Short and long-term complications of hypertensive disorders of pregnancy: lifelong cardiovascular risks we cannot ignore.

PURPOSE OF REVIEW: Hypertensive disorders of pregnancy (HDP) pose a significant threat to maternal cardiovascular health, with emerging research shedding light on the enduring risks beyond the gestational period. This review highlights updates regarding cardiovascular risks associated with HDP and their implications for long-term health. RECENT FINDINGS: Patients with a history of HDP are at an elevated risk of developing chronic hypertension, ischemic heart disease, stroke, valvular heart disease, and heart failure.Not surprisingly, patients with HDP experience higher rates of maternal and fetal adverse events in the antepartum and immediate postpartum periods, with high readmission rates for cardiovascular complications. The high risk of chronic hypertension after a HDP then leads to the development of subclinical disease over 5-10 years with overt cardiovascular disease becoming most prevalent in the decades following pregnancy. Early hypertension management in the antepartum and postpartum periods has lifelong health benefits and highlights the need for seamless postpartum transitions with close blood pressure monitoring and cardiovascular risk mitigation. SUMMARY: HDP significantly increases the risk of short and long-term adverse cardiovascular events. Integrated healthcare models that assess and address postpartum cardiovascular risk are necessary to improve the cardiovascular health and longevity of those effected by HDP.

A Rare Case of Obstructive Shock due to Cardiac Tamponade in a Term Pregnancy.

Obstructive shock due to cardiac tamponade is a rare, life-threatening occurrence in the peripartum period. Etiologies include preeclampsia, infection, autoimmune conditions, and malignancy. Early recognition of the underlying disease process allows for multidisciplinary treatment and a favorable outcome. A 33-year-old presented for cardiac tamponade identified in the peripartum period. She was diagnosed with preeclampsia with severe features immediately prior to her repeat cesarean delivery and received magnesium prophylaxis. Postoperatively, she developed hypotension, tachycardia, and shortness of breath and was found to have a pericardial effusion with tamponade physiology. She underwent pericardial drain placement which was initially successful. However, she had recurrent symptomatic tamponade and thus a pericardial window was performed resulting in improvement of her symptoms. Workup revealed pericardial inflammation possibly secondary to a viral source, and she was successfully treated with anti-inflammatory therapy. We hypothesize that this patient's cardiac tamponade was caused by inflammatory pericarditis exacerbated by severe preeclampsia. Preeclampsia is a disease characterized by cardiovascular remodeling and fluid shifts in other compartments and thus is theorized to have contributed to this patient's effusion. Cardiac tamponade should be considered in the differential for any parturient presenting with hypotension and shortness of breath.

Continuous non-invasive hemodynamic monitoring in early onset severe preeclampsia.

OBJECTIVES: Continuous hemodynamic monitoring offers the opportunity to individualize management in severe preeclampsia (PEC). We compared cardiac output (CO) and total peripheral resistance (TPR) measured by bioreactance (NICOM), Clearsite™ Fingercuff [CS), and 3D-echocardiography (3DE). STUDY DESIGN: This prospective observational study included 12 pregnant patients with early PEC. CO and TPR were measured simultaneously by NICOM, CS, and 3DE antepartum and 1-2 days postpartum. Using 3DE as the standard, CS and NICOM interchangeability, precision, accuracy, and correlation were assessed. RESULTS: Compared to 3DE-CO, CS-CO was highly correlated (R2 = 0.70, p = <0.0001) with low percentage error (PE 29%) which met criteria for interchangeablity. CS-TPR had strong correlation (R2 = 0.81, p = <0.0001) and low PE (29%). While CS tended to slightly overestimate CO (bias + 2.05 ±1.18 L/min, limit of agreement (LOA) -0.20 to 4.31) and underestimate TPR (bias -279 ±156 dyes/sec/cm5; LOA -580 to 18.4) these differences were unlikely to be clinically significant. Thus CS could be interchangeable with 3DE for CO and TPR. NICOM-CO had only moderate correlation with 3DE-CO (R2 = 0.29, p = 0.01) with high PE (52%) above threshold for interchangeability. NICOM-CO had low mean bias (-1.2 ±1.68 L/min) but wide 95% LOA (-4.41 to 2.14) suggesting adequate accuracy but low precision in relation to 3DE-CO. NICOM-TPR had poor correlation with 3DE-TPR (R2 = 0.32, p = 0.001) with high PE (67%), relatively low mean bias (238 ±256), and wide 95% LOA (-655 to 1131). NICOM did not meet the criteria for interchangeable with 3DE for CO and TPR. CONCLUSIONS: Clearsite Fingercuff, but not NICOM, has potential to be clinically useful for CO and TPR monitoring in severe preeclampsia.

Seizing the Window of Opportunity Within 1 Year Postpartum: Early Cardiovascular Screening.

Background Our objective was to assess new chronic hypertension 6 to 12 months postpartum for those with hypertensive disorder of pregnancy (HDP) compared with normotensive participants. Methods and Results We performed a prospective cohort study of participants with singleton gestations and no known preexisting medical conditions who were diagnosed with HDP compared with normotensive women with no pregnancy complications (non-HDP). Participants underwent cardiovascular risk assessment 6 to 12 months after delivery. Primary outcome was onset of new chronic hypertension at 6 to 12 months postpartum. We also examined lipid values, metabolic syndrome, prediabetes, diabetes, and 30-year cardiovascular disease (CVD) risk. Multivariable logistic regression was performed to assess the association between HDP and odds of a postpartum diagnosis of chronic hypertension while adjusting for parity, body mass index, insurance, and family history of CVD. There were 58 participants in the HDP group and 51 participants in the non-HDP group. Baseline characteristics between groups were not statistically different. Participants in the HDP group had 4-fold adjusted odds of developing a new diagnosis of chronic hypertension 6 to 12 months after delivery, compared with those in the non-HDP group (adjusted odds ratio, 4.60 [95% CI, 1.65-12.81]), when adjusting for body mass index, parity, family history of CVD, and insurance. Of the HDP group, 58.6% (n=34) developed new chronic hypertension. Participants in the HDP group had increased estimated 30-year CVD risk and were more likely to have metabolic syndrome, a higher fasting blood glucose, and higher low-density lipoprotein cholesterol. Conclusions Participants without known underlying medical conditions who develop HDP have 4-fold increased odds of new diagnosis of chronic hypertension by 6 to 12 months postpartum as well as increased 30-year CVD risk scores. Implementation of multidisciplinary care models focused on CVD screening, patient education, and lifestyle interventions during the first year postpartum may serve as an effective primary prevention strategy for the development of CVD.

Noonan syndrome and pregnancy outcomes.

BACKGROUND: Noonan syndrome is a genetic disorder with high prevalence of congenital heart defects, such as pulmonary stenosis, atrial septal defect and hypertrophic cardiomyopathy. Scarce data exists regarding the safety of pregnancy in patients with Noonan syndrome, particularly in the context of maternal cardiac disease. STUDY DESIGN: We performed a retrospective chart review of patients at Yale-New Haven Hospital from 2012 to 2020 with diagnoses of Noonan syndrome and pregnancy. We analysed medical records for pregnancy details and cardiac health, including echocardiograms to quantify maternal cardiac dysfunction through measurements of pulmonary valve peak gradient, structural heart defects and interventricular septal thickness. RESULTS: We identified five women with Noonan syndrome (10 pregnancies). Three of five patients had pulmonary valve stenosis at the time of pregnancy, two of which had undergone cardiac procedures. 50% of pregnancies (5/10) resulted in pre-term birth. 80% (8/10) of all deliveries were converted to caesarean section after a trial of labour. One pregnancy resulted in intra-uterine fetal demise while nine pregnancies resulted in the birth of a living infant. 60% (6/10) of livebirths required care in the neonatal intensive care unit. One infant passed away at 5 weeks of age. CONCLUSIONS: The majority of mothers had pre-existing, though mild, heart disease. We found high rates of prematurity, conversion to caesarean section, and elevated level of care. No maternal complications resulted in long-term morbidity. Our study suggests that women with Noonan syndrome and low-risk cardiac lesions can become pregnant and deliver a healthy infant with counselling and risk evaluation.

Mechanical Circulatory Support in Myocardial Infarction Complicated by Cardiogenic Shock: Impact of Sex and Timing.

Background: Sex differences in presentation, treatment, and outcomes persist in patients with acute myocardial infarction complicated by cardiogenic shock (AMICS). Sex-based outcomes of patients with AMICS undergoing percutaneous coronary intervention (PCI) with percutaneous left ventricular assist device (pLVAD) support are poorly defined. Methods: From January 2017 to August 2019, consecutive patients undergoing PCI who received Impella support within 48 â€‹hours of myocardial infarction were enrolled in the prospective RECOVER III postmarket registry. In-hospital survival and predictors of mortality were compared by sex. Results: A total of 358 patients (276 men and 82 women) were included. Women had lower baseline mean arterial pressure and shorter duration of pLVAD support compared with men. In-hospital adverse events were similar in women and men, including mortality (54% versus 46%, P = .25), major bleeding (11% versus 10%, P = .83), and vascular complications requiring surgery (8.5% versus 4%, P = .10). Women had better survival with pre-PCI versus post-PCI pLVAD implantation (59% versus 34%, P = .03), whereas survival in men was similar regardless of pre- versus post-PCI pLVAD support (56% versus 50%, P = .39). The number of inotrope/vasopressor use pre-pLVAD was the strongest predictor of mortality in women (OR 3.03, P = .01) but not in men (OR 1.18, P = .25). Conclusions: Survival of patients with AMICS treated with PCI and Impella support was 52% at hospital discharge and was similar for women and men. Women with AMICS may derive greater benefit from early pLVAD support prior to escalation of inotrope/vasopressors and had no evidence of increased risk of access-related complications.

Impact of Preoperative Lymphopenia on Survival Following Left Ventricular Assist Device Placement.

Lymphopenia has been implicated in poor outcomes in the heart failure population. However, the prognostic implication of lymphopenia in left ventricular assist device (LVAD) patients is unknown. We examine the impact of lymphopenia on all-cause mortality in this population over a 24-month period post-implantation. A total of 170 patients between June 2011 and July 2018 receiving permanent durable LVAD at a single center formed the study population. Criteria for lymphopenia on admission, defined as an absolute lymphocyte count (ALC) <1500 cells/µl, was met in 99 patients. A total of 11 patients were excluded: two with ALC >4800/µl and nine with incomplete data. Survival across groups was compared with a Kaplan-Meier plot and log-rank statistics. The Cox proportional hazard model was used to examine the association between lymphopenia and 24-month all-cause mortality. In the lymphopenia group, mean ALC was 909.6 ± 331.9 versus 2073.6 ± 501.1 in the non-lymphopenic group. Twenty-four-month all-cause mortality was significantly higher in the lymphopenia group (p = 0.009). The lymphopenic patients had worse unadjusted (hazard ratio [HR] = 2.14, confidence interval [CI] = 1.19-3.82; p = 0.01) and adjusted survival (HR = 2.07, CI = 1.13-3.79; p = 0.02). Further clinical investigations are required to assess the utility of continued clinical monitoring of ALC levels beyond LVAD placement.

Cardio-obstetrics: Recognizing and managing cardiovascular complications of pregnancy.

Pregnancy can exacerbate known cardiovascular disorders and unmask previously unrecognized problems. Patients with congenital heart disorders, valvular disease, primary pulmonary hypertension, hypertensive disorders of pregnancy, and acquired peripartum cardiomyopathy need a collaborative interdisciplinary team that includes a cardiologist with specialty training in obstetrics.

Access and Outcomes Among Hypertrophic Cardiomyopathy Patients in a Large Integrated Health System.

Background Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiomyopathy. Current guidelines endorse management in expert centers, but patient socioeconomic status can affect access to specialty care. The effect of socioeconomic status and specialty care access on HCM outcomes has not been examined. Methods and Results We conducted a retrospective cohort study that examined outcomes among HCM patients receiving care in the Yale New Haven Health System between June 2011 and December 2017. Patients were assigned to lower or higher socioeconomic status groups (LSES/HSES) based on medical insurance provider and to receivers of specialty care (SC) at Yale's Inherited Cardiomyopathy clinic or general cardiology care (GC). The primary outcome was all-cause death, and the secondary outcome was all-cause hospitalization. We identified 953 HCM patients; 820 (86%) were HSES and 133 (14%) were LSES. Forty-three (4.5%) patients died from cardiac and noncardiac causes. LSES patients within the general cardiology care cohort had significantly higher all-cause mortality compared with HSES patients (adjusted hazard ratio, [95% CI]=10.06 [4.38-23.09]; P<0.001). This was not noted in the specialty care cohort (adjusted hazard ratio, [95% CI]=2.87 [0.56-14.73]; P=0.21). The moderator effect of specialty care on mortality difference between LSES versus HSES, however, did not reach statistical significance (hazard ratio, 0.29 [0.05-1.77]; P=0.18). Specialist care was associated with increased hospitalization (adjusted hazard ratio, [95% CI]=3.28 [1.11-9.73]; P=0.03 for LSES; 2.19 [1.40-3.40]; P=0.001 for HSES). Conclusions Socioeconomically vulnerable HCM patients had higher mortality when not referred to specialty care. Further study is needed to understand the underlying causes.

Subaortic Stenosis With Elevated Aortic Gradients in a Pregnant Patient.

Subaortic stenosis is an obstructive lesion that may be exacerbated by pregnancy. We describe the management of a 39-year-old woman presenting at 37 weeks of pregnancy with a murmur who is found to have a subaortic membrane with severely elevated left ventricular outflow gradients. (Level of Difficulty: Beginner.).

Permanent Continuous Flow Left Ventricular Assist Devices Use After Acute Stabilization for Cardiogenic Shock in Acute Myocardial Infarction.

Cardiogenic shock complicating acute myocardial infarctions (CS-AMIs) carries high mortality rates. Early use of durable continuous flow left ventricular assist devices (CF-LVAD) in these patients has traditionally been discouraged. Therefore we sought to assess the efficacy and complications of CF-LVAD use in CS-AMI after stabilization with temporary mechanical support. From January 2006 to November 2014, nine patients underwent CF-LVAD implant after CS-AMI (Heartmate II, six; HVAD, three). All patients required temporary mechanical circulatory support (MCS) before CF-LVAD implant and were interagency registry for mechanically assisted circulatory support profile 1; average time from MI to CF-LVAD implant was 20 days. Overall seven of nine patients (78%) survived to discharge. Survival at 1, 3, 12, and 48 months was 100%, 89%, 67%, and 67%, respectively. Two patients were successfully bridged to transplant and four patients remain alive on device support. The most common post-LVAD complication was stroke, occurring in 55% of patients. Embolic strokes were mild in severity and all patients survived with only mild deficits; hemorrhagic strokes conferred the highest mortality. This study suggests CF-LVADs are potential but high-risk treatment options for CS-AMI patients who stabilize with temporary support. Further studies will help more clearly delineate the benefits and risks of CF-LVAD implant in this population.

Mechanical circulatory devices in acute heart failure.

Cardiogenic shock remains a leading cause of mortality despite advances in the treatment of myocardial infarction and advanced heart failure. Medical therapy can be inadequate, and patients may need mechanical circulatory support (MCS). The proper application of MCS requires knowledge of the underlying cause of acute heart failure, familiarity with the circulatory support devices, and the potential benefits and limitations of device therapy. This article describes the most commonly used temporary ventricular assist devices and their use in the various causes of cardiogenic shock.

Effect of QRS morphology on clinical event reduction with cardiac resynchronization therapy: meta-analysis of randomized controlled trials.

BACKGROUND: Cardiac resynchronization therapy (CRT) is effective in reducing clinical events in systolic heart failure patients with a wide QRS. Previous retrospective studies suggest only patients with QRS prolongation due to a left bundle-branch block (LBBB) benefit from CRT. Our objective was to examine this by performing a meta-analysis of all randomized controlled trials of CRT. METHODS: Systematic searches of MEDLINE and the Food and Drug Administration official website were conducted for randomized controlled CRT trials. Trials reporting adverse clinical events (eg, all-cause mortality, heart failure hospitalizations) according to QRS morphology were included in the meta-analysis. RESULTS: Four randomized trials totaling 5,356 patients met the inclusion criteria. In patients with LBBB at baseline, there was a highly significant reduction in composite adverse clinical events with CRT (RR = 0.64 [95% CI (0.52-0.77)], P = .00001). However no such benefit was observed for patients with non-LBBB conduction abnormalities (RR = 0.97 [95% CI (0.82-1.15)], P = .75). When examined separately, there was no benefit in patients with right-bundle branch block (RR = 0.91 [95% CI (0.69-1.20)], P = .49) or non-specific intraventricular conduction delay (RR = 1.19 [95% CI (0.87-1.63)], P = .28). There was no heterogeneity among the clinical trials with regards to the lack of benefit in non-LBBB patients (I(2) = 0%). When directly compared, the difference in effect of CRT between LBBB versus non-LBBB patients was highly statistically significant (P = .0001 by heterogeneity analysis). CONCLUSIONS: While CRT was very effective in reducing clinical events in patients with LBBB, it did not reduce such events in patients with wide QRS due to other conduction abnormalities.

Meta-analysis of randomized controlled trials on effect of angiotensin-converting enzyme inhibitors on cancer risk.

The renin-angiotensin system is an important mediator of tumor progression and metastasis. A recent meta-analysis of randomized controlled trials reported an increased risk of cancer with angiotensin receptor blockers. It is unknown whether angiotensin-converting enzyme (ACE) inhibitors may have a similar effect. Our primary objective was to determine the effect of ACE inhibitors on cancer occurrence and cancer death. Our secondary objective was to determine the effect of ACE inhibitors on occurrence of gastrointestinal (GI) cancers given previous concerns of increased risk. Systematic searches of SCOPUS (covering MEDLINE, EMBASE, and other databases) and the Food and Drug Administration official web site were conducted for all randomized controlled trials of ACE inhibitors. Trials with ≥1 year of follow-up and enrolling a minimum of 100 patients were included. Fourteen trials reported cancer data in 61,774 patients. This included 10 trials of 59,004 patients providing information on cancer occurrence, 7 trials of 37,515 patients for cancer death, and 5 trials including 23,291 patients for GI cancer. ACE inhibitor therapy did not have an effect on occurrence of cancer (I(2) 0%, risk ratio [RR] 1.01, 95% confidence interval [CI] 0.95 to 1.07, p = 0.78), cancer death (I(2) 0%, RR 1.00, 95% CI 0.88 to 1.13, p = 0.95), or GI cancer (RR 1.09, 95% CI 0.88 to 1.35, p = 0.43). In conclusion, ACE inhibitors did not significantly increase or decrease occurrence of cancer or cancer death. There was also no significant difference in risk of GI cancer.

Nasopharyngeal carcinoma--review of the molecular mechanisms of tumorigenesis.

Nasopharyngeal carcinoma (NPC) is a head and neck cancer rare throughout most of the world but common in certain geographic areas, such as southern Asia. While environmental factors and genetic susceptibility play important roles in NPC pathogenesis, the Epstein-Barr virus in particular has been implicated in the molecular abnormalities leading to NPC. There is upregulation of cellular proliferation pathways such as the Akt pathway, mitogen-activated protein kinases, and the Wnt pathway. Cell adhesion is compromised due to abnormal E-cadherin and beta-catenin function. Aberrations in cell cycle are due to dysregulation of factors such as p16, cyclin D1, and cyclin E. Anti-apoptotic mechanisms are also upregulated. There are multiple abnormalities unique to NPC that are potential targets for novel treatments.

Wnt signaling activation and WIF-1 silencing in nasopharyngeal cancer cell lines.

Aberrant activation of Wingless-type (Wnt) signaling pathway plays a critical role in oncogenesis of various human cancers. Wnt inhibitory factor-1 (WIF-1) is a secreted antagonist of Wnt signaling and acts through direct binding to Wnt in the extracellular space. Recently, we reported Wnt signaling in various human malignancies. In addition, we identified in lung cancer that WIF-1 is silenced due to promoter hypermethylation. In this study, we found constitutive activation of Wnt signaling and WIF-1 silencing in nasopharyngeal carcinoma (NPC) cell lines. Furthermore, by utilizing methylation-specific PCR and sequence analysis, we demonstrated that frequent hypermethylation of the WIF-1 promoter correlates with WIF-1 silencing in NPC cell lines. Our results indicate that aberrant Wnt signaling is a common event in NPC carcinogenesis linked with WIF-1 silencing in at least cell lines. Strategies targeting these molecules should be potentially promising in treating NPC.