive Medications)trial showed significant office and nighttime systolic blood pressure (BP) reductions in patients with hypertension following renal denervation (RDN) compared with sham-control patients, despite similar 24-hour BP reductions. We compared antihypertensive medication and BP changes among prespecified subpopulations. METHODS: The multicenter, randomized, sham-controlled, blinded SPYRAL HTN-ON MED trial (n=337) evaluated BP changes after RDN compared with a sham procedure in patients with hypertension prescribed 1 to 3 antihypertensive drugs. Most patients (n=187; 54%) were enrolled outside the United States, while 156 (46%) US patients were enrolled, including 60 (18%) Black Americans. RESULTS: Changes in detected antihypertensive drugs were similar between RDN and sham group patients in the outside US cohort, while drug increases were significantly more common in the US sham group compared with the RDN group. Patients from outside the United States showed significant reductions in office and 24-hour mean systolic BP at 6 months compared with the sham group, whereas BP changes were similar between RDN and sham in the US cohort. Within the US patient cohort, Black Americans in the sham control group had significant increases in medication burden from baseline through 6 months (P=0.003) but not in the RDN group (P=0.44). CONCLUSIONS: Patients enrolled outside the United States had minimal antihypertensive medication changes between treatment groups and had significant office and 24-hour BP reductions compared with the sham group. Increased antihypertensive drug burden in the US sham cohort, especially among Black Americans, may have diluted the treatment effect in the combined trial population. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02439775.
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Anti-Hipertensivos , Hipertensão , Humanos , Anti-Hipertensivos/uso terapêutico , Rim , Pressão Sanguínea/fisiologia , Denervação/métodos , Simpatectomia/métodos , Resultado do TratamentoRESUMO
BACKGROUND Renal denervation has proven its efficacy to lower blood pressure in comparison to sham treatment in recent randomized clinical trials. Although there is a large body of evidence for the durability and safety of radiofrequency-based renal denervation, there are a paucity of data for endovascular ultrasound-based renal denervation (uRDN). We aimed to assess the long-term efficacy and safety of uRDN in a single-center cohort of patients. METHODS AND RESULTS Data from 2 previous studies on uRDN were pooled. Ambulatory 24-hour blood pressure measurements were taken before as well as 3, 6, 12, and 24 months after treatment with uRDN. A total of 130 patients (mean age 63±9 years, 24% women) underwent uRDN. After 3, 6, 12, and 24 months, systolic mean 24-hour ambulatory blood pressure values were reduced by 10±12, 10±14, 8±15, and 10±15 mm Hg, respectively, when compared with baseline (P<0.001). Corresponding diastolic values were reduced by 6±8, 6±8, 5±9, and 6±9 mm Hg, respectively (P<0.001). Periprocedural adverse events occurred in 16 patients, and all recovered without sequelae. CONCLUSIONS In this single-center study, uRDN effectively lowered blood pressure up to 24 months after treatment.
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Hipertensão , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Masculino , Hipertensão/diagnóstico , Hipertensão/cirurgia , Hipertensão/tratamento farmacológico , Pressão Sanguínea , Anti-Hipertensivos/uso terapêutico , Monitorização Ambulatorial da Pressão Arterial , Artéria Renal/diagnóstico por imagem , Resultado do Tratamento , Rim , Simpatectomia/efeitos adversos , Simpatectomia/métodos , Denervação/métodosRESUMO
BACKGROUND: Arterial stiffening contributes to hemodynamic derangements in heart failure with preserved ejection fraction (HFpEF). We sought to investigate the impact of renal denervation on pulsatile left ventricular loading in patients with HFpEF and hypertensive patients without heart failure (control). METHODS: Patients underwent renal denervation for treatment of hypertension and were followed up at 3 months at a single center. A validated computer model of the arterial tree, noninvasive aortic flow curves, left ventricular volumes, and E/e' as inputs were used to determine key parameters of left ventricular vascular load. RESULTS: In comparison to controls (n=30), patients with HFpEF (n=30) demonstrated lower total arterial compliance (mean difference, -0.41 [95% CI, -0.72 to -0.10] mL/mm Hg), higher impedance of the proximal aorta (Zc: 0.02; 0.01 to 0.04 mHg·s/mL), premature wave reflections (shorter backward wave transit time normalized to ejection time: -3.5; -6.5% to -0.5%), and higher wave reflection magnitude (reflection coefficient: 7.3; 2.8% to 11.9%). Overall, daytime systolic (-9.2; -12.2 to -6.2 mm Hg) and diastolic blood pressures (-5.9; -7.6 to -4.1 mm Hg) as well as blood pressure variability (-2.0; -3.0 to -0.9 mm Hg) decreased after renal denervation. In patients with HFpEF, total arterial compliance (0.42; 0.17 to 0.67 mL/mm Hg) and backward transit time normalized to ejection time (1.7; 0.4% to 3.0%) increased; Zc (-0.01; -0.02 to -0.01 mm Hg·s/mL) and reflection coefficient (-2.6; -5.0% to -0.3%) decreased after renal denervation. This was accompanied by a symptomatic improvement in patients with HFpEF. CONCLUSION: HFpEF is characterized by heightened aortic stiffness and unfavorable pulsatile left ventricular load. These abnormalities are partly normalized after renal denervation.
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Insuficiência Cardíaca , Hipertensão , Humanos , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/cirurgia , Volume Sistólico/fisiologia , Função Ventricular Esquerda/fisiologia , Ventrículos do Coração , Hipertensão/diagnóstico , Hipertensão/cirurgia , Hipertensão/complicações , DenervaçãoRESUMO
Persisting iatrogenic atrial septal defects (iASD) after transcatheter mitral edge-to-edge repair (M-TEER) are associated with impaired outcomes. We investigated the natural history of relevant iASDs with left-to-right shunting post-M-TEER, predictors of spontaneous closure of iASD between 1 and 6 months post-M-TEER, and outcomes (heart failure [HF] hospitalization) in patients with spontaneous closure versus those with persistent iASD 6 months post-M-TEER. Patients with a relevant iASD 1-month post-M-TEER, who were treated conservatively in the randomized controlled MITHRAS trial, underwent clinical follow-up including transesophageal echocardiography 6 months post-M-TEER. Overall, 36 patients (median 77 [interquartile range 65-81] years; 36% women) completed the 6-months follow-up. Six (17%) patients had a spontaneous closure of the iASD. The eccentricity index of the iASD 1-month after M-TEER was the strongest predictor for spontaneous closure (Odds ratio 3.78; 95% confidence interval 1.26-11.33, p = 0.01) and an eccentricity index of < 1.9 provided a sensitivity of 77% at a specificity of 83% for iASD persistence (Area under the curve 0.83, p < 0.001) within 6-months post M-TEER.At follow-up, a numerical difference in the endpoint of HF hospitalization between the spontaneous closure and the residual shunt group (0% vs. 20%, p = 0.25) was observed. The eccentricity of the iASD was the strongest predictor for spontaneous closure at 1-months and an eccentricity index of < 1.9 is associated with a high persistence rate for 6 month after M-TEER. Clinical Trial Registration ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT03024268 Identifier: NCT03024268. a (red) is reflecting the mayor lengthwise dimension and b (blue) the mayor oblique dimension. The eccentricity index is calculated by dividing a through b. (Open circle) is depicting an example for a round iASD and (Open rhombus) an example for an eccentric iASD 1 month after M-TEER.
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Comunicação Interatrial , Insuficiência da Valva Mitral , Humanos , Feminino , Masculino , Cateterismo Cardíaco , Valor Preditivo dos Testes , Doença Iatrogênica , Resultado do TratamentoRESUMO
PURPOSE: Shock is a life-threatening condition characterized by substantial alterations in the microcirculation. This study tests the hypothesis that considering sublingual microcirculatory perfusion variables in the therapeutic management reduces 30-day mortality in patients admitted to the intensive care unit (ICU) with shock. METHODS: This randomized, prospective clinical multicenter trial-recruited patients with an arterial lactate value above two mmol/L, requiring vasopressors despite adequate fluid resuscitation, regardless of the cause of shock. All patients received sequential sublingual measurements using a sidestream-dark field (SDF) video microscope at admission to the intensive care unit (± 4 h) and 24 (± 4) hours later that was performed blindly to the treatment team. Patients were randomized to usual routine or to integrating sublingual microcirculatory perfusion variables in the therapy plan. The primary endpoint was 30-day mortality, secondary endpoints were length of stay on the ICU and the hospital, and 6-months mortality. RESULTS: Overall, we included 141 patients with cardiogenic (n = 77), post cardiac surgery (n = 27), or septic shock (n = 22). 69 patients were randomized to the intervention and 72 to routine care. No serious adverse events (SAEs) occurred. In the interventional group, significantly more patients received an adjustment (increase or decrease) in vasoactive drugs or fluids (66.7% vs. 41.8%, p = 0.009) within the next hour. Microcirculatory values 24 h after admission and 30-day mortality did not differ [crude: 32 (47.1%) patients versus 25 (34.7%), relative risk (RR) 1.39 (0.91-1.97); Cox-regression: hazard ratio (HR) 1.54 (95% confidence interval (CI) 0.90-2.66, p = 0.118)]. CONCLUSION: Integrating sublingual microcirculatory perfusion variables in the therapy plan resulted in treatment changes that do not improve survival at all.
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Choque Séptico , Humanos , Microcirculação , Estudos Prospectivos , Choque Séptico/tratamento farmacológico , Ressuscitação/métodos , Unidades de Terapia IntensivaRESUMO
Evidence from recent sham-controlled trials supports the use of endovascular renal denervation (RDN) to lower blood pressure in general as well as in treatment-resistant hypertension. According to recent studies, the effects of RDN are long lasting. Newer technologies using multipolar radiofrequency catheters and an additional ablation of the renal side branches as well as ultrasound with improved circumferential tissue penetration have made these advances possible. This has initiated a change of the perspective on RDN in clinical guidelines and has thereby set a cornerstone for a broader clinical application of RDN in the future.
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Background: Despite recent advances in the treatment of heart failure with preserved ejection fraction (HFpEF), the overall outcome is poor and evidence-based therapeutic options are scarce. So far, the only evidence-based therapy in HFpEF, sodium glucose linked transporter 2 inhibitors, has only insignificant effects in patients with a high EF (EF > 60%, HEF) when compared to a normal EF (EF 50%-60%, NEF). This could be explained by different biomechanical and cellular phenotypes of HFpEF across the range of EFs rather than a uniform pathophysiology. We aimed to investigate the concept of different phenotypes in the HEF and NEF using noninvasive single-beat estimations and to observe alterations in pressure-volume relations in both groups following sympathomodulation using renal denervation (RDN). Methods: Patients from a previous study on RDN in HFpEF were stratified by having HFpEF with an HEF or NEF. Single-beat estimations were used to derive arterial elastance (Ea), end-systolic elastance (Ees), and diastolic capacitance (VPED20). Results: Overall, 63 patients were classified as having an HEF, and 36 patients were classified as having an NEF. Ea did not differ between the groups and was reduced at follow-up in both groups (p < 0.01). Ees was higher and VPED20 was lower in the HEF than those in the NEF. Both were changed significantly at follow-up in the HEF but not in the NEF. Ees/Ea was lower in the NEF (0.95 ± 0.22 vs 1.15 ± 0.27, p < 0.01) and was significantly increased in the NEF (by 0.08 ± 0.20, p < 0.05) but not in the HEF. Conclusions: Beneficial effects of RDN were observed in the NEF and HEF, supporting the further investigation of sympathomodulating treatments for HFpEF in future trials.
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BACKGROUND: Left atrial (LA) reservoir strain provides prognostic information in patients with and without heart failure (HF), but might be altered by atrial fibrillation (AF). The aim of the current study was to investigate changes of LA deformation in patients undergoing cardioversion (CV) for first-time diagnosis of AF. METHODS AND RESULTS: We performed 3D-echocardiography and strain analysis before CV (Baseline), after 25 ± 10 days (FU-1) and after 190 ± 20 days (FU-2). LA volumes, reservoir, conduit and active function were measured. In total, 51 patients were included of whom 35 were in SR at FU-1 (12 HF and preserved ejection fraction (HFpEF)), while 16 had ongoing recurrence of AF (9 HFpEF). LA maximum volume was unaffected by cardioversion (Baseline vs. FU-2: 41 ± 11 vs 40 ± 10 ml/m2; p = 0.85). Restored SR led to a significant increase in LA reservoir strain (Baseline vs FU-1: 12.9 ± 6.8 vs 24.6 ± 9.4, p < 0.0001), mediated by restored LA active strain (SR group Baseline vs. FU-1: 0 ± 0 vs. 12.3 ± 5.3%, p < 0.0001), while LA conduit strain remained unchanged (Baseline vs. FU-1: 12.9 ± 6.8 vs 13.1 ± 6.2, p = 0.78). Age-controlled LA active strain remained the only significant predictor of LA reservoir strain on multivariable analysis (ß 1.2, CI 1.04-1.4, p < 0.0001). HFpEF patients exhibited a significant increase in LA active (8.2 ± 4.3 vs 12.2 ± 6.6%, p = 0.004) and reservoir strain (18.3 ± 5.7 vs. 22.8 ± 8.8, p = 0.04) between FU-1 and FU-2, associated with improved LV filling (r = 0.77, p = 0.005). CONCLUSION: Reestablished SR improves LA reservoir strain by restoring LA active strain. Despite prolonged atrial stunning following CV, preserved SR might be of hemodynamic and prognostic benefit in HFpEF.
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Fibrilação Atrial , Insuficiência Cardíaca , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/terapia , Função do Átrio Esquerdo , Cardioversão Elétrica/métodos , Átrios do Coração/diagnóstico por imagem , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/terapia , Humanos , Volume SistólicoRESUMO
BACKGROUND: Recent trials support the efficacy of renal sympathetic denervation (RDN) to reduce blood pressure (BP). Nevertheless, about one third of patients are considered non-responders to RDN. Previous retrospective analyses suggest arterial stiffness could predict BP response to RDN. AIMS: We prospectively assessed the potential of invasive pulse wave velocity (iPWV) to predict BP response to RDN. Additionally, we aimed to establish non-invasive models based on arterial stiffness to predict BP response to RDN. METHODS: iPWV, magnetic resonance imaging-based markers of arterial stiffness and the carotid-femoral pulse wave velocity were recorded prior to RDN in patients with treatment resistant hypertension. Changes in daytime BP after 3 months were analysed according to the prespecified iPWV cut-off (14.4 m/s). Regression analyses were used to establish models for non-invasive prediction of BP response. Results were compared to iPWV as reference and were then validated in an external patient cohort. RESULTS: Eighty patients underwent stiffness assessment before RDN. After 3 months, systolic 24h and daytime BP were reduced by 13.6±9.8 mmHg and 14.7±10.6 mmHg in patients with low iPWV, versus 6.2±13.3 mmHg and 6.3±12.8 mmHg in those with high iPWV (p<0.001 for both). Upon regression analysis, logarithmic ascending aortic distensibility and systolic baseline BP independently predicted BP change at follow-up. Both were confirmed in the validation cohort. CONCLUSIONS: iPWV is an independent predictor for BP response after RDN. In addition, BP change prediction following RDN using non-invasive measures is feasible. This could facilitate patient selection for RDN treatment.
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Hipertensão , Rigidez Vascular , Pressão Sanguínea/fisiologia , Denervação , Humanos , Rim/cirurgia , Análise de Onda de Pulso , Estudos Retrospectivos , Simpatectomia/métodos , Resultado do Tratamento , Rigidez Vascular/fisiologiaRESUMO
Background Recent trial results support the efficacy of renal sympathetic denervation in lowering blood pressure (BP). While BP reduction in general is associated with a clinically meaningful reduction in cardiovascular events and mortality, such a relationship has not been described for patients undergoing renal sympathetic denervation. Methods and Results Clinical events were assessed in patients who underwent renal sympathetic denervation at our center using telephone- and clinical follow-up, interviews with general practitioners, as well as review of hospital databases. Event rates were compared between BP responders (≥5 mm Hg 24-hour ambulatory BP reduction) and non-responders; 296 patients were included. Compared with baseline, 24-hour systolic ambulatory BP was reduced by 8.3±12.2 mm Hg and diastolic BP by 4.8±7.0 mm Hg (P<0.001 for both) after 3 months. One hundred eighty patients were classified as BP responders and 116 as non-responders. During a median follow-up time of 48 months, significantly less major adverse cardiovascular events (cardiovascular death, stroke, myocardial infarction, critical limb ischemia, renal failure) occurred in responders than in non-responders (22 versus 23 events, hazard ratio [HR], 0.53 [95% CI, 0.28 to 0.97], P=0.041). This was consistent after adjustment for potential confounders as well as confirmed by propensity-score matching. A proportional relationship was found between BP reduction after 3 months and frequency of major adverse cardiovascular events (HR, 0.75 [95% CI, 0.58 to 0.97] per 10 mm Hg 24-hour systolic ambulatory BP reduction). Conclusions Based on these observational data, blood pressure response to renal sympathetic denervation is associated with improved long-term clinical outcome.
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Isquemia Crônica Crítica de Membro , Hipertensão , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea , Monitorização Ambulatorial da Pressão Arterial , Denervação , Humanos , Hipertensão/tratamento farmacológico , Rim , Simpatectomia , Resultado do TratamentoRESUMO
OBJECTIVES: The authors investigated whether iatrogenic atrial septal defect (iASD) closure post-transcatheter mitral valve edge-to-edge repair (TMVR) is superior to conservative therapy (CT) and whether outcomes (death/heart failure [HF] hospitalization) differ between patients with and without an iASD post-TMVR. BACKGROUND: Transseptal access for TMVR can create an iASD, which is associated with impaired outcomes. Controversially, the creation of an iASD in HF has been linked to improved hemodynamics. METHODS: 80 patients with an iASD and relevant left-to-right shunting (Qp:Qs ≥1.3) 30 days following TMVR were randomized to CT or interventional closure of the iASD (MITHRAS [Closure of Iatrogenic Atrial Septal Defect Following Transcatheter Mitral Valve Repair] cohort), and 235 patients without an iASD served as a comparative cohort. RESULTS: All patients of the MITHRAS cohort (mean age 77 ± 9 years, 39% women) received their allocated treatment, and follow-up was completed for all MITHRAS and comparative cohort (mean age 77 ± 8 years, 47% women) patients. Twelve months post-TMVR, there was no significant difference in the combined endpoint of death or HF hospitalization within the MITHRAS cohort (iASD closure: 35% vs CT 50%; P = 0.26). The combined endpoint was more frequent among patients within the MITHRAS cohort as opposed to the comparative cohort (43% vs 17%; P < 0.0001), primarily driven by a higher rate of HF hospitalization (34% vs 8%; P = 0.004). CONCLUSIONS: In this randomized controlled trial, interventional closure of a relevant iASD 1 month after TMVR did not result in improved clinical outcomes at 12 months post-TMVR. Patients with an iASD are at higher risk for HF hospitalization independent of iASD management and warrant close follow-up. (Closure of Iatrogenic Atrial Septal Defect Following Transcatheter Mitral Valve Repair [MITHRAS]; NCT03024268).
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Comunicação Interatrial , Implante de Prótese de Valva Cardíaca , Insuficiência da Valva Mitral , Idoso , Idoso de 80 Anos ou mais , Cateterismo Cardíaco/efeitos adversos , Feminino , Implante de Prótese de Valva Cardíaca/efeitos adversos , Humanos , Doença Iatrogênica , Masculino , Valva Mitral/diagnóstico por imagem , Valva Mitral/cirurgia , Insuficiência da Valva Mitral/diagnóstico por imagem , Insuficiência da Valva Mitral/cirurgia , Resultado do TratamentoRESUMO
BACKGROUND: Arterial hypertension is the most common comorbidity in patients with heart failure with preserved ejection fraction (HFpEF) and mediates adverse hemodynamics through related aortic stiffness and increased pulsatile load. We aimed to investigate the clinical and hemodynamic implications of renal sympathetic denervation (RDN) in patients with HFpEF and uncontrolled arterial hypertension. METHODS: Patients undergoing RDN between 2011 and 2018 in a single-center were retrospectively analyzed and classified as HFpEF (n=99) or no HF (n=65). Stroke volume index and aortic distensibility were measured through cardiac magnetic resonance imaging, and left ventricular (LV) systolic and diastolic properties were assessed echocardiographically. RESULTS: At baseline, patients with HFpEF had higher stroke volume index (median 40 [interquartile range, 33-48] versus 33 [26-40] mL/m2, P=0.002), pulse pressure (69 [63-77] versus 61 [55-67] mm Hg, P<0.001), but lower LV-VPES100mm Hg (18 [10-28] versus 24 [15-40] mL, P=0.007) and aortic distensibility (1.5 [1.1-2.6] versus 2.7 [1.1-3.5] 10-3 mm Hg-1, P=0.013) as compared to no-HF patients. Systolic blood pressure decreased comparable in patients with HFpEF and no-HF patients following RDN (-9 [-16 to -2], P<0.001). After RDN stroke volume index (-3 [-9 to +3] mL/m2, P=0.011) decreased and aortic distensibility (0.2 [-0.1 to +1.1] 10-3 mm Hg-1, P=0.007) and systolic stiffness (P<0.001) increased in HFpEF patients. LV diastolic stiffness and LV filling pressures as well as NT-proBNP (N-terminal pro-B-type natriuretic peptide) decreased after RDN in patients with HFpEF (P=0.032, P=0.043, and P<0.001, respectively). CONCLUSIONS: Patients with HFpEF undergoing RDN showed increased stroke volume index, vascular, and LV stiffness as compared to no-HF patients. Following RDN those hemodynamic alterations and reduced systolic and diastolic LV stiffness were partly normalized, implying RDN might be a potential therapeutic strategy for arterial hypertension and HFpEF.