ABSTRACT
BACKGROUND: Treatment of left ventricular outflow-obstruction (LVOTO) in hypertrophic obstructive cardiomyopathy (HOCM) by short atrio-ventricular delay pacing has long-term hemodynamic results that are not inferior to myectomy, but publications comparing long-term morbidity following those treatments are lacking. METHODS: A search for HOCM-patients attending all ten hospitals in the West Götaland Region, Sweden, from 2002 through 2013, identified 251 patients (42 treated with myectomy, 88 with pacing and 121 conservatively). As the age at procedure was significantly lower in the myectomy-group compared to the pacing-group, morbidity was compared by case-control methodology, matching patients for age, maximal wall thickness and LVOT-gradient. We found 31 pairs who constituted the comparison-groups. Post-intervention median follow-up was 15.4 and 10.4 years in pacing- and myectomy-group, respectively. Post-procedural and long-term complications and re-interventions, length of stay, and cost of hospitalization were documented. RESULTS: Both treatments improved New York Heart Association class and LVOT-gradients significantly. There were fewer peri-procedural complications in the pacing-group compared to myectomy-group (3.2% and 35.5% p < 0.001). During follow-up pacemaker was implanted in 35.5% of myectomy-group for atrio-ventricular block, 9.7% peri-operatively, and 25.8% during late-follow-up. Furthermore, the pacing group had a superior freedom from all re-interventions, 90.3% versus 61.3% in myectomy-group (p = 0.003). Pacing patients had a shorter in-hospital stay (median 4 [IQR = 2] days) compared to myectomy 11 [7] days; P < 0.001). The mean cost of hospitalization was 74,000 ± 16,000 SEK for pacing and 310,000 ± 180,000 SEK for myectomy, p < 0.001. CONCLUSION: Pacing is a simple and reliable treatment for drug-refractory HOCM-patients with low rate of complications and costs.
Subject(s)
Cardiomyopathy, Hypertrophic , Cardiomyopathy, Hypertrophic/diagnostic imaging , Cardiomyopathy, Hypertrophic/surgery , Case-Control Studies , Humans , Morbidity , Sweden/epidemiology , Treatment OutcomeABSTRACT
AIMS: Invasive haemodynamic profiles at rest and during exercise after heart transplantation (HTx) have never been described in a randomized trial where de novo everolimus (EVR)-based therapy with early calcineurin inhibitor (CNI) withdrawal has been compared with conventional CNI treatment. We report central invasive haemodynamic parameters at rest and exercise during a 3 year follow-up after HTx in a sub-study of the SCandiavian Heart transplant Everolimus De novo stUdy with earLy calcineurin inhibitor avoidancE trial. We hypothesized that the nephroprotective properties, the less development of cardiac allograft vasculopathy (CAV), and the antifibrotic properties of EVR, in comparison with CNI-based immunosuppression, would demonstrate favourable invasive haemodynamic profiles in patients at rest and during exercise. METHODS AND RESULTS: Ninety of 115 HTx recipients randomized to EVR or CNI treatment performed right heart catheterization at rest and 68 performed right heart catheterization at exercise up to 3 years after HTx. Haemodynamic profiles were compared between EVR and CNI treatment groups. Resting haemodynamics improved in both groups from pre-HTx to the first follow-up at 7-11 weeks post-HTx and thereafter remained unchanged up to 3 years of follow-up. During follow-up, cardiac reserve during exercise increased with higher levels of maximum heart rate (118 to 148 b.p.m., P < 0.001), mean arterial pressure (103 to 128 mmHg, P < 0.001), and cardiac output (10.3 to 12.2 l/min, P < 0.001). No significant differences in haemodynamic parameters were observed between the EVR and CNI groups at rest or exercise. Isolated post-capillary pulmonary hypertension (mean pulmonary arterial pressure > 20 mmHg, pulmonary arterial wedge pressure ≥ 15 mmHg, and pulmonary vascular resistance <3) were measured in 11% of the patients at 7-11 weeks, 5% at 12 months, and 6% at 36 months after HTx. The EVR group had significantly better kidney function (76 mL/min/1 vs. 60 mL/min/1, P < 0.001) and reduced CAV (P < 0.01) but an increased rate of early biopsy-proven treated rejections (21.2% vs 5.7%, P < 0.01) compared with the CNI group at any time point. The differences in renal function, CAV, or early biopsy-proven treated acute rejections were not associated with altered haemodynamics. CONCLUSIONS: De novo EVR treatment with early CNI withdrawal compared with conventional CNI therapy did not result in differences in haemodynamics at rest or during exercise up to 3 years after HTx despite significant differences in renal function, reduced CAV, and number of early biopsy-proven treated rejections.
Subject(s)
Calcineurin Inhibitors , Heart Transplantation , Everolimus , Hemodynamics , Humans , Immunosuppressive Agents/pharmacology , Prospective StudiesABSTRACT
To evaluate the association between mild acute cellular rejection (ACR) and the development of cardiac allograft vasculopathy (CAV) after heart transplantation (HTx). Substudy of the SCHEDULE trial (n = 115), where de novo HTx recipients were randomized to (i) everolimus with early CNI elimination or (ii) CNI-based immunosuppression. Seventy-six patients (66%) were included based on matched intravascular ultrasound (IVUS) examinations at baseline and year 3 post-HTx. Biopsy-proven ACR within year 1 post-HTx was recorded and graded (1R, 2R, 3R). Development of CAV was assessed by IVUS and coronary angiography at year 3 post-HTx. Median age was 53 years (45-61), and 71% were male. ACR was recorded in 67%, and patients were grouped by rejection profile: no ACR (33%), only 1R (42%), and ≥2R (25%). Median ∆MIT (maximal intimal thickness)BL-3Y was not significantly different between groups (P = 0.84). The incidence of CAV was 49% by IVUS and 26% by coronary angiography with no significant differences between groups. No correlation was found between number of 1R and ∆MITBL-3Y (r = -0.025, P = 0.83). The number of 1R was not a significant predictor of ∆MITBL-3Y (P = 0.58), and no significant interaction with treatment was found (P = 0.98). The burden of mild ACR was not associated with CAV development.
Subject(s)
Heart Transplantation , Ultrasonography, Interventional , Allografts , Coronary Angiography , Graft Rejection/diagnostic imaging , Graft Rejection/etiology , Heart Transplantation/adverse effects , Humans , Male , Middle AgedABSTRACT
AIM: To investigate the prognostic value of early post-transplant hemodynamic measurements on 5-year mortality in cardiac recipients (HTx). METHODS: A right heart catheterization was performed in 290 heart transplantation (HTx) recipients at a one-year post-HTx evaluation. To study the effect of post-HTx hemodynamic variables on 5-year outcome, the cohort was stratified into several subgroups. For right atrial pressure (RAP), mean pulmonary artery pressure (MPAP), pulmonary artery wedge pressure (PAWP), and pulmonary vascular resistance (PVR), patients with values from the upper 10th percentile (high), were compared with those with values from the remaining lower 90th percentile (normal). For cardiac index (CI), patients with values from the lower 10th percentile (low) were compared with those with values from the remaining upper 90th percentile (normal). RESULTS: Death or re-transplantation within 5â¯years after the one-year control occurred in 44 patients (13%). Of those, death or re-HTx was related to graft failure in 20 of cases (45%) and non-cardiac causes in 24 of cases (55%). The risk of death or re-HTx was higher in the subgroup with MPAP above 23â¯mmHg than those equal to or below this value [hazard ratio 3.22, 95% confidence interval (CI) 1.49-6.97; Pâ¯=â¯0.003]. The association remained significant despite adjustment for several comorbidities. There were no differences in outcome between subgroups stratified with respect to high versus low RAP, PAWP, CI or PVR. CONCLUSION: Elevated pulmonary artery pressure at a first annual evaluation after HTx was the only hemodynamic variable that predicted impaired outcome in cardiac recipients.
ABSTRACT
BACKGROUND: A calcineurin inhibitor (CNI)-free immunosuppressive regimen has been demonstrated to improve renal function early after heart transplantation, but long-term outcome of such a strategy has not been well described. METHODS: In the randomized SCHEDULE trial, de novo heart transplant recipients received (1) everolimus with reduced-exposure CNI (cyclosporine) followed by CNI withdrawal at week 7-11 posttransplant or (2) standard-exposure cyclosporine, both with mycophenolate mofetil and corticosteroids; 95/115 randomized patients were followed up at 5-7 years posttransplant. RESULTS: Mean measured glomerular filtration rate was 74.7 mL/min and 62.4 mL/min with everolimus and CNI, respectively. The mean difference was in favor of everolimus by 11.8 mL/min in the intent-to-treat population (P = 0.004) and 17.2 mL/min in the per protocol population (n = 75; P < 0.001). From transplantation to last follow-up, the incidence of biopsy-proven acute rejection (BPAR) was 77% (37/48) and 66% (31/47) (P = 0.23) with treated BPAR in 50% and 23% (P < 0.01) in the everolimus and CNI groups, respectively; no episode led to hemodynamic compromise. Coronary allograft vasculopathy (CAV) assessed by coronary intravascular ultrasound was present in 53% (19/36) and 74% (26/35) of everolimus- and CNI-treated patients, respectively (P = 0.037). Graft dimensions and function were similar between the groups. Late adverse events were comparable. CONCLUSIONS: These results suggest that de novo heart transplant patients randomized to everolimus and low-dose CNI followed by CNI-free therapy maintain significantly better long-term renal function as well as significantly reduced CAV than patients randomized to standard CNI treatment. Increased BPAR in the everolimus group during year 1 did not impair long-term graft function.
Subject(s)
Calcineurin Inhibitors/administration & dosage , Coronary Artery Disease/epidemiology , Everolimus/administration & dosage , Graft Rejection/epidemiology , Heart Transplantation/adverse effects , Immunosuppressive Agents/administration & dosage , Adult , Calcineurin Inhibitors/adverse effects , Coronary Artery Disease/diagnosis , Coronary Artery Disease/etiology , Coronary Vessels/diagnostic imaging , Cyclosporine/administration & dosage , Cyclosporine/adverse effects , Dose-Response Relationship, Drug , Everolimus/adverse effects , Female , Follow-Up Studies , Glomerular Filtration Rate/drug effects , Glomerular Filtration Rate/physiology , Glucocorticoids/administration & dosage , Graft Rejection/immunology , Graft Rejection/physiopathology , Graft Rejection/prevention & control , Graft Survival/drug effects , Graft Survival/immunology , Humans , Immunosuppressive Agents/adverse effects , Male , Middle Aged , Mycophenolic Acid/administration & dosage , Mycophenolic Acid/adverse effects , Prospective Studies , Randomized Controlled Trials as Topic , Ultrasonography, InterventionalABSTRACT
Background: The impact of renal denervation (RDN) on muscle sympathetic nerve activity (MSNA) at rest remains controversial. Mental stress (MS) induces transient changes in sympathetic nerve activity, heart rate (HR) and blood pressure (BP). It is not known whether RDN modifies these changes.Purpose: The main objective was to assess the effect of RDN on MSNA and BP alterations during MS.Methods: In 14 patients (11 included in analysis) with resistant hypertension multi-unit MSNA, BP (Finometer ®) and HR were assessed at rest and during forced arithmetics at baseline and 6 months after RDN.Results: Systolic office BP decreased significantly 6 months after RDN (185 ± 29 vs.175 ± 33 mmHG; p = 0.04). No significant changes in MSNA at rest (68 ± 5 vs 73 ± 5 bursts/100hb; p = 0.43) were noted and no significant stress-induced change in group averaged sympathetic activity was found pre- (101 ± 24%; p = 0.9) or post-intervention (108 ± 26%; p = 0.37). Stress was associated with significant increases in mean arterial BP (p < 0.01) and HR (p < 0.01) at baseline, reactions which remained unaltered after intervention. We did not note any correlation between sympathetic nerve activity and BP changes after RDN.Conclusion: Thus, in our group of resistant hypertensives we find no support for the hypothesis that the BP-lowering effect of RDN depends on altered neurovascular responses to stress.
Subject(s)
Stress, Psychological/physiopathology , Sympathectomy/psychology , Aged , Arterial Pressure/physiology , Blood Pressure/physiology , Blood Pressure Determination/methods , Female , Heart Rate/physiology , Humans , Hypertension/physiopathology , Kidney/physiopathology , Male , Sympathetic Nervous System/physiology , Treatment OutcomeABSTRACT
BACKGROUND: Moderate and moderately severe renal impairment are common in patients with heart failure and reduced ejection fraction, but whether beta-blockers are effective is unclear, leading to underuse of life-saving therapy. OBJECTIVES: This study sought to investigate patient prognosis and the efficacy of beta-blockers according to renal function using estimated glomerular filtration rate (eGFR). METHODS: Analysis of 16,740 individual patients with left ventricular ejection fraction <50% from 10 double-blind, placebo-controlled trials was performed. The authors report all-cause mortality on an intention-to-treat basis, adjusted for baseline covariates and stratified by heart rhythm. RESULTS: Median eGFR at baseline was 63 (interquartile range: 50 to 77) ml/min/1.73 m2; 4,584 patients (27.4%) had eGFR 45 to 59 ml/min/1.73 m2, and 2,286 (13.7%) 30 to 44 ml/min/1.73 m2. Over a median follow-up of 1.3 years, eGFR was independently associated with mortality, with a 12% higher risk of death for every 10 ml/min/1.73 m2 lower eGFR (95% confidence interval [CI]: 10% to 15%; p < 0.001). In 13,861 patients in sinus rhythm, beta-blockers reduced mortality versus placebo; adjusted hazard ratio (HR): 0.73 for eGFR 45 to 59 ml/min/1.73 m2 (95% CI: 0.62 to 0.86; p < 0.001) and 0.71 for eGFR 30 to 44 ml/min/1.73 m2 (95% CI: 0.58 to 0.87; p = 0.001). The authors observed no deterioration in renal function over time in patients with moderate or moderately severe renal impairment, no difference in adverse events comparing beta-blockers with placebo, and higher mortality in patients with worsening renal function on follow-up. Due to exclusion criteria, there were insufficient patients with severe renal dysfunction (eGFR <30 ml/min/1.73 m2) to draw conclusions. In 2,879 patients with atrial fibrillation, there was no reduction in mortality with beta-blockers at any level of eGFR. CONCLUSIONS: Patients with heart failure, left ventricular ejection fraction <50% and sinus rhythm should receive beta-blocker therapy even with moderate or moderately severe renal dysfunction.
Subject(s)
Adrenergic beta-Antagonists/therapeutic use , Glomerular Filtration Rate/physiology , Heart Failure/drug therapy , Renal Insufficiency/physiopathology , Stroke Volume/physiology , Ventricular Function, Left/physiology , Aged , Cause of Death/trends , Comorbidity , Disease Progression , Double-Blind Method , Female , Glomerular Filtration Rate/drug effects , Heart Failure/epidemiology , Heart Failure/physiopathology , Humans , Male , Middle Aged , Prognosis , Renal Insufficiency/epidemiology , Stroke Volume/drug effects , Survival Rate/trends , Ventricular Function, Left/drug effectsABSTRACT
OBJECTIVES: The authors investigated the impact of coronary artery bypass grafting (CABG) on first and recurrent hospitalization in this population. BACKGROUND: In the STICH (Surgical Treatment for Ischemic Heart Failure) trial, CABG reduced all-cause death and hospitalization in patients with and ischemic cardiomyopathy and left ventricular ejection fraction <35%. METHODS: A total of 1,212 patients were randomized (610 to CABG + optimal medical therapy [CABG] and 602 to optimal medical therapy alone [MED] alone) and followed for a median of 9.8 years. All-cause and cause-specific hospitalizations were analyzed as time-to-first-event and as recurrent event analysis. RESULTS: Of the 1,212 patients, 757 died (62.4%) and 732 (60.4%) were hospitalized at least once, for a total of 2,549 total all-cause hospitalizations. Most hospitalizations (66.2%) were for cardiovascular causes, of which approximately one-half (907 or 52.9%) were for heart failure. More than 70% of all hospitalizations (1,817 or 71.3%) were recurrent events. The CABG group experienced fewer all-cause hospitalizations in the time-to-first-event (349 CABG vs. 383 MED, adjusted hazard ratio [HR]: 0.85; 95% confidence interval [CI]: 0.74 to 0.98; p = 0.03) and in recurrent event analyses (1,199 CABG vs. 1,350 MED, HR: 0.78, 95% CI: 0.65 to 0.94; p < 0.001). This was driven by fewer total cardiovascular (CV) hospitalizations (744 vs. 968; p < 0.001, adjusted HR: 0.66, 95% CI: 0.55 to 0.81; p = 0.001), the majority of which were due to HF (395 vs. 512; p < 0.001, adjusted HR: 0.68, 95% CI: 0.52-0.89; p = 0.005). We did not observe a difference in non-CV events. CONCLUSIONS: CABG reduces all-cause, CV, and HF hospitalizations in time-to-first-event and recurrent event analyses. (Comparison of Surgical and Medical Treatment for Congestive Heart Failure and Coronary Artery Disease [STICH]; NCT00023595).
Subject(s)
Cardiomyopathies/therapy , Coronary Artery Bypass , Heart Failure/therapy , Myocardial Ischemia/therapy , Aged , Cardiomyopathies/etiology , Cardiomyopathies/physiopathology , Female , Heart Failure/etiology , Heart Failure/physiopathology , Hospitalization , Humans , Male , Middle Aged , Mortality , Myocardial Ischemia/complications , Myocardial Ischemia/physiopathology , Recurrence , Stroke VolumeABSTRACT
Objective: In order to avoid effects of referral bias, we assessed risk factors for disease-related mortality in a geographical cohort of patients with hypertrophic obstructive cardiomyopathy (HOCM), and any therapy effect on survival. Methods: Diagnostic databases in 10 hospitals in the West Götaland Region yielded 251 adult patients with HOCM (128 male, 123 female). Case notes were reviewed for clinical data and ECG and ultrasound findings. Beta-blockers were used in 71.3% of patients from diagnosis (median metoprolol-equivalent dose of 125 mg/day), and at latest follow-up in 86.1%; 121 patients had medical therapy alone, 88 short atrioventricular delay pacing and 42 surgical myectomy. Mean follow-up was 14.4±8.9 (mean±SD) years. Primary endpoint was disease-related death, and secondary endpoint heart failure deaths. Results: There were 65 primary endpoint events. Independent risk factors for disease-related death on multivariate Cox hazard regression were: female sex (p=0.005), age at diagnosis (p<0.001), outflow gradient ≥50 mm Hg at diagnosis (p=0.036) and at follow-up (p=0.001). Heart failure caused 62% of deaths, and sudden cardiac death 17%. Late independent predictors of heart failure death were: female sex (p=0.003), outflow gradient ≥50 mm Hg at latest follow-up (p=0.032), verapamil/diltiazem therapy (p=0.012) and coexisting hypertension (p=0.031), but not other comorbidities. Neither myectomy nor pacing modified survival, but early and maintained beta-blocker therapy was associated with dose-dependent reduction in disease-related mortality in the multivariate model (p=0.028), and final dose was also associated with reduced heart failure mortality (p=0.008). Kaplan-Meier survival curves analysed in initial dose bands of 0-74, 75-149 and ≥150 mg metoprolol/day showed 10-year freedom from disease-related deaths of 83.1%, 90.7% and 97.0%, respectively (ptrend=0.00008). Even after successful relief of outflow obstruction by intervention, there was survival benefit of metoprolol doses ≥100 mg/day (p=0.01). Conclusions: In population-based HOCM cohorts heart failure is a dominant cause of death and on multivariate analysis beta-blocker therapy was associated with a dose-dependent cardioprotective effect on total, disease-related as well as heart failure-related mortality.
ABSTRACT
OBJECTIVES: First-generation radiofrequency renal denervation devices may have had limited efficacy due to incomplete circumferential ablation and dependence on individual operator technique. This study evaluated a next-generation catheter-based technology using ultrasound designed to maximize nerve coverage using circumferential ultrasound energy. METHODS: This was a prospective, multicenter, nonrandomized, postmarket study evaluating the safety and efficacy of an endovascular ultrasound renal denervation system (Paradise) in patients who met the European Society of Hypertension/European Society of Cardiology definition of resistant hypertension. Major exclusion criteria included renal artery stenosis and renal insufficiency. Patients were followed for 12 months. Safety and efficacy endpoints included procedural safety and renal artery patency, as well as changes in systolic office and 24-h ambulatory bllod pressure (BP) measurement. RESULTS: A total of 96 patients from eight European sites were included. Mean age was 63.9 years and 41% of patients were female. At baseline, mean 24-h ambulatory BP was 156.2/88.4â±â15.4/12.7âmmHg, and mean office BP was 176.2/95.0â±â20.6/16.0âmmHg. Patients were on average on 5.1â±â2.5 antihypertensive agents. At 12 months, the average 24-h ambulatory BP change was -7.5/-3.8â±â18.3/10.6âmmHg (Pâ=â0.0007; Pâ=â0.0024) with an average office BP change of -15.0/-7.0â±â27.0/12.3âmmHg (Pâ<â0.0001 for both). At 12 months, there was a single patient death unrelated to the device or procedure. CONCLUSION: This single-arm study represents the largest cohort of patients treated with endovascular ultrasound renal denervation to date. Within this trial, the therapy appeared safe and resulted in sustained reductions in both office BP and 24-h ambulatory BP through 12 months.
Subject(s)
Catheter Ablation/statistics & numerical data , Denervation/statistics & numerical data , Endovascular Procedures/statistics & numerical data , Hypertension/surgery , Renal Artery/innervation , Aged , Antihypertensive Agents/therapeutic use , Catheter Ablation/instrumentation , Catheter Ablation/methods , Cohort Studies , Denervation/instrumentation , Denervation/methods , Endovascular Procedures/instrumentation , Endovascular Procedures/methods , Female , Humans , Hypertension/drug therapy , Kidney/innervation , Male , Middle Aged , Prospective Studies , Renal Artery/surgery , Treatment Outcome , UltrasonographyABSTRACT
BACKGROUND: Coronary Artery Bypass Grafting (CABG) reduces mortality in Heart Failure (HF) and coronary artery disease (CAD) patients (pts). There is a paucity of data on the utilization of optimal medical therapy (OMT) in HF and CAD pts after revascularization and the impact on long term outcomes. We evaluate the impact of baseline use of OMT versus Non-OMT on long-term clinical outcomes in pts receiving CABG compared to patients with medical treatment alone (MED). METHODS: The STICH trial randomized 1212 pts with CAD and left ventricular ejection fraction (LVEF) ≤ 35% to CABG + MED versus MED alone. OMT was defined as a combination of 4 drugs: ACEI/ARB, BB, statin, and at least one antiplatelet drug at baseline, with a median follow up over 9.8 years. RESULTS: At baseline, 58.7% of the pts were on OMT (CABG 56.1%; MED 61.5%), remaining stable or increasing similarly for both groups during follow up, for example, at 1 year, CABG 73.2% and Med 74.3%. Age, gender, diabetes were similar. OMT pts had less atrial fibrillation, lower angina score class, less advance heart failure class and better renal function. There were no differences in LVEF and end systolic and diastolic volume index. OMT use at baseline was associated with a significantly lower all-cause mortality compared to Non- OMT pts (58.8% vs 67.6%, log-rank P<0.001), lower cardiovascular mortality (40.3% vs 51.4%, log-rank P<0.001) and lower HF death, 11.2% vs 15.6%, log-rank P<0.001). Sudden death was not different (21.5% vs 23.4%, P=0.058). In a multivariable Cox model, OMT was associated with a lower All-cause mortality (HR 0.78, 95%CI 0.66-0.91 P=0.001). The effect of OMT was similar for both CABG and MED only pts for these outcomes (p=0.189 for interaction). Hospitalization for HF was not reduced with OMT. CONCLUSION: OMT is associated with lower all-cause mortality in CABG eligible HF pts, regardless of the lower baseline risk among OMT pts and the performance of CABG. OMT should be strongly considered for all pts with ischemic cardiomyopathy regardless of whether CABG is performed. (AU)
Subject(s)
Coronary Artery Disease/prevention & control , Coronary Artery Bypass/mortality , Clinical Trial Protocol , Heart FailureABSTRACT
BACKGROUND: Heart failure (HF) and non-cardiac comorbidities often coexist and are known to have an adverse effect on outcome. However, the prevalence and prognostic impact of non-cardiac comorbidities in patients with HF with reduced ejection fraction (HFrEF) vs. those with preserved (HFpEF) remain inadequately studied. METHODS AND RESULTS: We used data from the Swedish Heart Failure Registry from 2000 to 2012. HFrEF was defined as EF < 50% and HFpEF as EF ≥ 50%. Of 31 344 patients available for analysis, 79.3% (n = 24 856) had HFrEF and 20.7% (n = 6 488) HFpEF. The outcome was all-cause mortality. We examined the association between ten non-cardiac comorbidities and mortality and its interaction with EF using adjusted hazard ratio (HR). Stroke, anemia, gout and cancer had a similar impact on mortality in both phenotypes, whereas diabetes (HR 1.57, 95% confidence interval [CI] [1.50-1.65] vs. HR 1.39 95% CI [1.27-1.51], p = 0.0002), renal failure (HR 1.65, 95% CI [1.57-1.73] vs. HR 1.44, 95% CI [1.32-1.57], p = 0.003) and liver disease (HR 2.13, 95% CI [1.83-2.47] vs. HR 1.42, 95% CI [1.09-1.85] p = 0.02) had a higher impact in the HFrEF patients. Moreover, pulmonary disease (HR 1.46, 95% CI [1.40-1.53] vs. HR 1.66 95% CI [1.54-1.80], p = 0.007) was more prominent in the HFpEF patients. Sleep apnea was not associated with worse prognosis in either group. No significant variation was found in the impact over the 12-year study period. CONCLUSIONS: Non-cardiac comorbidities contribute significantly but differently to mortality, both in HFrEF and HFpEF. No significant variation was found in the impact over the 12-year study period. These results emphasize the importance of including the management of comorbidities as a part of a standardized heart failure care in both HF phenotypes.
Subject(s)
Heart Failure/epidemiology , Stroke Volume/physiology , Aged , Aged, 80 and over , Comorbidity , Female , Heart Failure/mortality , Humans , Male , Middle Aged , Prevalence , Prognosis , Registries , Sweden/epidemiologyABSTRACT
We report the case of a 38-year-old man who presented with cardiac arrest 1 year after curative liver transplantation for Wilson's disease. Clinical work-up proofed myocardial copper and iron accumulation using mass spectrometry, which led most likely to myocardial fibrosis as visualized by cardiovascular magnetic resonance (unprecedented delayed enhancement pattern) and endomyocardial biopsy. Consequently, cardiac arrest due to ventricular fibrillation and subsequent episodes of sustained ventricular tachycardia were considered as primary cardiac manifestation of Wilson's disease. This can, as illustrated by our case, occur even late after curative liver transplantation, which is an important fact that treating physicians should be aware of during clinical follow-up of these patients.
Subject(s)
Copper/metabolism , Heart Arrest/etiology , Hepatolenticular Degeneration/complications , Liver Transplantation , Myocardium/metabolism , Ventricular Fibrillation/complications , Adult , Biopsy , Electrocardiography , Follow-Up Studies , Heart Arrest/diagnosis , Hepatolenticular Degeneration/diagnosis , Hepatolenticular Degeneration/surgery , Humans , Magnetic Resonance Imaging, Cine , Male , Mass Spectrometry , Myocardium/pathology , Ventricular Fibrillation/diagnosisABSTRACT
Renal denervation (RDN) is a potential modality in the treatment of patients with resistant hypertension (RH) and has shown beneficial effect on a variety of cardiovascular surrogate markers. Coronary flow reserve, as assessed by transthoracic Doppler echocardiography (TDE-CFR) is impaired in patients with hypertension and is an independent predictor of cardiac morbidity. However, data on the effect of RDN on TDE-CFR are scarce. The main objective of this study was to assess the effect of RDN on TDE-CFR. Twenty-six consecutive patients with RH (9 female and 17 male; mean age 62 ± 8 years; mean number of antihypertensive drugs 4·2 ± 1·6) underwent bilateral RDN. CFR was assessed at baseline and 6 months after intervention. Mean flow velocity was measured in the left anterior descending artery by transthoracic Doppler echocardiography at baseline and during adenosine infusion (TDE-CFR). Systolic office blood pressure was reduced at follow-up (174 ± 24 versus 162 ± 27 mmHG; P = 0·01). Mean systolic ambulatory blood pressure decreased from 151 ± 21 to 147 ± 18 (P = 0·17). TDE-CFR remained unchanged 6 months after intervention (2·7 ± 0·6 versus 2·7 ± 0·7; P = 0·67). In conclusion, renal denervation was not associated with any changes in regard to coronary flow reserve at 6-month follow-up.
Subject(s)
Blood Pressure , Coronary Circulation , Hypertension/surgery , Kidney/blood supply , Renal Artery/innervation , Sympathectomy/methods , Aged , Antihypertensive Agents/therapeutic use , Blood Flow Velocity , Blood Pressure/drug effects , Drug Resistance , Echocardiography, Doppler , Female , Humans , Hypertension/diagnostic imaging , Hypertension/physiopathology , Male , Middle Aged , Sympathectomy/adverse effects , Time Factors , Treatment OutcomeABSTRACT
BACKGROUND: Parvovirus B19 (PVB19) has emerged as one of the viruses possibly inducing chronic myocarditis and subsequent idiopathic dilated cardiomyopathy (IDCM). The aim of this work was to investigate the presence and long-term consequences of PVB19-DNA within myocardial biopsies from patients with IDCM and to compare the findings with those from donor hearts (control group). METHODS AND RESULTS: Forty hospitalized IDCM patients (age 47 ± 12 y) with mean left ventricular ejection fraction 27 ± 12% were included. The presence of PVB19-DNA in myocardial biopsies and of IgG and IgM antibodies in patient sera was analyzed. The control group consisted of 20 donor hearts. The follow-up time was 112 ± 57 months. PVB19-DNA was found in myocardial biopsies of both patients (73%) and control samples (55%; Pâ¯=â¯.25).Three deaths and 8 heart transplantations occurred in the IDCM group, and 6 deaths in the control group (ie, the recipients of the control hearts). No difference in transplantation-free survival between the PVB19-DNA positive/negative IDCM patients or transplant recipients was found. CONCLUSIONS: PVB19-DNA is a common finding in both patients with IDCM and in healthy donor hearts, not affecting prognosis. These findings support the view that PVB19 is an innocent bystander, frequently found in myocardium with low DNA copies, and not a plausible cause of IDCM.
Subject(s)
Cardiomyopathy, Dilated/pathology , Cardiomyopathy, Dilated/virology , Endocardium/pathology , Endocardium/virology , Myocardium/pathology , Parvovirus B19, Human/isolation & purification , Adult , Female , Follow-Up Studies , Humans , Male , Middle Aged , Prospective StudiesABSTRACT
Background The management of the cardiorenal syndrome in advanced heart failure is challenging, and the role of inotropic drugs has not been fully defined. Our aim was to compare the renal effects of levosimendan versus dobutamine in patients with heart failure and renal impairment. Methods and Results In a randomized double-blind study, we assigned patients with chronic heart failure (left ventricular ejection fraction <40%) and impaired renal function (glomerular filtration rate <80 mL/min per 1.73 m2) to receive either levosimendan (loading dose 12 µg/kg+0.1 µg/kg per minute) or dobutamine (7.5 µg/kg per minute) for 75 minutes. A pulmonary artery catheter was used for measurements of systemic hemodynamics, and a renal vein catheter was used to measure renal plasma flow by the infusion clearance technique for PAH (para-aminohippurate) corrected by renal extraction of PAH . Filtration fraction was measured by renal extraction of chromium ethylenediamine tetraacetic acid. A total of 32 patients completed the study. Following treatment, the levosimendan and dobutamine groups displayed similar increases in renal blood flow (22% and 26%, respectively) with no significant differences between groups. Glomerular filtration rate increased by 22% in the levosimendan group but remained unchanged in the dobutamine group ( P=0.012). Filtration fraction was not affected by levosimendan but decreased by 17% with dobutamine ( P=0.045). Conclusions In patients with chronic heart failure and renal impairment, levosimendan increases glomerular filtration rate to a greater extent than dobutamine and thus may be the preferred inotropic agent for treating patients with the cardiorenal syndrome. Clinical Trial Registration URL: https://www.clinicaltrials.gov . Unique identifier: NCT 02133105.
Subject(s)
Cardio-Renal Syndrome/drug therapy , Cardiotonic Agents/therapeutic use , Dobutamine/therapeutic use , Heart Failure/drug therapy , Renal Insufficiency/metabolism , Simendan/therapeutic use , Aged , Double-Blind Method , Female , Glomerular Filtration Rate , Heart Failure/complications , Hemodynamic Monitoring , Hemodynamics , Humans , Male , Middle Aged , Renal Circulation , Renal Insufficiency/complications , Renal Plasma Flow , p-Aminohippuric AcidABSTRACT
Aims: Hypertension (HTN) is a well-known contributor to cardiovascular disease, including heart failure (HF) and coronary artery disease, and is the leading risk factor for premature death world-wide. A J- or U-shaped relationship has been suggested between blood pressure (BP) and clinical outcomes in different studies. However, there is little information about the significance of BP on the outcomes of patients with coronary artery disease and left ventricular dysfunction. This study aimed to determine the relationship between BP and mortality outcomes in patients with ischaemic cardiomyopathy. Methods and results: The influence of BP during a median follow-up of 9.8 years was studied in a total of 1212 patients with ejection fraction ≤35% and coronary disease amenable to coronary artery bypass grafting (CABG) who were randomized to CABG or medical therapy alone (MED) in the STICH (Surgical Treatment for Ischaemic Heart Failure) trial. Landmark analyses were performed starting at 1, 2, 3, 4, and 5 years after randomization, in which previous systolic BP values were averaged and related to subsequent mortality through the end of follow-up with a median of 9.8 years. Neither a previous history of HTN nor baseline BP had any significant influence on long-term mortality outcomes, nor did they have a significant interaction with MED or CABG treatment. The landmark analyses showed a progressive U-shaped relationship that became strongest at 5 years (χ2 and P-values: 7.08, P = 0.069; 8.72, P = 0.033; 9.86; P = 0.020; 8.31, P = 0.040; 14.52, P = 0.002; at 1, 2, 3, 4, and 5-year landmark analyses, respectively). The relationship between diastolic BP (DBP) and outcomes was similar. The most favourable outcomes were observed in the SBP range 120-130, and DBP 75-85 mmHg, whereas lower and higher BP were associated with worse outcomes. There were no differences in BP-lowering medications between groups. Conclusion: A strong U-shaped relationship between BP and mortality outcomes was evident in ischaemic HF patients. The results imply that the optimal SBP might be in the range 120-130 mmHg after intervention, and possibly be subject to pharmacologic action regarding high BP. Further, low BP was a marker of poor outcomes that might require other interactions and treatment strategies. Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00023595.